Comprehensive Guide to Angina: Types, Pathophysiology, and Pharmacologic Management

Name: Antianginal Drugs Pharmacology | Dr Najeeb🩺
Uploaded: 2026-01-16T06:14:38.641751+00:00
Channel: Dr. Najeeb Lectures
Description: Summary and key takeaways on Comprehensive Guide to Angina: Types, Pathophysiology, and Pharmacologic Management, covering What Is Angina? Angina = central
Dr. Najeeb Lectures
Jan 16, 2026
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5 min read
YouTube video ID: nEWvcIG51ZE
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What Is Angina?

Angina = central chest discomfort (pressure, heaviness, burning) that may radiate to arms, neck, jaw, or epigastrium.
It reflects transient, reversible myocardial ischemia caused by an imbalance between oxygen supply and demand.
Classic episodes last 15 seconds to 15 minutes; >20 minutes usually progresses to myocardial infarction.
Major Types of Angina

Stable (Classical/Typical) Angina
Fixed atherosclerotic plaque >70 % lumen narrowing.
Ischemia occurs during exertion or emotional stress when the stenotic segment cannot dilate.
Pain resolves with rest or sublingual nitrates.
Variant (Prinzmetal) Angina
Coronary artery vasospasm with little or no plaque.
Can occur at rest, often in the early morning; more common in women.
Not relieved by rest alone; responds to coronary vasodilators.
Unstable Angina
Unstable plaque (thin‑cap, inflamed) that ruptures, ulcerates, or hemorrhages.
Platelet aggregation and thrombus formation cause dynamic obstruction.
Pain is more severe, frequent, may occur at rest, and does not respond to nitrates or rest.
If ischemia persists >20 minutes → myocardial infarction.
Core Therapeutic Principle

Reduce myocardial oxygen demand until it matches the limited supply. This is achieved by lowering: - Preload (venous return → end‑diastolic volume) - Afterload (arterial resistance) - Heart rate & contractility (chronotropy, inotropy)
Drug Classes & How They Fit the Principle

Class	Primary Mechanism	Effect on Preload/Afterload/HR/Contractility	Typical Indications
Nitrates (glyceryl trinitrate, isosorbide dinitrate/mononitrate)	Release NO → ↑cGMP → venous (strong) & arterial (weak) dilation	↓Preload (venous pooling) → ↓LV wall stress; modest ↓Afterload; improves collateral flow	First‑line for stable angina, acute relief (sublingual), prophylaxis (patches, oral SR)
Beta‑blockers (atenolol, metoprolol, propranolol)	Block β₁ receptors → ↓ SA‑node firing, ↓ AV‑node conduction, ↓ myocardial contractility	↓Heart rate, ↓stroke volume, ↓afterload (via reduced sympathetic tone)	Stable angina, post‑MI, hypertension; combined with nitrates to blunt reflex tachycardia
Calcium‑channel blockers (dihydropyridines: amlodipine, nifedipine; non‑dihydro: verapamil, diltiazem)	Inhibit L‑type Ca²⁺ channels → smooth‑muscle relaxation & ↓ Ca²⁺‑dependent myocardial contraction	Dihydropyridines: ↓Afterload (arterial dilation); Non‑dihydro: ↓HR & contractility + modest arterial dilation	Variant angina (vasospasm) → dihydropyridines; add‑on for stable angina when nitrates/β‑blockers insufficient
Antiplatelet/Antithrombotic (aspirin, clopidogrel)	Inhibit platelet aggregation → prevent thrombus on unstable plaque	No direct hemodynamic effect	Long‑term secondary prevention, especially in unstable angina/ACS
Statins	HMG‑CoA reductase inhibition → LDL lowering & plaque stabilization	No direct hemodynamic effect	Chronic risk‑factor modification; reduces progression to unstable plaque
Nitrates in Detail

Sublingual: onset 1‑2 min, duration ~30 min – ideal for acute attacks.
Oral SR/ER: onset 30 min, duration 6‑12 h – for prophylaxis.
Transdermal patch: onset ~30 min, duration 8‑12 h.
Tolerance develops after ~12‑16 h of continuous exposure; a 6‑8 h nitrate‑free interval restores responsiveness.
Adverse effects: severe headache (meningeal vessel dilation), facial flushing, orthostatic hypotension, reflex tachycardia (mitigated by β‑blockers).
Beta‑Blockers: Key Points & Contra‑indications

Reduce SA‑node automaticity → negative chronotropy.
Reduce AV‑node conduction → negative dromotropy.
Decrease contractility → negative inotropy.
Do NOT use in uncontrolled asthma/COPD, severe bradyarrhythmias, insulin‑dependent diabetes with frequent hypoglycemia (masking warning signs), peripheral vasospastic disorders (Raynaud), major depression, or acute decompensated heart failure.
Abrupt discontinuation after long‑term use can cause rebound tachycardia and hypertension due to β‑receptor up‑regulation.
Calcium‑Channel Blockers: Nuances

Dihydropyridines (amlodipine, nifedipine) act mainly on arterial smooth muscle → ↓afterload, useful for vasospastic (Prinzmetal) angina.
Non‑dihydro (verapamil, diltiazem) have stronger cardiac effects → ↓HR, ↓AV‑node conduction, modest arterial dilation; useful when heart‑rate control is needed.
Side‑effects mirror nitrates for dihydropyridines (headache, flushing) and β‑blockers for non‑dihydro (fatigue, bradycardia, possible heart block).
Excessive dosing can cause reflex tachycardia (due to blood‑pressure drop) or sinus arrest/complete heart block; combining with a β‑blocker or using a cardio‑selective CCB mitigates this.
Integrated Management Strategy

Acute Relief – Sublingual nitroglycerin ± oxygen; if pain persists, consider IV nitrates and add β‑blocker.
Chronic Control –
First line: Nitrates (long‑acting) + β‑blocker.
Add‑on: Dihydropyridine CCB if angina persists or for variant angina.
Alternative: Non‑dihydro CCB when β‑blocker contraindicated.
Plaque Stabilization & Risk‑Factor Modification – Statins, aspirin, smoking cessation, blood‑pressure & diabetes control, regular aerobic exercise.
Revascularization – PTCA (angioplasty) or CABG for >90 % stenosis or refractory symptoms despite optimal medical therapy.
Practical “Donkey” Analogy Recap

Heart = donkey carrying a load (preload) up a slope (afterload) many times per minute.
Ischemic donkey cries (angina) when the load or slope is too high.
Therapy = lighten the load (venodilators), smooth the slope (arteriolar dilators), and slow the donkey’s steps (β‑blockers/CCBs) so it can work without pain.
Quick Reference Table

Situation	Preferred Drug(s)
Stable exertional angina	Sublingual nitrate + β‑blocker; add dihydropyridine CCB if needed
Variant (Prinzmetal) angina	Dihydropyridine CCB (nifedipine/amlodipine) ± long‑acting nitrate
Unstable angina	Immediate antiplatelet (aspirin), anticoagulation, possible IV nitrates; β‑blocker if no contraindication; early invasive strategy
Contra‑indication to β‑blocker (asthma)	Nitrate + dihydropyridine CCB
Severe hypertension with angina	Combine CCB (afterload reduction) with nitrate; avoid reflex tachycardia by adding β‑blocker if tolerated
Monitoring & Follow‑Up

Assess frequency/intensity of chest pain, exercise tolerance, and side‑effect profile.
Verify nitrate‑free interval to prevent tolerance.
Check heart rate and blood pressure after initiating β‑blocker or CCB.
Lipid panel, HbA1c, and smoking status every 3‑6 months for secondary prevention.
When to Escalate

Pain lasting >20 minutes despite maximal medical therapy.
New‑onset rest pain, dynamic ECG changes, or rising cardiac biomarkers → treat as acute coronary syndrome and consider urgent revascularization.
Effective angina control hinges on matching myocardial oxygen demand to its limited supply—by reducing preload, afterload, heart rate, and contractility—using nitrates, beta‑blockers, and calcium‑channel blockers, while also stabilizing plaques with statins and antiplatelet agents and addressing lifestyle risk factors.
Frequently Asked Questions

Who is Dr. Najeeb Lectures on YouTube?

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Does this page include the full transcript of the video?

Yes, the full transcript for this video is available on this page. Click 'Show transcript' in the sidebar to read it.
What Is Angina?

- Angina = central chest discomfort (pressure, heaviness, burning) that may radiate to arms, neck, jaw, or epigastrium. - It reflects **transient, reversible myocardial ischemia** caused by an imbalance between oxygen supply and demand. - Classic episodes last **15 seconds to 15 minutes**; >20 minutes usually progresses to myocardial infarction.
When to Escalate

- Pain lasting >20 minutes despite maximal medical therapy. - New‑onset rest pain, dynamic ECG changes, or rising cardiac biomarkers → treat as acute coronary syndrome and consider urgent revascularization. --- Effective angina control hinges on matching myocardial oxygen demand to its limited supply—by reducing preload, afterload, heart rate, and contractility—using nitrates, beta‑blockers, and calcium‑channel blockers, while also stabilizing plaques with statins and antiplatelet agents and addressing lifestyle risk factors.
Helpful resources related to this video

If you want to practice or explore the concepts discussed in the video, these commonly used tools may help.
Nitroglycerin Sublingual Tablets Recommended
Provides rapid venous dilation to lower preload and relieve acute angina attacks; essential for on‑the‑spot symptom control
Amazon →
Atenolol 50 Mg Tablets
Selective β₁‑blocker that lowers heart rate and contractility, reducing myocardial oxygen demand in stable angina
Amazon →
Amlodipine Besylate 5 Mg Tablets
Dihydropyridine calcium‑channel blocker that dilates coronary arterioles, ideal for variant (Prinzmetal) angina and afterload reduction
Amazon →
Atorvastatin 20 Mg Tablets
Statin that lowers LDL cholesterol and stabilizes atherosclerotic plaques, decreasing the risk of progression to unstable angina or MI
Amazon →
Links may be affiliate links. We only include resources that are genuinely relevant to the topic.
Summarize another video
Full Transcript YouTube

