Pharmacology Lecture Slides on Angina Pectoris by Sanjaya Mani Dixit Assistant Professor of Pharmacology at Kathmandu Medical College

1. Angina Pectoris
Sanjaya Mani Dixit
Assistant Prof of Pharmacology

3. Angina pectoris
• Angina pectoris, the primary symptom of ischemic
heart disease, is caused by transient episodes of
myocardial ischemia that are due to an imbalance in the
myocardial oxygen supply-demand relationship.
• Sudden, severe, pressing chest pain starting sub-sternal
that often radiates to left arm.
• Strangling or pressure-like pain caused by cardiac
ischemia
• Due to imbalance between myocardium oxygen
requirement and oxygen supply.
Risk factors:
Age, sex, obesity, smoking, diabetes

4. Classification of angina
1. Exertional/Atherosclerotic angina (90%)
Stable, Classic,
Due to obstruction of coronaries by atheroma.
2. Variant, Vasospastic angina, Prinzmetal angina
Occurs at rest, sleep. Due to Spasm of coronary artery.
3- Unstable angina
Due to spasm and partial obstruction of coronaries.
Immediate precursor of myocardial infarction (MI)

5. DETERMINANTS OF CARDIAC O2 NEED
PRELOAD--Diastolic filling pressure
AFTERLOAD --Determined by arterial blood pressure and large artery stiffness
HEART RATE--Contributes to time-integrated fiber tension
MYOCARDIAL FIBER TENSION--A major determinant
(the higher the tension, the higher the O2 requirement)
CARDIAC CONTRACTILITY--Force of cardiac contraction

6. Pharmacological modification of the major determinants of myocardial O2 supply.
• This figure shows the primary hemodynamic sites of action of
pharmacological agents that can reduce O2 demand (left side) or enhance
O2 supply (right side). Some classes of agents have multiple effects.
• Stents, angioplasty, and coronary bypass surgery are mechanical
interventions that increase O2 supply.
• Both pharmacotherapy and mechanotherapy attempt to restore a dynamic
balance between O2 demand and O2 supply.

7. THERAPEUTIC STRATEGIES
Reducing oxygen demands
Reducing heart rate and contractility
Dilating systemic arteries and veins (  wall tension
by lowering heart loads)
Increasing oxygen supply
Dilating coronary arteries (  coronary blood flow)
Promoting regional distribution (  in ischemic
regions)
Others:
Anti- platelet coagulation and thrombus formation

9. Drug treatment of angina
Anti-anginal drugs are those that prevent, abort, or
terminate attacks of angina pectoris.
1- Acute attack
Short acting nitrates or nitrites
2- Prophylactic therapy
Long –acting nitrates
Calcium channel blockers
β- blockers

10. Drug treatment of angina
THERAPEUTIC STRATEGIES
• Nitrates, calcium blockers and beta-blockers
all reduce the O2 requirement in
atherosclerotic angina
• Nitrates and calcium blockers (but not beta-
blockers) can increase O2 delivery by
reducing vasospasm (only in vasospastic
angina)

11. Nitrates & Nitrites
Short acting
• Nitroglycerine NTG (Glyceryl trinitrate GTN)
Long Acting
• Isosorbide mononitrate
• Isosorbide dinitrate (SL-short acting)
• Erythrityl tetranitrate

12. NITROGLYCERINE (NTG)
• Most important of the nitrates
• Acts within 1-2 mins
• Available forms
• Sublingual
• Transdermal
• Sprays
• Injectable
• First-pass effect is 90%

13. Mechanism of Axn
• Nitroglycerine  NO
• Guanylyl cyclase and NO
activates increase
cGMP
• cGMP then
dephosphorylates
myosin light chain
(Myosin-LC-po4 ) to
myosin- LC
• End point muscle
relaxation.

14. Mechanism of Action
Nitrates decrease myocardial oxygen demand:
1. The primary effect is a reduction in venous
tone which results in venous pooling
decreasing venous return (decreased
preload).
2. Arteriolar tone is less effectively reduced
resulting in a decrease in PVR (decreased
afterload ) and decreased blood pressure.
3. No. 1 & 2 decrease myocardial wall stress
reducing O2 demand.
4. Dilation of coronary vessels exerts a minor
effect on increasing O2 supply.

