CVS Drugs Part 2 HTN and HF Flashcards
Treatment of HTN and HF
Thiazides MOA
inhibit sodium, potassium, and chloride reabsorption in the distal tubule resulting in mild diuresis (sodium and water excretion)
Thiazides most commonly used for primary HTN
hydrochlorothiazide (HCTZ) and chlorthalidone
HCTZ clinical indications
ideal starting agent for HTN, chronic edema or idiopathic hypercalciuria and can also be used to treat kidney stones and Meniere’s Disease
HCTZ adverse effects
hypokalemia, hyperuricemia (gout), hyperglycemia, hypotension, hyponatremia, and hypercalcemia
Thiazide contraindications
patients with a history of gout or hypercalcemia, pregnant women, anuria
HCTZ pharmacokinetics
administered orally and absorbed rapidly, eliminated primarily unchanged
HCTZ drug interactions
can increase the toxicity of digitalis and lithium and can cause significant hypokalemia if given with corticosteroids or ACTH
Chlorthalidone pharmacokinetics
only thiazide that is available in IV form, is structurally different from most thiazides, and has a long half life
Metolazone pharmacokinetics
structurally different from other thiazides and 10 times more potent than HCTZ, excreted unchanged in urine
Metolazone clinical indications
often used together with loop diuretics for the treatment of excess fluid (edema) in heart failure, safe to use in patients with renal insufficiency
Indapamide pharmacokinetics
undergoes hepatic metabolism and is excreted in both urine and bile
Indapamide clinical indications
uncommonly used but can treat hypertension and decompensated heart failure
Loop diuretics MOA
inhibits reabsorption of Cl-, Na+, K+, Ca2+, Mg2+, and HCO3- in the ascending loop on Henle resulting in loss of sodium, water, and high potassium in urine (more powerful diuretics than thiazides) leading to decreased preload and afterload
Loop diuretics
Furosemide, Bumetanide, and Torsemide
Loop diuretics adverse effects
hypokalemia, DEHYDRATION, DOSE-DEPENDENT OTOTOXICITY, hyponatremia, hypomagnesemia, hypotension, hyperuricemia (gout), and hyperglycemia
Furosemide clinical indications
preferred for treating hypertension in patients with low GFR (renal failure) and in hypertensive emergencies, also can treat peripheral edema in heart failure, decompensated cirrhosis, and acute pulmonary edema (limited mortality benefit)
Furosemide drug interactions
increases toxicity of ototoxic and nephrotoxic drugs and lithium, inhibited efficacy with probenecid and indomethacin, use caution in patients with sulfa antibiotic allergy as this is a sulfonamide-based med
Bumetanide clinical indications
most potent loop diuretic with the same clinical indications as Furosemide
Bumetanide adverse effects
large doses may cause severe myalgias, no ototoxicity, use caution in patients with sulfa antibiotic allergy as this is a sulfonamide-based med
Torsemide adverse effects
headache and dizziness
Potassium-sparing diuretics MOA
inhibit potassium secretion and sodium reabsorption in the distal tubule resulting in reduced potassium loss in the urine
Potassium-sparing diuretics
Amiloride, Spironolactone, Triamterene, and Eplerenone
Spironolactone MOA
aldosterone receptor antagonist that prevents sodium reabsorption and potassium excretion and androgen receptor blocker that inhibits androgen biosynthesis (conversion of androstenedione to testosterone)
Spironolactone clinical indications
can be co-prescribed with thiazides to treat edema in heart failure, ascites/cirrhosis, and nephrotic syndrome; resistant hypertension and primary hyperaldosteronism (secondary cause of HTN); acne and hirsutism
Spironolactone adverse effects
gynecomastia and increased risk for digitalis toxicity when co-administered, hyperkalemia, anuria, hypovolemia, hypertriglyceridemia, renal dysfunction/failure
Eplerenone MOA
aldosterone receptor antagonist that prevents sodium reabsorption and potassium excretion
Eplerenone clinical indications
used to treat edema in heart failure, resistant hypertension, and primary hyperaldosteronism
Eplerenone adverse effects
hyperkalemia, anuria, hypovolemia, hypertriglyceridemia, renal dysfunction/failure, less risk for gynecomastia than spironolactone
Amiloride MOA
distal tubule sodium channel inhibitor that directly increases sodium excretion and decreases potassium excretion in the urine
Amiloride clinical indications
3rd or 4th line agent to treat hypertension or heart failure specifically to compensate for potassium loss by other diuretics and can also be used to treat ascites and polyuria/polydipsia due to lithium-induced nephrogenic diabetes insipidus
Amiloride pharmacokinetics
more rapid onset than spironolactone
Triamterene MOA
distal tubule sodium channel inhibitor that directly increases sodium excretion and decreases potassium excretion in the urine
Triamterene clinical indications
typically paired with a thiazide to treat hypertension and also can be used to treat edema from various causes
Triamterene adverse effects
may turn urine blue, cause crystalluria and cast formation, and decrease renal blood flow (use caution in patients with renal disease)
Acetazolamide MOA
inhibits carbonic anhydrase in the proximal renal tubule promoting renal excretion of sodium, potassium, bicarbonate, and water
Acetazolamide adverse effects
metabolic acidosis, kidney stones, hyperammonemia in cirrhotic patients,
Acetazolamide clinical indications
used in prophylaxis for altitude sickness and in the treatment of open-angle glaucoma, less effective than thiazide or loop diuretics and used more commonly for its pharmacologic actions other than its diuretic effect
