Week 3: Congestive Heart Failure drugs Flashcards
List the progressive changes during heart failure and the physiologic response that tries to compensate for that failure.
- ability of heart to contract diminishes
- heart fails and biochemical level and can’t contract with enough force
- Initially, CO maintained by compensatory mechanisms: increased symp tone, increased renin-angiotensin activity
- Angiotensin II: direct vasoconstrictor to help raise BP, and stimulates aldosterone
- aldosterone stimulates Na and water reabsorption by kidney, raises bp and blood volume
- temporarily relieves the problem but then makes heart failure worse, heart is trying to work harder but can’t - compensatory mechanisms aren’t enough to maintain CO and signs of CHF appear
- Severe CHF–>pulmonary and peripheral edema
How do venous vasodilators, e.g. nitrates, help treat congestive heart failure?
- vasodilation of veins cause pooling in lower body, and decreases EDV/preload
- If heart failure patient is on relatively flat part of depressed Frank starling curve, CO won’t fall. And pulmonary congestion improves.
- note: nitroprusside has venous and arterial dilation properties
Describe mechanism and effect of Angiotensin converting enzyme (ACE) inhibitors?
- blocks conversion of Angiotensin I to II.
- decreases aldosterone secretion and Na/water reabsorption–>lower bp and volume
- blocking angiotensin II inhibits vasoconstriction–> decrease bp
- thus lowers workload of heart
- may also block remodeling of heart (caused by increased bp due to Angiotensin II)
List the ACE inhibitors.
- Captopril (capoten)
- Enalopril (vasotec)
- Lisinopril (Zestril)
What are the side effects of ACE inhibitors?
- dry cough: bc ACE inhibitors block metabolism of bradykinin, which allows kinins to build up in the lung, causing coughing and some edema
- postural hypotension: will go away
What are angiotensin receptor blockers (ARBs) and their side effects? List the names of ARBs.
-bind to angiotensin II receptors in adrenal cortex
-used when side effects prevent use of ACE inhibitors
-minimal side effects
Losartan (Cossar)
Candesartan (atacand)
Valsartan (Diovan)
Describe renin antagonists. Side effects? List names of drugs.
-Block actin of renin in converting angiotensinogen to angiotensin I. No angiotensin II causing vasoconstriction and no aldosterone causing Na and water reabsorption–>no increased bp
-minimal side effects
Aliskiren (Tekturna)
Explain the mechanism of aldosterone, and how aldosterone antagonists work. List the names of aldosterone antagonist drugs.
- Aldosterone binds to nucleus and causes upregulation of Na/K ATPase. Na+ is pumped out and K+ into the cell (blood side). This causes Na+ (and water) from the urine side to flow into cell to be reabsorbed.
- aldosterone antagonists bind to aldosterone receptor and act as antagonist with no agonist effect
- potassium sparing diuretic action
- spironolactone (Aldactone)
- eplerenone (Inspra)
- Triamterene: indirect aldosterone antagonist by closing epithelial Na channels
What are the side effects of spironolactone, Eplenerone, and Triamterene? (aldosterone antagonists)
- Spironolactone: similar to sex steroids and can bind to sex steroid receptors. Binding to estrogen receptor can cause males to develop breast (gynecomastia). Cause menstrual irregularities in women.
- Eplenerone doesn’t have agonist activity for sex steroid receptors
- Triamterene has fewer side effects because doesn’t bind to aldosterone receptor for action
How do arterial dilators such as nitroprusside, ACE inhibitors, ARBs, and renin antagonist affect a patient with CHF on the Frank Starling Curve?
- They decrease afterload. Shifts point on curve up (like inotropic effect but without increasing work), increasing SV but lowering pressure so to not cause pulmonary edema.
- also decrease preload via decreasing blood volume
How do diuretics work?
- ones that act of Loop of Henle called loop diuretics. Block Na, Cl, water reabsorption =furosemide (Lasix) and bumetanide (bumex)
- Metolazone (zaroxolyn) acts on proximal tubule, inhibits Na absorption
- decreases preload and SV
What are side effects of diuretics?
- Hypokalemia: loop diuretics results in loss of potassium and blood levels of K must be monitored
- hypotension
How do beta blockers work in the treatment of congestive heart failure? Side effects of using beta blockers for CHF?
Drugs used: metoprolol, atenolol, carvedilol
- mechanism unclear
- could stop binding of endogenous beta agonists to unregulated beta receptors that might be activated and cause a fatal arrhythmia
- may inhibit cardiac remodeling
- Side effects: acute effect-worsening of cardiac failure from decrease in CO.
What is the action of hydralazine?
- arterial dilator
- exact mechanism unknown, may act through NO
- combination therapy with isorbide dinitrate proven to be effect, dilate both veins and arteries
What is the action of dopamine on blood vessels?
LOW doses
-vasodilation, binds to DA-1 and inhibits NE, increases flow to renal and mesenteric arteries
INTERMEDIATE doses
-dual action, binds to sympathetic neurons and release NE, and bind to b1 receptor. Stimulates inotropic activity, increases contractility
HIGH doses
-a1 adrenergic activity, vasoconstriction of arterioles
ONLY given in hospitals via IV, major side effects result from too high a dose given