now today we will be discussing about
anti-anginal drugs but before I really
start the drugs I will briefly review
about the pathophysiology of important
type of anginais right first of all I
will Define that what is angina angina
is one of the very common symptom of
cardiac ischemia what is angina and
genome is a Indian is a symptom of
cardiac ischemia how we really Define
angina right angina is
it may be pain it may not be pain look
it is angina is a central chest
discomfort
or pain which may be just like pressing
pain or weight like discomfort or band
like discomfort or like a heavy weight
on the chest and this uncomfortable
feeling in the chest may be radiating to
one arm
or to the both arm or to the neck or to
the jaw or to the epigestion or may not
radiate at all or may be felt only in
the area of radiation
again let me explain what is angina
right angina means and China is a
clinical syndrome resulting from
transient reversible cardiac ischemia it
is resulting from transient reversible
cardiac myocardial ischemia
clinically present as
Central chest pain or chest discomfort
right and this feeling is less like a
pain more like a weight or like pressure
on the chest or like a constricting band
on the chest or sometimes as a burning
sensation right and this chest
discomfort or so-called pain
meridiate to one r or to the both are or
to the neck or to the jaw or to the
epigastrium or may not radiate at all or
sometimes may be felt only in the area
of radiation and why it is there it is
due to transient ischemia of The
myocardium is that right due to
imbalance in oxygen supply and demand
when oxygen supply is less to The
myocardium and demand is more and oxygen
supply needs of myocardium are not met
with that may produce the symptom
symptom complex but a very very
important point is which I have not
mentioned yet about angina is the
duration about in China
typically angina should not last more
than
20 minutes this cutoff point is very
very important usually angina lasts
somewhere between 15 second to 15
minutes
usually most of the angina last
somewhere between 15 second to 15
minutes
foreign which I want to really plant in
your mind is
that angina should not last or does not
last classically by more than 20 minutes
why because if severe chest ischemia
last more than 20 minutes that will lead
to myocardial infarction if we are chest
ischemia or myocardial ischemia
swear myocardial ischemia last more than
20 minutes then it will lead to
myocardial infarction and once there is
infarction of course it is not angina
because by definition angina is
transient reversible scheme of The
myocardium which does not lead to death
of myocardial cells which does not lead
to necrosis of myocardial cells now
typically there are three types of
anginas right
there is
classical in China
classical angina
classical Indiana is also called typical
angina
and classical Indiana typical angina or
another name for the same situation is
yes please
stable angina
stable
angina
and still another name is exertional
angina
desertional
angina
right this type of angina which is
classical angina or which is typical
engineer or which is called stable and
our exertional in China it has a special
type of pathophysiology under it right
now let me tell you what's wrong with
this patient
let's suppose this is a left ventricle
now
here is the coronary artery
suppose this is the coronary artery and
this has a atherosclerotic plaque
the scoring artery has atherosclerotic
plaque and this plaque
atherosclerotic block is obstructing the
Lumen more than 70 percent
if atherosclerotic plaque obstruct the
Lumen more than
70 percent then it is quite possible
that blood flow through the narrow area
may be enough during the resting stage
when patient is resting
the little blood which is coming through
the narrow area may be enough for the
resting myocardium
but as soon as there is increased work
of The myocardium for example when
patient is doing some exertion or due to
some emotional stress or any reason if
heart rate goes up right
then if there is increased work of The
myocardium
then this stenotic point
cannot dilate
and this point does not allow extra
blood for The myocardium which is
demanding more oxygen due to increased
work
and then relative ischemia will go up
again let me tell you exactly what
happens let me make a diagram if I
remove this piece of myocardium outside
this is a piece of myocardium
right
this is the vessel
coronary vessel
now in this coronary vessel let me
repeat in case of which angina classical
Indiana there is atherosclerotic plaque
and this atherosclerotic plaque
will produce symptoms of angina
when it is obstructing more than 70
percent of the lumen if 70 of the Lumen
is blocked by this block right that will
that may produce enough blood for the
resting myocardium but when myocardium
Works extra during tachycardia or
emotional upset so when patient is doing
exercise or there is any type of
increased cardiac work whenever there is
increased cardiac work usually the
healthy vessel dilate and provide extra
blood but this stenotic point cannot
dilate so whenever there is more work
stress on the heart this narrow Point
cannot provide extra blood and this part
of The myocardium this is called
vulnerable myocardium this part of The
myocardium this will become relatively
ischemic does that right and this part
of The myocardium when it becomes
ischemic this is the source of anginal
pain or in general discomfort
is that right now
because this obstruction is stable it
does not changes overnight
this obstruction is stable so usually
the patient's symptoms are also stable
for example that patient has really
predictable exercise that he can walk so
much and then he will get the anginal
pain or in general discomfort
is that right and this type of angina is
always precipitated by exertion or
emotional upsides right and usually
relieved by taking rest the classical
angina is usually relieved by taking
rest because just when you when patient
who was walking and exalting and
myocardium started working more and
demanding more oxygen and because this
point did not
dilate so it could not provide extra
oxygen to the extra working myocardium
ischemia section
start if patients start taking rest
right usually within three four minutes
or few minutes cardiac work in this area
will become so low
cardio work in this area after taking
rest cardiac work in this area will
become so low that it will be able
right
its demand will be able to meet with the
reduced Supply so angina will disappear
is that right or other way to reduce
this type of anginais by giving the
nitrates by giving the nitrates I will
explain later how the nitrates work but
this in China is very predictably
responsive to the nitrates as soon as
you take sublingual nitrates right
within few minutes your stable angina's
pain should disappear
is that clear but one point which is
very important that if this obstruction
become more than 90 percent then even in
General Pain may occur at rest because
if it is obstructed producing
obstruction more than 90 percent of the
Lumen only 10 percent of the Lumen is
perfusing then this so this this very
low perfusion is even not to able to
meet the demands of the resting
myocardium now
this was your classical angina right one
more point which is very important about
the classical angina is that
The myocardium which is more near to the
endocardium this is the deepest
myocardium
is that right and this is a myocardium
which is in superficial area
this is sub pericardial myocardium and
this is sub-endocardial myocardium and
this is the middle myocardium now the
point which I want to highlight
that out of this innermost Zone
middle zone of myocardium and outer zone
of myocardium
first of all ischemia occur to the inner
most Zone why because when chest wall is
when they sorry this myocardial muscle
is Contracting against the blood present
in the cavity right this is the
innermost layer of The myocardium this
layer of The myocardium innermost layer
of The myocardium which is compressed by
the external myocardium and the blood in
the cavity
is that right and when this myocardium
which is called sub endocardial
myocardium is compressed then the micro
circulation through this the small
vessels through this myocardium is also
compressed
is that right so whenever heart is
Contracting strongly it is the inner
myocardium which is most deprived of
perfusion right
and during even a normal heart the outer
myocardium is better perfused and inner
myocardium is poorly perfused is that
right am I clear to everyone this is few
words about classical angina then there
is another type of angina
and this angina
is entirely different than the classical
yeah this is Prince Madame jayana I'm
going to discuss some of my students are
in love with Prince metal right and
remember it now look in this case
real problem is not the atheroseclerotic
layer in this patient atrocyclerotic
leaves are not responsible for the
symptomatology of
angina there may be either very small
atherosclerotic lens or there are not
actually real problem is that coronary
artery has fluctuating tone
right now look at it this is the point
what has happened there is
vasospasticity what is there there is a
Vaso coronary artery spasm right and
this spasm lead to myocardial ischemia
but here the point is very important
ischemia will go to the innermost area
as well as middle area even outer area
is that right because in case of
classical angina there were less blood
coming and this less blood was
preferentially
perfusing the outer myocardium and inner
myocardium was deprived but when we go
to this type of angina which is due to
coronary tone fluctuation it is also
called Prince Metals angina which is
mainly due to coronary arteries
plasticity either with a little bit
atheroseclerotic lean or with no
astrological layer is that right in this
case ischemia will occur throughout the
wall of The myocardium and this is
called transmural ischemia this is
called trans mural ischemia is that
right the this type of angina is not
related with the exertion
this type of angina is not related with
the blood pressure this type of angina
is not related with tachycardia this
type of angina May precipitate even with
when patient is at rest
this type of angina is more common in
females I don't know this plastic
disease why because spasticity is more
common in females but fluctuation
coronary artery tone is more common in
human females so
what really happens that this angina has
been called it has two names one is
Prince metal angina
but there's Metals angina
and other is variant angina variant
angina
now this print metal angina or variant
angina this is basically coronary
vasospastic angina this is coronary Vaso
 angina why I am explaining these
two so clearly because the treatment of
both are slightly different from each
other is that right if I draw a big
piece of myocardium here
here what you will find that coronary
artery
right it has undergone
spasticity
so naturally angina is ischemic pain
ischemia is present throughout the wall
of The myocardium and this ischemical
trans
Ural ischemia right this was what type
of ischemia
yeah this is hemia was sub-endo
cardial
sub endocardial myocardial ischemia is
that in only in the deeper part right
this is full thickness right
now
this type of angina is not related with
the exertion and it is not relieved by
taking rest is that right then we come
to third type of angina
the third type of angina is called
unstable angina and
stable
angina
first let me explain the pathophysiology
of unstable angina then I will tell you
exactly why it is called unstable
angina in patient with unstable angina
what is really there there is unstable
coronary plaque the astrometers plaque
and coronary artery is
unstable
right let me explain it more clearly
suppose this is the piece of myocardium
here is coronary artery
here is etromatous plaque
but the real problem is
that this electromatous plaque is
unstable unstable mean maybe it has
we call such plaques vulnerable plaque
vulnerable plaque means which are not
stable plaques these are having very
thin fibrous cap and lot of inflammatory
activity going on within the plaque and
such plaque May undergo severe acute
changes for example this plaque May
undergo fissuring or ulceration or
erosion or it may undergo inter-block
Hemorrhage any type of acute change may
occur in the block and when there's
acute change in this plaque then its
surface become very irregular and
thrombogenic right when this is this
plug surface is ulcerated or arrogant or
it is fissured or it is ruptured or
there is interlock hemorrhages all these
things expose highly thrombogenic
content from the
throma and platelets will stick on that
platelets will
stick on that let me make it even more
clear if I unlike this area like this
this is the coronary artery this was the
stable plant this was the
stable plan here is let's suppose
another plaque which is unstable and
this plug has very much Disturbed
surface right and over this this is the
intraplock cholesterol and other things
then then superficial layer is Disturbed
maybe there is ulceration or erosion or
fishing or rupture and then platelet
stick on it
these are the platelets which are
sticking on it just platelet adhesion as
well as there is platelet
aggregation platelet adhian plus
platelet aggregation right and there may
be even super super added fibrinogen
fibrinogen which is converted into
fibrin
is that right
because of coagulation process the
coagulate super added coagulation
process converts soluble fibrinogen into
insoluble fibrin over the surface of the
platelet and when platelet plug is load
is
having the deposition of fibrin then
whole this thing is called thrombus all
this thing is called thrombus now look
when this Earth
thrombus has formed over an unstable
plaque this is a right there will be
severe ischemia there will be severe
ischemia and the severe ischemia
right will be initially in deeper part
of The myocardium sub-endocardial
cardium
initially the very sphere ischemia is in
deeper part of myocardium but if this
thrombus remember if this thrombus
occludes the
complete Lumen of the vessel then
ischemia may become transmural is that
right now what you have to remember is
that this unstable plaque has led to the
formation of little plug and coagulation
process over it resulting into thrombo
Tech situation so plaque with super
added thrombus is a dynamic obstruction
this is a dynamic obstruction because
platelet and thrombus keep on changing
their size right and keep on changing
their Mass
size so the degree of occlusion is also
Dynamic so we can say this clock is not
stable because this plaque is not stable
at any moment it may develop a thrombos
and then thrombos may enlarge and
produce severe ischemia this wear
ischemia if it lasts more than 20
minutes now listen with open ears if the
sphere ischemia lasts more than 20
minutes this will under this my
dependent myocardium will undergo
infarction
and if you treat the patient well within
20 minutes
right and due to thrombolysis
or there is spontaneous symbolizes or
pharmacologically induced thrombolysis
within 20 minutes it means infarction
will not be there right due to this
reason this type of angina is said
unstable angina because it is so
unstable that if it is not managed well
if within if it's a obstruction of the
Lumen last more than 20 minutes or 30
minutes it may fall to the category of
myocardial infarction is that clear
right and this type of angina by
definition it is very sphere in China
okay write down the definition of
unstable antenna unstable angina is
severe angina of recent onset
or angina with progressively increasing
frequency
orangana with progressively increasing
frequency or angina
which is precipitated
which is precipitated by progressively
reducing exertion or even at rest let me
repeat it again
what is unstable Indiana unstable in
China is a dangerous angina because if
it's not manageable it has a high chance
to convert into
myocardial infarction right it does not
remain stable as an angina and what is
the underlying pathology of unstable
angina
it has unstable arithmetal Spark
with super added what
thrombo's formation and even this
platelet May release some vasospastic
element
and sometimes there is even added
vasospastic element as well so how many
things are there yeah it may release
from books and A2 yes that may produce
visual spasticity excellent so it has
astrometers plaque which is undergoing
acute changes it may develop platelet
plug on the platelet plug it may develop
deposition of fibrin then there may be
local production or vasoconstructor by
the Disturbed plaque and the super added
thrombus and may lead to visual
spasticity is that right and this type
of angina if it lasts longer it's very
severe pain and well classical
you know diagnostic point is write it
down this angina does not respond well
to nitrates and taking rest because you
have to differentiate the patient of
stable angina with the unstable angina
the classical differences that stable
angina patient or classical in general
patient as soon as this patient take
rest or take nitrates within few minutes
pain will disappear but when will go to
the unstable angina right unstable
angina cannot be relieved by taking rest
and cannot be relieved by taking
nitrates
is that right that is the diagnostic
point so whenever you have a patient
with very sphere in China and patient is
not angina is not disappearing with the
taking rest or not disappearing with the
sublingual nitrates right the real uh
you know diagnostic point is they say
when patient has taken sublingual Nitric
tablets
three times
three times within 15 minutes
when a patient of angina is taken
sublingual nitrates
three times within 15 minutes and pain
is not relieved and it is unstable
angina until proved otherwise it is
unstable in China until proved otherwise
is it clear now
look at the pathophysiology of all these
three situations
these situations are different because
these situations are different their
management is going to be different let
me tell you very basic clue when you are
thinking
your strategies pharmacological
strategies to manage this patients look
attention here
classical angina right
it is basically precipitated by
increased work of the myocardia it is
precipitated by increase
work of The myocardium so the best
therapy should be to reduce the work of
The myocardium we have to use those
drugs in this case which classically
reduce the work of the
myocardium right most effective strategy
is that angina is due to increased work
so we so treatment should have those
pharmacological modalities which will
reduce the
work of myocardium work off
Mayo cardium if we reduce the work of
myocardium that will of course lead to
reduced oxygen demand
and if you have reduced the oxygen
demand
right
the management during the acute phases
that you should reduce the work of the
heart so that there should be reduced
oxygen demand and when there is so you
have to reduce the oxygen demand so much
that reduced oxygen demand become equal
to the reduced oxygen supply
you have to re-establish the balance
between oxygen supply and demand here
the art of management is reduce the work
of The myocardium so much
that reduced oxygen demand becomes equal
to the reduced oxygen supply
and then symptoms of angina will
disappear
but when you come to this patient this
is due to vasospasticity do you think
reducing the work of heart will help
this patient no
this is the spasm right so art of
management the best strategy in this
patient is
you do coronary
weather
dilation
you have to use the drugs which
classically dilate the coronary artery
now listen carefully
coronary weather do not work very
effectively in this case
coronary weather dilator work
wonderfully for the prince metal angina
the best drug presently is
foreign but of course nitrates can also
dilate the coronary artery if it is
pasted but you have to remember here in
this case in this case
if you use a drug which will only dilate
the coronary artery will not be much
helpful help will be very little the
reason being here arthromatous plaque is
a fixed obstruction
and atheros
metacyclerosis are seclorosis of artery
due to anthroma is not amenable to
significant dilatation if you give
coronary dilator maybe if there is some
super added
little bits plasticity that may be
relieved but because obstruction here is
not Dynamic obstruction is
fixed so usually by increasing the
perfusion of
strategies don't work well except either
you do big game here for example
coronary
what is this p t c a
that is percutaneous transluminal
coronary angioplasty
that that may help in this case or you
do cabbage
that is coronary artery bypass grafting
so that you provide the flow around the
obstruction
right so we can say that because in
stable angina atromatous plaque is
stable
but it is a fixed obstruction so by
drugs it cannot be easily dilated during
the acute phase
is that right but point one thing in the
long run these patients should be
advised
these patients should be advised to
reduce the risk factor for
atheroseclosure
during the acute phase when angina is
there right that moment you have to give
a drug which will reduce the work of the
heart so that reduced work and reduce
oxygen demands meet the reduced oxygen
supply
but in the long long run these patients
and rather all of the patients with
angina you have to advise for
widen the risk factor for
atherosclerosis or managing them for
example smoking should be stopped
diabetes should be managed well
hyperlipidemia should be managed well
hypertension should be managed well
lifestyle should be improved for example
stressful lifestyle should be reduced
sedentary lifestyle should be reduced
exercise should be done so all those
advice to prevent the social sclerosis
they they are required in all these
patients but during the acute phase
when patient is really having angina
what will help reducing the work of the
heart
the name of the medication I will go of
course the whole lecture will come to
this thing and I will tell you how the
drugs combinations come and how they
interact with each other and what
combinations are good in which
situations
I'm going to make sure good doctor right
but first yeah Jamie what's your
question
yeah
yes but if you really want to manage
them
without drugs then you can do either you
pass a catheter into coronary and with
balloon angioplasty
where you know you stretch out this
point and you put a medicated stunt
there right that is one treatment which
will not discuss today because we are
going to discuss the anti and general
drugs right uh second is you do coronary
bypass graft right when you come to this
situation the best do you think in this
case we need ptca no now you know by
Logic you know that in this situation
with a you don't need to do ptca
and of course here you don't need to do
cabbage there's no bypass there's no fun
in doing bypass grafting just give the
drugs which keep the coronary artery
dilated that's it
now we come to this drug
this type of situation
this this type of patient really tests
to your medical you can say knowledge
and competence right the test of your
medical competences
by the patient with unstable angina only
good doctors manage them in a good way
first you have to understand
pathophysiology before we start the
management
there are four components
in this whole game
you know Leon is here this is the area
which is involving the lion
right now what are the points here
number one there is a throma
stable or unstable
which is unstable undergoing acute
change this is one problem number two
there's platelet aggregation
platelet
aggregation
and plus
fibrin deposition leading to
thrombus formation
plus there may be added component of
whether
spasm
now what should be the strategies to
manage this patient
first of all
first of all you should give the drugs
which disperse the platelet from there
thrombolytic drugs anti-platelet agents
what do you think look here do you think
in these two cases you need
anti-platelet agents immediately no but
remember in the long run we also give
them aspirin as antipolated agent
because you never know when this plug
may become
unstable in future but if you put this
patient on aspirin right future risk of
convert conversion of this
stable angina into unstable will be
reduced but the point which I want to
put in your mind that in this case is
that treatment modalities are
anti-platelet drugs antithromolytic
drugs anti-platelet or anti
thrombolytic drugs
you understand why you want to dissolve
the thrombus
as soon as this patient come you ask him
to chew aspirin
the simple aspirin does Wonder
right because it will not allow more
platelet to stick on this obstructed
point
right
antiplated drugs should be given of
course there's more such serious
situation in acute phase you need to
give oxygen and more important than that
again you have to reduce the work of
work off
myocardium hard plus you have to give
coronary
artery
dilator
in a nutshell look to me in a nutshell
an unstable Engineers you have to do
everything what you do in stable angina
Plus
very important point you have to give
some drugs which should be able to
dissolve the thrombus
and the thrombolitical drugs are of
course not required in stable angina and
they're not required in transmitter
am I clear any question here
no question
now
I will discuss into detail that what are
the methods to reduce the work of
myocardium
is that right because this is the work
of The myocardium which determines the
demand of the oxygen and in these
patients ideally we should increase the
supply of oxygen and we should decrease
the
work of the heart now we'll talk about
what are the determinants of the work of
the heart then we will see how drugs
modify the determinants related with the
work of the Heart Is there any question
no
there are many ways to explain the work
of the heart but I will explain in a
very very simple way
right
in the terms of preload afterload
right so and contractility
now I want to know what is your concept
of preload what is preload have you
heard of the term of freeload when we
talk about cardiovascular system what is
preload
you don't feel what is okay Raul is
going to tell us
what is after load
or preload
s okay okay I will tell you first first
I will give you an analogy
you know your heart is a donkey
you don't know it I will tell you our
heart is like a donkey like it does
donkey work all the time
pumping the blood all the time taking
from the venous side pumping into
arterial side right and we will see what
are the problems of an ischemic donkey
malnourished donkey
and how you can help a malnourished
donkey is that right
look
this is good
you have friends as donkeys then you
must be protected from lot of nasty
things
it's good to have donkey friends
right
now listen listen
attention plays
here is your heart
I don't know how to draw a good donkey
right
first I'll talk about the normal heart
okay let's make it a healthy
it's a happy happy donkey it's a healthy
myocardium having lot of oxygen supply
good nutrition all right now
what is the function of this donkey
this donkey has to take some preload
preload is the load on the donkey which
it has to carry upward
first you imagine there's a donkey which
is having some load on it and with this
load it has to go upward is that right
and it has to go against this resistance
this is the
resistance
against which this donkey has to perform
right and here is the low pressure
donkey will work up build a pressure and
take some preload here
and deposit something here for example
here it was 140 ml
any deposit here
70 ml
and then this donkey will come
back
right it's 50 percent it has low
downloaded there
so this was the stroke work of donkey
during one stroke and deposited 50 ml
there and come back again take 70 ml
more and again go back now how much work
a donkey is doing listen it's very easy
to understand just a minute
we're talking about donkey right how
much work per minute it is doing it
depends on number one how much preload
is there if you put more preload work of
the donkeys
more
if you are putting the more load on the
donkey work of the donkey more number
two if you increase the resistance
angle against which it has to work work
of the donkey will be more
is that thirdly how many times per
minute it moves if it moves for example
one 30 times per minute work is
increased
now imagine ischemic myocardium the
ischemic myocardium is actually like a
donkey which is undernourished like a
donkey which is undernourished now it is
under nourished donkey very weak
and no more smiley
this is
now what is happening look
this donkey has to it has less oxygen
supply
now due to any reason in classical
engine I'm talking about if you take
this like this
what has what has happened
resistance against which it is working
is increased
if it is to work like this can it work
well
no and it will start crying the cry is
the vaginal pain
the donkey is crying The myocardium is
crying because it is under angina pain
now if this donkey cannot work well how
you can help him what are the methods to
help the ischemic myocardium ideal ideal
thing should be you provide more
nutrition
to the donkey this is one way give more
perfusion this is the ideal thing
secondly you can help it by reducing the
preload
right you can reduce the load on the
heart before it works you can reduce the
load on The myocardium or load on the
donkey before it start working
third strategy is you reduce the what is
this
resistance
against which myocardium is Contracting
right now this is called preload
the load on The myocardium before it
work and resistance okay is which it was
performing this is called after load
myocardium perform against the arterial
resistance you know arterial the narrow
and myocardium has to pump against that
impedance is that right that is after
