Heart Failure Drugs-1

Question 1

Positive inotropic drugs: Digitalis Catecholamines
- increase cytosolic (free) calcium by inhibiting the cell Na+K+ATPase thus activating the Na+/Ca++ exchanger (=> Ca++ in)

Answer 1

Digitalis glycosides (Digoxin)

Question 2

Positive inotropic drugs: Digitalis Catecholamines
- Stimulate beta-adrenoreceptors (+- alpha-receptors) to increase Ca++ entry

Answer 2

Catecholamines (Dobutamine)

Question 3

Positive inotropic drugs: PDE-III Inhibitors Calcium-Sensitizers
- Sensitize contractile filaments to Ca++ (increase contractility)

Answer 3

Calcium sensitizers (Pimobendan)

Question 4

Catecholamines (sympathomimetic):
What is the drug of choice for cardiogenic shock?

Answer 4

Dobutamine
- Synthetic catecholamine
- need to be administered intravenously

Question 5

Catecholamines (sympathomimetic):
- Endogenous catecholamine & precursor of NorEpi
- Similar effects to Dobutamine
- beta 1/2, high dose alpha 1, DA 1/2 (vascular dopaminergic receptors - vasodilation)
- Higher tendency to increase heart rate and cause vasoconstriction

Answer 5

Dopamine
- need to be administered intravenously

Question 6

Catecholamines:
What is a potent vasoconstrictor, used in hypotensive patients unresponsive to fluid therapy and dopamine?

Answer 6

Nor-Epinephrine
- Endogenous neurotransmitter | catecholamine liberated from postganglionic adrenergic nerves
- alpha 1 > beta 1/2
- Minimal chronotropic effects and impact on cardiac output

Question 7

Catecholamines (sympathomimetic):
What is the drug of choice for cardiac arrest (resuscitation)?

Answer 7

Epinephrine (Adrenaline)
- Endogenous catecholamine
- beta 1 = beta 2 w/ alpha 1 effects at higher dose

Question 8

Cardiovascular Effects of Catecholamines:
- increase Contractility (inotropic)
- increase heart rate (chronotropic)
- increase Propagation velocity (dromotropic)
- increase Relaxation (lusitropic)
- increase Excitement of normal and subsidiary pacemaker cells in the heart (bathmotropic)

Answer 8

Beta-adrenergic effects

Question 9

Cardiovascular Effects of Catecholamines:
- increase Mixed vasoconstriction (arterial + venous)

Answer 9

Alpha-adrenergic effects

Question 10

Ca2+ Sensitizers:
- Inodilatore
- Ca++ sensitization (of sarcomeric proteins)
- Opening of ATP-dependent K+ channels on vascular smooth muscle -> arteriolar and venous vasodilation
- Vasodilation helps to “unload” failing ventricles
- Minimal impact on ventricular ectopy

Answer 10

Pimobendan (Vetmedin)
- Chewable, flavored tablets
- Safe drug!
- Indications:
- Dogs w/ CHF
- Ocult DCM (Doberman Pinshers)
- Preclinical MVD

Question 11

Definition:
Agents with inotropic effects that also cause vasodilation leading to decreased systemic and/or pulmonary vascular resistance

Answer 11

Inodilator

Question 12

(T/F) Dobutamine prolongs the duration and increases the force of contraction (effect delayed but lasts longer)

Answer 12

False, Pimobendan not Dobutamine

Question 13

Mechanism of Positive Inotropy:
Block of Na+K+ ATPase

Answer 13

Digoxin

Question 14

Na+ -K+ ATPase (pump) at cardiomyocyte membrane,
blocked by digoxin, leads to accumulation of:

Answer 14

Na i+

Question 15

List the Effects of Digitalis Glycosides (Digoxin):

Answer 15

• Mild positive inotropic effect
• Baroreceptor Senseitization
  - increase Vagal Tone
  - decrease Sympathetic tone
• Antiarrhythmic properties
  - decrease Resting heart rate
  - decrease Ventricular response rate in AFib
• Pro-arrhythmic properties
  - Related to Ca2+ influx

Question 16

List the major indication for Digoxin:

Answer 16

• Controlling rate in Afib (AV node)

Question 17

List the contraindications for Digoxin:

Answer 17

• Ventricular ectopy
• Renal failure
• Brady-arrhythmias
• decrease K+ (hypokalemia may induce toxicity)
• GI tract disease

Question 18

What are the adverse effects of Digoxin?

Answer 18

• Anorexia
• GI signs
• Arrhythmias
  (renal excretion)

Question 19

Which of the following is NOT a potential reason for digitalis toxicity?
a. hypokalemia
b. Acute liver failure
c. Chronic renal failure
d. Drug overdose
e.Concurrent application of high-dose of diltiazem

Answer 19

b. Acute liver failure