Drugs for Heart Failure (Kruse) Flashcards
Heart failure occurs when
-cardiac output is inadequate to provide oxygen needed by the body
Causes of HF
- diminished coronary blood flow (CAD)
- Damaged heart valves
- External pressure around the heart
- Vitamin B deficiency
- Primary cardiac muscle disease
- Others
Compensatory changes associated with HF
- Decreased CO–>decreased carotid firing–>increased sympathetic discharge–>increased force and rate of contraction, increased preload and increased after load to try to increase CO
- Decreased CO–>decreased renal blood flow–>increased renin release—>increased Ang II–>increased sympathetic discharge and increased preload, after load and cardiac remodeling
Drug therapy of heart failure: historic focus on end point components
- volume overload (congestion)–>diuretics
- Myocardial dysfunction (heart failure)–>positive inotropic agents
- Does not reduce mortality in patients with HF
Drug therapy of heart failure: current therapies target organs/systems other than the heart
- Renin-angiotensin-aldosterone system
- Sympathetic NS
- Have been shown to reduce mortality
Hemodynamic responses to pharmacologic interventions in HF
-Combination of drugs (like diuretic, vasodilator and inotropic agents) are used to treat HF and can significantly improve low output symptoms and congestive symptoms
Which class of diuretics are the most efficacious for reducing volume overload?
-Loop diuretics
Loop diuretics prototype
-Furosomide and ethacrynic acid
MOA of loop diuretics
-Inhibit the luminal Na/K/2Cl cotransporter (NKCC2) in the TAL
Loop diuretics results in
- decreased intracellular K+ in TAL
- Decreased back diffusion of K+ and positive potential
- Decreased reabsorption of Ca2+ and Mg2+
- Increased diuresis
- Ion transport virtually non-existent; among the most efficacious diuretics available
Indications for Loop diuretics
- Edema
- Heart Failure
- Hypertension
- Acute renal failure
- Hypercalcemic states
Adverse effects of Loop diuretics
- Hypokalemia
- Alkalosis
- Hypocalcemia
- Hypomagnesemia
- Hyperuricemia
- Ototoxicity
- Sulfonamide hypersensitivity (not all)
Swollen tongue and nagging cough is associated with what drug?
-ACE inhibitors (e.g. Enalapril)
If patient cannot tolerate ACE inhibitor due to adverse effects (swollen tongue, caugh), an appropriate replacement would be what class of drug?
-Angiotensin Receptor Blocker (e.g. Losartan)
Effects of Angiotensin II
-Arterial vasoconstrictor
-Increases retention of sodium and water
-Increases aldosterone secretion
-Promotes catecholamine release from the adrenal medulla
-Promotes arrhythmias
Promotes vascular and cardiac hypertrophy and remodeling
-Stimulates myocyte death
Three key effects of ANG II
- Altered Peripheral resistance–>rapid pressor response
- Altered renal function–>Slow pressor response
- Altered Cardiovascular structure–>vascular and cardiac hypertrophy and remodeling
Ways to inhibit Angiotensin II
- Inhibit ACE (-prils)
- Inhibit AT receptors (sartans)
- Inhibit renin (aliskiren)
Drug used to treat palpitations, 3rd heart sound and its adverse effects include paroxysmal atrial tachycardia (atrial fibrillation) with block at toxic concentrations
-Digoxin
Cardiac glycosides prototype drug
-Digoxin