Lecture 3- Anti-anginal Drugs

Question 1

Angina pectoris

Answer 1

-angina= principal symptom of ischaemic heart disease (CAD)
-occurs when the oxygen supply to the myocardium is insufficient for its needs
-symptoms; sudden, severe pressing chest pain radiating to the neck, jaw, back and arms
-pain is triggered by exertion, cold or excitement

Question 2

Classes of angina pectoris

Answer 2

*stable;
-predictable chest pain on exertion
-produced by an increased demand on the heart and is caused by a fixed narrowing of the coronary vessels
*unstable;
-characterised by pain that occurs with less and less exertion, culminating in pain at rest
*variant;
-uncommon
-occurs at rest and is caused by artery spasm
-symptoms= caused by decreased blood flow to the heart muscle due to spasm of the coronary artery

Question 3

Treatment strategies in angina pectoris

Answer 3

-improve perfusion of the myocardium
-reduction in metabolic demand by the heart
-both^

Question 4

Organic nitrates

Answer 4

*nitroglycerin
*isosorbide mononitrate
*isosorbide dinitrate
-nitrates = effective for all types of angina
-^ can cause a rapid decrease in myocardial oxygen demand = rapid resolution of symptoms

Activation of the enzyme guanylate cyclase—> increases cGMP leading to dephosphorylation of myosin light chains = decrease in contractile force of the heart

Question 5

Organic nitrates continued

Answer 5

-nitrates decrease myocardial oxygen demand
-reduce venous tone= venous pooling decreasing venous return
-arteriolar tone= less effectively reduced

Question 6

Pharmacokinetics

Answer 6

-time and onset of action= main difference between nitrate preparations
*nitroglycerin= first-pass metabolism= administration is sublingual (rapid absorption and onset)
*nitroglycerin= administered transdermally as a patch
*isosorbide mononitrate + isosorbide dinitrate = long-acting nitrates= relatively resistant to first pass metabolism

Question 7

Side effects of organic nitrates

Answer 7

-headache due to vasodilation
-postural hypotension + syncope = observed with sublingual use
-tachycardia

Question 8

B-adrenoreceptors; atenolol, metoprolol + acebutolol

Answer 8

-b-adrenoreceptor blockers= decease oxygen demand of the myocardium by lowering the heart rate and contractility (decrease cardiac output) particularly in increased demand associated with exercise
-effects are caused by blocking b1 receptors

Question 9

Calcium channel blockers

Answer 9

-Ca2+ channel blockers protect tissue by inhibiting the entrance of ca2+ into cardiac + smooth muscle cells of the coronary and systemic arterial beds
-all blockers produce some vasodilation + negative inotropic effects
-some agents have more effect on cardiac muscle but all serve to lower bp

Question 10

Calcium channel blockers continued

Answer 10

*nifedipine= works mainly on the arteriolar vasculature- decreasing afterload.
Causes= flushing, headache, hypotension + peripheral oedema
*verapamil= main effect on cardiac conduction- decreasing heart rate thereby oxygen demand.
-much more negative inotropic effect compared to other Ca2+ channel blockers
-mot used as an antianginal unless there is tachycardia
*diltiazem= more effective against variant angina
-less effect on heart rate