load that is the resistance so if you
really want to help the strong key
number one increase the perfusion number
two reduce the preload number three
reduce the
afterload the resistance
and next point is in strategy
be merciful to this donkey and and
reduce its number of visits
not 140 per minute it should be maybe 65
per minute if this donkey with less
preload working against less resistance
and total number of stroke per minute or
less
maybe it's work is so much less that
even in ischemic donkey can perform well
do you understand it
so now I will put the analogy on the
truth and real thing
but you should not forget your heart is
a
donkey it needs constant
perfusion
right and when it is reduced perfusion
one way to help this trunk is reduce the
work of the Donkey reduce the work of
the heart how you can reduce the work of
the heart reduce the preload
or reduce the afterload and reduce the
total heart rate all these things will
help the donkey to manage this crisis
right what was your question
how do I reduce the resistance and the
preload yeah I'm going to explain now Mr
Abdul has asked that what are the real
thing how you reduce the preload and how
you reduce the afterload this is your
question we are going to do that thing
pharmacologically very soon right yes
Jamie
oh yes he is thinking how we can give
nutrition to of course you increase
Nutrition By dilating the coronary
artery so that it carries more blood to
the ischemic area
that is so simple
you know look
to reduce to increase the nutrition to
the ischemic myocardium you should
dilate the coronary artery or you should
do the thrombolysis
so that more nutrition come donkey is
Happy secondly you reduce the preload
pre-load is the end diastolic volume on
which myocardium has to contract so you
should have reduced the preload what is
preload pre-load is the end diastolic
volume the volume of the blood at the
end of the dastly on which the onset of
systole work myocardium has to contract
on the end diastolic volume if this
volume is less then work of The
myocardium is less thirdly
Sicily has to generate enough tension
to push the blood against the resistance
of the arteriolar construction
what is afterload this heart is working
against this resistance what is this
resistance
this is the total peripheral resistance
arteriola
constriction
so if your arterioles constrict too much
this slope will go up Donkey may fall
down you get it and if there's arterial
or dilatation the slope will come down
you understand it
in the same way blood volume is
increased preload will increase
if venous return is more preload is more
venous return is less preload is
less
are you clear
now I will put donkey little bit on the
side and talk about your real heart
beautiful heart
I
will just keep our example of donkey
here
right this is your donkey going up
just give me donkey
weeping
and its legs are really in trouble
all right and here is the preload
it is carrying
and this is the afterload the resistance
against which it is working is that
right
so now
will come to the real thing and let me
explain it to you
this diagram all of you should draw
this is the right heart
here is your lung
here is your
left heart
now what is really happening now we'll
see how the NTN General drugs should
work
right
this is your vascular system in the
periphery
here is your aorta okay I'll make it
more simple diagram
this is your arterial tree
here are arterials
these are the
arterials
going to the capillary beds is that
right
these are different tissues
right and here is your
Venus system
it's a very simple diagram
this blue light blue system is your
venous side this red system is your
arterial side is that right and blood
from this will go to the lungs their
blood gets oxygenated and oxygenated
blood comes to
left heart
is it right and of course we should not
forget that here is your oxygenation
business
now we have to see
first the management of for example this
may be liver
right this is circulation maybe through
git
this is circulation maybe through the
skeletal muscle you understand it
and look these are arterioles these are
arterolar smooth muscles
is that right
and this is the venous side
now
this is right heart of course
and there's left heart there
now let's see what's happening in angina
classical angina I told you in classical
in China
there is a fixed obstruction there
because there's fixed obstruction there
whenever hard work more let's suppose
this partial person is exerting whenever
he does a little bit exertion or
whenever there's little tachycardia
Demand on oxygen increases but this
point cannot dilate further so it cannot
provide further oxygen and this part of
The myocardium we can say this part of
myocardium is vulnerable myocardium
right out of this the most vulnerable is
a
in our most myocardium
is that right now we will see how this
problem start and how drugs can correct
it
first lesson what's wrong with this
patiently learn is very Advanced maybe
80 percent of the cluvian whenever this
person does a little bit exertion or
whenever there's little bit tachycardia
due to emotional fluctuation a
sympathetic overflow
heart will increase its cardiac work
increase cardiac work will demand more
oxygen but this point cannot provide
extra oxygen so dependent myocardium
become ischemic and that produces the
symptomatology of angina
and if this point is very severe during
one week this patient may develop angina
many time now how do you manage this
angina
this is undernourished donkey
we have to help him
right
now one way is that we give the listen
one way is that you reduce the Venus
return because this is the end diastolic
volume and end diastolic volume is also
called end diastolic pressure right and
diastolic volume lead to end diastolic
pressure in the cavity and that is also
called preload
now from today onward every doctor
should know very clearly what is preload
preload is amount of the blood present
in The ventricle on which ventricle has
to start its squeezing action
on which ventricle Astro started
successing action or simply preload is
the end diastolic volume the volume on
which ventricle has to contract
right
so it is the load on The myocardium
before myocardium contract before The
myocardium start Contracting this is a
load on myocardium
now one way is
now listen whenever preload is more
you know the basic rule Frank starling's
law what is the Frank starring law more
you stretch the myocardial fiber more it
contracts
do you know this law it means more you
stretch more you contract
what does it mean it means more you
stretch more it contracts more it
demands oxygen
now you develop the relationship of
oxygen wealth now what is the stretching
Factor on The myocardium and astrolic
volume
if you have more preload or you have
more antasolic volume or you have more
antioxolic pressure it means there's
more stretch in The myocardium it means
myocardium has to contract more strongly
it means it will demand less oxygen or
more oxygen more oxygen now very simple
technique if somehow
this is one problem that whenever there
is more preload this demand more demand
for the oxygen you understand it
secondly another thing which most of the
doctors don't understand
that when there is more and diastolic
volume there is more pressure in the
cavity when there is more pressure in
the cavity
interventricular intra ventricular
cavity pressures are high Whenever there
is more and diastolic volume and
whenever this pressure is high it will
further compress this
my inner myocardium and make it more
vulnerable to ischemia so it means that
whenever there is a high
and diastolic volume there is higher
pre-stretch on The myocardium there is a
higher work of The myocardium and this
is higher intra cavity pressure and
there is a higher compression on the
deeper myocardium and further risk of
ischemia now what you do
you should do something listen you
should give some pharmacological agent
which reduces the preload now how do you
reduce the preload now we are going to
be merciful to this donkey we are
reducing this preload
how will reduce this brief load how will
reduce the cardiac filling very simple
from where the blood is coming into
heart blood is coming from the Venus
side
blood is coming to the ventricular
cavity from where
venous side is maintaining the venous
return and filling out the myocardium
now very simple technique you give a
drug which is vino dilator we dilate all
the Wayans
if you give Vino dilator drugs
very strong Vino dilators do you think
blood will now will be pulled into
periphery or it will be coming back to
the heart
paper every so one of the master drug
technique should be which we should give
such drugs to such patients
which are strong Vino dilators so
patients veins dilate
when veins dilate then blood is pulled
over here venous return is reduced
when venous return is reduced then
cardiac filling is
reduced and when cardiac filling is
reduced then pre-load is reduced when
preload is reduced it means that and now
the pre-stretch on The myocardium is
reduced so contractility is reduced
oxygen demand is reduced and myocardium
may be happy even with reduced oxygen
supply and ischemia may disappear so
this is so simple all those drugs which
are Vino dilators are pre-load reducers
right all those drugs which are we know
that later the preload reducers right
they reduce the load from here and of
course your donkey should be happy
it is carrying less load secondly
another thing look donkey with more load
will eat well a donkey with less load is
going to enjoy his food well
less less load so what exactly this is
what happened with myocardium Dr diet
that when you reduce the preload donkey
will eat better how
very simple look here when you reduce
the preload intra cavity pressures are
less
when intra cavity pressures are less
then compression on the deeper
myocardial circulation is less so even
with less perfusion better will be
better flow will be coming to the deeper
myocardial you understand the beauty of
this point number one
this is undernourished
you reduce the load
right so that it can work well and
whenever you reduce the cavity pressure
even the compression on the deeper
myocardium become less and even with
less flow
there will be better perfume to deeper
part is that right so this will
alleviate or terminate the
skinny or reduce the skin yeah so best
way one of the way one of the strategy
to reduce the work of the heart is you
reduce the preload to reduce the end
diastolic volume you reduce the end
diastolic pressure when all these
parameters are reduced then stretch on
The myocardium is reduced then according
to friends Starling law tension is
reduced and work of the heart is reduced
oxygen demand is reduced and may be
reduced oxygen demand is now able to
meet with
reduce Supply
here let's Supply the laplaces lie as
well right what was that that pressure
is directly proportional to the tension
produced in the pressure in the cavity
the pressure which is generated in the
cavity is directly proportional to the
tension produced in the wall
tension produced in the wall and radius
right now look at the beauty of it
listen listen now it's my turn to
explain your turn is in mcqs I'm just
developing a logic logical thinking oh
my friends you are all of you excited
too much without any lady around listen
uh what I'm talking about
I don't know why my class is a men's
show here now listen what is happening
that let's suppose this mean arterial
pressure is 100 millimeter of mercury
so it means that left ventricle has to
produce the pressure in the cavity of at
least 100 to eject the blood
is that right
let's listen
approximately it is not normal you know
ischemic now so what we are talking
about that pressure it has to generate
this pressure
for this pressure right if we reduce the
venous return it means we reduce the
radius
and when we reduce the radius
then heart has to
produce if same pressure
then it will produce more tension in the
wall or less tension in the wall
look again
previously when when and diastolic
volume was more radius was more and it
was suppose supposed to produce pressure
of 100 unit
pressure of 100 unit when you give the
gave the venodilators blood pulled here
less blood coming here radius become
less when radius become less than to
produce the same pressure it has to
build more tension in the wall or less
tension in the wall so it has to be more
contractility less contact
this is the beauty that actually when n
diastolic volume is reduced preload is
reduced radius is reduced then uh to
generate the same pressure myocardium
has to develop less tension so it means
that myocardium becomes more efficient
because when there is less tension
When there's less tension then less work
is there then less oxygen need is there
so we say heart become efficient because
hard with look heart with larger radius
for producing
the pressure given pressure
it needs larger tension but when you
reduce the preload you reduce the end
diastolic volume actually with the
Lesser tension buildup it can give the
same
pressure output
so it means myocardium become more
efficient what is the efficient
myocardium more efficient myocardium is
which is with less oxygen giving more
pressures generating more pressures and
inefficient ventricle is which is with
high tensions and high radius giving the
pressure so as you keep on increasing
the radius of ventricle it becomes
inefficient ventricle as you keep on
decreasing the radius of the ventricle
it become more efficient you understand
it so what really happens that when a
patient is
now you imagine there is a man
in his mid 50s heavy smoker hypertensive
diabetic
recently fought with his own wife and
girlfriend is not giving any attention
right and he has Financial stress going
to the bank will probably money is far
less walking against the cold wind
right what is happening there is some
tachycardia he's exerting against the
wind right and maybe uh cold wind is
producing arteriola construction hard
has to pump against more resistance
so he developed ischemic chest pain
but he's intelligent man his diagnosis
was done one year back and he often on
suffered with angina he immediately
bring
his top is walking sit down on the
sidewalk
from his pocket he bring out the tablet
of glyceride primitrate put it under the
tongue within one to two minutes this
tablet will start working
what it will do don't tell me that it
will go to the coronary artery and
dilate
this patient was a patient of stable
angina he was having fixed obstruction
so even though nitrates can dilate the
coronary artery but dilatation will not
be significant at the stenotic point so
it may not help much the real help will
come that within 2-3 minutes rather than
within one to one and a half minute
nitrates will dilate most of the veins
so while he's sitting veins will dilate
or better to standing so the pulling
should be better he is standing the
sublingual nitrate veins will dilate
cardiac filling will be reduced preload
will be reduced
work of the heart will be reduced intra
cavity pressures will be reduced radius
will be reduced and eventually the
tensions to be generated are less and
oxygen demand of myocardium are less and
what will happen to him his pain may
disappear
depends on listen uh now it's very
interesting question he is simply taking
rest can reduce the pain answer is yes
but for example he just rest and keep on
remembering his wife
and what she said in the morning and why
she was not Cooperative yesterday night
tachycardia may continue
you know you can reduce you can make
your body to rest you cannot force your
heart to rest
hard as its own logic
is that right so uh secondly look at the
bank where money is less in checks he
needs more that's also precipitating
tachycardia
is that right
so do you think that he can make
everyone to rest in the world answer is
no he can physically rest of course it's
Health but still if tachycardia is going
on then we have to have more drugs one
of them is okay if you take rest and
pain disappear it's very wonderful but
if it does not disappear he should take
sublingual nitrate and even if not take
if he has taken 0.3 milligram of the
sublingual light rate pain does not
disappear in three four minutes what
should you do high dose take another
dose of sublingual nitrate
is that right
so that he should make sure somehow pain
should disappear and pain should not
last more than
20 minutes right he should be rushing to
hospital forget about the bank and the
girlfriend and the wife right because
now he's developing the risk for
myocardial infarction now listen
this is one way to help his
undernourished heart so how do you have
helped the Donkey
one way to help the donkey was yes
please decrease foreign
now let me Define what is after load
after load is the resistance against
which myocardium has to produce the
stroke volume
after load is the impedement to the
outflow of the left ventricle and if
aorta is healthy then most of the
impedance or the resistance is offered
by the
most of the resistance is offered by
what
arteriole degree of arteriolar
construction total peripheral resistance
is determined by the sum of the
resistance of all arteries in the body
systemic arterials
if arterials are very narrow then heart
has to generate
has to push the blood against higher
pressure
and if arterioles are dilated then heart
has to generate against low pressure now
please listen to me because again
laplace's law will come into the play
look
if this patient has strong arterial
Construction
if he has strong arterial construction
he is again thinking about the
unfortunate things in his life or maybe
someone pass very beautiful and he
become excited again adrenal income and
artificial construct
right
so if the article the constructing too
much
then to push the blood through the
system he need to produce more pressure
or less pressure
more pressure let's suppose now he has
to produce the pressure of 140
millimeter of mercury
it means in this patient if there is
strong arteriola construction the
pressure to be generated or more
pressure requirements are more
and if there's too much arteriola
construction it means donkeys are
working against
higher slope
of course more chances to sleep more
chances it should need more energy so if
there is arterial construction it has to
generate higher pressure if it has to
generate higher pressure with the given
radius it has to have less tension or it
has to produce more tension more it
means Whenever there is a significant
artery construction then for the left
heart to generate the perfusion through
most of the body systemic circulation
to maintain good pressure right it has
to maintain good tension and when it has
to increase the tension it means it has
to increase its work and when it has to
increase its work its oxygen demand is
more as I told you whenever there's
arterial construction this point moves
like this resistance become more now
donkey has to travel this it needs more
power and energy or less power and
energy more so its oxygen demand will be
more more
right so how you will help this patient
another way to help this donkey is that
do arteriola dilatation give a drug
which will dilate the arterial if you
give a drug which can dilate the
arterioles then the resistance against
which it has to work has gone
decrease now look at this donkey how
happy is that even though there is back
breaking but still he is happy why
because preload has been reduced at the
top you have given arteriola
dilator right so we can say that this
was the function of
we know
dilator and this movement
that this has moved into this direction
this is a function of
arteriolo
dilator
is that right so when you give
arteriolodilator the resistance of blood
resistance offered to the blood to move
from arterial tree to the
capillary system and Venus system has
been reduced so pressure will drop in
this area and when pressure in arterial
tree will drop then it has to generate
less pressure and has to generate less
tension to maintain the cardiac output
is that right so work of the heart will
be
less and when work of the heart is less
then of course oxygen need is less and
when oxygen lead is need is less then
even with this stenotic plaque little
bit oxygen coming may be enough for The
myocardium which is working less is that
right so what are the best way to help
that donkey number one give winodilator
and reduce preload number two give
arteriola dilator and reduce
after load to reduce after load when
pre-load and after load is reduced it
means that work of the heart is reduced
even malnourished heart will not cry
much and not much in general cries
is that clear so what is the best
arteriologer answer is calcium channel
blockers calcium
Channel
blockers
is that right calcium channel blockers
are wonderful arteriologer
and some of them also reduce the
activity in the heart I will go into
detail later that nifedipine and related
drugs are very good arteriola dilator
and Verapamil
is actually also reducing heart in
another way hard work in another way
let me tell you how now another way look
here
yes
classical angina yeah
right we are still talking about
classical angina now
you have reduced the preload you have to
reduce the afterload now donkey is very
heavy happily singing whistling and
going up and down
you can do more Mercy to the donkey how
you should reduce the total number of
wizards ups and down
you should reduce the heart rate
if you reduce the heart rate
right
right if you reduce if you reduce not
digitalis it is it is going to kill him
because digitalis will increase
contractility and demand will be more
now look
not digital is forget it now what we are
talking about that we have to reduce the
total cycles per minute that will also
make the donkey happy if you are donkey
you will be happy under these
circumstances when your total Cycles are
reduced
so we should give some drug which is
negatively
chronotropic which is negatively
chronotropic and negatively chronotropic
drugs should be inhibiting essay node
the drug should be inhibiting SA node
right let's suppose here is your heart
ischemic heart you want to reduce the
heart rate and if you want to reduce the
heart rate
right you can choose two types of drug
let's remain focus on this
you know as a note produces
depolarization which is under calcium
dependent this calcium
SA node has calcium dependent
depolarization so if you give calcium
channel blockers what will happen
that calcium current in astronaut will
decrease
total number of action potentials
produced by acetode will be reduced
is that right and that will produce
negative
coronopropy that will produce negative
chronotropy or other thing is
who is the stimulant to as anode
is epinephrine or norepinephrine
endogenous you know endogenous catacola
means epinephrine and norepinephrine
stimulate the acinode through beta-1
receptors
so another way
that don't let the donkey run too much
let the donkey walk comfortably right
how to reduce the
heart rate to reduce the heart rate one
way is to give calcium channel blocker
other ways you protect the heart from
the action of endogenous catecholamines
to protect the heart from the action of
endogenous catecholamines so these
endogenous catecholamine work on the
heart through beta1 receptor because
they work through beta 1 receptor why
don't you give beta blockers
another group of drug will be beta
blocker beta blocker act on the essay
node and reduce heart rate and calcium
channel blocker also work on the acetode
and reduce
heart rate
right negative chronotropic action
secondly
you know myocardial cells
their contractility depend on calcium
loading you know it or not
myocardial cells contractility depends
on
calcium loading plus this calcium
loading may be through voltage-gated
calcium channels or this calcium loading
may be influenced by beta1 receptors
adrenergic
receptors
you know beta1 adrenaline receptors load
the calcium into myocardial cells or
calcium is also triggered into
myocardium during the plateau phase
through the voltage-gated calcium
channels l-type calcium channels you
know it
okay now
calcium either goes through the
what is this channel calcium channel L
Type calcium channel or catecholamine
stimulate the beta1 hydrologic receptor
and these receptors will activate you
must be knowing activate G stimulatory
which will stimulate adrenal cyclists
that will increase intracellular cyclic
amp that will drive protein kinase a
which will phosphorylate the calcium
channels and further calcium loading do
you think just hard
we have to reduce the work of the
hardening or increase the work of art
we want to reduce the work of art one
way to reduce the work of the heart is
reduce the calcium loading to The
myocardium so that it contracts with
less tension so it worked less
and demand less oxygen so you can give
here what should be the drug here my
friend
calcium channel blocker
or what should be the drug here
beta
blockers
you get it now you look at it that those
calcium channel blockers which work on
the heart like vapormel or dilt Azam
they can reduce the heart rate and
reduce the contracted stroke volume and
reduce the cardiac output and reduce the
work of the heart your understanding and
that also helps in
angina
so how many ways to help the angina look
now look carefully to me number one we
want to help this ischemic donkey reduce
the load
reduce the preload what is the drug now
to reduce the preload what is the name
of the drug we know dilators
reduce the preload like nitrate or you
reduce the
afterload what is that
calcium channel blockers or ask the
donkey please don't run slow down slow
down no hurry no worry and don't forget
to see the flowers
right heart should be slowed down
for slowing of the action slowing of the
rate and slowing of contractility
this is achieved by direct action of
beta blockers and calcium channel
blockers on the heart
is that right any question so this was
just basic information the basic
strategies used in management of
classical angina is that right after the
break we'll go into detail of every
group of drugs we'll talk first in
detail about the nitrates then we'll
talk about calcium channel blockers and
beta blockers right
now you have the concept now I'll teach
you what are they done
so by the discussion which we have
learned that there are three drugs used
in classical management of angina these
three drug groups are
nitrates
there are
beta blockers
there are calcium channel blocker
calcium channel blocker
these are the three classical drugs
right in the management of
angina
I will explain the advantages and
disadvantages of these drugs but there
are other things which are also
important in the management of angina
right for example I told you in the long
term management of angina we should
modify
modify the risk factor
risk factor for the development of for
development of atherosclerosis
is that right for example if someone has
stable angina
you should stop smoking or if he's
hypertensive or diabetic these things
should be managed if he has
dyslipidemias those should be managed
right sedentary lifestyle should be
abandoned patients should start
Physically Active lifestyle right
so that his what should happen the
further progression of atherosclerotic
disease should be reduced and even by
modifying these risk factor ah some some
regression in the atherosephology lens
has also been seen
one thing second thing which is very
important we should take the drugs which
are plaque stabilizers
do you know the group of drugs which can
stabilize the plaques atherosclerotic
plaques
plug stabilizers yes what is that drug
stabilizers
the most wonderful drug in this group
are statins
statins
so in the for the long run management
you have to manage the risk factors as
well as you have to use start using the
statins which are not only reducing the
not only their cholesterol lowering drug
right but statins also reduce the
progression of the plaque development
either under the influence of Statin the
unstable plaque right gradually
stabilize or the stable plaque has less
chance to undergo acute changes is that
right so it means if a patient who is
having stable angina and he has some
atherosical neurotic lens in coronary
artery if he is on the long term use of
statins then there is less chance that
these stable anthromas or plaques may go
under acute changes
third time
that especially those patients who have
undergone unstable angina you have to
give
anti-platelet drugs and T
platelet
and antithrombotic or thrombolytic drug
or anti thrombotic drugs
right now these are long-term management
is it clear
that risk factor management you
stabilize the flux by giving the statins
and you give long term aspirin juice or
other anti-plated drugs so the chances
of formation of platelet Aggregates is
less
right but classical management remains
around the
nitrates beta blockers and calcium
channel blocker in today's discussion we
will concentrate more on nitrates beta
blockers and calcium channel blockers
and we will have a separate full lecture
on anti-platelet drugs and fibrinolytic
or thrombolytic drugs is that right
now let's concentrate on nitrates
first of all I will tell you how the
nitrates work
and what are the nitrate drugs
these are also called Nitro vasodilators
right one of the term which is coined is
Nitro vasodilator so simply nitrates
nitrates
now the drug which are present in this
group of nitrate they are glyceryl
trinitrate glyceryl Tri nitrate
right then another drug which is present
in this group is
isosorbide dinitrate
ISO
sorbide
dinitrate
and another important drug in this group
is
isosorbide mononitrate that is
isosorbide
mono
nitrate
glyceride Tri nitrate
glyceryl with three nitrates Tri nitrate
isosorbite
mono
nitrate
now
glyceryl trinitrate how it is given to
the patient in which forms
most commonly it is given sublingual
or buccal suppress
or oral palettes
right
why we give it in the oral cavity the
reason being that if you take orally
