Chapter 16: General Overview Drugs Flashcards
What are the names of ACE inhibitors? (6)
Captopril Enalapril Fosinopril Lisinopril Quinapril Ramipril
What are the names of RAA receptor blockers? (4)
Candesartan
Losartan
Telmisartan
Valsartan
What are the names of B-adrenoreceptor blockers? (3)
Atenolol
Carvedilol
Metoprolol
What are names of diuretics? (4)
Bumetanide
Furosemide
Hydrochlorothiazide(HCTZ)
Metolazone
What are names of direct vasodilators? (4)
Hydralazine
Isosorbide dinitrate
Isosorbide mononitrate
Sodium nitroprusside
What are names of inotropic agents? (4)
Digoxin
Dobutamine
Inamrinone
Milrinone
What are names of aldosterone antagonists? (2)
Eplerenone
Spironolactone
What are the actions on the heart of ACE inhibitors?
ex: enapril
- decrease vascular resistance, venous tone and blood pressure
- reduce preload and afterload (increase CO)
- improve symptoms in patients also taking thiazide/loop diruetics and/or digoxin
What are the indications of enapril use?
- single agent therapy in patients with mild dyspnea on exertion who don’t show symptoms of edema
- indicated in all patients presenting with left ventricular failure
- ACE inhibitors may be used with diruetics, B-blockers, and aldosterone antagonists
- initiate ACE inhibitors after MI
What are the pharmokinetics of ACE inhibitors?
- oral administration, presence of food may decrease absorption
- pro drugs except for captopril
- renal elimination
- ramipril and fosinopril require only once-daily dosing
What are the adverse effects of ACE inhibitors?
- postural hypotension, renal insufficiency
- hyperkalemia, angioedema
- persistent dry cough
- shouldn’t be used in pregnant women
What are the actions of angiotensin receptor blockers on the cardiovascular system?
-lower BP, used in HF as a substitute for ACE inhibitors in patients with severe cough or angioedema
What are the pharmokinetics of angiotensin receptor blockers?
- orally active and require once daily dosing
- losartan
- eliminated in urine and feces
- all are highly plasma protein bound except for candesartan which has a large volume of distribution
What are adverse effects of angiotensin receptor blockers?
- similar to ACE inhibitors but do not produce cough
- contradindicated in pregnancy
What are the benefits of administering B blockers?
- improved systolic function and reverse cardiac remodeling
- decrease HR and inhibit release of renin
- prevent direct deleterious effect of NE on cardiac muscle
What are the two B-blockers approved for use in HF?
-carvedilol and metoprolol
What is the mechanism of carvedilol and metaprolol?
- C: nonselective B-blocker and also blocks alpha- adrenoreceptors
- M: B1-selective antagonist that reduces mortality
When are B-blockers recommended?
-all patients with heart disease except those at high risk of acute HF but may not show any symptoms
What is the mechanism of diuretics in HF?
- relieve pulmonary congestion an peripheral edema
- reduce symptoms of volume overload, orthopnea and paroxysmal nocturnal dyspnea
- dec
What is the mechanism of diuretics in HF?
- relieve pulmonary congestion an peripheral edema
- reduce symptoms of volume overload, orthopnea and paroxysmal nocturnal dyspnea
- decrease venous return to the heart which decreases cardiac worklad and O2 demand
- loop diruetics are the most commonly used diuretics
What is the mechanism of direct vasodilators?
- decrease in cardiac preload by increasing venous capacitance
- arterial vasodilators reduce systemic arteriolar resistance and decrease afterload
- nitrates are commonly used
- if patient is intolerance of ACE inhibitors, combo of hydralazine and isosorbide dinitrate may be used (effective in black patients)
- hydralazine decreases afterload and organic nitrate reduces preload
What is the general mechanism of inotropic agents? ex: digitalis glycosides
-increase contractility of the heart and increase cardiac output by increasing cytoplasmic Ca2+ concentration that enhances contractility of the heart
What is the specific mechanism of digitalis glycosides?
