Lipid Lowering Flashcards
(34 cards)
Cholestyramine: classes
bile acid sequestrant
cholesterol reduction
Cholestyramine: PD
forms a non-absorbable complex with bile acids in 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 LDL receptors on cell surface of hepatocytes > reduces LDL chol by 10-20% (maximum)
Cholestyramine: PK
virtually no absorption; excreted in feces; peak effect 3 weeks
Cholestyramine: Tox
> 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
Cholestyramine: Interactions
may diminish absorption of statins, steroids, digoxin, warfarin
Cholestyramine: special
provided as a powder for oral suspension; be sure to drink liquids with it
Cholestyramine: Misc
our earliest lipid-lowering drug, not used much now due to ADRs. may be used if patient can’t afford a statin.
Colestipol: what is the class representative?
Cholestyramine
Nicotinic Acid/Niacin: classes
pharmacologic class–vitamin; therapeutic class–cholesterol-lowering agent
Nicotinic Acid/Niacin: PD
lowers BOTH TG and LDL-chol; decreased production of VLDL > decreased production of LDL > increase in LDL receptor in liver; modestly effective as single agent, usually used in combination; can also raise HDL cholesterol
Nicotinic Acid/Niacin: PK
well absorbed, large first pass effect (to nicotinamide); Tmax 45 min; half-life 45 min; urinary excretion of unchanged drug and metabolite
Nicotinic Acid/Niacin: Tox
many patients develop skin flushing, which can be lessened by taking aspirin; some patients develop hepatitis
Nicotinic Acid/Niacin: interaction
absorption decreased by cholestyramine
Nicotinic Acid/Niacin: Special
in 1930s found to be a vitamin (B3) that cured pellagra; renamed niacin in 1940s; partially converted in the body to nicotinamide, which is NOT active in lowering lipids, but is active in forming NAD; avoid in patients with CAD, heavy ethanol use
Gemfibrozil: classes
Pharm–Fibric acid derivative; Rx–Lipid-lower agent
Gemfibrozil: PD
cellular mechanism of action remains unclear (prob related to inhibit lipolysis and decrease hepatic fatty acid uptake, inhibit hepatic secretion of VLDL); produces slight reduction in LDL-chol levels (-4%); most useful in treatment of hypertriglyceridemia in types IV and V hyperlipidemia (-31%); may increase HDL-chol (+6%)
Gemfibrozil: PK
well absorbed; oxidized in liver to two inactive metabolites; half-life 1-2 h;
Gemfibrozil: Tox
elevation of LFTs; myositis; GI distress; avoid in patients with renal, hepatic, or biliary tract disease, can cause hepatitis
Gemfibrozil: Interactions
therapeutic effects increased with statins, but may potentially increase toxicity (liver, muscle) as well
Gemfibrozil: bottom line
only 4% effective, can cause hepatitis: no one uses due to bad risk to benefit ratio
Clofibrate: class representative?
Gemfibrozil
Lovastatin: class
Pharm class–Lactone; Therapeutic class–cholesterol-lowering drug; primary and secondary prevention of CAD
Lovastatin v atorvastatin?
Lovastatin = original, atorvastatin = more powerful. Lovastatin: even at max dose, only 35-40% reduction in LDL chol. For pts with very high levels, have to rx other drugs (like atorvastatin). High dose of atorvastatin can reduce LDL chol by 60%.
Lovastatin: PD
Parent drug (lactone) is transformed to an active metabolite, which inhibits HMG-CoA reductase, the early and rate-limiting step in the synthesis of cholesterol. Inhibition is not complete. Leads to up-regulation of LDL receptors on hepatocytes, so that liver cells can import more cholesterol. Leads to reduction in LDL-chol (10-50%), increase in HDL (small)