glycerol trinitrate through the git when
it goes to the liver
in the liver this drug is inactivated
because glycerol trinitrate is having a
very high first pass effect first pass
effect mean when a drug is taken orally
when this drug is passing first time
through the liver most of it is
inactivated or destroyed so glycerol
trinitrate has a very high very high
ratio of very strong first pass effect
that is why when you take a tablet off
glycerol trinitrate right you just put
it in the oral cavity under the tongue
from there it will melt and dissolve and
this dissolve will go through lingual
veins of course into this veins from the
head and neck into speed of vena cava so
it will go to the systemic circulation
without passing through the liver
is that right when you take this drug
sublingually or in the oral cavity
as buccal Supply this will go from the
veins of the head and neck drain into
superior vena cava going to the right
heart pump to the pulmonary circulation
drug goes to the left heart and through
the left heart drug is pumped into a
whole systemic circulation in this way
we get the drug reaching to the systemic
veins without passing through the liver
so that is why within one to two minutes
this sublingual dose will start its
action that if there's a person who gets
intermittent angina right he should keep
if a person get intermittent exertional
in China this person person should keep
a supply of tablets off
glyceryl trinitrate and he can use it in
two ways number one whenever angina
precipitate you can take the table at
sublingually
or
he can juice this tablet's profile
actually that whenever he knows there
are situations which will provoke angina
right prophylactic juice for example he
is going two flights of stair so before
going those flights of stair he should
take nitrates and then go up
the right this reduces the on you can
say total number of attacks per week is
that right so glyceryl trinitrate which
is given sublingually tablet or Supply
right start action within two minutes
and it continues its section for about
30 minutes
onset of action is
two minutes and it continues its action
up to 25 to 30 minutes
right duration
is that right this is one thing second
thing which is important is that there
are oral sustained release tablets also
oral sustained release tablets also for
nitroglycerin nitroglycerin or glyceryl
trinitrate they are one and the same
thing it is also called Nitro
glycerine
it is one and the same thing right
another is that now there are available
oral sustained release tablets they
start their action uh within 30 minutes
an action continues up to six hours six
to eight hours
oral
sustained release
tablets right
they start their action within 30
minutes
and the continue Direction up to six to
eight hours
it is minutes
of course then you can understand if
angina is already starting you have to
give
sublingual tablets is that right because
it will start action within one to two
minutes right because if you take oral
strained release right it will take 30
minutes to start and of course in acute
phase it is not good it is for
prophylactic rules here I want to tell
one thing attention plays if someone
gets angina attack only very
occasionally you should keep glyceride
tablet with him and use them as required
and use them as required but if someone
is getting angina more frequently then
he should take the nitrates more
regularly on daily basis
is that right
for example yeah again someone who is
developing angina very finally he should
keep the supply off you can say uh uh
sublingual tablets and whenever he needs
he can put one tablet either
prophylactically or during the acute
attack right but he should not take
a regular tablets of nitrates but if
there is another person who is
developing angina of exertion very
regularly very very frequently then he
must take nitrates on regular bases and
when he is taking nitrates for regular
bases either he will take the oral
sustained release or he can take
transdermal application
trans
thermal application
yeah these are transdermal patch or you
apply the ointment on the skin you know
you take from the tube bring a little
bit ointment and apply it on uh you can
say one inch to two inch area right from
there it will be absorbed and it will be
going to the blood right this
transdermal application this also start
action Within
30 minutes it also starts section within
30 minutes and continue the section from
8 to 12 hours
now one thing note here as far as onset
of action very fast and termination
action also very fast is sublingual
applications but when you take it orally
or transdermally it takes about half an
hour to start the action and it takes
many hour of duration for which the drug
remain active in the body so this was
about the mitroglycerin now few words
about isosorbide dinitrate now
isosorbide dinitrate can also be taken
orally
and sublingually it may have some
lingual as well as oral preparations
right sublingual preparation of the
isosorbide nitrate they start action
within five minutes and it continues up
to
start within five minutes and it
continues up to one hour
so again in emergency preferably you
should have nitroglycerin if it is not
available
and if you are taking the regular drug
then you can take the oral slower
release tablet and that start of oral
slow release tablet and that start
action within 30 minutes right and
terminates its action within eight hours
is it clear
and my terminate section within eight
hours or around eight hours then there
is isosorbide dinitrate right
and an isosorbide dinitrate the tablets
are taken orally
mono nitrate sorry please correct it as
now we are going to discuss mononitrate
right isosorbite mononitrate and
isosorbide mononitrate is the oral
extended release
tablets and these overall extended
release tablets start their action
within 30 minutes
right but it continues its section for
long time sometimes up to 12 hours
12
hours
right overall
extended release
ah look yeah slow release it is
releasing the product up to eight hours
extended uh release mean it is going
beyond that actually they depend on how
the drug has been compressed and what
are the physical nature of the drug is
that right for example a tablet which
you can dissolve very rapidly in the git
right it will be released into blood for
shorter time but another tablet which is
present in the git but molecules are too
much compressed and they very gradually
dissolve they will take longer time and
they to dissolve and keep on releasing
the product to blood for longer time
you get me or not right now here I want
to tell you one thing extremely
important
that is that you cannot continue get the
patient protected with nitrates 24 hours
because if nitrates are used for longer
time
the loose Direction
you don't know this then you must know
what really happens
if you give nitrates more than 12 hours
or 18 hours continuously
after that efficacy of nitrates is lost
what is the mechanism they are not very
clear but there is something very
important for example this is the smooth
muscle of a vein or artery
how the nitrates work the nitrates go
into this smooth muscle nitrate drug
and these nitrate drugs release their
nitric oxide
and later on I will explain how this
nitric oxide produces vino dilatation or
arteriologation it's a very strong
vinodulator and it is slight arteriolo
dilator as well you can say we know
dilation is like this in compared to
arterial dilation at therapeutic doses
so why
because smooth muscle of
winds can release Nitro nitric oxide
more effectively from the drug a smooth
muscle of artery attention please
if drug is going into smooth muscle vein
as well as in the smooth muscle of
artery
drug itself is not active from the drug
we have to release the active product
what is the active product nitric oxide
not nitrous oxide nitrous oxide is you
know an aesthetic agent this is nitric
oxide so nitric oxide is one of the very
important you can say intracellular
signaling molecule
for the smooth muscle
it's so important that the person who
discovered its role they were awarded
with Nobel Prize
is that right just to tell it's so
important
otherwise let's come back now why this
drug is stronger we know dilator and
weak arterio later
answer is that this drug goes within the
venous smooth muscle and artificial
smooth muscle in the same amount
but venous smooth muscles are more
efficient in extracting the nitric oxide
from the
drug molecule but arterial smooth muscle
are poorly
extracting the nitric oxide from the
parent molecule drug so due to this
reason when nitrate concentration in the
venous blood and arterial blood is same
but still we know dilatation is more an
arteriologation is less because there is
more release of nitric oxide in the
venous smooth muscle less release of
nitric oxide and arterial smooth muscle
this is one point secondly
they believe the enzymes the enzymes
which
help in release of
nitric oxide from nitrates
right these enzymes
actually develop the phenomenon of
these are enzymes of sulfhydrol proteins
they show the phenomenon of
tolerance
what really happens that if you keep on
providing the drug
right Within
15 to 20 hours around 14 15 hours of
regular application of presence of the
nitrates then these enzymes stop working
and they're unable to release the nitric
oxide from nitrates
your understanding
okay I'll explain it again for example
I'm giving you nitrates
every eight hourly
and I'm covering United with the nitrate
for 24 hours
nitrate will keep we know dilator very
well for about 16 hours after that
nitrates mediated Vino dilatation is
lost why because the enzyme which was
supposed to extract nitric oxide out of
the drug these enzymes stop working
and these enzymes need a gap of six to
eight hours daily
to restart their function
you understand it
that is why the best way to treat the
patient badly is give the nitrates
regularly
every patient who is a nitrate daily
should be on six to eight hours or 10
hours
nitrate free interval so that tolerance
does not develop what is your concept of
Tolerance that you should keep on giving
the drug regularly
right
the pharmacological action of the drug
is lost after some time
right bodies start tolerating the drug
right so nitrates show a very high
degree of Tolerance Within
12 to 15 hours or 16 hours is that right
now why I'm highlighting this thing
because whenever you use nitrates for
your patients always provide some
nitrate free
is that right so that tolerance should
not develop now you must be thinking
that patient may get severe angina
during the nitrate free interval and
don't forget there's the Other Drug beta
blocker that's the beauty of it that you
give the nitrate with beta blocker in
cases where where angina attacks are
very frequent so that when patient is
not under nitrate protection patient
should be under production of
beta blockers I will explain how the
beta blockers protect the heart am I
clear
so Point number one nitrate drug show a
strong tendency for the mechanism of
Tolerance right every patient who is on
regularly nitrates should have at least
eight hours of nitrate free interval so
that mechanisms which keep the nitrate
functional
right nitrate mechanisms functional they
should not become tolerant is that right
and
one way
to manage the patient during the nitrate
free interval is that patient may be put
if he is having high frequency of
attacks patient may be put on the beta
blockers or calcium channel blockers am
I clear number two look exertional
angina absorptional angina is more in
the daytime or at night
in the daytime until you are not doing
something very special at night
right so most of the patient know these
are very important if you are going to
do something special you have to take
special care of yourself so most of the
patient most of the patients who have
exertional angina
right the risk of angina is during the
day time when you become emotionally
upset so you become physically exerting
right so the nitrate interval nitrate
free interval in these patients should
be provided when at night
so you have to remember
that patient who display the strong
exertional angina or classical in China
or stable angina nitrate free interval
should be at night for example they
should use nitrate patches in the
daytime for 12 hours they should use the
patch for 12 hour they should
remove the patch because when you apply
the transdermal application these
patches they are constantly releasing
the nitrates into blood right but after
12 hours you should remove the patch
because if you keep the patches for 24
hour patches will these drug will lose
its efficacy am I clear
but if you talk about
uh variant angina or Prince metal angina
Prince metal and Janna has a high chance
to be precipitated in morning hours
right when adrenaline level in the blood
is high catecholamine level so for them
nitrate free interval should be in the
evening time
so you have to intelligently design the
treatment for a given patient nitrate
treatment am I clear yes
we are not talking about unstable right
now we are talking about classical
angina and in a classical mean stable
and transmetal classical in China is
related with exertion right so usually
patient should be covered with nitrates
in the daytime and because most of the
people don't exert much during sleep so
I must say that nitrate free interval
should be provided at the sleeping time
yes is that right but when we talk about
uh a patient on the prince metal angina
Prince metal and China is usually is
more frequent in the morning because
there is fluctuating coronary artery
tone and usually in the morning
adrenergic
Supply is more is that right and the
more chances that patients will
precipitate Prince metal in China in the
morning hours due to that reason we
don't give them ah you can say nitrate
free interval at night or early morning
we give them nitrate free interval in
the evening times
they get a tablet before sleeping and
they take a tablet just after wake up
they miss the tablet in the evening am I
clear or noon now listen another thing
about these nitrates there is a very
interesting phenomenon of historical
interest when we talk about nitrates you
know nitrates were very commonly used in
ammonium nitrates and Other Drugs when
you are making explosives
and in second world war in those years
when
people were working in the factories
where they were building explosives
right workers develop a very special
type of syndrome they developed a
disease called Monday disease
Monday disease
Monday disease what was this Monday
disease actually what was happening to
these patients that after the weekend
enjoying a lot when they come on the
factory if there are 1000 worker most of
them develop severe headaches and
flushing and dizziness and after one two
days it will be okay
right now they came to know what is the
mechanism actually uh in those factories
in those times uh nitrates were not
properly contained in the instruments so
the workers who were getting they were
also inhaling nitrate many nitrates are
volatile like ml nitrate is fully
volatile and you can say other nitrates
which we are using these days like
isosorbide dinitrate the solid at room
temperature so those volatile nitrates
were going to their circulation so these
patient all the week right they were
getting good nitrate
inadvertently is that right
do do during the weekend their enzymes
recover and when they come in the Monday
morning get the nitrates enzymes will
convert the nitrate into nitric oxide
and they will develop severe weather
dilatation and when vesselton head and
neck will undergo weather dilatation
they will develop sphere
headache and flushing and when most of
the veins will dilate venous pooling
will occur venous return will reduce
cardiac output will drop and they will
develop postural hypotension and
dizziness
but within Monday and Tuesday they will
develop tolerance to the drug the rest
of the day is
there will be no complication
you are getting me so every Monday or
whenever they come from holidays they
develop severe headache and with that
they develop flushing and they develop
postural hypertension and all the stuff
is getting almost right and during as
week is advancing these symptoms already
used
is that clear so this was one problem
which was called Monday disease yes
the symptoms now I'm going to tell you
many of these patients used to get what
dependence on nitrates especially some
of these workers who are having some
degree of atherosclerosis all the weak
they don't get angina these workers and
on weekends they get in China and they
blame it to their family situation
is that right so I just wanted to tell
you this some something interesting
about the nitrates right that there are
two concepts related with the nitrates
number one was Monday disease number two
was nitrate dependence Monday disease
mean that when the Monday they will come
they will get the nitrates and produce a
lot of nitric oxide in the body and
develop toxicity of nitrate right but as
the weak will go by the enzymes will
become uh you can say non-functional and
now nitrates will not be converted into
nitric oxide and Monday's symptoms will
disappear right and some of the patient
will even develop nitrate dependence
they're all the weak they don't get any
in general attack if they are having a
tendency from China so they were getting
the therapy of angina
inadvertently from their uh unknowingly
they were getting the therapeutic doses
of nitrates and when they go for
holidays they develop the ice cream
heart disease symptomatology right isn't
it interesting yes right now I will come
to this fact that how the nitrates
exactly work at molecular level
right how the nitrate relax the
smooth muscles I did not talk about the
molecular bases that how the nitrates
relax the venous smooth muscle and to
some degree arterial smooth muscle now
what we will do first we will understand
the normal mechanism of smooth muscle
contraction and then we will talk about
how nitrates alter those smooth muscle
contraction it can relax the smooth
muscles of veins there will be Vino
dilation and if they do relax a little
bit smooth muscle of arteries they will
produce arterial dilatation let's see at
molecular level first physiology and
then pharmacology first what is the
physiology of smooth muscle contraction
and relaxation and how the nitrates
modify let's suppose here the smooth
muscle it's really very big one
right
no
first I'll talk about how the normal
smooth muscle contraction occur you know
smooth muscle can also get calcium from
outside
and this calcium can also release the
calcium from
yes endoplasmic reticulum of smooth
muscle endoplasmic reticulum of smooth
muscle is a good store of
calcium
so calcium is released
from the
sarcoplasmic reticulum I should call it
endoplasmic reticulum because
sarcoplasmic reticulum is a term which
is used for myocardial endoplasmic
reticulum right now when this calcium
come out this calcium bind with the
protein and this protein is called
yeah what is the name of this protein
what is it called
call Modio Len right so this call Model
N is a protein which is modulated by
calcium
so when calcium bind with curl Model N
what call modeling is this complex is
going to do I think diagram is a bit
dirty but I never made it with this
intention so calcium will bind with the
cold metal in and calcium carb model and
complex it will do a very important
thing that this complex will activate an
enzyme and that enzyme is
called
myosin
myosin
myosin light chain
light chain
kinase
what is the name of this enzyme
myosin
light chain
kinase
and what is the function of this ah
enzyme
myosin light chain kinase right actually
calcium carb model in complex activate
the myosin light chain kinases and what
is the function of myosin light chain
kinase actually myosin light chain
kinase lead to phosphorylation of myosin
light chains let's suppose
this is the
you can say
sarcomere type Arrangement it's not
truly a sarcomere in smooth muscle but
let's suppose these are actins and what
is here
myosin this is a heavy chain of myosin
and here these are the
light change of
myosin
now you know that when this myosin heads
and light chains myosin interact with
the actin they will produce contraction
of smooth muscle right these are the
myosin binding
sides these are myosin binding act
inside remember there is no troponin
here and there is no tropomyosin so
don't confuse it with the
skeletal muscle R and or myocardial
muscle in smooth muscle there is no
troponin or tropomyosin smooth muscle
the special mechanism of contraction is
that myosin light chain kinases will
lead to
phosphorylation of they will lead to
phosphorylation of
light chains so phosphates are binding
with the
light chains and when
these phosphates are binding with the
light chains then light chains develop
these phosphorylated light chains have a
capacity to bind with
acting
now listen carefully
that how then actin myosin will start
binding and contraction will start is
that right this is the normal physiology
that calcium level rises into into
intracytosol
Rising calcium this is also having
calcium dependent contraction but
different mechanism here is no proponent
you know in the heart in myocardial cell
calcium bind with proponent here calcium
point is called Madeline
light chain kinases myosin light chain
kinases lead to phosphorylation of
yes they will lead to phosphorylation of
light chains and when light chains are
phosphorylated right what really happens
that light chains develop the capability
to interact with the
with the actin and contraction will
start is that right this is normal
physiology of contraction
now relaxation how the smooth muscle
relax
how the smooth muscle relax
for this purpose there is a monkey-like
enzyme here
foreign
what it is doing it will snatch Veda
phosphates from here
right
what is this enzyme doing
it has some transplanted here also
right so this monkey enzyme what is the
function of this that this enzyme when
is activated and this activation will
lead to D phosphorylation or removal of
phosphate from light chain
because it removes the phosphate what
should be its name
myosin light chain phosphatases
it's so simple it is myosin light chain
yes phospha
phospha
is is
phosphatase so it means that when you
want listen now careful the central
concept is the central concept is
phosphorylation and D phosphorylation of
myosin light chain when we want
contraction of smooth muscle then we
phosphorylate the light chains when we
want relaxation of smooth muscle we
dephosphorylate the light chains am I
clear now smooth muscles have
intrinsically high level of myosin light
chain phosphatizes
is that right so contraction dependent
depends on constant action of myosin
light chain kinases as long as now
listen carefully as long as smooth
muscle has high level of calcium
for that much duration myosin light
chain Kinesis are activated through
calcium carb model and complex as far as
as long as myosin light chain kinases
are activated they will keep the light
chains
light chains phosphorylated and
phosphorylated light chains will keep on
intermittently interacting with the my
actin myosin and producing sarcomere as
soon as look calcium level become less
for example more calcium is not released
rather calcium is pumped
back into its stores
or calcium from here is thrown out
so as soon as calcium become low carb
model in
has dissociation with the calcium car
modeling is inactive it does not
activate myosin light chain kinases and
myosin light chain kinases do not
phosphorylate when they stop
phosphorylating actually the
phosphorylation continues through this
phosphatases and smooth muscle relaxers
now look
one way to relax the smooth muscle is
kill this thing
if you want to relax the smooth muscle
you actually inhibit what is this
myosin yes light chain
kinases if you inhibit the myosin light
chain kinases what will happen
right that it's a light chains will be
no more
light chains will be no more
phosphorylated is that right
yes now the thing is that
How We Do It
the drugs answer is nitrates
how the nitrates
inhibit this enzyme you get me because
this enzyme is going to produce what
thing
light chain kinases and precipitate
contraction now let's see how it is
working
let's suppose the nitrates come
nitrate drug come into the smooth muscle
nitrates nitrates release which enzyme
which Subs active substance nitric oxide
right
you remember there was some enzyme here
which was responsible sulphideal
containing proteins which are
responsible to release the nitrate from
night release the nitric oxide from
nitrate and these are the enzyme which
display the phenomenon of Tolerance but
anyway if patient has these enzymes
active nitrates will release the nitric
oxide nitric oxide will bind with a
special type of enzyme here and that
enzyme is
present into
cytosol
what is the name of this enzyme
yes
nitric oxide will bind to the what is
this
enzyme
what is the name of this enzyme yes
please
this is cytosolic governale cyclase
what is the name of this enzyme
cytosolic
guanalis
cyclist
right when nitrates bind with cytosolic
guanalyl cycle is what this is going to
do
it will convert yes it will convert
what is the function of this enzyme yes
it will convert GTP into cyclic GMP
it is not adrenal cyclist it is going
allyl cyclists you know adrenal alcohol
cycle is convert 80 if it is adrenal
cyclase it will convert 80 P into cycle
amp but this is not adenylial cyclase
what is this go on allyl cyclist so this
goanalyl cycle is convert GTP into
cyclic GMP
when cyclic GMP levels are high
right this will bind whether a special
type of
enzyme and this enzyme is called what is
the name of this enzyme this is
protein
kinase G what is the name of this
protein kinase G why we call it protein
kinase G because this enzyme is a
protein
right and it has a kinase activity
kinase mean phosphorylating activity and
its phosphorylating activity depend on
GMP cyclic GMP so this is called
protein kinase G and what is the
function of protein kinase G
foreign
it is going to
inhibit the action of light chain
right this is going to inhibit the
action of
foreign
light chain and how it does by
phosphorylating the light chain look at
it it has Port what it has port
phosphates in the mouth of
light chain kinases when light chain
kinas is itself phosphorylated it is
inhabited remember most of the protein
on phosphorylation are activated
some of the proteins on phosphorylation
are inhibited myosin light chain is one
of the protein that when this protein is
phosphorylated it becomes inhabited
now you recap it nitrates come into
smooth muscle release nitric oxide
nitrix oxide stimulates cytosolic when
Ally cyclists that converts GTP into
cyclic GMP when intracellular cyclic GMP
become High it activate protein kinase G
protein kinase G
thus phosphorylation of
phosphorylation of
myosin light chain and when myosin light
chain gets phosphorylated right then
myosin light chain is non-functional and
inhibited and then myosin light chain is
inhibited there is no more
phosphorylation of myosin light chains
and phosphatase will lead to D
phosphorylation and when ah phosphatase
mediated myosin light chain phosphate is
mediated dephosphorylation is not
compensated by phosphorylation by this
then D phosphorylated light chains fail
to interact with actin and smooth muscle
relax this is a molecular basis of
action of nitrate and after that we'll
recap a little bit what is the
physiological basis of nitrate we've
already discussed a little bit how
nitrate basically did you manage the
angina okay I will just repeat it in few
words that once smooth muscles of veins
are relaxed what will happen
we know Venus pooling and Venus return
to heart is reduced preload in the heart
is reduced and preload on the heart is
reduced please stretch on myocardium is
reduced contractility of myocardium is
reduced and oxygen command is reduced
number one number two when Venus return
is reduced pre and diastolic volume is
reduced intra cavity pressures are less
so the less compression on sub
endocardial myocardium so slightly
increase blood flow
third nitrates do produce direct
arteriola dilatation to some degree in
the coronary arteries
but when there is fixed nautical iron
right there is only slight Improvement
because when there is fixed nauticalane
if it has a little bit associated with a
spasm that may be relieved
but there's a very special mechanism how
in the heart it helps look here this is
ischemic myocardium
now look at this carefully
this is the
major Cardinal trunk coming
and this is divided into two branches
here
let's suppose this branch has
atherosclerotic lens let's concentrate
on it
this branches atherosclerotic ions now
what will happen
that this area
will become ischemic this is the
dependent
area is that right but outer area has a
good perfusion outer area has a
now these three vessels
these are called collateral Supply
because main Supply was coming from
this was the main Supply to this
myocardial piece and if there were
chronic ischemia the ischemic area keep
on releasing the
angiogenic growth factor so what really
happens that from repeated ischemia
ischemic area releases endogenic growth
factor and over the time there will be
development of collateral to the
ischemic Zone collateral Supply now look
here
when you will give nitrates the stenotic
point may not dilate significantly but
actually the collateral Pathways May
dilate and there may be extra blood
coming from the collateral as well so
that may also help in termination of
angina
so how then Jenna is terminated by
nitrates I've discussed three mechanisms
rather I will discuss four let's recap
do you remember four or not most
important single most important point
you should mention strong window
validation
strong reduction in and diastolic volume
and preload and and reduce cardiac work
this is one mechanism second reduction
in intra cavity pressures