- regulation of cytosolic Ca2+ concentration: decrease Na concentration gradient so that the Na*/Ca2+ exchanger cannot extrude Ca2+ from the myocyte in exchange for Na+ (the concentration gradient is a major determinant of the net movement of ions)
- > there is also a Na+/K+ ATPase exchanger which restores the concentration gradient of Na+ so when digoxin is used to inhibit this Na+/K+ exchange the resting membrane potential is increased which makes the cardiac cell more excitable
-increased contracility of the cardiac muscle:
What is the specific mechanism of digitalis glycosides?
- regulation of cytosolic Ca2+ concentration: decrease Na concentration gradient so that the Na*/Ca2+ exchanger cannot extrude Ca2+ from the myocyte in exchange for Na+ (the concentration gradient is a major determinant of the net movement of ions)
- > there is also a Na+/K+ ATPase exchanger which restores the concentration gradient of Na+ so when digoxin is used to inhibit this Na+/K+ exchange the resting membrane potential is increased which makes the cardiac cell more excitable
- increased contracility of the cardiac muscle: increased myocardial contraction leads to a decrease in end diastolic volume, increases the ejection fraction
- > the improved circulation results in a decrease of sympathetic stimulation which reduces peripheral resistance
digoxin slows down conduction through the AV node which accounts for its use in atrial fibrillation
What are the indications of digoxin?
- indicated in patients with severe left ventricular systolic dysfunction after inititation of ACE inhibitors and diuretic therapy
- major indication: HF with atrial fibrillation
- not indicated in patients with diastolic or right sided HF
What is the general mechanism of inotropic agents? ex: digitalis glycosides, B-adrenergic agonists, phosphodiesterase inhibitors
-increase contractility of the heart and increase cardiac output by increasing cytoplasmic Ca2+ concentration that enhances contractility of the heart
What are the pharmokinetics of digoxin?
digoxin: -very potent and eliminated in the kidneys
- large volume of distribution becuase it accumulates in muscle
digitoxin: much longer half life and metabolized by the liver before being excreted in the feces
What are the adverse effects of digoxin?
- hypokalemia
- renal insufficiency
- severe toxicity results in ventricular tacchycardia
- GI: nausea anorexia
- CNS: headache, fatigue, blurred vision
What are factors predisposing to digoxin toxicity?
- electrolyte disturbances: hypokalemia can percicpitate cardiac arrythmias , hypomagnesemia and hypercalcemia
- drugs: quinidine, verapamil, and amiodarone can cause digoxin intoxication by displacing digoxin from tissue protein binding sites and by competing with digoxin for renal excretion
What is the mechanism of B- adrenergic agonists?
ex: dobutamine
- positive inotropic effect and vasodilation
- dobutamine: increases intracellular cAMP which activates protein kinase which phosphorylates Ca2+ channels allowing Ca2+ to enter mycoardial cells
- IV infusion most commonly used to treat acute HF in a hospital setting
What is the mechanism of phosphodiesterase inhibitors?
Inamrinone and milirinone increase intracellular concentration of cAMP
-short term use IV
What is the mechanism of aldosterone antagonists?
What is the mechanism of aldosterone antagonists?
ex: spironolactone and eplerenone
- patients with HF have elevated levels of aldosterone due to angiotensin II stimulation and reduced hepatic clearance of hormone
- spironolactone: direct antagonist of aldosterone, reserved for most advance cases of HF; causes retention of K+ as a side effec
- eplerenone: competitive antagonist of aldosterone at mineralocorticoid receptors; lower incidence of endocrine related side effects; reduces mortality in patients with left ventricular systolic dysfunction and HF after acute MI
What are the steps of treatment in patients with HF?
Stage A: high risk with no symptoms
- risk factor reduction, patient education, treat underlying cause (HT/diabetes/dyslipidemia)
- ACE inhibitors and ARBs in some patients
Stage B: structural heart disease, no symptoms
-ACE inhibiots or ARB blockers in all patients, B-blockers in some patients
Stage C: structural heart disease, precious or current symptoms
- ACE inhibitors and B-blockers in all patients
- dietary sodium restriction, diuretics and digoxin
