Lipid Lowering Flashcards
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)
Lovastatin: PK
About 30% absorbed; onset of action 3 days; peak effects in several weeks; excreted in feces; metabolized primarily by CYP 3A4
Lovastatin: tox
check LFTs and CPK during first year of use, because of risk of hepatitis, myopathy, myositis, and even rhabdomyolysis (rapid acute death of skel muscle – rare!!!)
Lovastatin: interactions
Additive effects with cholestyramine, nicotinic acid, ezetimibe; gemfibrozil and niacin may increase risk of myopathy; erythromycin and others may inhibit CYP 3A4 metabolism, thereby causing increased accumulation and toxicity
Lovastatin: special
Avoid in patients with pre-existing hepatitis, muscle disease, and pregnancy (X). Want to AVOID grapefruit juice, any other drug that inhibits the activity of 3A4. Even if you take an average dose of a statin, more likely to cause side effects.
Ezetimibe: classes
Pharm class–2-azetidinone compound; Therapeutic class–cholesterol absorption inhibitor
Ezetimibe: PD
Selectively blocks the intestinal absorption of cholesterol and related phytosterols, by acting at the level of the small bowel brush border; causes reduction of hepatic cholesterol stores, and an increase in the blood clearance of cholesterol; when used as monotherapy, can lower LDL-chol by up to 18%; often used with a statin; recent work suggests that while it can lower LDL-chol, it may not add to overall clinical efficacy (clinical endpoints)
Ezetimibe: PK
Given orally; Tmax 4-12h; extensively metabolized to the glucoronide; F 35-60%; t 1/2 = 22 h
Ezetimibe: tox
HA in about 8%, diarrhea in about 4%
Ezetimibe: interactions
Use in combination with dietary therapy, as monotherapy, or in combination with a statin (is available as Vitorin, ezetimibe + simvastatin); bile acid sequestrants may decreas F
Ezetimibe: special
Use with caution in patients with hepatic or renal impairment