so there is less extra vascular
compression on the deeper myocardial
vessels so better perfusion third
uh nitrates
can dilate the collateral Pathways and
provide additional blood to the ischemic
area
fourth nitrate at higher doses can do at
least to some arterial or dilatation and
if there is even little arteriola
dilatation that helps in reduction of
afterload that health and reduction of
the resistance against which myocardium
is
Contracting that further reduces the
work of the heart and reduces further
helps and reduction of ischemia is that
right so these were molecular mechanisms
of how nitrates work and when we talk
about preload mechanisms and we talk
about how that is that is physiological
mechanisms how the nitrates work let's
have a break now
we are going to discuss the side effects
or adverse effects of
nitrates
right
now the side effects of nitrate mainly
stem from exaggerated pharmacological
actions nitrates and
side effects
of nitrates right or adversifiers
number one thing that nitrates produce
severe headache and this is the most
common side effect of nitrates that they
produce headache
and they also produce facial Flushing
now why
let me tell you why they produce
headache remember all the drugs which
are strong vasodilators can do have a
capacity to produce headache now tell
you this headache is a very special type
of headache we call it
probing headache now let me tell you the
mechanism of probing headache let's
suppose this is your cranial cavity
and these are the vessels which are
going through foramina to the
cranial cavity these are the artery
meningeal arteries or other arteries
which are passing through the foramina
to the
central nervous system and you know the
internal side of the cavity cranial
cavity is lined by Dura
matter and this dura mater makes a
sleeve
around these
arteries
write this durometer makes a sleeve
around these arteries
and this Dural sleeve which extend along
these arteries
now actually
listen very carefully
this point durometer point these are
very very rich in pain receptors
these are very rich in
pain receptor these Dural sleeves they
are having lot of pain receptors now
when you produce arterial or dilatation
arteries are dilating constructing
dilating with every pulse during every
systolic pulse now listen carefully with
every systolic expansion
arteries Hammer the pain receptors
against the bone
and that produces severe throbbing
headache
what really happens that all those
arteries where all those drugs which
produce strong arterial dilatation right
if they produce arterial dilatation of
the vessels which are passing through
meninges these vessels are surrounded by
meningeal
Dural sleeves and these Dural sleeves
are very very rich in pain receptors so
when Our arteries are significantly
dilated during every systolic expansion
arteries hit the Dural sleeve
with the pain receptors against the bone
and that produces severe throbing
headache headache with every pulse is
that right this is the basic mechanism
how
headache is produced with nitrates one
of my teachers used to say if a patient
is taking nitrates and develop headache
tell the patient we are sure drug is
original drug has started its function
right so as drug reached to the
meningeal artery meningo arteries start
dilating or vessels passing through the
foramina cranial foramina dilate and
beat the dura metal pain receptors
against the bone
with that arteries of the face and skin
are more sensitive to the action of the
nitrates due to that reason many people
when they take nitrates not only they
develop severe headache but with that
they also develop dilatation of facial
arteries and facial blood flow and they
develop facial Flushing
is that right
then another extremely important
sideways most common side effect was
headache and most important side effect
is postural hypo tension
now let me tell you what is postural
hypotension
postural
hypo
tension now first I have to explain the
normal physiology
right that how blood pressure changes
and cardiac output changes with change
in posture and what happens when patient
is on nitrates
most important side effect is postural
hypotension now how the side effect
occur first let me explain the basics
that let's suppose
here is your heart
and
you know that from here there is
venous side
and this is
the venous blood return to the
right heart
and you know it that from here it will
go to the
lungs and through the lungs it will come
to the
left heart
is that right
now
and here is your let's pose
just a minute if we draw the aorta
on the aorta there are
what is this
rotate sinus
what is it
they rotate
sinus
now listen carefully
what really happens
first about the normal person and then
about the
now in a normal person from lying down
position from the lying down position if
normal person suddenly stand up what
happened in the body when he is suddenly
stand up the venous blood pulls into
lower part of the body
this point number one normal person from
lying down position with suddenly stand
up Venus blood pool into lower part of
the body so Venus return is
reduced so cardiac filling is reduced
and of course and diastolic volume is
reduced so that will lead to reduced
cardiac output you understand when a
lying down position person suddenly
stand up initially for a very brief time
this reduction in venous return due to
pooling into lower part of the body
the reduced cardiac reduced venous
return reduced cardiac filling reduced
cardiac output reduced stroke volume
this reduced stroke volume produces less
blood pressure and there are
baroreceptors in the Carotid sinus
immediately as soon as cardiac output is
reduced through the barrel receptor
information goes to the central nervous
system right information goes to the
central nervous system to the
medulla
right and from the medulla Vaso motor
centers are stimulated which centers are
stimulated
Vaso motor centers are stimulated and
sympathetic outflow occurs what occurs
sympathetic outflow occurs this
sympathetic outflow look here the
sympathetic fibers will lead to we know
they will lead to we know construction
right they will act on venous smooth
muscle
and release on the venous smooth muscle
what thing
not epinephrine
so what really happens that sympathetic
outflow has two functions number one it
will fire on the
sympathetic outflow on the veins and
squeeze the vein
so the normal person
as soon as you stand up
and there is reduced cardiac output it
activate the compensatory mechanisms and
reflects compensatory mechanism produces
Vino construction so that cardiac venous
return should be maintained so that
cardiac output should be maintained and
cardiac output should not drop
significantly and for prolong time
am I clear
in this way if you you are young healthy
people from lying down position when you
stand up you don't get any problem
because the reflex
neuronal reflexes so squeeze the veins
so that venous return should be
maintained am I right now you imagine
patient of nitrates
on the nitrates what happens that from
lying down position if you suddenly it's
okay this patient is going to run away
now from the lying down position
this patient is on the nitrates as soon
as you stand up of course Venus pooling
will occur of course cardiac output will
initially drop of course baroreceptors
will be activated and these Barrel
receptor you can say sensory nerves will
stimulate and form the medulla that
there is reduced cardiac output of
course sympathetic nervous system will
fire
but if nitrates are working on these
smooth muscles can sympathetic nervous
system induce significant contraction
answer is no
so if sympathetic reflex mechanism can
not stimulate what
contraction right it means venous return
will not be
maintained
so there will be prolonged
reduction in Venus return and there will
be prolonged reduction in cardiac output
and in this person from lying down
position when he will stand up he will
develop significant significant fall in
blood pressure systolic blood pressure
is that right and we say with the
posture
from lying down poster to suddenly
standing posture he has developed High
poor tension his blood pressure has
dropped because compensatory mechanism
could not maintain the blood pressure
right because veins was dilated and they
did not respond to a sympathetic
overflow am I right
so we say this patient will develop
postural
yes
hypotension this type of hypotension is
also called orthostatic hypotension so
postal hypertension or orthostatic
hypotension is a condition in which
neurovascular mechanism cannot uh you
can say constrict the veins on standing
and cannot maintain the
Venus return and they cannot maintain
the cardiac output and swear and
prolonged drop in cardiac output right
on standing will lead to postural
hypotension or orthostatic hypertension
am I clear
right now
due to this thing the blood flow to the
brain is increased or decreased
decrease this prolonged reduction in
blood flow to the central nervous system
will produce light-headedness and that
prolonged reduction
perfusion to the central nervous system
will produce vertigo
that will produce dizziness or vertigo
and with that if it becomes really too
much then blood flow to the whole
cerebral cortex becomes so low
the cerebral cortex does not work and
you know cerebral cortex is responsible
to maintain your Consciousness when
cerebral cortex does not work you become
transiently unconscious a syncopal
attack occur so many patients when you
give them antihypertensive drugs those
anti-hypertensive drugs which interfere
either with the
output of sympathetic nervous system or
interfere with the we know Construction
such drugs have a risk of producing
postural hypotension and such patient
will come back to you Doctor I had the
hypertension hypertension did not do
anything to me because most of the time
mild to moderate hypertension is
asymptomatic
right but doctor you give me the drug
and after taking your table ads when I
wake up in the morning I develop severe
dizziness headache and sometimes you
know two days back I fell in the
washroom because I got unconscious
so you have to be careful when you are
prescribing these drugs right that how
how you can alleviate these side effects
am I clear so one of the very important
side effect is postural hypotension
there is systolic drop significant
systolic drops on standing up position
with that number two position is there
is lightheadedness and dizziness and
sometimes even transient loss of
consciousness due to global cerebral
hypoperfusion
am I clear right so this is something we
have to take care about these patients
that nitrates do should be adjusted in
such a way that patients should not
undergo
postural hypertension and another thing
which is very important look
when Venus return is reduced attention
plays any drug which significantly
reduces the venous return
you know that reduces cardiac output and
of course venous return reduced and
diastolic volume reduce cardiac output
reduced and there's strong stimulation
to vasomotor centers and their strong
sympathetic outflow please listen very
carefully this is I told you already
that this sympathetic outflow will fail
to squeeze the vein but this sympathetic
outflow will be able to stimulate
heart and if there is essay node here
then this will stimulate the SNR
so this patient with hypotension will
develop severe reflex tachycardia do you
think this is good for a general patient
no no that is why we have to give the
other friend
of this drug who is the friend of
nitrates beta blockers so when we give
beta blocker they prevent The Reflex
tachycardia which may be precipitated by
nitrates
again let me repeat it that when you are
giving nitrates right this significant
we know dilatation
in a way it is good for us and sometimes
it is not good for us why it is good and
therapeutically useful because winners
pooling reduces winners return reduces
and diastolic volume and that reduces
the work of the heart and reduces the
oxygen demand and angina is
terminated terminated is that right but
sometimes if Venus return is too much
reduced and endospholic volume is too
much reduced then cardiac output is too
much reduced that may lead to
severe sympathetic outflow especially
from when patients undergo postural
change from lying down position to
standing up and when patients stand up
is that right this sympathetic outflow
will fail to construct the vein but it
will be very successful in stimulating
the
and the sympathetic stimulation will
also produce positive inotropic sorry
positive chronotropic action and
positive ionotropic action of course
these two things increase the work of
the heart right so we should give some
other drug along with nitrate to prevent
the side effects so we should block the
beta receptors in the heart so that
sympathetic nervous system does not
drive the heart wild is that right and
the drug in combination should come as
beta blocks
is that clear right so these were some
side effects with the nitrates I have
talked about that this headache there is
flesh and facial flushing there can be
hypotension there can be reflex
tachycardia which may precipitate
patient will not come and say doctor I
have reflex tachycardia patient will
complain about palpitations how Jamie
how do you define the palpitations
what are palpitations or palpitations
hello okay he says this is something
like feeling like something coming out
of chest yes this is one of the
expression for palpitation but
palpitation in medical term is different
you say palpitation is
in medical terms palpitation is
unpleasant awareness of cardiac activity
either you think something is coming out
of chest or you feel something is coming
out of throat but actually what is
palpitation that patient becomes
unpleasantly aware of cardiac heartbeat
because because so many of these
patients due to reflex tachycardia May
complain about palpitations is that
right but remember sometimes you are
pleasantly aware about the cardiac
activity sometimes when you are with
your certain circumstances especially
after exercise or some special company
you are and you feel palpitation
pleasantly that is not to be treated
medically is that right so medically we
talk about palpitation is unpleasant
awareness about the cardiac activity is
that right unpleasant word is very
important we will be talking about
beta blockers and their role in patient
with angina right first of all few words
about the beta blockers beta blockers
are the drugs which block reversibly or
competitively reversibly
or competitively
competitive
lay
beta
adrenergic receptors
you know adrenergic receptors are
classified like this
receptors for
epinephrine norepinephrine and dupe
right receptors for catecholamine they
are classified like Alpha receptors and
beta receptors right we will not talk
about Alpha receptor today because beta
blocker do not act on Alpha adrenergic
receptors they mainly work on the beta
adrenergic receptors and beta adrenergic
receptors are divided into two
categories that is
beta 1 adrenergic receptors and beta to
adrenergic receptor
right
beta1 adrenergic receptors are
present mainly on the heart beta1
adrenergic receptors are present mainly
on the
heart
let me show you the beta1 adrenergic
receptor distribution of the heart
here is your essay node
here is your
yes AV node very good bundle of fails
and bundle
branches now
beta1 adrenergic receptors are present
on essay node
they are present on Atria
they are present on AV node
they are present or percentage of fiber
and specialized conduction pathway and
they are present on ventricular
myocardium
so it means that beta 100 energy
receptors are present on
specialized myocardium as well as
general myocardium specialized
myocardium is acetode Av node and
conduction pathway
and general myocardium is real
myocardium and ventricular myocardium
which does the function of contractility
so we can say beta1 receptors are
present throughout the heart and here I
would like to mention that
now there is release of norepinephrine
from the nerve endings and through the
circulation
you know Adrenal medulla
releases epinephrine into circulation so
through the circulation
epinephrine reaches to all
heart epinephrine goes to all myocardium
and through the nerves there is arrival
of norepinephrine epinephrine and
norepinephrine they work on this point
number one as a node
when they work on the essay node
this is star one action I can write it
that when the work on essay node okay I
will write star one action star one
action is the action on the S note and
that will produce positive chronotropic
activity Chrono
tropic
effect positive chronotropic effect mean
increase in heart rate this is the
normal function of
beta 1 receptor stimulation
then when beta 1 receptors are
stimulating the AV node there is star
two action
and beta 1 receptors are stimulating the
AV node then conduction through the AV
node become fast and that produces
positive
dromo
tropic
effect or action that is increase
conduction
yeah through the AV node right by action
on the SN word it produces positive
chronotropic action by action on the
even ordered produces positive
Tropic action remember AV node is like a
drum between the artery and ventricle
every node is like a drum between the
Eritrean ventricle so things which
increase the activity of Av node
reduction they are positive dromotropic
and things or drugs which reduce the
conduction through V node the negative
dromotropyl then
star three action is that
epinephrine or norepinephrine stimulate
the beta's one receptor on contractile
myocardium and that produces increased
contractility called positive inotropic
action so star three action is positive
inotropic action that is action of by
stimulation of beta 1 receptors on the
myocardial contractility when those
receptors are estimated there is
increase
when epinephrine stimulates the beta-1
receptors on myocardium myocardial
contractility is increase and we say
that is a positive
I know
tropic
action or effect am I clear
so this is the main action of
beta 1 receptors on the
heart
moreover beta 1 receptors have
their receptors or in the bronchial
smooth muscle
normally beta 1 beta 2 receptors now we
are talking about beta two receptors
which are two receptors act on the
bronchial smooth muscle and normally
produce Broncho
dilation bronchiole
dilation normally
number one number two beta2 receptors
they work on the liver
hepatocytes have beta2 receptors and
when this beta2 receptors are stimulated
on the hepatocytes there is
increase glyco
Geno license
it means when epinephrine is more in the
blood epinephrine will act on the
hepatic which are two receptors and
produces the breakdown of glycogen
and when there's breakdown of glycogen
there is increased
glycogenolysis and that lead to the
release of glucose from the liver
thirdly beta2 receptors act on the
pancreas and which are two receptor
stimulation when it act on the pancreas
really releases glucose
gone and this glucagon also act on the
liver
and when glucagon act on the liver okay
again let me repeat that Peter 2
receptor stimulation produces glucagon
and this glucagon will act on the liver
and increase glucose
Neo
Genesis gluconeogenesis mean production
of glucose from known carbohydrate
sources is that right so it means that
beta2 receptors can directly release the
glucose from the liver
beta 2 receptor activation
on the liver can directly release the
glucose by breakdown of glycogen plus
beta2 activation can release glucagon so
it can act on the liver and increase
gluconeogenesis and further release the
glucose into blood
is that right
and beta2 has many other functions also
right now they are not relevant with us
now we are going to discuss about the
beta blockers beta blocker drugs are the
drugs which will block The beta-1
receptors
and if they are non-selective drug they
will also block the beta to receptor now
let's talk about those drugs into detail
I've told you very briefly few actions
of beta 1 and beta2 receptors when these
receptors are activated now we go to
that these
beta blocker drugs they reversibly are
competitively bind with the beta
receptors and block them and these beta
blockers are non-selective drugs
non-selective
beta blockers which will block the beta
1 as well as they will block the beta2
receptors they will block the beta 1
receptor as well as beta2 receptors the
classical example of the drug in this
category is propranolol
Pro Prana
wall and there are others also but the
minimum you have to remember that the
classical example of non-selective beta
blocker is propranolar but there are
some other drugs
write the beta blockers and at low doses
the specially block
beta 1 receptor receptor they work more
on the beta 1 receptors so they are
called selective
beta1 blockers
and the classical drug in this category
are selective beta 1 receptors blockers
these are Atenolol Atenolol
acidolol
right the drugs which are present in
this and atenolol occipitalol and
metoprolol Vito
Pro law again listen
one category is non-selective beta
blocker which block beta1 and beta 2
both
then there is selective category which
block mainly beta one receptor at low
doses but remember this selective action
is lost at higher doses for example
Atenolol at lower doses will block
mainly beta 1 receptor right but as you
keep on increasing the dose beta2
blocking will also start again beta 1
selectivity is only
relative term because these drugs block
more beta 1 and the block less beta2
right but they do block beta 2 to some
extent and if the dose is increased then
the selectivity is lost and while
blocking beta 1 at higher doses they
also block the beta 2 am I clear once
you have made this concept you know beta
1 receptors are present on the heart
that is why beta 1 blockers are also
called cardio selective beta blocker
cardio
selective because they specially work on
the heart
oh
cardio selective beta blockers so what
are cardio selective beta blockers these
are the group of beta blockers which are
beta1
blocker at load hoses am I clear
now once we have talked a little bit
about these drugs beta blocker let's see
what is their role in angina
what are the advantages of beta blockers
in angina right let's suppose here is
your heart
okay let's make a smaller heart
okay I need to clean it again
right so we have a heart over here
again what is here essay
node and what's here
even all right and park Angel system
right and then now
I told you beta1 is suppressor on essay
node
right they are on AV node
as well as an atria and they're present
on
now these are all beta1 receptors so
heart is well decorated with beta 1
receptor let's suppose we give a beta
blocker drug when we give a beta blocker
drug what this drug is doing
it will bind
with the adrenergic receptors on acinode
on AV node as well as on The atriant
ventricle
so it means that sympathetic action will
be lost
on
heart
so
when snored beta1 receptors are blocked
then Epson nodal stimulation by
catecholamine is reduced by endogenous
catecholamine is reduced so heart rate
will go up or down
it will go down so actually it produces
negative chronotropic action this
positive chronotropic effect of
endogenous
endogenous when snode is blocked that
will lead to
Point number one is when SA node is
blocked by the beta blocker there will
be negative chronotropic action and
heart rate will reduce and when
you can say AV node is blocked having
its beta receptor blocked then
conduction through every node will
become slow and that that will become
negative dromotropic action and when
beta 1 receptors are blocked on contract
contractile
ventricular myocardium ventricular
myocardium is no more driven by
endogenous catecholamines and
conductivity of ventricle is reduced and
that produces
negative chronotropic action in a
nutshell what can we say
that beta blockers reduce the electrical
activity of the heart as well as reduce
the mechanical activity of the heart so
simple to state that beta blockers
reduce the beta1 blocker especially they
reduce the electrical activity of the
heart as well as mechanical activity of
heart when electrical activity in the
heart is reduced this reduced normal
automaticity and negative chronotropic
action heart rate will reduce
conductivity through the AV node is
reduced and mechanical activity is
reduced it means contractile it is
reduced now listen
when beta blockers reduce heart rate
as well as the reduce the contractility
it means they reduce the stroke volume
so if they are reducing the heart rate
and stroke volume it means they are
reducing the cardiac output it means
they are reducing cardiac work
if heart rate is slow you know donkey is
moving less cycle
I think you should not forget the donkey
so the donkey is moving less cycles and
this is Contracting slowly
is that right and with less tension
so what really happens the cardiac work
is reduced and when cardiac work is
reduced there's reduced need of
oxygen
this is how beta blockers help that
primarily they lead to reduction in
heart rate
and reduction in heart rate due to
negative chronotropic action and
reduction in
stroke volume due to negative ionotropic
action and both things lead to reduced
cardiac output to reduce work of the
heart reduce need of oxygen am I clear
yes
no positive chronotropic increase the
heart rate negative chronotropic
decrease the heart rate listen
catecholamine stimulate the beta-1
receptor and positive chronotropic
action
problematenolol block the beta-1
receptor and reduce the heart rate Amic
layer
look of course we have to negative
chronotropic well reduce the heart rate
and reduce the conductivity and of
course reduce the contract a
that is of course you are right I need
it
yeah again listen first was physiology
that normally we are physiological some
sympathetic tone and some epinephrine in
our blood right this physiological
epinephrine keeps
it's a node somewhat stimulated
AV node somewhat simulated and
contractility is someone stimulated
somewhat stimulated am I clear
now what is the advantage of beta
blockers now beta blockers reduce the
heart rate reduce the contractility
eventually reduce the cardiac work and
reduce the need for oxygen so beta
blockers reduce the work of the heart
reduce the need of oxygen so do you
think when your heart is well protected
by beta blockers
is work is less do you think rational
engineer will easily precipitate no no
secondly extremely important thing not
only at resting situation it is good you
know when this patient is resting
right with the classical angina this
patient is resting and without his on
beta blocker so the heart rate is less
than normal maybe heart rate is 65 not
85.
right so even resting heart rate is less
so we can say resting work of the heart
is reduced less chance of vagina during
rest and even if this person starts from
some exertion person with beta blocker
starts from exertion or he undergoes
some emotional turmoil
right
beta blockers when
you are on the beta blockers and you
undergo some emotional excitement or
emotional tension epinephrine is
released if your beta receptors are
blocked can appear different really
drive your heart rate up no
or when you start a version of physical
activity you know sympathetic tone goes
up
and your heart rate should go up but do
you think if you are on beta blockers
your heart rate go up no so the beauty
of beta blocker is that not only it
protect the heart when person is
emotionally and physically comfortable
but it also protect against the cardio
acceleration
during the emotional stresses and during
physical aversion
right so these patient of angina if they
are protected with the beta blocker if
they are on the beta blocker when they
do physical exertion heart rate will
increase only slightly
a work of the heart will not be
increasing too much right that is why
that total episodes of angina will be
reduced
is that right so this patient with
angina can have beta blocker and then he
can afford to go under some excitements
or emotional fluctuations
because beta blockers will keep the
heart well protected from the internal
flooding of epinephrine
is that right so no risk of angina or
less risk of angina or even Mi am I
clear yes
the point which I want to tell another
that nitrates and beta blockers make a
very good couple
nighters and beta blockers make a very
wonderful couple they help each other
you know very good couple very good man
and a lady what they are doing you I
know you know what they are doing but
the good thing which they are doing is
both of them are good for each other and
they try to
compensate for the shortcomings of each
other if husband has some you can say
shortcomings or adverse action maybe
wife will compensate if there's a good
wife and if wife has some adverse effect
on community on the Family Life husband
will try to compensate now we will see
when you combine the nitrates and beta
blockers they make a very wonderful
couple very happy and beautiful couple
they try to increase the advantages of
each other and try to
cancel the side effects of each other
let's see how they do it now we discuss
the combination of nitrates with beta
blockers you know that nitrates produce
Vino dilatation should I make a diagram
or without diagram we discuss
without diagram
okay what really happens nitrates are
strong
what
we know dilators right let's suppose
here is your heart I will make a very
simple diagram
and here is your Venus input
to the heart
and here is your
arterial
system
very simple diagram right here is your
central nervous
system
right
this is the baroreceptor system from
where from arterial tree from
aortic body they produce input to
central nervous system is that right and
this is the sympathetic outflow
this is sympathetic outflow
now sympathetic outflow is going to the
heart
right sympathetic outflow is going to
the veins and of course sympathetic
outflow is going to the arteries right
so these are beta 1 receptor in the
heart this is the beta1 receptor on the
