Hyperlipidemia drugs Flashcards
Outline the exogenous pathway of cholesterol and lipid uptake
Lipids and cholesterol from the gut–> Chylomicron–> LPL to distribute to tissues–> hepatic uptake
CHolesterol either used in bile or repackaged with VLDL–> LPL in peripheral tissue and obtain lipids–> IDL–> LDL(cholesterol deposition)
Endogenous pathway of cholesterol and lipids
HMG coA reductase in order to make endogenous cholesterol
- Needed for cell repair, growth, bile
Repackaged with VLDL to go to peripheries
LPL–> converts VLDL to IDL or LDL
LDL causes deposition in peripheries and arteries but HDL will uptake some CE, causing reuptake from periphery
WHat are the different classes of hyperlipidemia
TYpe 1: CM uptake issue, LPL insufficiency
Type 2a: High LDL, LDL receptor issue
Type 2b: High VLDL and LDL, too much VLDL
Type3: HIgh IDL, IDL reuptake issue
Type 4: just high VLDL
type 5: cm and VLDL
What are the different classes of drugs for Hyperlipidemia
- Niacin (Lipolysis inhibitor)
- Fibrates
- HMG coA reductase inhibitor (statins)
- Sterol absorption inhibitors
- Fat absorption inhibitors
What is the MOA of Niacin
Niacin (vitamin B3) is taken orally and converted into nicotinamide. Nicotinamide inhibits lipolysis in fat and peripheral tissue decreasing the production of VLDL, and decreasing the downstream LDL
Increases HDL
Reduces fibrinogen and increase tissue plasminogen activator, anti-thrombotic in artherosclerosis and hyperlipidemia
Indications and adverse effects of niacin
Indication: High VLDL–> type IIb, type IV
Adverse effects: flushing and pruritus, uricemia
What is the MOA of fibrates
Fibrates: gemfibrozil, fenofibrate, clofibrate
Peroxisome proliferate activated receptor alpha protein
Fibrate increases the peripheral clearance, increases expression of LPL in peripheral tissue hence reducing TG levels (VLDL decrease)
Decreased secretion of VLDL by liver
Increased HDL
Indications and adverse effects of fibrates
Indications: Helps with Dysbetalipoproteinemia
Adverse effects: rashes, GIT issues, myositis, gall stones
MOA of Bile acid binding resins
Cholestyramine taken orally. Bind to negatively charged bile acids, prevent the reabsorption of the bile acids into the enterohepatic circulation
Increases the LDL receptors of liver, can cause increase in VLDL as more endogenous production is needed,
Indications and adverse effects of bile acid binding resins
Indication: Type 2a- high LDL, need to reduce, usually used with niacin if got type 2b
adverse effects: steatorrhea, malabsorption of ADEK, constipation, nausea and flatulence
Statins MOA
Statins like lovastatin, simvastatin are HMG coA reductase inhibitors (rate limiting step of cholesterol production)
decreases endogenous production of cholesterol and causes increased uptake from the peripheries (increase LDLR)
Hence it helps to decrease LDL, VLDL levels and reduces risk of coronary artery disease and heart failure
Indications and adverse effects of statins
Indication:all hyperlipidemia,
Adverse effects:
- Hepatic failure
- contraindicated in pregnancy due to issues in cholestrol synthesis in babies
- Muscle myopathy
WHen are statin administered and why
Oral intake at night
Basal level of cholesterol production is highest at night
MOA of sterol inhibitors
ezetimibe
Inhibition of cholesterol transporters in the intestine (NPC1L1)
decreased cholesterol absorption from the intestines, decreasing LDL usually used with statins
Adverse effects and clinical indications of sterol inhibitors
Clinical indication: high LDL,
Adverse effect: hepatic failure
