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Pharmacology > Drugs used in heart failure > Flashcards

Drugs used in heart failure Flashcards

1
Q

Digitalis glycosides and its mechanism

A
  • 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)
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2
Q

Cardiac effects of glycosides

A
  • 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
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3
Q

Digoxin

A
  • 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
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4
Q

Electrical effect of glycosides

A
  • 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
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5
Q

Positive inotropic drugs

A
  • Digitalis glycosides: Digoxin
  • Beta-Adrenergic agonists: Dobutamine
  • Phospodiesterase inhibitors: Inamrinone, Milrinone
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6
Q

Beta-Adrenergic agonists

A
  • 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
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7
Q

Phosphodiesterase inhibitors

A
  • 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
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8
Q

ACE inhibitors and their mechanism

A
  • 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
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9
Q

ACE inhibitors; cardiac actions

A
  • Decrease vascular resistance, venous tone, and blood pressure
  • Reduce preload and afterload –> increased CO
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10
Q

ACE inhibitors; indications

A
  • 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
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11
Q

ACE inhibitors; adverse effects

A
  • Postural hypotension
  • Renal insufficiency
  • Hyperkalemia
  • Angioedema
  • Persisten dry cough
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12
Q

Positive inotropic drugs

A
  • Digitalis glycosides: Digoxin
  • β-Adrenergic agonists: Dobutamine
  • Phospodiesterase inhibitors: Inamrinone, Milrinone
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13
Q

β-Adrenergic agonists

A
  • 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
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14
Q

Angiotensin-receptor blockers (ARBs) and their mechanism

A
  • Losartan, Candesertan, Telmisartan, Valsartan
  • Competetive antagonists of the angiotensin type 1 receptor
  • Do not affect bradykinin levels
  • Adverse effects: Postural hypotension, renal insuffiency, hyperkalemia
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15
Q

ARBs; indications

A
  • Treatment of hypertension
  • Use in HF is as a substitute for ACE inhibitors in patients with severe cough or angioedema
  • Contraindicated in pregnancy
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16
Q

Carvedilol

A
  • Nonselective β-blocker
  • Also block α1-adrenoreceptors
  • Reduce morbidity and mortality in patients with HF
17
Q

Diuretics

A
  • 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
18
Q

β-blockers

A
  • 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
19
Q

Vasodilators

A
  • 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
20
Q

Aldosterone antagonists

A
  • 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)
21
Q

Order of therapy in CHF

A
  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)
22
Q

Order of therapy in AHF

A
  1. Loop diuretic
  2. Positive inotropic agent
  3. Vasodilators
23
Q

Prophylaxis against endocarditis

A
  • 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)
24
Q

Therapy for endocarditis

A
  1. Ampicyllin + Sulbactam + Gentamycin
  2. Vancomycin + Gentamycin + Ciprofloxacin
  3. Vancomycin + Gentamycin + RMF
25
Q

AMI therapy

A
  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

Pharmacology (16 decks)

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