Drugs used in dyslipidemia

Question 1

Simvastatin, atorvastatin, rosuvastatin

Answer 1

• MOA
• inhibit HMG-CoA reductase
• Effects
• reduce cholesterol synthesis and up-regulate LDLr on hepatocytes
• modest reduction in triglycerides
• Clinical
• atherosclerosis, ACS
• Kinetics, tox, int.
• oral, duration 12-24h
• tox: myopathy, hepatic dysfunction
• int: CYP3A4, 2C9 related

Question 2

Fenofibrate, gemfibrozil

Answer 2

• Fibrates
• MOA
• PPAR-α agonists
• Effects
• decrease secretion of VLDL
• increase LPL activity
• increase HDL
• Clinical
• hypertriglyceridemia, low HDL
• Kinetics, tox, int.
• oral, duration 3-24h
• tox: myopathy, hepatic dysfunction

Question 3

Colestipol, cholestyramine

Answer 3

• Resins
• MOA
• bind bile acids in gut, preventing reabsorption
• increases cholesterol catabolism
• upregulates LDLr
• Effects
• decreases LDL
• Clinical
• elevated LDL, digitalis toxicity (through chelation), pruritus
• Kinetics, tox, int.
• oral, taken with meals, not absorbed
• tox: constipation, bloating
• int: interferes with absorption of some drugs and vitamins

Question 4

Ezetimibe

Answer 4

• Sterol absorption inhibitor
• MOA
• blocks sterol transporter NPC1L1 in intestinal brush border
• Effects
• inhibits absorption of cholesterol, including reabsorption from cholesterol excreted in bile
• decreases LDL and phytosterols
• Clinical
• elevated LDL, phytosterolemia
• Kinetics, tox, int.
• oral, duration 24h
• tox: low incidence of hepatic dysfunction, myositis

Question 5

Niacin

Answer 5

• MOA
• decreases catabolism of apoA1
• reduces VLDL secretion from liver
• Effects
• increases HDL
• decreases lipoprotein(a), LDL
• Clinical
• low HDL, elevated VLDL & Lp(a)
• elevated LDL in statin-unresponsive or intolerant patients
• Kinetics, tox, int.
• oral, large doses
• tox: gastric irritation, flushing, low indcidence of hepatic toxicity
• may reduce glucose tolerance