Cardiovascular Flashcards
Calcium Channel Blockers
Nifedipine, amlodipine, verapamil, diltiazem
(verapamil, diltiazem = non-dihydropyridines)
MECHANISM: Block voltage-dependent L-type Ca channels of cardiac and smooth muscle, reducing muscle contractility
Vascular smooth muscle (DHP): amlodpinie=nifedipine>diltiazem>verapamil
Heart (nonDHP): verapamil>diltiazem>amlodipine=nifedipine (“verapamil=ventricle”)
CLINICAL USE: HTN, angina, arrhythmias (not nifedipine), Prinzmetal’s angina, Raynaud’s.
TOXICITY: Cardiac depression (nonDHP’s), AV block, peripheral edema (common), flushing, dizziness, and constipation.
Hydralazine
Hydralazine and Minosidil
Direct arteriolar vasodilators
MECHANISM: Increase cGMP –> smooth muscle relaxation. Vasodilates arterioles>veins; afterload reduction.
CLINICAL USE: Severe hypertension, CHF. First-line therapy for hypertension in pregnancy, with methyldopa (alpha-agonist, dec catecholamine release)
Frequently coadministered with a Beta-Blocker to prevent reflex tachycardia.
TOXICITY: Compensatory tachycardia (contraindicated in angina/CAD), fluid retention, nausea, headache, angina. Lupus-like syndrome.
Malignant hypertension treatment (List 5 drugs)
Nitroprusside, nicardipine, clevidipine, labetalol, fenoldopam.
Nitroprusside
Malignant hypertension treatment
Short acting;increases cGMP via direct release of NO (and CN-). Can cause cyanide toxicity. (give amyl nitrate).
Balanced arterial/venous vasoodilator; decreases both preload and afterload –> Stroke volume unchanged, deliver same CO at a lower LVEDP.
Continuous in an IV.
Fenoldopam
Malignant hypertension treatment
Dopamine D1 receptor agonist (inc cAMP) - coronary, peripheral, renal, and splanchnic vasodilation. Decreased BP and increased natriuresis.
Diazoxide
Malignant hypertension treatment
K+ channel activator in smooth muscle –> relaxation and hyperpolarization. Blocks VG Ca2+ channels.
Nitroglycerine
MECHANISM: Vasodilate by releasing nitric oxide in smooth muscle, causing inc in cGMP and smooth muscle relaxation. (Do not use with sildenafil, causes a very large increase in cGMP).
Dilate veins >> arteries. Decreases preload (dec venous return due to venodilation)
CLINICAL USE: Angina, pulmonary edema
TOXICITY: Reflex tachycardia, hypotension, flushing, headache, “Monday disease” in industrial exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend results in tachycardia, dizziness, and headache upon reexposure.
NOTE: nitrate-free interval at night prevents tolerance.
Minoxidil
Contains nitric oxide moiety –> vasodilator and opens K+ channels. Used as an antihypertensive and for androgenic alopecia.
Ergonovine
Ergot alkaloid that constricts vascular smooth muscle (alpha-antagonist and 5-HT agonist), used to diagnose Prinzmetal’s angina.
In pts with hypercontractile coronary artery segments, low doses induces coronary spasm, chest pain, and ST-segment elevation.
Bepridil
Ca2+ channel blocker used for anti-angina only (second line)
NOT FOR HTN
HMG-CoA reductase inhibitors
Lovastatin, pravastatin, simvastatin (greatest risk of myopathy), atorvastin, rosuvastatin
First Line Lipid-lowering agents
Statins metabolized by CYP450 except pravastatin. *Beware P450 inhibitors (i.e. macrolides) may inc heptotoxicity and rhabdomyolysis.
Effect on LDL: Decrease by 20-50% due to inc LDL-R expression on hepatocytes secondary to decreased de novo cholesterol synthesis.
Effect on HDL: Inc 2-15%
Effect on triglycerides: Decrease
MECHANISM: Inhibit conversion of HMG-CoA to mevalonate (rate limiting step in cholesterol synthesis)
TOXICITIES: Hepatotoxicity (Inc LFT’s, discontinue if >3x nl. baseline). Rhabdomyolysis - especially when used with fibrates or niacin. Fibrates inc. the concentration of statins.
Niacin
Niacin - Vitamin B3
(aka nicotinic acid)
Effect on LDL: Decrease
Effect on HDL: Increase 25-35%, most effect agent for increasing HDL
Effect on triglycerides: Decrease (second line)
MECHANISM: Inhibits lipolysis in adipose tissue; reduces hepatic VLDL secretion into circulation, Inc HDL by reucing clearance.
TOXICITIES: Red, flushed face (Mediated by prostaglandins) that is decreased by ASA or long-term use.
Hyperglycemia (insulin resistance) –> acanthosis nigricans
Hyperuricemia (exacerbates gout)
Hepatotoxicity at high doses
Increased Vasodilation (decrease HTN meds if pt is taking any)
Bile Acid Resins
Cholestyramine, colestipol, colesevelam
Effect on LDL: Decrease Alot: Liver takes up Cholesterol to make new bile acids (GOOD)
Effect on HDL: Slightly increased
Effect on triglycerides: Slightly increased - due to inc VLDL and inc TG synthesis in liver (BAD) –> Hypertriglyceridemia
MECHANISM: Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more
Toxicities: Patients hate it; tastes bad, causes GI discomfort (constipation and bloating - avoid in pts with diverticulosis), decreased absorption of fat-soluble viatmins, decreased warfarin and digoxin absorption, Cholesterol gallstones due to dec BA’s
Cholesterol Absorption blockers
Cholesterol Absorption blockers - Ezetimibe
Effect on LDL: Decreases (second line)
Effect on HDL: No Change
Effect on triglycerides: No Change
MECHANISM: Prevents cholesterol absortion at small intestine border. Synergistic with Statins
TOXICITIES: Rare inc LFTs, diarrhea.
Use as monotherapy in pts who cannot tolerate statin toxicity/myopathy
Fibrates
Fibrates: Gemfibrozil, clofibrate, bezafibrate, fenofibrate
Effect on LDL: Decreased
Effect on HDL: Increased (10-20%)
Effect on triglycerides: Decreased ALOT; Best agent for dec TG’s (First line)
MECHANISM: Increase LPL by activating PPAR-alpha binding, which increases lipoprotein lipase activity and decreases hepatic VLDL secretion –> TG clearance
TOXICITIES: Myositis (especially fenofibrate), hepatotoxicity (inc statin concentration, inc LFTs), cholesterol gallstones via inc cholesterol syntehsis, dec 7alpha-hydroxylase (BA synthesis)