Drugs Influencing Cardiac Structure and Function

Question 1

What is digoxin?

Answer 1

A cardiac glycoside that provides symptomatic relief for heart failure

Question 2

What are the effects of digoxin?

Answer 2

Increases intracellular calcium to give better myocyte contraction

Question 3

What is the adverse effect of digoxin?

Answer 3

ventricular dysrhythmia - caused by a late after depolarisation due to a spike in calcium

Question 4

What is the mechanism of digoxin?

Answer 4

inhibits sodium/potassium ATPase which leads to decreased calcium extrusion so more calcium will accumulate in the sarcoplasmic reticulum to increase calcium release with each action potential

Question 5

How does digoxin cause late after depolarisations?

Answer 5

By blocking calcium extrusion to the point where stores are full

Question 6

What is the therapeutic index for digoxin?

Answer 6

Low

Question 7

Where else does digoxin act apart from the heart?

Answer 7

On other excitable tissues e.g. the gut causing effects like anorexia and nausea and the CNS causing effects like drowsiness, confusion and psychosis

Question 8

When is there increased toxicity of digoxin?

Answer 8

With low potassium, high calcium and renal impairment

Question 9

What is the half life of digoxin?

Answer 9

40 hours

Question 10

What is the volume of distribution of digoxin?

Answer 10

400L - due to high affinity binding to muscle

Question 11

How does sympathetic activity lead to increased contractility?

Answer 11

beta adrenoceptors activate adenyl cyclase which converts ATP to cAMP which activates PKA which phosphorylates calcium channels and leads to increased calcium

Question 12

What is amrinone?

Answer 12

A phosphodiesterase inhibitor - decreases the breakdown of cAMP to AMP which leased to increased opening of calcium channels to improve contractility

Question 13

What is dobutamine?

Answer 13

A beta adrenoceptor agonist used to increase contractility

Question 14

What are the adverse effects of dobutamine?

Answer 14

increases cardiac work so increases cardiac demand for oxygen and also at risk for arrhythmias

Question 15

What happens to beta adrenoceptors in chronic heart failure?

Answer 15

sympathetic compensation leads to over activation of beta adrenoceptors which leads to reduced beta adrenoceptor expression and impaired beta adrenoceptor coupling and an overall reduced sensitivity of beta adrenoceptors to beta adrenoceptor agonists and sympathetic drive

Question 16

What are inotropes?

Answer 16

Agents that increase the contractile force of muscular contraction in the heart e.g. digoxin, amrinone, dobutamine - used for symptomatic relief but symptoms will progress with long term use

Question 17

What drugs are used to reduce preload in cardiac failure?

Answer 17

venodilators, diuretics, aldosterone receptor antagonists, vasopressin receptor antagonists

Question 18

What drugs are used for venodilation?

Answer 18

nitrates

Question 19

What drugs are used to reduce after load in cardiac failure?

Answer 19

arterial vasodilators, ACE inhibitors, AT1 receptor antagonists, beta-adrenoceptor antagonists