veins
or veins sorry it has Alpha One
receptors and arteries these are alpha
one receptors now as you imagine listen
please carefully what is happening when
you give nitrates we know dilatation
occur
when there's significant Vino dilatation
venous return is reduced cardiac filling
is reduced
is that right
cardiac output is reduced and cardiac
work is reduced all this thing is good
for angina
but there is one problem with nitrate
when they work too much there's too much
we know dilatation cardiac out filling
is too much reduced cardiac output may
be dangerously reduced and when there's
two might decrease in cardiac output
nitrates by reducing the cardiac output
right stimulate the reflex tachycardia
the stimulate the reflex we know
construction the stimulus that reflects
arteriola construction but because
nitrates keep the veins dilated so this
reflects
we know construction will not be there
but there's a problem
when nitrates dilate the winds too much
sympathetic overflow will stimulate the
heart and there may be reflex
tachycardia so there in nitrates there's
increased risk of
heart rate increase and the risk of
increase
stroke volume
because beta 1 receptors are also here
is that right so it means nitrate giving
nitrate is good in one way but in some
patient by producing reflex sympathetic
activity right there may be increased
risk of heart rate and increased stroke
volume and that may
increase the work of the heart so in
this way the work of heart which was
reduced by reducing the preload has been
canceled
if we give beta blocker listen carefully
if we give beta blocker here
then nitrate induced
reflects sympathetic activity will not
write will not be successful because
beta blockers do not allow the
sympathetic nervous system to work on
the heart
and secondly beta blocker do not allow
uh right in this way nitrate
and used reflex tachycardia is reduced
by
beta blockers so in this way beta
blocker
help the
patient to cancel some of the side
effects of
nitrates am I clear
now we come
of course nitrate is good in return it
should also help the action of beta
blocker now let's come to the beta
blocker and what it is doing I told you
beta blocker slow the heart rate and
slow the contractility
and when beta blockers are slowing the
heart rate and slowing the contractility
and reducing the contractility it means
total Venus fill in time if your heart
rate is less then diastolic time is
more if your heart rate is less it means
that
totals cardiac cycle the more or less
per minute
less if cardiac cycle the less then
naturally diastolic time will increase
and it means that any drug which reduces
the heart rate increases the diastolic
filling time
so it means beta blocker favor the
ventricular filling
so beta blockers increase and diastolic
volume
secondly another bad thing which beta
blockers do is contractility is reduced
and when contractility is reduced then
less stroke volume is ejected and more
is retained and again and diastolic
volume will increase it means one of the
disadvantage of beta blocker is that
they increase the end diastolic
volume do you think it is good for a
Jana patient or bad it is bad for a
Janna patient here the nitrates will
help how by keeping the veins so much
dilated that in spite of there is more
diastolic duration still Venus feeling
will be less
is that right in this way again in a
short in a nutshell
advantage of beta blocker is that it
reduces the heart rate reduces the
contractility and reduces the work of
the heart and by doing these things it
is good for anjana patient but
unfortunately by the same thing it
increases and diastolic volume which is
bad for the patient of
angina
patient of angina but if you are giving
with the beta blocker nitrates nitrate
will take care of this unwanted action
of the beta blocker that beta blocker
should reduce the heart rate should
reduce the contractility but there
should not be increased and diastolic
volume but beta blockers do increase and
diastolic volume if given alone so if
nitrates are given with them they will
keep the veins enough dilated that in
spite of
prolonged diastolic
filling and in spite of slow
contractility still and diastolic volume
is not
increased right so in this way both
drugs help each other again because it's
so important to understand this
combination I will repeat it in
now one sentence
listen what is the advantages of
combination of nitrates and beta
blockers in a patient with angina
classical angina listen side effect of
the nitrates are partially compensated
by the beta blockers side effects of the
beta blockers are partially compensated
by nitrate how
when we give nitrate alone they may
precipitate reflex tachycardia and
and that may lead to again increase in
cardiac work
so whenever with the nitrate beta
blockers are there nitrates will not be
able to precipitate reflex tachycardia
because beta sub 1 receptors are blocked
and in this way this unwanted action of
nitrate is abolished
then when beta blockers are given alone
if beta blockers are given alone they do
reduce the heart rate they do reduce the
contractility in this way they do reduce
initially
cardiac work but unfortunately when
heart rate is reduced too much and when
contractility is reduced too much then
end diastolic volume
increases
with low heart rate and with reduced
contractility and diastolic volume
increases because at low heart rate
there's longer diastolic duration so
this is longer time to fill the
ventricle and if there's low
contractility then less amount of the
blood is ejected and total pooling
become more so it means beta blockers
are good and bad how they are good by
protecting the hard against tachycardia
and protecting the heart against
contractility they are good by reducing
the heart rate by reducing the
contractility by reducing the work of
the Heart by reducing the oxygen demand
they are good but by increasing the
industrial equal volume they are bad but
when nitrates are given along with beta
blockers then
beta blocker tend to increase and
astolic volume but nitrate tend to
reduced and diastolic volume so this
unwanted action of beta blocker is
canceled in the presence of nitrates
is that right that is why combination of
nitrates and beta blocker make a
wonderful combination
is that clear
now we come to one more thing some
important side effects of
beta blockers some extremely important
side effects of beta blocker every
doctor should know what are the
contraindications for the beta blocker
before I really go for contraindication
for beta blocker or special precautions
and use of beta blocker I tell you one
thing very important
side effects of beta blockers in detail
I will discuss when I discuss the beta
blockers with autonomic nervous system
right but first thing which I'm going to
tell those side effects as well as
contraindication together
is that right
no no I will give it more clearly now
hold on
first first lesson lesson plays be a
tentative
what I was saying I think you are
getting tired maybe my we are about to
finish but most important part of the
lecture come now because if you give
beta blocker to a wrong person you may
kill her
right and you should not do that then
while trying to reduce
uh you know beat up in China of a
asthmatic patient you give beta blocker
and kill him with asthma
yeah so this this mistake should not be
done so let's talk about what are the
special precautions with use of beta
blocker
the most important precaution is never
stop the drug abruptly if you have been
given given it for long time
when you are using beta blocker for a
long time never ever stop the beta
blockers abruptly why can you tell me
why
why we should not stop the drug abruptly
the reason being beta 1 receptors has
been blocked by the drug for a long time
and when the scepters are blocked for
very long time when receptors are
blocked for very long time receptor
undergo up regulation
for example you are the patient with
angina and you are using beta blocker
from last three years
in these three years you have been
keeping the receptor blocked so
receptors will undergo down regulation
or up regulation
up regulation receptor concentration
will decrease or increase on the heart
increase look at the diagram hold the
heart is overloaded and overly decorated
with the receptors
whenever you block a receptor for long
time receptor goes up regulation
whenever you stimulate a receptor
strongly for long time receptor go down
regulation is that right so patient on
the beta blockers for long time have
upregulated beta receptors now
if patient has higher concentration of
receptor then you are keeping these
receptors well blocked with
beta blockers no problem to the patient
but if you suddenly stop the drug
unfortunately certainly this heart with
upregulated beta1 receptor become
exposed to the endogenous epinephrine
and norepinephrine and they will be very
strong stimulation of endogenous
catecholamine to this heart suddenly
heart rate will go up Suddenly what is
this cardiac stimulate contractility
will go up
and that may enormously increase the
heart rate and contractility and that
may enormously increase the work of the
heart and that may dangerously increase
oxygen demand and if your narrow vessel
cannot meet their demand
very dangerous
what angina's or even four myocardial
infarction May precipitate
I hope you'll remember it in your
lifetime
right that if you are giving beta
blockers for a long time then bitter one
receptors in the heart are up regulated
and when beta1 receptors are upregulated
what really happens
what really happens
right that as soon as you abruptly stop
the beta blockers by mistake
right endogenous catecholamine will
drive the heart Wild
suddenly heart rate will go up
contractility will go up and cardiac
work will go up oxygen demand will go up
and if narrow vessels cannot meet that
oxygen demand where is sphere ischemia
may lead to even precipitation of
myocardial infarction
is that right
now we will we shall be discussing about
the side effects and contraindications
of beta blockers
uh disrespect of beta blocker is very
heavily tested in all the medical exams
the reason being that beta blockers are
very important drugs they are very
widely used drugs but they have to be
used with lot of precautions already we
have discussed that if you are using
beta blockers on the long term basis for
your patient never stop them abruptly
because that may precipitate ischemic
heart disease episodes is that right so
whenever you are going to stop beta
blockers after after a long term use you
should taper off the doors over
7 to 14 days so over one to two weeks
you should reduce the dose of beta
blockers gradually
then there are some
side effects related with the use of
beta blockers very important side effect
is fatigue
patient feels
fatigue
now this fatigue may be due to some
Central mechanism That central nervous
system is slightly inhibited and this
fatigue may be due to peripheral
mechanisms as well
you know that uh
beta 2 receptors
are responsible for certain degree of
vasodilatation and skeletal muscles did
you know that or not
right their blood vessels look here the
blood vessels which are going to the
muscles
must write these blood vessels have less
alpha 1 receptors and these blood
vessels are having more beta2 receptors
you must be knowing that when
epinephrine act on Alpha 1 receptor rate
produce
arterioloconstriction but when
epinephrine work on beta2 receptors it
produces Vaso dilation right so we can
say in the peripheral circulation there
is Alpha One
mediated
Vaso
construction normally
Construction in a normal person
and in the peripheral circulation in
normal person there is beta 2 mediated
yes
mediated
Vaso dilation
naturally the blood vessels which are
rich in Alpha One receptors they undergo
there is a construction on epinephrine
right and blood vessels like blood
vessels or the muscles which are rich in
beta2
you know receptor as the undergo base of
dilatation while keeping this in mind
now you imagine if you put the patient
on beta blockers
right and if beta blocker drugs are
blocking the peripheral
again
if you are putting the patient on beta
blockers and if beta blockers are
blocking The beta2 receptors of
peripheral vasculature
beta2 receptors will not work because
they're blocked by the drug what will
happen beta-2 mediated vasodilation will
be lost right so the concept is when you
give the beta blockers especially
non-selective beta blockers when they
block the peripheral vasculature beta2
receptors then beta2 receptor mediated
visual dilatation is lost and plus blood
vessel become slightly constructed in
this patient if they do exercise
do you think their vessels can dilate
well
how they will dilate beta 2 mediated
visual validation is lost
you know during exercise when
sympathetic flow is there is the right
increased sympathetic outflow is there
during exercise that lead to beta2
mediated visual validation of the blood
vessels especially to the muscles and if
patient is already on beta blockers then
if you do some exertion or patient is
doing some exercise even though
sympathetic outflow will be there but
sympathetic outflow will not be able to
stimulate the peripheral beta-2 receptor
to mediate wizard validation so there
will be loss of beta 2 mediated wizard
allocation in the patients who are on
the beta blockers and of course if your
blood vessels are not dilating during
your exercise can you have exercise for
longer time you cannot and you will get
fatigued too early and you will develop
some degree of exercise intolerance you
get it so this is one of the common
problem that patients who are on the
beta blockers they develop a resting
fatigue and especially they develop
fatigue during physical assertion right
too early right one of the mechanism may
be that there is loss of beta 2 mediated
vasodilation right so there is no
incremental increase in the blood flow
to the muscles
am I clear
then another important thing is that
beta blockers which go to the central
nervous system they produce sleep
disturbances right they produce
sleep disturbances many patients develop
insomnia
and
some of the beta blockers which go to
the central level system they also
produce nightmares
red sleep disturbance and night
nightmares are another problem related
with the use of beta blockers right then
as you know adrenergic nervous system
stimulates the
as you know adrenergic Drive stimulates
the central nervous system of course
beta blockers are anterior energy drugs
so what happened they suppress the
central nervous system very little but
sometimes it may precipitate in some
patients depression
it may precipitate in some patients
depression
right
and
last but not but not the least important
side effects especially in the mail
there's yes
importance you know males talk about
immediately
yes importance right failure to maintain
enough erection right that is also seen
with the patient on the beta blockers so
now we'll come to the special
contraindication and special precautions
which must be used for the patient with
beta patients on the beta blockers right
now for this regard we will talk about
thank you
foreign
there are five situations which you
should remember
very well right I will explain them the
five conditions at least where beta
blockers should not be used or you
should be very very careful right now
what are those five conditions
first I'll tell you what are those five
conditions and then I will tell you that
why beta blockers are contraindicated in
those five conditions
you know this is a death star this is a
death star and death even may occur uh
in some of these conditions and beta
blockers are used it must be Black Star
this five
conditions number one is
asthma
asthma
or other
copds what are copds
chronic obstructive
pulmonary diseases right here this is
the beta blockers should not be used I
will explain why second condition is
diabetes mellitus especially those
diabetic patients who are insulin
dependent
were insulin dependent
beta blockers should are contraindicated
or should not be used I will explain of
course why then
peripheral
vasospastic diseases like Raynaud's
phenomenon Reynolds disease or in arts
phenomenon right the patient in which
there is peripheral vasospastic
situation beta blockers should not be
used
then patient with Brady eurythmias right
patients who are already having right
Brady arrhythmias
ready
Mayans right in these patients beta
blockers should not be used and of
course if someone has already depression
will you use the beta blockers
yeah he will get more depressed so these
are the five conditions in which beta
blockers should not be used or very
carefully I will deal these conditions
one by one first of all why beta
blockers are contraindicated in
corn chronic obstructive
pulmonary diseases
right why
first I will talk about normal
what normally is going on in your lungs
and what happens when you give the beta
blockers listen carefully
actually
normally you know
smooth muscles of bronchial
broncular smooth muscles
they're very rich Let's suppose this is
bronchial system right and bronchial
smooth muscles they're very rich in uh
these are two receptors this is
bronchial's post Booth muscle I just
showed you one bronchial smooth muscle
and it is very very rich in beta2
adrenergic receptors what are these
beta2 heteronergic receptors
normally what happens that your
endogenous
category means
endogenous category means stimulate
beta2 receptors on bronchial smooth
muscle and normally
you know there is beta2 mediated yes
bronchodilatation Bronco dilation
so
normally you have a slight degree of
bronchodilatation maintained by the
beta2 activity right by the endogenous
catecholamines
now
when you give up beta blockers to normal
person there may be slight loss of this
which are two mediated bronchodilatation
and in a normal person it may not be a
big problem
but those patient
who have coronary pulmonary chronic
obstructive pulmonary diseases they have
a tendency to develop they are already
having a tendency to have obstruction to
the Airways is that right these patient
may be asthma patients
as stomach patient
COPD these patients may be yes chronic
bronchitis patient
chronic bronchitis patient these
patients may be emphysema
emphysema patients and of course the
patient with
bronchiatases
he act
says so these patients patients with
asthma patient with chronic bronchitis
patients with emphysema where there's
loss of elasticity in the lung and
bronchial cannot be kept open properly
and
patient with bronchitis is in all these
conditions there's always some degree of
Airway obstruction
patient
come to you and due to some hypertension
or due to some cardiac indication you
inadvertently by mistake put these
patients on the beta blocker especially
non-selective beta blockers like
Propranolol there will be certain laws
of beta2 mediatase bronchodilidation and
because they have already a degree of
Broncho obstruction so what happened
this loss of beta 2 bronchodilation May
precipitate very severe
bronchoconstruction and sometimes this
may be fatal
right so you have to be very careful
that whenever you are going to
administer to a patient beta blockers
right and right you must be sure that
patient does not have any disease like
chronic obstructive pulmonary disease am
I clear why because there's loss of
beta2 mediated bronchodilatation which
is very important in the patient with
coronary
chronic obstructive lung diseases right
this is one condition
and here you have to remember that in
these diseases even it is better to
avoid the selective beta blockers
because selective beta blocker like
Atenolol even though they are having
more action to block the beta1 and uh
they have less section on the beta2 but
still to some degree they do block The
beta2 receptors so why to take the risk
am I clear
then we come to the very important
concept that why patient with severe
diabetes are labile diabetes or the
patient with insulin dependent diabetes
why this patients should not be given
beta blockers patient of diabetes
mellitus especially who are insulin
dependent
let me tell you
the main problem with the patient on the
insulin dependent diabetic patient is
that sometimes they develop severe
hypoglycemic attack you know why for
example if I'm a severely diabetic
patient and you are managing Me by in
injections of insulin then I have
a risk of developing
hypoglycemia what could be the reason
no actually insulin is given in a
standardized ways you will measure my
requirements of insulin and give me but
what really happens for example patient
has taken insulin injection but has not
taken food
what are the conditions in which insulin
dependent diabetics can develop
hypoglycemia write it down the
conditions in which insulin dependent
diabetics May develop severe
hypoglycemia right so hypoglycemia May
develop when patients are taken insulin
but not
food
he may develop
or patient has taken insulin and after
that he has taken food but he has
vomited out
vomiting so you lost the food and
Insulin which has gone and will
precipitates we are hypoglycemia
or patient has taken insulin and even he
has taken food but that day he has done
specially more physical activity
excessive
excessive
physical activity
and of course this patient has entered
advertently taken extra amount of
insulin is taken
insulin more than what he really needed
right so under all these circumstances
and many other circumstances patients
who are insulin dependent they develop
hypoglycemia now listen carefully I'm
going to explain that when insulin
dependent patients develop
hypoglycemia when insulin dependent
patient develop hypoglycemia how the
body responds is that right then I will
explain how the beta blocker interfere
with the body responses right first I
will tell you that if you are if I'm
insulin independent diabetic and I'm
undergoing hypoglycemia how my bodily
mechanisms are
activated right later on I will tell you
how beta blockers interfere with those
bodily mechanisms listen
for example this is my circulatory
system
this is my circulatory system what is
happening the primary problem is
Hypoglycemia hypoglycemia means that
glucose level is dangerously
low
is that right now whenever glucose level
is low
there are some physiological responses
activated
some neuronal responses are activated
and some endocrine responses are
activated number one that whenever
glucose level is low what really happens
that
your central nervous system is
activated low glucose will stimulate the
central nervous system and that will
lead to very strong sympathetic outflow
that will lead to very strong
sympathetic
outflow
now this sympathetic outflow is good for
the patient the patient who is having
what is the patient problem
hypoglycemia as hypoglycemia gets more
and more severe
there is stronger sympathetic outflow
from central nervous system
now what are the advantages of these
sympathetic outflow number one these
sympathetic outflow will produce warning
signs warning symptoms
for the patient
right for example
that this patient
May undergo tachycardia
turkey
and many patients right or this patient
with tachycardia May develop tremors
is that right so
and even patient may develop sweating
now
listen These Warnings symptoms are very
important for the patient why they are
important the reason being that if I am
insulin dependent diabetic and if my
glucose level is going down with the
experience I will learn that whenever I
develop palpitations tachycardia leading
to palpitations and whenever I develop
Tremors and sweating
probably my glucose level is low and I
should abort hypoglycemia by taking a
lump of sugar immediately actually all
the patient whom you put on insulin it's
always wise that expose them
purposefully to hypoglycemia and then
educate them how they these are the for
example if your first time putting a
patient on insulin so why is that tell
him that you're going to expose him to
the hypo and then really give a little
more amount of insulin and when you go
hypo then he will develop this warning
signs and tell him how to recognize this
warning sign and tell them that these
warning signs are the signs are due to
hypoglycemia then offer him some sugary
drink or lump of sugar and
educate him that how he will take it and
how he the symptoms of hypoglycemia will
disappear is that right so thank God
that patient when they undergo sphere
hypoglycemia nature provides the patient
nature provides the patient with warning
symptoms is that right now when you put
the patient on beta blocker listen
carefully when you put the patient on
beta blocker drugs right there is beta 1
mediated tachycardia and this beta-2
mediated primers so patient who is on
beta blockers will he be aware he will
develop the warning sign on hypoglycemia
no so this is one problem that patients
who are diabetic
and insulin independent and
unfortunately you have put them on beta
blockers so whenever they develop
hypoglycemia right they will not develop
the warning signs of hypoglycemia so
patient will not be aware of that he is
going into progressively
deeper hypoglycemia
which are two receptors when they are
stimulated you know beta2 receptors are
present on the muscle spindles and when
beta2 receptors are stimulated that
leads to Tremors is that right so which
are two mediated
primers beta2 adrenergic receptors lead
to Tremors and of course beta 1
hydrologic receptor lead to tachycardia
so there's loss of tachycardia there's
loss of Tremors so we can see that this
drug leads to one problem
which this drug is doing one dangerous
thing that there's loss of
warning symptoms of
warning yes
symptoms of
hypo
glycemia this is one problem so patient
is handicapped that patient never gets
aware that he is undergoing hypoglycemia
and he does not take exogenous sugars am
I flat
now
what is the next step
next step is that liver should provide
the
glucose
liver should provide the extra let's
suppose here is a hepatocyte
here is a
hepato side
now what really happens that when your
glucose level is going down
two humoral actions will occur
two humoral actions will occur number
one of course a lot of adrenaline is
released by adrenal gland due to
sympathetic overflow so there's a lot of
epinephrine in the blood
and normally this epinephrine Act
through
beta2 receptors these are beta2
receptors where on hepatocytes so
normally what happens when your blood
glucose level is down due to increased
sympathetic activity not only there are
warning symptoms but increased
sympathetic activity also increases
epinephrine in the blood and this
epinephrine will act on adrenergic
receptors on hepatocytes and when this
epinephrine will act on the hepatocytes
what will happen that intracellular
signaling eventually lead to breakdown
of yes glycogen there is glycogen so
glycogen will be broken down under these
signals into
glucose and this glucose will be
provided to the blood from the
hepatocytes
is that right what a beautiful normal
mechanism that whenever you develop
hypoglycemia not only body is giving
given warning about that at the
patient's conscious level but
endogenously increase epinephrine
stimulate the beta-2 adrenergic
receptors on hepatocytes and they give
intracellular signal which order the
glycogen break down into glucose and
liver start hepatocytes start releasing
glucose into blood to counteract the
hypo
glycemia
is that right it's good news the bad
news
so good news unfortunately when you give
the beta blockers they block the
receptor here
so endogenous mechanism to compensate
for hypoglycemia by glycogenol lysis is
lost this is the action of propranolol
propron and LOL block The beta2
receptors on the hepatocytes and then
epinephrine induced
glycogenolysis is lost so glycogenolysis
cannot be done and hepatic glucose
cannot be released to compensate for the
decreasing glucose level in the blood am
I clear so now it's a good news or bad
news it's a bad news is that right now
not only this another help normally come
and that help come from pancreas
you know what pancreas produces under
sphere hypoglycemia pancreas produces
glucagon it produces
glucagon
and this glucocon also has the receptors
right on what
hepatocytes
glucagon has also receptors on the
hepatocytes
and when glucagon activates the
hepatocytes and gives signals to the
hepatocytes these Master metabolic cells
what they will do they will start
converting the fatty acids and amino
acids into glucose
right what will be the result the
conversion of fatty acids and amino acid
to
Watson
to
glucose
right
and this process is called
gluconeogenesis
let's define what is gluconeogenesis
gluconeogenesis is the metabolic process
in which we make glucose from
non-carbohydrate sources
right and in the liver the process of
gluconeogenesis is activated by
glucagon
right so it means that there are two
mechanisms
right that one mechanism is
look
from the liver we can get glucose by two
mechanism number one we can get glucose
by breakdown of glycogen number two we
can get glucose by breaking the fatty
acids and amino acids and using their
carbon skeletal skeletons using the
fatty acids and amino acids carbon
skeletons to build new glucose is that
right the first process breakdown of
glycogen is called glycogen lysis and
the second process is called
gluconeogenesis now look at it
here's again beta blockers make a
trouble actually
beta receptors are present
beta 2 Beta receptors are present on
glucagon release in South
you know this is a glucagon releasing
cell and what really happens that during
hypoglycemia glucagon releasing cells
release glucagon which will do
gluconeogenesis unfortunately
beta blockers also block these receptors
so it means data blockers reduce their
release of glucagon
beta blockers reduce the release of
glucagon and when glucagon release is
impaired then liver is unable to do
gluconeogenesis
now let's sum up what's happening look
here attention
that when a patient is on beta blockers
