Lipid lowering drugs Flashcards
Cholestyramine
bile acid sequestrate for lowering cholesterol
forms a non-absorbable complex with bile acids in the small bowel (releasing Cl); inhibits enterohepatic reuptake of intestinal bile salts; increases fecal loss of bile acids > increases bile acid synthesis > increases cholesterol synthesis > increases expression of hepatocyte LDL cell surface receptors > reduces LDL chol by 10-20% max
virtually no absorption, excreted in feces, peak effect 3 weeks
> 10% of patients have GI problems including gas, bloating, diarrhea, constipation; may interfere with absorption of fat-soluble vitamins, and drugs including digoxin, warfarin, thyroxine
may diminish absorption of statins, steroids, digoxin, warfarin
provided as a powder for oral suspension; take with liquids
4gm once a day, up to 6 times daily
note: earliest lipid-lowering drug, not used much now
nicotinic acid
vitamin for cholesterol-lowering agent
lowers both TG and LDL; decreased production of VLDL > decreased production of LDL > increase in LDL receptors in liver; modestly effective as single agent, usually used in combination; can raise HDL
well absorbed, large first pass effect (to nicotinamide); Tmax 45 m, half-life 45m; urinary excretion of unchanged drug and metabolite
can cause skin flushing, can be lessened by aspirin; some patients develop hepatitis
absorption decreased by cholestyramine
cures pellagra; nicotinamide not effective in lowering lipids, active in forming NAD; avoid in patients with CAD, heavy EtOH use
for pellagra, 100mg tid; hyperlipidemia 0.5-2gm tid after meals
recent study showed no clinical benefit in combo therapy with statin
Gemfibrozil
fibric acid derivative for lipid lowering
cellular mechanism is unclear, but probably involves inhibited lipolysis/hepatic fatty acid uptake to inhibit VLDL; produces slight decrease in LDL (4%); most useful in treatment of hypertriglyceridemia in familial types (31%) and may increase HDL (6%)
well absorbed, oxidized in liver to two inactive metabolites; half life 1-2h
elevation of LFTs, myositis, GI distress, avoid in patients with renal, hepatic, or biliary tract dz
synergistic effect with statins, but increased risk of toxicity to liver or muscle
600mg po bid
Lovastatin
(atorvastatin is the king of the statins now… more potent effects)
lactone for lowering cholesterol, primary and secondary prevention of CAD
converted to active metabolite which inhibits HMG-CoA reductase. Inhibition is not complete. Leads to upregulation of LDL receptors, hepatocytes can import more cholesterol. LDL reduction (10-50%), small increase in HDL. (atorvastatin LDL reduction up to 60%)
about 30% absorbed, onset of action 3 pays; peak effects in several weeks, excreted in feces, metabolized primarily by CYP3A4
check liver function tests (LFT) and creatine phosphokinase (CPK) for 1st year of use, risk of hepatitis, myopathy, myositis, and (rarely) rhabdomyolysis
additive effects with cholestyramine, nicotinic acid, ezetimibe, gemfibrozil, niacin may increase risk of myopathy; erythromycin and others inhibit CYP3A4 metabolism, causing increased accumulation and toxicity
Avoid in patients with pre-existing hepatitis, muscle disease, and pregnancy (X)
20mg po qd with dinner; may increase to 80mg po qd, or switch to more potent statin
ezetimibe
2-azetidinone compound for inhibiting cholesterol absorption
selectively blocks intestinal absorption of cholesterol and phytosterols at level of small bowel brush border; reduction of hepatic cholesterol stores and increase in blood clearance of cholesterol; when used as mono therapy, can lower LDL-chol by 18%; often used with a statin; recent work suggests that while it can lower LDL, may not add to overall clinical efficacy
given orally; tmax 4-12h; extensively metabolized to glucoronide; f 35-60%; t1/2 = 22h
headache in 8%, diarrhea in 4%
combo with dietary therapy, mono therapy, or combination with statin; bile acid sequestrates may decrease F
use caution in patients with hepatic or renal dz
10mg po qd