15. CLINICAL USES
Acute anginal pain
CHF & LVF
Potential antidote for cyanide poisoning
Esophageal spasm
Biliary colic
Myocardial infarction (MI)

16. S/Es
Most common toxic effects are responses evoked by vasodilation
• Tachycardia
• Orthostatic hypotension (direct extension of venodilator
effect)
• Throbbing headache from meningeal artery vasodilatation
• Flushing, weakness, sweating
• Methemoglobinemia at high blood concentration
Withdrawal symptoms may occur (an indication of tolerance)
when nitrate agents are tapered or discontinued, this may
precipitate anginal attacks.

17. Tolerance
Tolerance
Attenuation of haemodynamic & anti-
ischaemic effect of nitrates occurs if nitrates
are continuously present in the body. This
tolerance weans off rapidly (within hours)
when the body is free of the drug.

18. β-Blockers
• The Beta1 receptor antagonism affords heart the
necessary conditions for the treatment of angina.
• β-Blockers decrease O2 demands of the myocardium by
lowering the heart rate and contractility (decrease CO)
particularly the increased demand associated with
exercise.
• They also reduce PVR by direct vasodilation of both
arterial & venous vessels reducing both pre- and after
load. However, preload may increase due to decreased
inotropicity.

19. β-Blockers
• β1 antagonists reduce the frequency and severity of
anginal episodes particularly when used in combination
with nitrates. β-Blockers in combination with nitrtates
can be quite effective.
• β1 antagonists have been shown to improve survival in
post MI patients and decrease the risk of subsequent
cardiac events & complications.
• Contraindications
Asthma & COPD
Diabetes, bradycardia, PVD

20. Reasons for Using Nitrates and Beta Blockers in
Combination in Angina
• Beta Blockers prevent reflex tachycardia and contractility
produced by nitrate-induced hypotension.
• Nitrates prevent any coronary vasospasm produced by Beta
Blockers.
• Nitrates prevent increases in left ventricular filling pressure
or preload resulting from the negative inotropic effects
produced by Beta Blockers.
• Nitrates and Beta Blockers both reduce myocardial oxygen
consumption by different mechanisms.
• Nitrates & Beta Blockers both increase sub-endocardial
blood flow by different mechanisms.

21. Ca+2 Channel Blockers
Ca+2 channel blockers protect tissue by inhibiting the entrance of Ca+2 into
cardiac and smooth muscle cells of the coronary and systemic arterial beds.
All Ca+2 channel blockers produce some vasodilation (↓ PVR) and are negative
inotropes.
Some agents also slow cardiac conduction particularly through the AV node thus
serving to control cardiac rhythm.
Some agents have more effect on cardiac muscle than others but all serve to
lower blood pressure.
CHF patients may suffer exacerbation of their failure as these are negative
inotropes.
They are useful in Prinzmetal angina in conjunction with nitrates.

24. Ca+2 Channel Blockers
Nifedipine:
It works mainly on the arteriolar vasculature
decreasing afterload, it has minimal effect of
conduction or heart rate.
It causes flushing, headache, hypotension and
peripheral edema (vasodilation related effects). It
also has some slowing effect on the GI
musculature resulting in constipation.
A reflex tachycardia associated with the
vasodilation may elicit myocardial ischemia in
weak patients, as such it is generally avoided in
non-hypertensive coronary artery disease.

25. Ca+2 Channel Blockers
Verapamil:
The agents has its main effect on cardiac conduction
decreasing HR and O2 demand.
It also has much more -ve inotropic effect than other
Ca+2 channel blockers. It is a weak vasodilator.
Because of its focused myocardial effects it is not used
as an antianginal unless there is a tachyarrhythmia.
It interferes with digoxin levels causing elevated plasma
levels; caution and monitoring of drug levels are
necessary with concomitant use.

26. Diltiazem:
This agent function similarly to Verapamil
however it is more effective against Prinzmetal
angina.
It has less effect on HR.
Ca+2 Channel Blockers

27. Other treatment methods
Myocardial revascularization corrects coronary
obstruction either by-
• Coronary artery bypass grafting
• Coronary angioplasty and stenting

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