and patient is diabetic patient and
Insulin dependent this patient may
undergo extremely severe hypoglycemia
right and why these patients undergo
very severe
hypoglycemia one reason is that when
such patient is on beta blockers right
whenever hypoglycemia occur patient does
not develop warning symptoms so patient
is never knowing that how or that
patient is suffering with hypoglycemia
and patient does not take external
glucose is that right
this is problem number one problem
number two beta blockers also impair the
internal hepatic glucose release
in hypoglycemia how do they impair
in a normal person epinephrine
stimulates the hepatocytes to produce
glucose from glycogenolysis and normally
epinephrine also stimulates the glucagon
producing cells so that glucagon should
act on the hepatocyte and produce new
glucose from gluconeogenesis these are
the two main hepatic mechanisms which
provide the glucose to the blood
Whenever there is hyper glycemia
unfortunately patient who is on the beta
blockers a hepatic beta2 receptors are
blocked so epinephrine induced
glycogenolysis cannot be induced
so this source of hepatic glucose Supply
is lost so secondly when patient is on
beta are two blockers right then
glucagon releases also impaired so
gluconegone glucagon mediated
gluconeogenesis cannot be done and
further a loss of internal supply of
compensatory glucose from the liver so
patient is not taking the glucose from
outside and hepatic gluconeogenesis and
glycogenolysis is impaired an internal
glucose is also not released from the
liver so patient goes into where is
severe hypoglycemia and patient may
develop even is very severe irritation
and patient may develop fats or even
we're going to Coma right so of course
you don't want this for your patient if
you don't want for this patient so next
time you have to be careful for what
that when a patient has insulin
dependent diabetes mellitus don't put
them on beta blockers look for
alternative drugs am I clear okay now we
come to the third thing
here Alto it's wise not to use beta
blockers patients who have peripheral
patients who have peripheral
vasospastic tendency what is Reynolds
disease or Reynolds phenomenon actually
in the north phenomenon
peripheral vessels of the limbs
specially vessels of the hands the
undergoes severe with the spasticity
sometimes again
what happens in the north disease or the
North phenomenon that patient has a
tendency to develop severe
vesospasticity of the peripheral vessels
is that clear and that may make you know
a hands cold and pale and you know the
first they will become very pale and
cold and then later on they may undergo
reactive cyanotic and then reactive
hyperemia right these whenever this is
cities precipitated that will lead to
cold extremities and painful extremities
and if patient who has such tendency if
unfortunately you put such patient on
beta blockers due to some indication
what will happen the beta2 mediated
peripheral vascular visual dilatation is
lost
what really happens that if such patient
is put on the beta blockers then
endogenous epinephrine cannot keep a
small degree of dilatation in the
peripheral vessels and patient is
already a tendency for viso spasticity
so beta 2 mediated loss of visual
dilatation will lead to intense business
possibility and severe problem in the
patient with
peripheral vascular disease am I clear
then we come to the patient with Brady
arrhythmia this is the most easy to
explain
of course if there's a patient even if
he is having angina or Mi or congestive
cardiac failure but along with these
problems he has
breadierythmiasmia mean that any patient
who is having let's suppose one example
of bloody urhmias
sinus
bradycardation
right if someone has his SA node too
much suppressed
if SN note is working very less we say
there is sinus bradycardia if heart rate
is less than 60 per minute
in the daytime or heart rate is less
than 60 per minute 50 per minute
in the sleeping
in the waking state if your heart rate
is less than 60 per minute this is sinus
bradycardia or during the sleep if heart
rate is less than 50 per minute that is
also sinus bradycardia or due to some
reason AV node is not working well maybe
if you notice patient is on some drug or
there's some pathology with the AV nerd
and there is some degree of heart block
heart block mean that impulses from The
Atrium are not transmitted to the
ventricles in a normal fashion there's
undue delay for the actual impulses to
go to The ventricle or maybe if initial
impulses are
all together not able to go to the
ventricular such conditions are called
heart blocks right now in such patients
uh epinephrine Through The beta2
receptors is normally responsible to
stimulate acinod and
evenode
is that right epinephrine normally
stimulate essay node and AV node is that
right normally
epinephrine
even norepinephrine norepinephrine comes
from sympathetic nerve endings write it
down norepinephrine is mainly released
from sympathetic
nerve endings an epinephrine is mainly
released from Adrenal medulla so
epinephrine and norepinephrine through
activation of beta-1 receptors on SA
node and AV node they act as stimulated
reagents is that right now if a patient
has already bready arrhythmia either
patient is having sinus bradycardia or
nodal blocks
and at the top you supply the patient
with beta blockers you block these
receptors so in a patient who has
already Brady arrhythmia if you abolish
the catecholamine mediated stimulation
to asinode and AV node
simple mild to moderate radial will
immediately convert into very severe
degree of
yeah that's the right and due to that
reason if you have a patient with a
tendency of Brady arrhythmias please
don't try beta blockers there
am I clear for example if the partial
Block in the AV node and some of the
impulses from HD are going down to
ventricle and some impulses are not
going but once you give the beta blocker
maybe none of them Pulses from Atria go
to The ventricle is it clear right
another important thing with bloodier
in acute
in acute
congestive cardiac failure now this is a
very important point to understand you
have to be really
very sharp to understand this point
because these days we use beta blockers
as a treatment in patient with
congestive cardiac failure but if
someone has very acute congestive
cardiac failure then we should not give
the beta blockers because that may
worsen the symptom you know beta
blockers are negative inotropic agents
right they reduce the contractility
do you know that or not right and if
patient has already mechanical
impairment of the heart and very severe
mechanical impairment right would you
like to give the patient some negative
anotropic agent answer is no but here
you have to remember these days beta
blockers have become one of the standard
drug use in patient with congestive
cardiac failure why they are used in
congestive cardiac failure I will
explain in lecture on congestive cardiac
failure management but the point which
you have to remember that if a patient
is severely under very severe mechanical
failure of the heart right of course
beta blocker should not be done
that's the right because beta blocker
and heart failure have a long term
benefit but if a patient is in such a
sphere failure and you give the beta
blocker maybe patient does not live for
long-term benefit patient dies with
complete failure am I clear so use of
beta blockers and cardiac failure has to
be very very judicious
is that clear
and now in the end I told you beta
blocker should not be given in patient
with depression I think there's no fun
in explaining that I told you one of the
important side effect of beta blocker is
mental depression of course patient if
patient is already having mental
depression and at the top right you give
him beta blocker for hypertension or as
antiarismic drugs or as antine general
drug she will go into very deep
depression and maybe this person commits
suicide
it's also very bad news isn't it so I
hope my very good students will remember
that beta blockers should be used in
these conditions better not to be used
or to be used with lot of care or best
is that that you should consult your
seniors if you have to use them
Emma glare other
and depression is so simple let me tell
you when your adrenergic activity is
more
you are excited or you are depressed
excited so it means person who is
depressed already he has reduced
adrenergic activities in his brain
when you will study the pathology of
depression one of the reason of
depression is the monoamines in central
of a system are reduced the action of
epinephrine norepinephrine dupe and
dopamine and certain especially these
are reduced in depression already
patient has reduced
adrenergic activity in the brain and due
to that reason he has depression at the
top you give some beta blocker and block
the remaining activity of the
sympathetic nervous system what do you
think patient will be excited
he will go into deeper depression some
of them become so depressed even they
don't have energy to commit suicide
why I'm telling you this because those
patients who are extremely depressed and
they don't have energy to commit suicide
when you give them antidepressant drug
this sometimes a little little get
better and get energy to commit suicide
so you have to be careful when you
patient manage the patients of
depression right let's have a break
now today we are going to talk about the
calcium channel blockers and their role
in patients with angina right so our
major discussion is calcium
channel blockers and their role in yes
please
Roland angina
first of all I will tell you that what a
what calcium channel blockers are going
to do for example if you give a patient
calcium channel blockers calcium channel
blockers are group of the drugs which
will bind with the calcium channels
which calcium channel voltage grated
calcium channel you must know the many
types of calcium channels right and our
drugs use a selected special group of
calcium channels and which calcium
channels voltage grated calcium channels
and which type of voltage-gated L Type
so what we say that they are competitive
Blocker of L Type
calcium
Channel block you may be thinking that
why I am stressing that they are
blocking a specific type of calcium
channel why it is so important to know
it the reason being that calcium influx
in the cell operates many biological
functions
right for example calcium influx in the
neurons releases neurotransmitter
calcium influx in the Endocrine cells
releases the hormones
calcium and flux and smooth muscles and
skeletal muscles that can lead to
contractility in the same way calcium
and flux and the myocardial cells also
produces contractility
now
when we want a particular drug which
should be used use useful in the patient
with cardiovascular diseases we want
that drug should block the calcium
channels only in The myocardium and
smooth muscles so that vascular diameter
should be altered and myocardial
activity should be altered but we do not
want any drug which will also block the
calcium channels which are involved in
neurotransmitter release and we do not
want any type of calcium channel blocker
which will block the Endocrine cells
calcium influx so that endocrine release
should be disturbed
so what I was saying that there are many
types of calcium channel blockers some
are controlling the neurotransmitter
release others are controlling
exocytosis of the
Endocrine cells now these two types of
channels should not be blocked if we
have a drug which can block all the
calcium channels that will go into trash
basket
right so what I wanted to put that when
we are using calcium channel blocker in
cardiovascular diseases we need such
drugs which will specifically block the
calcium channels which are present in
the myocardial cells and the smooth
cells of the blood vessels is that right
now the calcium channels which are
calcium channel blocker which are
presently available to us they are
basically I will mention three classical
runs
three classical drug even though there
are now many new drugs but all of them
are compared and contrasted with these
three classical calcium channel blockers
one calcium channel blocker is called
nephedepine
the fed the pain very commonly used
and you should be able to compare and
contrast the actions of nifida pain with
the actions of
Delta as m
deltaia
them
and
third important classical drug and
calcium channel blocker is Verapamil
now just knowing the name of these drugs
here is not enough
you must know how they are different
from each other because even though all
of them work on the cardiovascular
system but the way they work is
significantly different
now what is the difference
let's talk about
this is your heart
right
let's suppose here is your heart and
this is atrial myocardium
and here is
ventricular
myocardial
right first I will tell you in the heart
which tissue is dependent on calcium
right then we'll talk about how the
drugs block it basically
as a node depolarization is calcium
dependent Point number one is that
SA node
depolarization is calcium dependent
number two AV nodal depolarization is
also
AV nodal depolarization is also calcium
dependent now let me stress first
depolarization in snode is calcium
dependent depolarization in atrial
muscle is sodium dependent this is a
very big difference
you must write it down that in the
myocardial tissue in the whole
myocardium right some of the myocardial
tissue is having depolarization which is
calcium dependent and some of the
myocardial tissue has depolarization
which is sodium dependent and let's make
it like this depolarization myocardial
depolarization Mayo
cardial depolarization right which can
divide it into calcium dependent
depolarization and sodium influx
dependent depolarization
now which are the calcium
dependent essay node and
AV node
as a node and even Oda calcium dependent
depolarization and sodium dependent
depolarization are
irritial myocardium atrial General
myocardium
and ventricular General myocardium
remember acetone and AV nod are also
myocardial tissue but it is specialized
in myocardial tissue
myocardial tissue
law it is specialized it has lost the
capacity the myocardial cell in snode
has lost the capacity for
contractility
but acquired the capacity of
automaticity automaticity mean increased
tendency to produce automatic
depolarization
in the same way AV node is also
specialized to myocardium it's a general
myocardium specialized myocardium
modified myocardium what is special
thing about AV node the myocardial cells
which are present in AV node have again
lost the capacity to contract and they
have acquired the capacity to
for slow conduction my friend no
so that current from Atrium will be
passing through EV nodes so slowly that
Atria should complete their contraction
fill the ventricle only then current
will come to The ventricle and
ventricles will contract is that right
so what I wanted to say
that The myocardium in the heart has two
types of myocardium there is General
myocardium and there is specialized
myocardium General myocardium is General
atrial contact and myocardium General
ventricular myo contractile myocardium
right but specialized myocardium is
acinode and AV node plus per conjure
system you know system that is also
specialized modified myocardial fibers
the bundle branches and
turkanja fibers
but remember
that this fibers
their depolarization is sodium
dependent
right so now today onward you have to
remember that specialized myocardium is
acinode Av node and prochanger system
General myocardium is atrial contraction
and ventricular contraction is that
right calcium dependent electrical
activity is seen in
depolarization is calcium dependent and
sodium dependent depolarization is
atrial and ventricular myocardium plus
one specialized tissue which is also
sodium dependent not calcium dependent
so you may be thinking why I'm stressing
it the reason being that there are some
drugs which act as calcium channel
blocker so they will reduce electrical
activity in this tissue
and the other drugs which are
sodium channel blocker they will mainly
act the electrical activity of Atria
ventricular and per congest system is
that clear
Amorite this is one thing right that
there is calcium dependent automaticity
here this calcium dependent conductivity
here because this is a function of
automaticity this is a function of
conductivity slow conduction
but one more thing even though listen
carefully even though the atrial and
ventricular myocardium has
depolarization which is due to sodium
but contraction of Atria and ventricle
depends on
oh
again listen carefully
atrial and ventricular depolarization is
sodium dependent but contractility of
atrial ventricular is
calcium dependent is that right now in a
nutshell we can say calcium dependent
activities in the heart so that then
we'll know that when calcium channel
blockers are given what really happens
physiology linked with pharmacology now
we can say what are the calcium
dependent
cardiac activities cardiac activities
calcium dependent
this is the right which can be modified
by
calcium channel blockers one thing we
already know
yes SA node Plus
AV node depolarization
second thing should be clear
plus ventricular not depolarization but
contraction
but contraction it means when we will
give calcium channel blockers to reduce
the activity of
as a node electrical activity of as
anode will reduce the electrical
activity of Av node plus will reduce the
calcium channel blocker will reduce the
mechanical activity of Eritrea and
ventricle you know heart has basically
electrical activity and
vent and mechanical activity is that
right so we can say now we go that if
you give a calcium channel blocker what
will happen to heart if there is a
calcium channel blocker which can block
the calcium channels in the heart what
really happens
again
what will happen to us a node
it cannot depolarized it's very easy to
understand if s a node is exposed to the
calcium channel blocker it cannot go
under depolarization easily the rate of
depolarization will be slow
right it means
tendency of SL node to produce automatic
impulses
slow so there we say that there is
reduced automaticity calcium channel
blocker when they act on SA node they
reduce the automaticity and reduced
automaticity is
technically called we say that there is
negative
yes chronotropic action Chrono
Tropi
so calcium channel blocker when they act
on as a node they'd
slow down the rate of depolarization of
Sno they inhibit the automaticity of as
a node total number of cardiac impulses
generated per minute by asinode has been
reduced of course that will lead to
reduced heart rate that will lead to yes
reduce heart
right and this phenomenon is called
negative chronotropic action right so
one action of the calcium blocker is
negative chronotropy secondly when
calcium channel blockers will work on
what is this
AV node what will happen here it was
acid nodal activity now AV node
it's very easy when essay node is under
the calcium channel blocker and you know
AV node is calcium dependent
depolarization so again electrical
activity in asinode is suppressed major
function of acetone was AV node was that
it was transferring the impulses from
atr2 ventricle when every node is
suppressed then transfer of impulses
from Atria to The ventricle is further
reduced or suppressed is that right so
we can say that there's pathological
depression of
conductivity
there is pathological dependent of the
depression of conductivity through the
AV node is that right and that is called
negative yes please dromo
is that right and that will lead to if
this action become excessive that will
lead to what problem
if the section become excessive
yeah bradycardia noodle bradycardia
simply we call it heart blocks
what are heart blocks hard blocks are
conditions in which impulsives from the
Atria
right impulses from the Eritrea
are going to The ventricle either with
undue delay or they are not going at all
what is the heart block the term is also
called heart block the same thing is
also called there is another term for
this we call it nodal block there can be
heart block there can be nodal block and
some people call it junctional block
all these are the same thing heart block
or noodle block or a junctional block
these terms are used that whenever
normally what happen attention plays
every atrial impulse
will conduct from ATR Atrium to The
ventricle
with normal delay delay of 0.1 second it
means when atrial impulse reaches
even node it is held there for how much
time 0.1 second so that Atria completes
their contraction and fill the
ventricles only then current is released
but let's suppose you have given some
calcium channel blocker now rather than
0.81 second maybe this delay is taking
0.2 second so it is normal due delay or
undue delay
it is undue delay and if every impulse
listen now carefully if every impulse
from Atrium is going to The ventricle
but with undue delay we say first degree
heart block what is that
first degree
heart block when every impulse from
Atrium eventually goes to the ventricle
but within due delay and in second
degree heart block
probably AV node is further suppressed
probably we notice further suppressed
then second degree heart block occur
what is second degree heart block some
of the impulses from Atrium go down and
some are aborted they are not allowed to
go down
is that right in first degree heart
block every impulse from here was going
down but with undue delay and second
degree heart block some of them pulses
will be allowed to go down and others
not for example snode is firing at the
rate of 80
but AV not allow only 14 buses down so
irritial activity will be 80 per minute
and ventricular activity will be 40 per
minute so we call it second degree heart
block and if really there is much
toxicity due to calcium channel blocker
then there will be very big problem
that if there's too much toxicity of
calcium channel blockers and suppress
the evenode so much that AV node cannot
conduct any atrial impulse to The
ventricle we say this complete heart
block what is that complete heart block
or we simply called it
third degree heart block so this is
partial heart block
this is also first degree and second
degree both are partial heart block
because
and in this case none of the actual
impulses is able to pass through the AV
node to ventricle we call it complete
hard
block is that clear
now why I'm explaining it because we
have to relate the physiology with the
pharmacology and
blocker and toxic actions of calcium
channel blocker so this is one thing can
happen and here I should also mention as
I have told you that AV node is normally
suppressed by calcium channel blocker
and if it is too much suppressed it will
produce heart blocks but if snode is
suppressed first snode will reduce its
automaticity for example your heart rate
is 90 per minute I give you calcium
channel blocker which specially work on
essay node your heart rate may become 60
per minute 50 per minute
and if there's too much
right we say that when heart rate is
suppressed less than 60 per minute we
say the problem is sinus what is that
bradycardia so it is one of the side
effect of calcium channel blockers sinus
Brady cardia and when we say there is
sinus bradycardia one heart rate
is less than 60 due to reduced
automaticity of
as a node and heart rate is less than 60
due to reduced automaticity of as a node
and if you are really giving very heavy
dose of calcium channel blocker very
toxic dose and as a node stop working
what term we use it there is what term
is used we say there is sinus
there is sinus
arrest
it is completely arrested no function of
s a node if there's a very heavy dose of
calcium channel blocker right for
example very heavy dose of calcium
channel blocker here will produce sinus
arrest no automaticity displayed by SA
node and very heavy dose here will
produce complete heart block is that
right so we'll say that there is sinus
rest
look look just a minute when you give
calcium channel blocker asynode and AV
node electrical activity reduce
as a some reduced electrical activities
are said to be bready arrhythmias what
are they called Brady eurythmia heart
has gone out of rhythm on the
bradycardia side slow side Brady
arrhythmias may be related to acetone or
they may be related to AV node or to the
both when Brady arrhythmias are here
these are called sinus bloody
arrhythmias when they are here we call
it nodal Brady arrhythmias sinus are
simple sinus bradycardias or if sinus
activity totally stop we say that there
is sinus rest noodles are first degree
heart block second degree heart block
and third degree heart block is that
Claire
right now this was the action of calcium
channel blockers on snod and AV node
right which are calcium dependent
depolarizing tissues now we come to the
action of the calcium channel blockers
on contractile myocardium especially
ventricular myocardium what happens in
The ventricle normally you know in the
plateau phase some calcium goes in when
there's depolarization of The ventricle
during Plateau phase there is calcium
going on
that calcium trigger the release of
calcium from sarcoplasmic reticulum and
that total calcium act on
proponent and pull the tropomyosin away
so that actor myosin can contract so we
can say that calcium in flux during the
plateau phase of action potential
triggers the release of intracellular
stores of calcium within the myocardial
cell a lot of calcium which is present
in the myocardial cell that is that is
going to lead to contractility is that
right now listen if you give calcium
channel blockers right then uh calcium
channels which are throwing the calcium
during the plateau phase they are
blocked with the drug
so it means Ruger calcium to The
myocardium is increased or decreased
decrease then intracellular release of
calcium is also decreased then of course
contractility is decrease and the term
which will be used is yes please
the term which is used again listen on
calcium channel the block on these cells
calcium is not going in and ultimately
there is suppression of
calcium dependent contractility this
reduced calcium dependent conductility
when contractility is reduced the term
which is used is yes Jamie what is the
term
then culture
negative inotropic effect negative I
know
trophy
actually negative inotropy means there
is yes there is reduced
strength
strength of
contraction
is that right negative inotropy mean
that there is reduced contraction
reduced strength of contraction but
while
not only strength of contraction is
reduced even velocity of contraction is
also reduced by blocking the calcium
channel channels for example let me
explain that let's suppose this is a
graph showing the contractility is that
right normal contractility is that
during the systole pressure will go up
contraction tension will go up and then
tension will come down and then there is
dastly is that right this is the normal
dynamics of systolic contraction
is that right now
this is the total
what strength of contraction
this is the strength of contraction and
here's the time frame
y-axis you have time on x axis you have
strength of contraction is that right
this is normal now let me draw the graph
when calcium channel blocker is given
and calcium channel blocker is given
number one
there is
reduced total contraction
this process the total contraction has
been reduced this is called negative
inotropy total contraction has been
reduced and relaxation is also
reduced now look at the phenomenon
normally
this is a
High Velocity with which it will go to
the peak contraction and with high
velocity it will relax
but after calcium channel blocker the
velocity with which with weight the
tension will develop
and tension will be lost that velocity
has been reduced as well as strength has
been reduced for example normally to go
to the peak tension this was the time
taken
but after the calcium channel blockers
the time taken
for Peak tension is prolonged
now so we can say when calcium channels
block the myocardial calcium calcium
channel blockers block the calcium
channels in the contractile myocardium
there is reduced contraction as well as
this reduced velocity right because when
you reduce the contraction oxygen demand
of the heart is reduced and when you
reduce the contractility velocity that
also further reduces the oxygen demands
so what is the term used when velocity
of contraction is reduced you have
already told me the term when there is
reduced
strength of contraction
the reduced strength of contraction we
say there's negative inotropy when there
is reduced velocity of contraction what
is the term used
when there is gas
reduced velocity of contraction
T of
contraction and relaxation it slowly
contract and slowly relaxes because this
thing will reduce the oxygen demand when
you reduce the strength of contraction
oxygen demand is reduced when you reduce
the
velocity of contraction oxygen demand is
further reduced what is the terms used
okay 10 dollar price for this
no one needs ten dollar all of you are
very rich
now he asked what is the question
no I'm just telling you that don't
concentrate on ten dollars concentrate
on the topic what I'm saying yeah uh I'm
cons I'm just telling that by giving the
calcium channel blocker and please add
it even by giving the beta blockers
both have the same action they reduce
the total strength of contraction they
also reduce the velocity of contractile
mechanism
both of them calcium channel blockers
and beta blocker reduction in strength
of conduction is called a negative
inotropy reduction in
velocity of contraction is called yes
ten dollars question
I think ten dollar is fine to you
negative dromotropy is reduced
conduction
remember reduced normal automaticities
negative chronotropy reduced normal
conduction is
negative
dromotropy reduced strength of
contraction is called negative inotropy
and reduced velocity of contraction is
called
yeah Sean is going to tell what is that
