Lesson C1 - Drugs for the Treatment of Angina Pectoris & Congestive Heart Failure Flashcards
what are the 3 major classes of antianginal drugs?
1) the organic nitrates which include the
short-acting nitroglycerin, and the long-acting isosorbide dinitrate; (2) the β-adrenergic
antagonists of which propranolol is a prototype drug; and (3) the calcium channel blockers of
which nifedipine is a prototype drug
Angina pectoris was first described by the English physician
William Heberden in 1768
Angina pectoris (a choking pain in the chest) is usually due to
lipid deposits in the coronary
arteries hindering blood flow (atherosclerosis).
The pain arises from
diminished blood flow and a diminished oxygen supply to an area of
the heart muscle.
To reduce the pain, one must
decrease the oxygen requirement of the heart
and/or increase the oxygen supply to oxygen deficient areas of the heart muscle
Angina pectoris is precipitated by the four “E’s”, namely
Eating, Exercise, Excitement, Exposure
to cold.
organic nitrates relax the smooth muscle of blood vessels and exert their
therapeutic effect by
Relaxation of large veins, leading to vasodilation and by Dilating large coronary arteries
Nitroglycerin enters blood vessels and is converted in blood vessels into nitric oxide.
Nitroglycerin therefore owes its effectiveness to its conversion into a normal body constituent,
nitric oxide.
In endothelial cells lining blood vessels, the enzyme nitric oxide synthase catalyses the
conversion of arginine into
citrulline and nitric oxide.
Nitric oxide passes from endothelial cells
into smooth muscle cells where it activates the enzyme guanylyl cyclase and leads through a
series of steps to
relaxation of the blood vessel
Therapeutic Uses of GTN
For termination of an individual attack, Prevention of individual attack and Chronic prophylaxis
An alternative drug used for chronic prophylaxis of angina pectoris is a
β-adrenergic blocking
agent. In order to understand the mechanism of action of β-adrenergic blocking drugs, such as
propranolol, in angina it is necessary to understand that angina is precipitated by factors that
increase sympathetic nervous system (SNS) activity, e.g. stress and exercise.
Increased SNS activity results in an increase in heart rate and an increase in myocardial (heart
muscle) contractility. This in turn leads to an increase in
cardiac output and an increase in
myocardial oxygen requirement resulting in the pain of angina.
A β-adrenergic blocking drug such as propranolol will block β receptors in the heart, thereby
decreasing heart rate and myocardial contractility. As a result, cardiac output and myocardial
oxygen requirements will
decrease and therefore the pain of angina will be alleviated.
Newer drugs or drugs in development, modify cardiac work load by
either slowing the heart
by altering electrical conduction or alter the metabolism of the heart to require less oxygen.
