Cardiac and Vascular Pharmacology

Question 1

What is congestive heart failure (CHF) and what is the aim of treatment?

Answer 1

Cardiac output below normal range

Increase contraction force

Question 2

What are the 2 main approaches to CHF treatment and which drugs are used for these?

Answer 2

Indirect - reduce workload and vascular resistance - e.g. ACE inhibitors, vasodilators, diuretics
Direct - increase contraction force - use inotropes - e.g. cardiac glycosides, B1-adrenoceptor agonists

Question 3

What are the effects of digitoxin?

Answer 3

Increases contraction force - increases cardiac output

Decreases contraction rate

Question 4

How does digitoxin work?

Answer 4

Binds to K+ binding site of Na+/K+-ATPase - inhibits
Increases intracellular Na+ - decreases Na+ electrochemical gradient
Inhibits Na+/Ca2+ exchanger - less Ca2+ out - increased intracellular Ca2+ - increased contraction force
Stimulates vagal activity - inhibits AV node

Question 5

What is the effect of too much digitoxin?

Answer 5

Heart block - low therapeutic index

Question 6

Name a B1-adrenoceptor antagonist used to treat CHF and explain why

Answer 6

Carvedilol

Reduces sympathetic stimulation - slows heart rate

Question 7

What are adrenoceptor treatments of hypertension?

Answer 7

A1 antagonists - e.g. prazosin - block receptors on vascular smooth muscle
A2 agonists - e.g. clonidine - blocks autoreceptors on sympathetic nerve - also inhibits vasomotor centre in medulla - switches off sympathetic drive

Question 8

What is the mechanism of direct vasodilator treatments for hypertension, and name a drug used

Answer 8

Minoxidil
Blocks ATP binding to KATP channels - remains open - hyperpolarisation - closes L-type Ca2+ channels - vasodilation
Can block Ca2+ channels directly - e.g. nifedipine

Question 9

What is the mechanism of organic nitrate treatment for hypertension and name a drug used

Answer 9

Glyceryl trinitrate

Denitrated in smooth muscle cell - activates protein kinase G - relaxes muscle - arteriolar dilation

Question 10

What is coronary artery disease and how is it treated?

Answer 10

Artery blocked on one side of heart - ischaemic area of myocardium
Nitrates - dilates collaterals linking arteries on each side - blood shared equally - circumvents blockage - increases blood flow to ischaemic area