17 18 Yan+dyslipidemia+session+review.pdf

Dyslipidemia Statin drugs identified as fungal metabolites: type 1 statins This structure, known as statin pharmacophore, binds to HMG-CoA reductase HO HO O O O OH O O O CH3 CH3 CH3 CH3 Lovastatin (Mevacor®) O O O O O O- Na+ HO OH CH3 Simvastatin (semi-synthetic) (Zocor®) Pravast...

Dyslipidemia Statin drugs identified as fungal metabolites: type 1 statins This structure, known as statin pharmacophore, binds to HMG-CoA reductase HO HO O O O OH O O O CH3 CH3 CH3 CH3 Lovastatin (Mevacor®) O O O O O O- Na+ HO OH CH3 Simvastatin (semi-synthetic) (Zocor®) Pravastatin (Pravachol®) Statin drugs as HMG-CoA reductase inhibitor • The levels of liver LDL receptor greatly affect blood LDL levels • Higher LDL receptor-lower LDL levels • A high fat diet could limit the effect of a statin drug as high fat diet lowers LDL receptor levels on liver cell membrane Drugs for the management of blood lipids Drug class HDL-C (%) LDL-C (%) TG (%) Statins  5-6  25-28 11-15 Bile acid sequestrants  3-4  9-18 Relatively No change Cholesterol absorption inhibitors 1  15-18  5-10 Fibrates  6-18  4-11  21-35 Nicotinic acid  26-32  17-18  27-35 Cholestyramine is a bile acid sequestrant Ezetimibe is a cholesterol absorption inhibitor Fibrates and elevation of HDL • Fibrates increase fatty acid oxidation in muscle and liver and lipogenesis in the liver • Fibrates are most effective at reducing VLDL (TG) and increasing HDL • Fibrates act as PPAR ligands that stimulate gene transcription Yan PHAR 7334 Session quiz questions and answers 1. Which of the following dyslipidemia medications decreases blood LDL-cholesterol but has relative little effect on blood triglycerides? a. statins *b. cholestyramine c. niacin d. fibrate 2. Which of the following dyslipidemia drugs lowers blood LDL-cholesterol via targeting peroxisome proliferator-activated receptor-α (PPAR-α)? a. Statins b. Bile acid sequestrants c. cholesterol absorption inhibitors *d. fibrates e. nicotinic acid 3. Which of the following dyslipidemia drugs exists in food, but the quantity of it ingested in food does not have measurable effect on serum cholesterol levels? In other words, the action of this drug is a pharmacological effect that requires the administration of large doses of the drug each day. a. Statins b. Bile acid sequestrants c. cholesterol absorption inhibitors d. fibrates *e. niacin 4. A high fat diet tends to limit the effect of a statin drug on blood LDL levels because a. statins are inhibited by high fat diet b. VLDL particles bind to and inhibit statins *c. a high fat diet lowers the level of liver plasma membrane LDL receptors d. the uptake of statins is inhibited by chylomicrons e. the effect of the statin is counteracted by HDL 5. Which of the following lipid modifying drug class has the greatest effect on blood LDL levels? a. bile acid sequestrants *b. statins c. cholesterol absorption inhibitors d. nicotinic acid e. fibrates 6. Cholestyramine can lower blood cholesterol by a. an indirect mechanism involving LDL *b. reducing liver cholesterol store by preventing recycling of bile acids c. inhibition of HMG-CoA reductase d. increasing the synthesis of chylomicrons e. inhibition of conversion of VLDL to LDL 7. Which of the following describes the mechanism of action of statin drugs? a. binding of the statin pharmacophore to the active site of its target b. binding of the drugs to liver LDL receptors c. inhibition of cholesterol synthesis in liver and other tissues *d. both a and c above are correct e. both b and c above are correct 8. Ezetimibe (zetia) decreases blood LDL by a. blocking the synthesis of VLDL *b. inhibiting the absorption of cholesterol in the intestine c. increasing cholesterol synthesis in the liver d. binding to bile acids e. blocking the conversion of VLDL to LDL 9. Which of the following can potentially lower fasting triglycerides (VLDL) by more than 20%? 1. fibrates 2. statin 3. ezetimibe (zetia) 4. nicotinic acid a. Answers 1, 2, and 3 are correct b. Answers 2 and 4 are correct c. Answers 1 and 3 are correct *d. Answers 1 and 4 are correct e. All answers are correct 10. What is the rationale for combining ezetimibe (zetia) with simvastatin to generate Vytorin? *a. to inhibit synthesis of cholesterol in the liver that counteract ezetimibe action b. to reduce skin flushing side effects c. to prevent metabolism of ezetimibe to its glucuronide e. to prevent conversion of ezetimibe glucuronide to ezetimibe in the intestine