Hypertriglyceridemia Drugs Flashcards
What are the two main drugs used for hypertriglyceridemia?
Niacin
Fibrates (including Gemfibrozil and Fenofibrate)
What are effects of Niacin and Fibrates on triglycerides, LDL, and HDL levels?
Decrease triglycerides
Increase HDL
Minor effects on LDL
At what serum triglyceride level would you really recommend a drug to specifically lower a patient’s triglyceride levels?
Above 500 mg/dL, when they have a higher risk of pancreatitis
Niacin = Vitamin……?
Niacin = Vitamin B3
Niacin
Primary Clinical Effect
Lowering triglycerides and increasing HDLs
Niacin MOA
GPR109A Receptors
GPR109A receptors on adipocytes. Niacin agonizes these receptor to inhibit beta-adrenergic recpeotrs and decrease cAMP production. Decrease hormone sensitive lipase activity and lower free fatty acids in the blood
Niacin MOA
DGAT2
Niacin inhibits DGAT2, an enzyme that normally converts free fatty acyl CoAs into triglycerides in the liver. Niacin leads to decreased triglyceride synthesis in the liver
Niacin MOA
ApoCIII
Niacin decreases apoCIII activity, which is an LPL inhibitor. Increase LPL activity leads to enhanced degradation of triglycerides in capillary beds.
Niacin MOA
ApoA1
Increased expression of apoA1, leading to increased half life of HDLs.
Niacin MOA
Lipoprotein A
Lipoprotein A inhibits conversion of plasminogen to plasmin. Niacin inhibits Lipoprotein A, thus allowing more plasmin to digest clots and decrease risk of clots, stroke, and MI
Niacin
Adverse Effects
Skin flusing (prostaglandin release)
Inhibit uric acid secretion (predispose to gout)
Exacerbate peptic ulcer disease
Niacin
Contraindications
Peptic Ulcer disease
Gout
Diabetics
Impaired liver function
Fibrates
List the two fibrates
Gemfibrozil and fenofibrate
Fibrates
General MOA
Fibrates act as ligands for nuclear hormone transcription factor PPAR-alpha. Activate PPAR-alpha to promote expression of genes in lipoprotein structure, function, and metabolism
Fibrates MOA
ApoCIII
Fibrates decrease apoCIII, an inhibitor of LPL. Increase LPL expression in muscle, leading to more fatty acid oxidation and clearance in the periphery.
Fibrates MOA
ApoA1
Increase ApoA1, AII synthesis in hepatocytes, leading to increased HDL in serum
Fibrates
Clinical Uses
Hypertriglyceridemia with low HDL
Familial dysbetaproteinemia/ Type III hyperlipoproteinemia
Fibrates
Adverse Effects
Gallstones - due to less bile acid production.
Gemfibrozil may cause increased risk of rhabdomyolysis when taken with statins.
Fibrates Drug Reactions
For both Gemfibrozil and Fenofibrate
High displacement of protein-bound drugs like warfarin and sulfonylureas
Fibrates Drug Reactions
Gemfibrozil and Statins
Gemfibrozil competes with statins for the OATP2 transporter and inhibits statin glucoronidation.
Taking gemfibrozil with statins leads to increased statins in the serum, which may cause increased risk of rhabdomyolysis.
Fibrates
Contraindications
Pregnant/lactating women
Severe hepatic or renal dysfunction
Pre-existing gallbladder disease
Fish Oils
Therapeutic Uses
Adjunct to diet in treatment of hypertriglyceridemia
Cause a minor increase in HDLs, lower serum triglycerides, may also increase LDLs.
Fish Oils
MOA
May inhibit genes involved int riglyceride synthesis
Anti-inflammatory effects