Anti-Hyperlipidemics

Question 1

Which drugs inhibit HMG-CoA reductase and describe their pharmacokinetics?

Answer 1

Statins are HMG-CoA reductase inhibitors. They are highly suscpetible to the first pass effect, but they subsequently affect the liver. Excreted in the bile.

Note: lovastatin and simvastatin are prodrugs

Question 2

What is the mechanism of action of statins?

Answer 2

Statins are HMG-CoA Reductase inhibitors which is the enzyme of the rate-limiting step in cholesterol synthesis. When intracellular cholesterol is reduced, LDL receptor expresssion is increased removing LDL from the circulation.

Question 3

What are the adverse effects (3) and contraindications (4) of statins?

Answer 3

adverse effects - elevations of aminotransferase, elevations of creatinine kinase, rhabdomyolysis

Contraindications - pregnancy, skeletal muscle myopathy, and liver disease. Should only be used in children with homozygous hypercholesterolemia.

Question 4

What is the MOA for niacin?

Answer 4

Niacin inhibits the lipolysis of TGs reducing FFAs, VLDLs, and LDLs. Increases HDLs.

Note: suffers extensive first-pass metabolism

Question 5

What is the use of niacin?

Answer 5

Often combined with a bile acid sequestrant or HMG-CoA reductase inhibitor for treatment of hypercholesterolemia.

Question 6

What are the adverse effects (6) and contraindications (3) of nicain?

Answer 6

Adverse effects - flushing, pruritis, uncomfortable warmth, dry skin, rash, and hepatotoxicity.

Note: Flushing can be managed with a once-daily dose of aspirin or ibuprofen

Contraindications - liver disease, acute peptic ulcer, and diabetes mellitus

Note: Niacin-induced insulin resistance

Question 7

Give two examples of fibric acid derivatives?

Answer 7

gemfibrozil and fenofibrate

Question 8

Describe the pharmacokinetics of the fibric acid derivatives.

Answer 8

They are well absorbed with a meal. Gemfibrozil has a short half-life and fenofibrate has a long half-life.

Question 9

Describe the mechanism of action in fibric acid derivatives.

Answer 9

Fibric acid derivatives are agonists for the transcription of PPARalpha which increases LPL. VLDL and LDL decrease while HDL increases.

Question 10

What are the uses of fibric acid derivatives?

Answer 10

used in hypertriglyceridemias and abetalipoproteinemia

Question 11

What are the adverse effects (5) of fibric acid derivatives?

Answer 11

GI disturbance (decrease with progressive therapy)
Lithiasis (increased biliary secretion of cholesterol)
myositis, myopathy, and rhabdomyolysis

Question 12

Name three bile acid sequestrants?

Answer 12

colestipol, cholestyramine, and colesevelam

Question 13

What is the mechanism of action for bile acid sequestrants?

Answer 13

Bile acid sequestrants are large compounds which are positively charged and bind to negative bile acids. The loss of bile acids causes increased cholesterol sequestration into more acids. This increases hepatocyte LDL expression reducing blood LDL levels.

Question 14

What are the therapeutic uses of bile acid sequestrants?

Answer 14

they are used for type IIa and IIb hyperlipidemia

Question 15

What are the adverse effects (3) and contraindications (3) of bile acid sequestrants?

Answer 15

Adverse effects - GI disturbances, impaired absorption of fat soluble vitamins and drugs

Contraindications - diverticulitis, bowel disease, and cholestasis

Question 16

What is ezetimibe?

Answer 16

Cholesterol absorption inhibitor

Question 17

What is the mechanism of action of ezetimibe?

Answer 17

Prevents intestinal absorption of cholesterol by inhibiting the NPC1L1 protien. Also inhibits reabsorption of bile cholesterol.

Question 18

What are the indications and contraindications (1 each) for ezetimibe?

Answer 18

Used for hypercholesterolemia. Avoid with bile acid sequestrants, decreases drug absorption.