Acetazolamide pharmacokinetics
administered orally or IV, 90% protein-bound and eliminated renally, use caution in patients with sulfa antibiotic allergy as this is a sulfonamide-based med
Mannitol MOA
osmotic diuretic that promotes diuresis in the kidney by increasing the concentration of filtrates in the kidney and inhibiting the reabsorption of water in the proximal renal tubule and the glomerulus
Mannitol adverse effects
headache, nausea, dizziness, polydipsia, confusion, and chest pain, and may initially increase central venous pressure (BP) and induce heart failure in susceptible patients
Mannitol clinical indications
administered IV only and used to decrease intraocular pressure in glaucoma and decrease intracranial pressure, can also be used to increase lithium excretion in states of lithium toxicity
Mannitol contraindications
heart failure and pulmonary edema
Treatment of acute hypercalcemic crisis
immediate treatment with Furosemide (Lasix) and saline rehydration to achieve urine output of 200 mL/hr
Calcium levels indicative of acute hypercalcemic crisis
calcium levels greater than 14 mg/dL or calcium levels greater than 12 mg/dL in symptomatic patient
Symptoms of acute hypercalcemic crisis
hypertension, vascular calcification, shortened QT interval on ECG, impaired concentration, confusion, fatigue, muscle weakness, nausea, abdominal pain, anorexia, constipation, pancreatitis, polydipsia/polyuria resulting from nephrogenic diabetes insipidus, and nephrolithiasis resulting from hypercalciuria
Nephrogenic diabetes insipidus
disease process where the kidneys have partial or complete resistance to the effects of antidiuretic hormone (vasopressin) resulting in the excretion of large amounts of diluted urine, it is often hereditary but also can be caused by drugs (lithium, amphotericin B, ofloxacin, orlistat) or other disorders
Treatment of nephrogenic diabetes insipidus
Hydrochlorothiazide alone or in combination with other drugs such as Amiloride ( helps maintain potassium level), for some patients a low sodium and low protein diet is suggested
ACE inhibitors MOA
suppress the synthesis of angiotensin II and release of aldosterone from adrenals resulting in natriuresis (decreased preload) and decreased peripheral vascular resistance - vasoconstriction (decreased afterload)
ACE inhibitors
enalapril, captopril, and lisinopril
ACE inhibitors clinical indications/advantages
first-line treatment of HTN in patients with high coronary artery disease (CAD) risk, diabetes, stroke, heart failure, myocardial infarction, or chronic kidney disease - preferred in patients with diabetic nephropathy because they are renoprotective (stabilize renal function) and blood glucose levels are not impacted significantly
ACE inhibitors adverse effects
first dose hypotension, dizziness, proteinuria, rash, tachycardia, hyperkalemia, headache, cough, and angioedema
Enalapril pharmackinetics
administered oral or IV where the oral form is a prodrug that is converted to active form intestinally - enalaprilat
Captopril adverse effects
agranulocytosis or neutropenia - not common first line agent
Enalapril clinical indications
used to treat heart failure, hypertension, and diabetic kidney disease
Lisinopril clinical indications
used to treat hypertension and heart failure and also helps slow down the progression of diabetic kidney disease
Lisinopril pharmacokinetics
not a prodrug
Lisinopril adverse effects
side effects of all ACE inhibitors and can also cause some lowering of blood glucose
ARB MOA
antagonist at angiotensin II receptors in vascular smooth muscle that produce arteriolar and venous dilation and block aldosterone secretion
ARB advantages
have been shown to help slow the effects of diabetic neuropathy
ARB adverse effects
dry cough, hyperkalemia, skin rash, hypotension, and altered taste
ARBs
Losartan, Valsartan, Candesartan, Olmesartan
Losartan pharmacokinetics
administered once daily and undergoes extensive first-pass metabolism converting it to an active metabolite
Losartan clinical indications
treatment of HTN (especially in patients with LVH) and diabetic neuropathy, lowers serum uric acid levels, reduces chance of stroke
Valsartan pharmacokinetics
administered twice daily and metabolized to inactive metabolites
Valsartan clinical indications
treatment of HTN, the first ARB approved for the treatment of heart failure
Candesartan pharmacokinetics
administered once daily and metabolized to inactive metabolites
Olmesartan pharmacokinetics
administered once daily and metabolized to inactive metabolites
Olmesartan clinical indication
used to significantly reduce mean blood pressure
Aliskiren MOA
inhibits renin which prevents the conversion of angiotensinogen to angiotensin I, acting early in the RAAS
Aliskiren clinical indication
treatment of HTN
Aliskiren adverse effects
diarrhea, cough, angioedema
Aliskiren pharmacokinetics
metabolized by CYP3A4 so there is potential for many drug interactions
Aliskiren contraindications
pregnancy
Ambrisentan MOA
selective type A endothelin receptor antagonist
Bosentan MOA
nonselective endothelin receptor antagonist
Ambrisentan clinical indications
used alone or in combination with tadalafil in the treatment of pulmonary arterial hypertension (PAH) to improve exercise ability and delay clinical worsening of PAH
Ambrisentan adverse effects
edema, nasal congestion, palpitations, abdominal pain, constipation