Drugs used in heart failure

Question 1

Furosemide

Answer 1

• MOA
• loop diuretic: decreases NaCl and KCl reabsorption in thick ascending loop of Henle
• Effects
• increased excretion of salt and water
• reduces preload and afterload
• reduces pulmonary and peripheral edema
• Clinical
• acute & chronic heart failure
• severe hypertension
• edema
• Kinetics, tox, int.
• oral, IV, duration 2-4h
• tox: hypovolemia, hypokalemia, orthostatic hypotension, ototoxicity, sulfonamide allergy

Question 2

Hydrochlorothiazide

Answer 2

• MOA
• decreases NaCl reabsorption in distal convoluted tubule
• Effects
• same as furosemide, but much less efficacious
• Clinical
• mild chronic failure, mild-moderate hypertension
• hypercalcuria
• Kinetics, tox, int.
• oral, duration 10-12h
• tox: hyponatremia, hypokalemia, hyperglycemia, hyperuricemia, hyperlipidemia, sulfonamide allergy

Question 3

Spironolactone

Answer 3

• MOA
• blocks cytoplasmic aldosterone receptors in collecting tubules
• Effects
• increases salt & water excretion, reduces remodeling
• Clinical
• chronic heart failure
• aldosteronism
• hypertension
• Kinetics, tox, int.
• oral, duration 24-72h (slow onset & offset)
• tox: hyperkalemia, antiandrogen actions

Question 4

Captopril

Answer 4

• MOA
• inhibits ACE - reduction of AII by inhibiting conversion from AI
• Effects
• arteriolar and venous dilation
• reduces aldosterone secretion
• reduces cardiac remodeling
• Clinical
• chronic heart failure, hypertension, diabetic nephropathy
• Kinetics, tox, int.
• oral, t_1/2 2-4h but given in large doses so duration 12-24h
• tox: cough, hyperkalemia, angioneurotic edema
• int: additive with other angiotensin antagonists

Question 5

Losartan

Answer 5

• MOA
• antagonize AII effects at AT₁ receptors (angiotensin receptor blocker, ARB)
• Effects
• like ACE inhibitors
• Clinical
• like ACE inhibitors, used in pt intolerant to ACE inhibtors
• Kinetics, tox, int.
• oral, duration 6-8h
• tox: hyperkalemia, angioneurotic edema
• int: additive with other angiotensin antagonists

Question 6

Carvedilol

Answer 6

• MOA
• competitively blocks β₁ receptors
• Effects
• slows heart rate, reduces blood pressure
• Clinical
• chronic heart failure - slows progression
• reduce mortality in moderate and severe heart failure
• other indications - see ch.10
• Kinetics, tox, int.
• oral, duration 10-12h
• tox: bronchospasm, bradycardia, AV- block, acute decompensation

Question 7

Digoxin

Answer 7

• MOA
• Na⁺/K⁺-ATPase inhibition→reduced Ca²⁺ expulsion & increased Ca²⁺ stored in SR
• Effects
• increases cardiac contractility, cardiac parasympathomimetic effect (slowed HR, slowed AV conduction)
• Clinical
• chronic symptomatic heart failure
• rapid ventricular rate in atrial fibrillation
• Kinetics, tox, int.
• oral, parenteral, duration 36-40h
• tox: nausea, vomiting, diarrhea, arrythmias

Question 8

Isosorbide dinitrate

Answer 8

• MOA
• venodilator
• releases NO, activates guanylyl cyclase
• Effects
• venodilation, reduces preload and ventricular stretch
• Clinical
• acute and chronic heart failure, angina
• Kinetics, tox, int.
• oral, duration 4-6h
• tox: postural hypotension, tachycardia, headache
• int: additive with other vasodilators and synergistic with phosphodiesterase type 5 inhibitors

Question 9

Hydralazine

Answer 9

• Arteriolar dilator
• MOA
• increases endothelial NO synthesis
• Effects
• reduces blood pressure and afterload, results in increased output
• Clinical
• reduced mortality with hydralazine + nitrates
• Kinetics, tox, int.
• oral, duration 8-12h
• tox: tachycardia, fluid retention, lupus-like syndrome

Question 10

Nitroprusside

Answer 10

• Combined arteriolar and venodilator
• MOA
• releases NO spontaneously
• activates guanylyl cyclase
• Effects
• marked vasodilation
• reduces preload and afterload
• Clinical
• acute decompensation, hypertensive emergencies
• Kinetics, tox, int.
• IV only, duration 1-2min
• tox: excessive hypotension, thiocyanate and cyanide toxicity
• int: additive with other vasodilators

Question 11

Dobutamine

Answer 11

• MOA
• β₁ selective agonist, increases cAMP synthesis
• Effects
• increases contractility, output
• Clinical
• acute decompensated heart failure
• intermittent therapy in chronic failure reduces symptoms
• Kinetics, tox, int.
• IV only, duration a few minutes
• tox: arrythmias
• int: additive with other sympathomimetics

Question 12

Dopamine

Answer 12

• MOA
• D receptor agonist, higher doses activate β and α receptors
• Effects
• increases renal blood flow, higher doses increase cardiac force and blood pressure
• Clinical
• acute decompensated heart failure
• shock
• Kinetics, tox, int.
• IV only, duration a few minutes
• tox: arrythmias
• int: additive with other sympathomimetics

Question 13

Milrinone

Answer 13

• MOA
• phosphodiesterase type 3 inhibitor
• decreases cAMP breakdown
• Effects
• vasodilator, lowers peripheral vascular resistance
• increases contractility
• Clinical
• acute decompensated heart failure
• increases mortality in chronic failure
• Kinetics, tox, int.
• IV only, duration 3-6h
• tox: arrythmias
• int: additive with other arrythmogenic agents

Question 14

Nesiritide

Answer 14

• Natriuretic peptide
• MOA
• activates BNP receptors, increases cGMP
• Effects
• vasodilation, diuresis
• Clinical
• acute decompensated heart failure
• Kinetics, tox, int.
• IV, duration 18 minutes
• tox: renal damage, hypotension, may increase mortality