Lipid lowering drugs

Question 1

Lipid lowering drugs

Answer 1

• HMG-CoA inhibitor - STATINS
• PCSK9 inhibitor - EVOLOCUMAB, ALIROCUMAB
• fibrates - GEMFIBROZIL, FENOFIBRATE
• OMACOR
• bile acid binding resins - CHOLESTYRAMINE
• inhibitors of intestinal sterol absorption - EZETIMIBE

Question 2

MOA of statins

Answer 2

• inhibit HMG-CoA reductase (inhibit rate limiting step in cholesterol synthesis)
• upregulate LDL receptors on cell surface due to cholesterol depletion -> receptors bind and internalize circulation LDLs

Question 3

statins PK

Answer 3

oral, taken in evening (endogenous cholesterol synthesis rates higher as less food eaten)

Question 4

is statins contraindicated in pregnancy?

Answer 4

yes, cholesterol is important for fetal development

Question 4

statins adverse effects

Answer 4

• rhabdomyolysis (tea coloured urine)
• liver impairment

Question 4

MOA PCSK9 inhibitor

Answer 4

• inhibit to PCSK9, prevents PCSK9 from binding to LDL receptors and endocytosis -> increase LDL receptors on cell surface to internalize circulation LDL

Question 4

PCSK9 inhibitor mode of administration and Thalf

Answer 4

• IV
• 10-20 days (very long)

Question 4

indications for PCSK9 inhibitor

Answer 4

• high LDL-C in familial hypercholestrolaemias if intolerant to statins
• together with statin in additional LDL lowering

Question 5

Fibrates MOA

Answer 5

• interact with PPAR-alpha to increase activity of lipoprotein lipase (breaks down VLDL) -> VLDL levels decrease, HDL levels rise

Question 5

PCSK9 inhibitor adverse effects

Answer 5

• hypersensitivity in some patients
• inflammatory reaction at site of injection
• nasopharyngitis
• sinusitis

Question 5

Fibrates clinical indications

Answer 5

• hypertriglyceridemias with VLDL elevation, especialy for dysbetalipoproteinemia

Question 6

Fibrates adverse effects

Answer 6

• nausea
• skin rashes
• gall stones
• myositis

Question 7

Omacor MOA

Answer 7

• reduce triglyceride (TG) production and increase TG clearance
• inhibit diglyceride acyltransferase (responsible for TG synthesis)
• increase free fatty acid breakdown by beta oxidation

Question 8

omacor PK

Answer 8

• oral, taken with food
• metabolized by liver

Question 9

omacor clinical indications

Answer 9

• Type IV
• Type IIb along with statins
• NOT FOR Type I

Question 10

omacor adverse effects

Answer 10

• contraindicated for ppl allergic to fish
• GI
• may increase LDL-C in some patients (counterproductive)
• reduce production of TXA2, can increase bleeding time

Question 11

cholestyramine MOA

Answer 11

• binds to bile acids & bile salts -> lower bile acid concentration -> hepatocytes increases conversion of cholesterol to bile acids -> increase uptake of LDL in hepatocyte

Question 12

cholestyramine clinical indications

Answer 12

• hypercholesterolemia (IIa)
• hyperlipidemia (IIb) -> combine with niacin

Question 13

cholestyramine dosage form

Answer 13

• oral

Question 14

cholestyramine adverse effects

Answer 14

• GI (nausea, constipation, flatulence)
• impaired absorption of vitamins K, A, D, E

Question 15

Ezetimibe MOA

Answer 15

• inhibit NPC1L1 at small intestine to reduce cholesterol absorption
  **useful even in NO cholesterol diet -> body produces and excretes cholesterol into intestinal tract on its own as well

Question 16

Ezetimibe clinical indications

Answer 16

• reduce LDL (more effective when combined with simvastatin -> vytorin)

Question 17

Ezetimibe adverse effects

Answer 17

• diarrhoea, flatulence
• rhabdomyolysis
• reversible hepatotoxicity