Inotropic drugs: limitations in HF

Question 1

Categories of positive inotropic agents

Answer 1

• cardiac glycosides
• beta agonists
• phosphodiesterase inhibitors (PDEi)
• calcium sensitizing agents

Question 2

Major goal/target of positive inotropic agents

Answer 2

increase effective intracellular Ca2+ concentration

Question 3

Major indications for use of digitalis (2)

Answer 3

• treatment of chronic CHF in the presence of atrial fibrillation
• treatment of chronic CHF when there is confirmed S3 gallop

Question 4

Digitalis =

Answer 4

-plant source of digitoxin and digoxin

Question 5

Digitalis MOA

Answer 5

• blocks Na+/K+/ATPase pump (which normally pumps Na+ in and K+ out)
• blockage –> increase [Na+]in
• increased [Na+]in –> Na+/Ca2+ exchanger begins pumping Na+ out and thus bringing Ca2+ in –> increased [Ca2+}in

Question 6

Negative effects of Digitalis

Answer 6

– Increase intravascular Ca++ too
– Increase sympathetic tone by activation of CNS descending pathways
– Decrease NE reuptake

Question 7

Positive effects of Digitalis

Answer 7

-Increase parasympathetic (vagal) tone
– Increase renal blood flow thereby decreasing circulating blood volume
– Positive inotropic effect decreases sympathetic tone by
resolving the symptoms of CHF

Question 8

Digoxin half-life and route of elimination

Answer 8

• t1/2=1.7 days

- ROE=renal excrete of unchanged drug; limited hepatic metabolism

Question 9

Digitoxin half-life and route of elimination

Answer 9

• t1/2=7 days

- ROE=hepatic degredation w/renal excretion of metabolites

Question 10

Problems w/positive inotropic agents (5)

Answer 10

1. Tachyphylaxis (desensitization, tolerance)
2. Substantially increased MVO2
3. Increased risk of sudden death (proarrhythmic)
4. Generally not orally active
5. Very short plasma half-life