Drugs used in heart failure

Question 1

Digitalis glycosides and its mechanism

Answer 1

• Digoxin - most widely used
• Positive inotropics
• Enhance cardiac muscle contractility and, thus increase CO by increased cytoplasmic calcium concentration
• Inhibit Na/K ATPase –> cause increse in intracellular Na
• Incresed Na, decreases the driving force for the Na/Ca exchanger –> increased intracellular Ca
• The resting membrane potential may increase (-70mV)

Question 2

Cardiac effects of glycosides

Answer 2

• Increased ventricular ejection
• Decreased end-systolic and end-diastolic size
• Increased CO
• Increased renal perfusion
• Compensatory it will decrease sympathetic outflow –> decrease HR, preload and afterload
• The myocardial oxygen demand will diminish

Question 3

Digoxin

Answer 3

• Digitalis glycoside
• Positiv inotropic effect
• Indicated in patients with severe left ventricular systolic dysfunction
• Treatment of chronic HF
• Major indications is HF with AF
• Quinidine increase digoxin serum levels

Question 4

Electrical effect of glycosides

Answer 4

• Increase PR interval
• Flattening of T wave
• Shortened QT, inversion of the T, and ST depression may occur later
• Increased automaticity is a toxic effect –> may evoke extrasystoles, tachycardia or fibrillation
• Its effect is inhibited by increased extracellular potassium and magnesium, and enhanced by increased extracellular calcium

Question 5

Positive inotropic drugs

Answer 5

• Digitalis glycosides: Digoxin
• Beta-Adrenergic agonists: Dobutamine
• Phospodiesterase inhibitors: Inamrinone, Milrinone

Question 6

Beta-Adrenergic agonists

Answer 6

• Dobutamine
• Most commonly used inotropic agent after Digoxin
• Increase the intracellular cAMP, which results in the activation of protein kinase
• Activated protein kinase phosphorylates a Ca-channel, which increases calcium flow into the cell, thereby enhancing contraction
• IV infusion
• Primarly used in treatment of acute HF in hospital

Question 7

Phosphodiesterase inhibitors

Answer 7

• Inamrinone, Milrinone
• Prevent hydrolysis of cAMP and, thus, prolong the action of protein kinase
• Activated protein kinase, phosphorylates a Ca-channel, which increases calcium flow into the cell, thereby enhancing contraction
• Also cause vasodilation
• Long-term therapy increase morbidity and mortality, and should therefor not be used in CHF

Question 8

ACE inhibitors and their mechanism

Answer 8

• Captopril, Enalapril, Fosinopril, Lisinopril, Quinpril, Ramipril
• Block angiotensin-converting enzyme (ACE), that cleaves Angiotensin I to the potent vasoconstrictor Angiotensin II
• Also inhibit degradation of the potent vasodilator bradykinin
• Decrease secretion of aldosterone, resulting in decreased sodium and water retention

Question 9

ACE inhibitors; cardiac actions

Answer 9

• Decrease vascular resistance, venous tone, and blood pressure
• Reduce preload and afterload –> increased CO

Question 10

ACE inhibitors; indications

Answer 10

• Considered, along with diuretics, among the first-line drugs for CHF
• Indicated in patients with all stages of left ventricular failure
• May be used as single-agent therapy in patient with mild dyspnea on exertion and do not have edema
• It is recommended that ACE inhibitors be initiated immediately after MI
• Contraindicated in pregnancy

Question 11

ACE inhibitors; adverse effects

Answer 11

• Postural hypotension
• Renal insufficiency
• Hyperkalemia
• Angioedema
• Persisten dry cough

Question 12

Positive inotropic drugs

Answer 12

• Digitalis glycosides: Digoxin
• β-Adrenergic agonists: Dobutamine
• Phospodiesterase inhibitors: Inamrinone, Milrinone

Question 13

β-Adrenergic agonists

Answer 13

• Dobutamine
• Most commonly used inotropic agent after Digoxin
• Increase the intracellular cAMP, which results in the activation of protein kinase
• Activated protein kinase phosphorylates a Ca-channel, which increases calcium flow into the cell, thereby enhancing contraction
• IV infusion
• Primarly used in treatment of acute HF in hospital

Question 14

Angiotensin-receptor blockers (ARBs) and their mechanism

Answer 14

• Losartan, Candesertan, Telmisartan, Valsartan
• Competetive antagonists of the angiotensin type 1 receptor
• Do not affect bradykinin levels
• Adverse effects: Postural hypotension, renal insuffiency, hyperkalemia

Question 15

ARBs; indications

Answer 15

• Treatment of hypertension
• Use in HF is as a substitute for ACE inhibitors in patients with severe cough or angioedema
• Contraindicated in pregnancy

Question 16

Carvedilol

Answer 16

• Nonselective β-blocker
• Also block α1-adrenoreceptors
• Reduce morbidity and mortality in patients with HF

Question 17

Diuretics

Answer 17

• Loop diuretics (Furosemide) most commonly used diuretic in HF
• Thiazides (Hydrochlorothiazide) are sometimes sufficient for mild CHF
• Relieve pulmonary congestion and peripheral edema
• Decrease preload –> decrease cardiac workload and the oxygen demand

Question 18

β-blockers

Answer 18

• Atenolol, Carvedilol, Metoprolol
• Decrese HR and inhibit release of renin
• Prevent the direct deleterious effects of NE on the cardiac muscle fibers
• Decrease remodelig, hypertrophy, and cell death
• Recommended for all patients with heart disease, except those who are at high risk but with no symptoms and those with acute HF

Question 19

Vasodilators

Answer 19

• Nitroprusside, Nitroglycerin, Hydralazine, Isosorbide dinitrate
• Dilation of venous vessels –> decrease preload
• Dilation of arterial vessels –> decrease afterload
• Nitrates are commonly used in congestive HF
• Hydralazine and Isosorbide dinitrate used in CHF

Question 20

Aldosterone antagonists

Answer 20

• Spironolactone
• Direct antagonist of aldosterone
• Prevent salt retention, myocardial hypertrophy, and hypokalemia
• Reserved for the most severe cases of HF
• Adverse effects: GI disurbances (ulcers), CNS effects (confusion, lethargy), endocrine abnormalites (decreased libido, gynecomastia)

Question 21

Order of therapy in CHF

Answer 21

1. Loop diuretics to relieve signs or symptoms of volume overload
2. ACE inhibitors (or ARBs if ACE not tolerated)
3. β-blockers
4. Digoxin (or other positive inotropic drugs)

Question 22

Order of therapy in AHF

Answer 22

1. Loop diuretic
2. Positive inotropic agent
3. Vasodilators

Question 23

Prophylaxis against endocarditis

Answer 23

• S. Aureus and S. Epidermidis
  1. Cafazolin (before and 3-4 times after surgery)
  2. Clindamycin (before/after dental extraction)
  3. Metronidazole (before/after dental extraction)

Question 24

Therapy for endocarditis

Answer 24

1. Ampicyllin + Sulbactam + Gentamycin
2. Vancomycin + Gentamycin + Ciprofloxacin
3. Vancomycin + Gentamycin + RMF

Question 25

AMI therapy

Answer 25

1. Morphine - iv. 2-4 mg every 5 min
2. O2 - 4L/min
3. Nitroglycerin - sl. or iv. infusion
4. ASA - po. 325 mg
5. Reperfusion - Heparin or LMWH, streptokinase or t-PA
6. Beta-blocker
7. ACE-inhibitor