Lipid-lowering Flashcards
Nicotinic Acid (Niacin, Niacor)
Drug class: vitamin, cholesterol-lowering agent
PD: lowers both TG and LDL, decreased production of VLDL and LDL, leading to increase in LDL receptor in liver, modestly effective as single agent, usually used in combination, can also raise HDL
PK: well absorbed, large first pass effect (to nicotinamide), Tmax 45min, half-life 45min, urinary excretion of unchanged drug and metabolite
Toxicity: skin flushing, which can be lessened by taking aspirin, hepatitis for some
Interactions: absorption decreased by cholestyramine
Special issues: found to be a vitamin B3 that cured pellagra, renamed niacin in the 40s, partially converted in the body to nicotinamide, which is NOT active in lowering lipids, but is active in forming NAD, avoid pts with CAD, heavy etoh use.
Cholestyramine (Questran, Colestipol)
Drug class: bile acid sequestrant, cholesterol-lowering agent
Dynamics: 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 salts, leading to upregulated expression of LDL receptors on hepatocytes to replenish bile acids. Reduces LDL cholesterol by 10-20% max.
PK: virtually no absorption, excreted in feces, peak effect 3wks
Toxicity: >10% pts have GI issues including gas, bloating, diarrhea, constipation, may interfere with absorption of fat-soluble vitamins, and drugs including digoxin, warfarin, thyroxine
Interactions: may diminish absorption of statins, steroids, digoxin, and warfarin
Special issues: provided as a powder for oral suspension, be sure to drink liquids in it
Note: earliest lipid-lowering drug, not used as much now due to ADR
Gemfibrozil (Lopid, Fenofibrate)
Drug class: fibric acid derivative, lipid-lowering agent
PD: cellular mech remains unclear, inhibit hepatic secretion of VLDL, produces slight reduction in LDL (-4%), most useful in treatment of hypertriglyceridemia in types IV and V hyperlipidemia (-31%), may increase HDL (+6%)
PK: well absorbed, oxidized in liver to two inactive metabolites, half-life 1-2h
Toxicity: elevation of LFTs, myositis, GI distress, avoid in pts with renal, hepatic, or biliary tract disease
Interactions: therapeutic effects increased with statins, but may potentially increase toxicity (liver, muscle) as well
Special issue: contraindicated in pts with renal or liver disease
Atorvastatin (Lipitor)
Drug class: HMG-CoA reductase inhibitor, primary and secondary prevention of CAD
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 LDLR on hepatocytes. Reduction in LDL (-10-65%)
PK: rapidly absorbed, extensively metabolized, likely mostly by CPT 3A4, metabolites accounts for most of its activity, active metabolites have half life of 20-30h
Toxicity: check LFTs amd CPK (muscle) during first year of use, because of risk of hepatitis, myopathy, myositis, and even rhabdomyolysis (rare)
Interactions: additive effects with cholestyramine, nicotinic acid, ezetimibe. gemfibrozil, niacin may increase risk of myopathy, erythromycin, cyclosporine, fluconazole, and others may inhibit CYP 3A4 metabolism, thereby causing increased accumulation and increasing toxicity.
Special issues: avoid in pts with pre-existing hepatitis, muscle disease, and pregnancy (X)
Ezetimibe (Zetia)
Drug class: 2-azetidinone compound, cholesterol-absorption inhibitor
PD: selectively blocks the intestinal absorption of cholesterol and related phytosterols, by acting at the level of 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 up to 18%, often used with statin, may not add to clinical efficacy.
PK: given orally, tmax 4-12h, extensively metabolized to glucoronide, F: 35-60%, half life: 22h
Toxicity: HA in about 8%, diarrhea in about 4%
Interactions: use in combination with dietary therapy, as monotherapy, or in combination with a statin (available as Vitorin, ezetimibe + simvastatin), bile acid sequesteants may decrease F
Special issues: use with caution in pts with hepatic or renal impairment
