Hypertriglyceridemia Drugs

Question 1

What are the two main drugs used for hypertriglyceridemia?

Answer 1

Niacin

Fibrates (including Gemfibrozil and Fenofibrate)

Question 2

What are effects of Niacin and Fibrates on triglycerides, LDL, and HDL levels?

Answer 2

Decrease triglycerides
Increase HDL
Minor effects on LDL

Question 3

At what serum triglyceride level would you really recommend a drug to specifically lower a patient’s triglyceride levels?

Answer 3

Above 500 mg/dL, when they have a higher risk of pancreatitis

Question 4

Niacin = Vitamin……?

Answer 4

Niacin = Vitamin B3

Question 5

Niacin

Primary Clinical Effect

Answer 5

Lowering triglycerides and increasing HDLs

Question 6

Niacin MOA

GPR109A Receptors

Answer 6

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

Question 7

Niacin MOA

DGAT2

Answer 7

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

Question 8

Niacin MOA

ApoCIII

Answer 8

Niacin decreases apoCIII activity, which is an LPL inhibitor. Increase LPL activity leads to enhanced degradation of triglycerides in capillary beds.

Question 9

Niacin MOA

ApoA1

Answer 9

Increased expression of apoA1, leading to increased half life of HDLs.

Question 10

Niacin MOA

Lipoprotein A

Answer 10

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

Question 11

Niacin

Adverse Effects

Answer 11

Skin flusing (prostaglandin release)
Inhibit uric acid secretion (predispose to gout)
Exacerbate peptic ulcer disease

Question 12

Niacin

Contraindications

Answer 12

Peptic Ulcer disease
Gout
Diabetics
Impaired liver function

Question 13

Fibrates

List the two fibrates

Answer 13

Gemfibrozil and fenofibrate

Question 14

Fibrates

General MOA

Answer 14

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

Question 15

Fibrates MOA

ApoCIII

Answer 15

Fibrates decrease apoCIII, an inhibitor of LPL. Increase LPL expression in muscle, leading to more fatty acid oxidation and clearance in the periphery.

Question 16

Fibrates MOA

ApoA1

Answer 16

Increase ApoA1, AII synthesis in hepatocytes, leading to increased HDL in serum

Question 17

Fibrates

Clinical Uses

Answer 17

Hypertriglyceridemia with low HDL

Familial dysbetaproteinemia/ Type III hyperlipoproteinemia

Question 18

Fibrates

Adverse Effects

Answer 18

Gallstones - due to less bile acid production.

Gemfibrozil may cause increased risk of rhabdomyolysis when taken with statins.

Question 19

Fibrates Drug Reactions

For both Gemfibrozil and Fenofibrate

Answer 19

High displacement of protein-bound drugs like warfarin and sulfonylureas

Question 20

Fibrates Drug Reactions

Gemfibrozil and Statins

Answer 20

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.

Question 21

Fibrates

Contraindications

Answer 21

Pregnant/lactating women
Severe hepatic or renal dysfunction
Pre-existing gallbladder disease

Question 22

Fish Oils

Therapeutic Uses

Answer 22

Adjunct to diet in treatment of hypertriglyceridemia

Cause a minor increase in HDLs, lower serum triglycerides, may also increase LDLs.

Question 23

Fish Oils

MOA

Answer 23

May inhibit genes involved int riglyceride synthesis

Anti-inflammatory effects