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Hyperlipidemia tx
UVa med pharmacology block 3
| Question | Answer |
|---|---|
| Statins | HMG-CoA reductase inhibitors - tx hyperlipidemia - lowers intracellular cholesterol levels, induces SREBP, incr LDLR expression-> incr LDL clearance from blood lowers LDL 18-55%, TG 7-30%, incr HDL 5-15% dose dependent reduction, should take in evening |
| What are side effects of statin therapy? | myopathy (rhabdomyolysis) occurs in <.1%, incr @ high dose drugs that block CYP450s or glucuronidation (pharkinetics) or other anti-lipid drugs (phardynamics), niacin increases to 3% gemfibrozil 5%, combinations can be worse abnormal liver function (<1% |
| What statins do we need to know | Atorvastatin - lipitor Simvastatin - zocor/generic Pravastatin - pravachol/generic Rosuvaststin - crestor Fluvastatin - lescol Lovastatin - mevacor/generic |
| Nicotinic acid - niacin | B vitamin - tx hyperlipidemia - decr lipolysis in adipose->less FA for TG synthesis->decr VLDL synth->less LDL - increases HDL lowers TG 20-50%, LDL 5-25%, incr HDL 15-30% only 1/2 px's tolerate drug long term due to side fx |
| what are side effects of niacin? | GI: epigastric distress, hepatotoxic Skin: flushing, itching, rash, acanthosis nigrans other: hyperuricemia, arrhythmia, glucose intolerance (insulin res px's), amblyopia CI's: chronic liver dx, severe gout, diabetes, peptic ulcer dx |
| What are CI's of statin therapy? | active or chronic liver disease. Women who are pregnant or may become pregnant, nursing mothers |
| Ezetimibe | Cholesterol absorption inhibitor - inhibs NPC1L1-> blocks cholest transport into enterocytes, reduces cholest content of chylomicrons lowers LDL 18% used in combination w/statins |
| what are side effects of Ezetimibe? | muscle weakness and increase in liver enzymes (when in combination w/statins) cyclosporine and fenofribrate increase levels, bile acid binding resins decrease absorption CI's: active/chronic liver dx, preggers, nursing mothers |
| What are the relative potencies of different statins? | rosuvastatin> atorvastatin> simvastatin> pravastatin> lovastatin |
| Colsevelam | sequestrant - insoluble +charged resin - tx hyperlipidemia - decrs bile acid cycling by 85%->decrs FXR activity/incrs CYP7a expression->incr bile salt & up reg's LDL-R - lowers LDL 15-30%, modest HDL incr used w/statins or alone when LDL alone very high |
| What are side effects of bile acid binding resins (colsevelam)? | GI discomfort - constipation, flatulance, nausea, diarrhea, epigastric fullness interferes w/absorption of lipid soluble drugs - digoxin, warfarin, thiazides, beta-blockers, etc. (take drugs 1-4hrs before resin) causes rise in TG's CI's: px's w/high TG |
| Gemfibrozil/Fenofibrate | fibrates - tx high TG's, hyperlipidemia- activate PPARalpha-RXR->incr FA oxidation->decr TG levels->decr VLDL - also incr lipoprotein lipase express TG decr 20-50%, LDL 5-20%, HDL incr 10-20% Gem increases Statin side fx, feno does not |
| what are side effects of fibrates (Gemfibrozil/fenofibrate)? | increase chance of cholesterol gallstones due to super saturated bile mild myopathy - resolves w/discontinuation (severe in px's w/chronic renal dx), can cause leukopenia CI's: preggers or nursing, severe renal dx, severe hepatic dx |
| Omega 3 Fatty acids | tx hyperTG (>500) - mech not well def'd - agonist of PPARalpha (similar to fibrates), may inhib TG synthesis TG decr 50%, HDL incr 9%, large doses 4g/day CI'd in fish allergies, tx may raise LDL |
Created by:
sam.mrosenfeld
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