negative
clinotropin kalino
tropia excellent so
someone will get 10 dollars later right
reduced clinotropy so today when you
talk to your friends you can say calcium
channel blocker reduce the heart rate
reduce the conduction through every node
reduce the contractility reduce the work
of the heart and reduce oxygen demand so
they are good in angina but when you
talk to a Cardiologist then you should
talk in a better term
calcium metal blockers are negative
chronotropic drugs their negative
dromotropic drugs their negative
inotropic drugs as well as their
negative planotropic drugs right and
then you mentioned because heart rate is
reduced and contraction Dynamics are
reduced so what happens total oxygen
work of the heart is reduced per minute
work is reduced and oxygen demand is
reduced and when oxygen demand is
reduced you remember in the beginning of
the lecture I told you on stable angina
what was the problem there was
astrological erotic plaque which was
given small amount of blood flow to
myocardium
right so whenever you develop
tachycardia or whenever you develop
extra work of the heart whenever you
develop the extra work of the heart what
really happens that atherocyclerotic
obstruction cannot be dilated
that is fibrous tissue and plaque right
so whenever your heart oxygen demand is
more
let's suppose this is myocardium piece
and this was your
coronary Supply and let's suppose this
coronary Supply here is obstructed more
than suppose 80 percent obstructed or
seventy percent obstructed now the
little blood which is coming due during
the with little blood which is coming
through the obstruction that may be
enough for the resting myocardium but
whenever myocardium undergoes increase
work during tachycardia or when patient
is exerting right this point cannot
dilate
so the dependent myocardium will become
ischemic and that will precipitate
classical angina and China and China of
exertion rangina with excitement
or emotional tension you are
understanding
you remember that what was the trick to
manage this in China One of the trick
was that reduce reduce the work of the
heart so much and reduce the demand of
oxygen of the heart so much that reduced
demand of oxygen is now matching with
the reduced supply of oxygen
do you get it and this function can be
achieved with calcium channel blockers
because calcium channel blocker reduce
the heart rate reduce the contractility
of course when heart rate is reduced
when there's reduced heart rate and
there is reduced contractility and when
there is reduced contractility it means
reduced stroke volume so that will lead
to reduced cardiac output and of course
reduced cardiac work that will lead to
reduced cardiac oxygen demand
is that right so by reducing the heart
rate and reducing the contractility and
stroke volume we reduce the cardiac work
and reduce the oxygen demand and in a
typical angina what we really wanted we
wanted to reduce the amount of oxygen so
much that reduced
demand of oxygen by The myocardium is
matching now with the reduced supply of
oxygen and patient does not feel
ischemic pain
am I clear
this is how uh calcium channel blockers
work on the heart and help in
termination of symptoms of angina but
there's still more to be said
the very special thing which I would
love to mention is that nifedipine
okay that I will mention later when I go
into detail of their differences what's
your question
I will explain this I've just mentioned
calcium channel blockers can be used in
classical in China right now I've just
told that but in classical in China
first you should try nitrates and beta
blockers if both of them are not
effective then you add the calcium
channel blockers is that right am I
clear but I will explain some further
functions of calcium channel blocker
then we'll integrate the information
that how it is beneficial some other
types of angina as well right
now we have just concentrated only the
action of
calcium channel blockers on The
myocardium that is electrical how the
calcium channel blockers alter the
electrical activity of heart and how
calcium channel blockers alter the
mechanical activity of the heart
mechanical and electrical activity of
heart now we'll make a diagram and you
must remember this in a good way
okay here is again our hard back
already you know how much we have
discussed about it
remember when I will draw diagram you
see I'm very careful that atrial
myocardium should not touch the
ventricular myocardium why because
between the atrial myocardium and
ventricular myocardium there's fibrous
partition ring the only connection
between the atrial myocardium and
ventricular myocardium is normally AV
node this is the only electrical window
between the Itchy and The ventricle in a
normal subject
right this is what we have seen that
what are the now
you see here is
what was this arterial side and what was
thing on this side
Venus
side right and you must be knowing
already that what are here
these are the capability beds in
different
tissues right and you know blood is
coming through arterials
to the tissues
and leaving through veins
now
now you will see the integrated function
of
calcium channel blockers
where cardiac function and Vascular
functions are correlated
we have only discussed about that it
produces
X here reduces heart rate
X here and reduces
yes reduces conductivity right and X
here and reduces
contractility and stroke volume this is
what we have already discussed in a
nutshell with all the mechanism
but we have to remember one more thing
that calcium channel blockers also act
on the smooth muscles calcium channel
blockers also act on the smooth muscles
of arterials right you know here are the
arterials
is that right this is arteries and
arteries
now you know articles are the major
resistance vessel when blood flow is
moving from the arterial tree to the
venous side the major resistance to the
flow is offered by arterial all of you
know that now
actually calcium channel blockers also
work on the arterial right because
arteriola smooth muscle is also
dependent on calcium influx through the
calcium channel system and Drug also
block here so it means when arterial or
smooth muscles are not getting enough
calcium in the presence of calcium
channel blockers what will happen will
the contract strongly or weekly
when calcium is unable to enter in
smooth muscles of arterioles
then arterioles will construct strongly
or weekly weekly if they constrict
Weekly right
when you give calcium channel blockers
which work on the artery roller smooth
muscle and calcium is not going into
entering into arteriola smooth muscle
well then articular smooth muscle relax
and when arterial smooth muscle relax
diameter of Articles is more then the
blood flow from the arterial site to
venous side it will have more resistance
or less resistance
again when you are giving calcium
channel blockers calcium channel blocker
relax these filters
so now the resistance to the blood flow
from arterial side to the venous side is
more or less
less blood will vary
reduced vasoconstriction
Jamie let me explain it again to you
listen
when you give calcium channel blockers
calcium cannot enter into these smooth
muscles
so they cannot contract well so they
will relax so there will be production
of visual dilatation
but but the right term should be that in
the presence of calcium channel blockers
smooth muscles of Articles cannot
constrict well so of course
physiologically what is there Vaso
arteriola
dilation and when these arteriolar
system is dilated
blood can move from arterial side to
window side easily
is that right it means resistance to the
flow from arterial side to venous side
is reduced or we can say total
total peripheral resistances
reduced
is it right total peripheral resistance
is reduced it means
that when you give calcium channel
blockers if it produces arterial or
dilatation
it means now left heart is working
against more resistance or less
resistance
you know function of the left heart is
that it should contract push the blood
through arterial side into the venous
side
now once you if some calcium channel
blocker work on the arterial then relax
the arterioles then left heart is
working against less resistance now
listen carefully how do you define after
load
we say
ventricles have preload and after load
preload is the amount of blood which is
present in The ventricle at the end of
diastole
is that right so preload is the amount
of the blood which is in The ventricle
on which ventricle has to produce its
squeezing action Contracting action is
that right that is preload what is after
load have you heard of this term what is
afternoon
what's after load
after load is the resistance against
which left ventricle has to perform
I think I should repeat them about the
donkey a little bit
hard is like a donkey
look this is your heart
right now this donkey has to go 70 times
per minute up take some load here and
come back
it carries normally heart is filled with
how much blood 140 ml this is a load on
the donkey before its start function so
we call it pre-load what is it preload
and once donkeys start moving up
systole start it is moving against the
slope
slope is acting as a resistance right
now donkey is moving against the
resistance and when donkey is moving
against the resistance right this
resistance against which donkey has to
perform right that is called
after load what is it called
after
load
is that right so preloaders
the amount on the donkey before it
starts performing after Lotus the
resistance against which it has to
perform is that right of course is very
stupid donkey you know what it does it
goes at the top
out of normally what it does during one
cycle it takes 140 ml there through
there only 70 ML and Carries back 70 ml
down
right so amount which originally it had
it is called and diastolic volume
and the resistance against which it has
to pump the blood that is after load
and whatever it leaves here is stroke
volume
and whatever it brings on the back is
called end systolic volume the volume in
the heart at the end of the system is
that right I told you that what what is
angina
angina is a myocardium which is crying
due to ischemia producing pain
is that right angina is a crying donkey
right if you want to reduce the cries of
donkey you must reduce the ischemia
right very simple thing number one you
reduce the load
we discussed in previous lectures that
we should reduce the preload donkey will
be happy
is that right number two why don't you
reduce the
yes after load if you reduce it like
this donkey will be happy or sad
I think you know donkey is very well
that's right he knows donkeys will be
very happy so what really happens when
you give vinodilators and it relax
listen now an angina treatment when you
give nitrates what are nitrates nitrates
are we know dilators when you give the
Vino dilators veins dilate blood pool
over here and less blood is going to the
ventricles so it means when you give
nitrates this reduced filling of the
ventricle and this reduced and diastolic
volume and nitrates are all the drugs
which are Vino dilator they are actually
the drug which reduce the preloads
and in angina you have to reduce the
preload as well as you have to reduce
afterloads so that heart should act on
less amount of volume and should act
against less amount of resistance so the
work of the donkey should be reduced
so that donkey performed well with the
reduced Supply reduced nutrition so how
do you reduce the
resistance against which the donkey has
to perform how you can what are the
drugs which can bring this slope down
yeah all the drugs which are strong
arteriolodilator
that's the basic concept all the drugs
which dilate the artery holes they
reduce the resistance against which the
myocardial donkey has to perform so it
means that all the drugs which are
arteriola dilators are primarily
after load reducers from today onward
please never forget we know that later
that pre-load reducers artery
after load reducers right am I clear
so some calcium channel blocker okay let
me tell you what is that some the
classical independent and related drugs
in the Philippine classically relaxes
arterial
when it I take the tablet of nifedipine
it will classically more act on the
arterial and less act on the heart
right
so in the Philippine is special type of
calcium channel blocker we also call
them dihydropyridine group die
Hydro
pyridine
derivative
now in the Philippine and some related
calcium channel blockers like amlodipine
nifedipine amlodipine philodipine is
that right these are the calcium channel
blocker which work more on the calcium
channel the smooth muscle and work Less
on the calcium channels of
hard so they are primarily arteriolo
dilators so when you give drug like
nifida pain it will relax the arterioles
and heart will be pumping against less
resistance so this oxygen requirement is
less Emma clear so yeah
yeah
now listen again back there were
multiple ways to manage the angina one
way was reduce the load on the Donkey
pre-load here we use the drugs which are
we know dilators like nitrates and if
you want to reduce the slope
what what group of drugs should be used
in angina
yes arterial dilators and if you further
want to help this crying donkey what can
you do lose you reduce the load you are
donkey lover now you reduce the load you
reduce the
slope after that do a favor to donkey
ask the donkey to make a favor to the
donkey that if it is making 90 cycles
per minute let it make only 60 Cycle per
minute the uncle will be sad or happy
very happy is that right reduce the
heart rate and even don't ask the donkey
to run with the load let it walk it
comfortably
what is that
negative not only heart rate but
negative climotropy with less velocity
it is moving is that right so not only
you reduce the preload not only you
reduce the afterload but help the Donkey
by reducing the
by reducing the
number of Cycles and the velocity of
cycle
it means we have to produce negative
chronotropy as well as negative inotropy
that will also reduce the work of the
donkey you get it or not
so now listen carefully here we put
which drug
which group three loader reducers
nitrates
pre-load reducers are
nitrates right we know dilator we know
dilators
and by reducing this
slope we are giving arterial law
dilator and in which arterial dilator
classically it is nepheidipine and
related drug
calcium channel blockers which are
nifedipine amlodipine philodipine and
related drugs is that right once you
have now you have reduced the preload
you have reduced after load then lets
the donkey reduce its work during the
cycle
the drugs which will reduce heart rate
and which will reduce
contractility
that will also help the donkey here the
drugs are number one beta blockers
if the drugs are beta blockers you know
beta blockers reduce the
what is that they reduce the essay node
activity and reduce the heart rate if
your heart rate is 90 you give beta
blocker it may become 60. so donkey is
happier that it has per minute it has to
produce less Cycles number two
beta blocker is also reduced
contractility
beta blocker is also reduce
contractility so further so donkey will
not only produce less Cycles but it will
produce the Cycles comfortably these are
right Amma clear and now please
concentrate on calcium channel blockers
in the Philippine mainly work on the
arterios
and Verapamil mainly work on the heart
because listen carefully please
concentrate
the calcium channels in smooth muscles
are slightly different than the calcium
channel on myocardium
calcium channels on smooth articulous
smooth muscles are slightly different
than the calcium channels in the heart
some calcium channel blockers work more
on
arterial arterial side some calcium
channels work more on heart and some
calcium channels work on both of sides
if you know this group you can really
combine the drugs as they should be
listen the food opinion is mainly what
mainly working working on arterial Arty
roller dilator and this is working
mainly on heart so we can say and this
is going to work on both
now listen carefully let me draw this
thing that Delta exam look at it just
work on the heart as well as work on the
arterial
it has work on the heart
as well as arterioles and this is the
action of Delta enzyme which has a
balanced action it is arteriolo dilator
as well as negative chronotroper as well
as negative dromotroper as well as
negative inotroper as well as negative
clino dropper
do you get it so Delta enzyme
reduces artery construction so it is
reducing pre after load sorry Delta Azam
reduces afterload as well as reduces the
cycling of the heart and
reduces heart rate as well as
contractility but when you come to the
vapormel look here vapormel
this is the Verapamil on the heart it
has strong action there's stronger
action on the heart but weaker action on
arterial only this so we can say rapamyl
is more cardio selective and the feeder
pin is more arteriola selective both of
them are calcium channel blocker but
this is more
selective or arterial or selective and
Verapamil is more
cardio selective and deltaism work on
both sides now why I'm so much stressing
this thing let me tell you when you give
a person a feeder pain it mainly
produces arteriola dilatation and
reduces diastolic blood pressure and
reduces the afterload reduces the
resistance against which heart has to
perform this is a function of
nephedipine now very important concern
extremely important concept there's one
type of angina
in which
ischemia to the heart is due to coronary
vasospasticity there is one type of
angina special type of angina in which
the real pathology is not astrology and
the real pathology is the coronary
arteries undergo
repeated spasticity the coronary
spasticity what is the name of that
engineer
Prince metal engine excellent it is not
classical engineer it is Prince medal in
Jannah what is Prince metal and Janna
it's a special type of anjana in which
car there is coronary visual spasticity
in this type of angina amount out of
these calcium channel blockers attention
plays in Prince metal angina coronary
vessels plastic coronary arterial tree
is in Prince medal in China
which drug will be the best nephedipine
a diltazam or Verapamil which is the
best you want to dilate the arteries
coronary is an artery the filter pain so
you have to remember it it's a classical
drug for
Prince metal angina
it's a classical drug for vasospastic
angina
now you understand it that when a
patient has angina due to coronary
artists spasticity then you need a drug
which will dilate the arterials we need
what nifedipine but in case of classical
angina this partial obstruction due to
astral signalotic plaque in that case
all of them can be used
why because if there is partial
obstruction I told you in the last
diagram if there's partial obstruction
this small amount of blood prickling to
The myocardium and whenever myocardium
has increased demand ischemiah
is the right classical angina and
classical angina in the Philippine can
also help because in classical angiana
the Philippine dilates
peripheral arterioles reduces the
afterload and even in
classical angina Verapamil can also be
helpful because in classical in China we
need to reduce the work of the heart and
Grappa milk can reduce the work of the
Heart by reducing
heart rate and contractility now please
listen special aspect
you know an angina patient this is
reducing
the vascular Construction
so it is somewhat like nitrates the
feeder pain is somewhat like nitrates
even though nitrates are mainly we know
dilator and the vitamin is mainly
arteriola dilator but both of them bring
the blood pressure down
please listen carefully
what happens if you give nitrate to the
patient what will happen we know
validation and if you give calcium
channel blocker of variety with the
nifedipine artesial load annotation of
course both of them will bring the blood
pressure down and Ice told you told you
previously that whenever blood pressure
goes down this reflex
tachycardia
because whenever blood pressure will go
down Barrow receptors will fire from the
carotid sinus and activate the
sympathetic outflow from central nervous
system you know that right so whenever
blood pressure goes down sympathetic
outflow will occur powerful sympathetic
outflow so when you give the patient
nitrates or you give the patient
nifedipine or you give the combination
of these drugs patient has a tendency to
develop
hypotension and that hypotension has a
tendency to precipitate reflex
tachycardia and that reflects
tachycardia may increase the work of the
heart
do you understand it that tachycardia
sympathetic overflow may increase the
work of the heart that is why a wise
doctor will combine these drugs with
beta blocker
so that arterial dilatation or we know
dilator
system
when it produces strong sympathetic
outflow let the sympathetic system fire
but you put a block there what is that
block
beta blockers which do not allow the
sympathetic nervous system to increase
the heart rate that is why classically
it's good to combine these drugs because
in angina we know the letters in our
digital dilator are very good we know
the letter reduce the preload after
dilator reduce the sorry arterial or
later reduce the afterload but if these
two things are too much reduced there's
a risk of
reflex tachycardia and reflects
tachycardia can be blocked by beta
blocker is that right but another way to
control the reflex tachycardia there's
another way let me tell you rather than
using this calcium channel blocker why
don't you use this one or that one
because if you use Verapamil with
nitrates what will happen nitrates will
do vinodalator and precipitate reflex
tachycardia system
nitrates will do vinodilator and may
precipitate The increased sympathetic
outflow this increased sympathetic
outflow will try to increase the
activity in AC node
AV node and contract LED it is bad but
with
nitrates if you have combined the
varapamil it is strongly inhibiting
acinode and evenode and this so action
of
sympathetic stimulatory action of
sympathetic nervous system is canceled
by inhibitory action of the Verapamil
you could not understand
yeah no what I was trying to say
what I was trying to tell you was that
those drugs which produce reflex
tachycardia
reflex tachycardia is dangerous you
should have some way to prevent The
Reflex tachycardia right listen one way
the best way to prevent The Reflex
tachycardia is that somehow you keep the
essay node and myocardium somewhat
inhibited
the Keep The myocardium inhibited one
way is give the beta blockers other way
to inhibit The myocardium is give those
calcium channel blockers which are
cardio selective
do you get it Jamie now what are the
implications of this listen carefully
all calcium channel blockers are not
same primarily I have divided them into
three groups when you give injection of
nifedipine to someone but usually it is
given orally
if someone is on nifedipine what is the
risk reflects tachycardia but when
someone is on heavy rapamyl what is the
rift risk Direct bradycardias
nitrates are risk for tachycardia as
well as nifedipine is also risk for
tachycardia because nitrates dilate the
veins
reduce the blood pressure
the phytovin dilates the arteries again
blood pressure goes down again
tachycardia this is what I'm trying to
put in your mind that all the drugs
which reduce the blood pressure
significantly has a tendency to produce
reflex activation of the heart they have
a tendency to produce reflex sympathetic
activation of the heart is in angina
such activation is good or bad
it's bad we don't want it is that right
is it clear yes so what can we do we can
do number one with the nitrates or with
the nifedipine when you add the
beta blockers so let them
stimulate the sympathetic outflow but
beta blocker keep the sympathetic
receptors blocked so sympathetic system
powerfully activated but unable to drive
the heart wild is that right then their
second strategy also
if you don't want to give beta blocker
for example someone has asthma
he has angina and with that asthma
asthma
chronic obstructive airway disease will
you give beta blockers no in previous
lecture I have mentioned that beta
blocker May precipitate strong Bronco
construction or someone has very severe
diabetes can you give beta blocker you
have to be very cautious now you have to
give nitrate and you don't want to give
beta blocker but nitrous you are giving
giving in heavy dose so if you have are
worried about that nitrates may not
precipitate
calcium channel blocker but you should
be wise don't add the filter pin to
these drugs you will add
so that what what's the beautiful
combination that nitrates dilate the
winds
right
even if some reflex
tachycardiosympathetic activation is
there but Verapamil is keeping SA node
AV node and myocardium inhibited so that
it is not responsive to
sympathetic over stimulation plus
whenever we will of course by reducing
heart rate and contractility will also
reduce the oxygen demand but there is
one thing
wrapper milk can produce sinus arrest
can produce
noodle arrest heart blocks wrapper milk
and precipitate
cardiac failure if there's too much
negative inotropy
did you get it but can the Philippine
can precipitate such things
no so these were the important delicate
differences within the group
that even though these drugs are grouped
as one group calcium channel blockers
but as a good doctor
you must know that this is mainly
arterial director it is mainly cardio
inhibitor and it works on the both
parameters
am I clear to all of you
right so under what circumstances we use
calcium channel blocker the special uses
of calcium channel blockers are number
one the uses of calcium channel blockers
number one calcium channel blockers are
used in angina
but again you should talk about this
classical angina and there is
Prince metal angina In classical in
China
right with nitrates
plus beta blocker if you want to add
calcium channel blocker is the Right In
classical angina you can use any one of
them
right any one of them depending upon
which parameter you want to change but
in case of what is this
what is the battle angina the best drug
is nifedipine because it is coronary
artery dilator the Philippine is
coronary artery dilator is that right
here I will mention one more calcium
channel block occur this is called
depredile
a new calcium channel blocker
they pray there
actually this is a very special of
culture type of calcium channel blocker
number one it produces coronary
arteriologation number two it blocks the
cardiac sodium and potassium channels
now listen careers unusual drug
like the nifedipine it can do coronary
articular dilatation
like other calcium channel blocker it
can inhibit acetode Avi node and
contractility but it has additional
function it can block some of the sodium
and the passion channels I will explain
into detail during a rhythmias
that when sodium channels and potassium
channels are dysfunctional when sodium
channels and potassium channels are
dysfunctional a very special type of
unique type of arrhythmias are produced
these are called torsa D pointas have
you heard of them
okay I will explain it there but I just
mentioned here there's a very special
type of
twisting points actually Q are as
complex goes like this for few QRS
complexer having points upward then for
few beats they are having downward then
again they have upward so this type of
special type of tachycardia is called
tachycardias with twisting points
now this type of tachycardia I will
explain in the lecture with arrhythmia
it is due to defective sodium or
potassium channels so this type of you
can say disease can be managed by
depoidal which is calcium channel
blocker sodium channel blocker potassium
channel blocker as well as coronary
dilator so when a patient comes to you
with angina plus a tendency for parsati
pointers what is the best drug
is it right the best drug is
The Prado
okay and I will mention
that nifedipine has a very special group
what is the name of that group dihydro
pyridine derivatives these derivatives
are more arteriolodilator and less
cardio suppressor
is that right but reflexively they can
stimulate the cardiac activity is that
right and now let's go to the side
effects of
calcium channel blockers there's a good
news very easy to understand
side effects of nifedipine are like
nitrate side effect
and side effects of vipamila like
beta blockers
because this is cardio inhibitor
and beta blockers are a cardio inhibitor
and nitrates are Wizard or later and
nifedipine is also vasov dilator but let
me tell you what are the major side
effects related with these drugs
the Philippines especially because it is
arteriola dilator right if article the
two might dilated
especially in the head and neck that may
produce severe throbing headache I told
you the mechanism of headache in the
lecture and
previous lecture right again
so what happens in the Philippine
nifedipine right when it produces strong
arteriolodilator and if arteries passing
through the meninges when they dilate
too much right
you can
how the arteriola dilated drug produce
the headache these are the vessels which
are passing through foramina this is
intracranial cavity it is extracranial
area these are the blood vessels which
are passing through this area and I told
you that these blood vessels which are
passing through the foramina they are
having sleeves off
they're having sleeves off
what is this Dura matter
and this part of the durometer which is
making a sleeve around the blood vessels
when they are passing through foramina
cranial blood vessels this part of the
sleeve has unique very very sensitive
pain receptors what are these
pain receptors so what really happens
any drug which produces strong
vasodilatation has a tendency
to produce severe headache how this
headache is produced let's remain
focused let's suppose you take any
strong arterial dilator it may be the
Philippine
it may be hydralazine or any other drug
it when these are