ANTIHYPERLIPIDEMIA - STATINS AND FIBRATES

8 Antihyperlipidemia Drug Classes

HMG-CoA reductase inhibitors (statins)

Fabric acid derivatives

Niacin / nicotinic acid

Bile acid binding resins

Sterol absorption inhibitors

MTP inhibitors

ApoB-100 inhibitor

PCSK9 inhibitors

HMG-CoA reductase inhibitors (7)

Main 3

Ator-

Rosu-

Simvastatin

Others

Lova

Prava

Fluva

Pitava

HMG-CoA reductase inhibitor MOA

Inhibits mevalonate conversion in hepatic cholesterol synthesis

Competitive inhibition - decreased mevalonate

Increases LDL receptors expression on hepatocytes promoting LDL uptake

Lovastatin & simvastatin PK

Prodrug hydrolysed in GIT to active B-hydroxyl

Pravastatin PK

Open active lactone ring

NOT metabolized by CYP

Ator, Fluva, Rosuvastatin PK

Active as given

Only completely absorbed statin

Fluvastatin

The rest: 40-75%

High half life statins (3)

RAP Long

Rosuva 19hrs

Atorva 14 hrs

Pitava 12 hrs

Statin whose absorption is NOT enhanced by food

Prava

Pitavastatin

Excretion of statins

Mostly bile

5-20% urine

Low intensity statins and doses

Fluva 20-40mg

Prava 10-20mg

Simva 10mg

Moderate intensity statins and doses

Rosuva 5-10mg

Atorva 10-20mg

Pitava 2-4mg

Fluva 80mg

Prava 40-80mg

Simva 20-40mg

High intensity statins and dosage

Atorva 40-80mg

Rosuva 20-40mg

Statins CIs

Liver disease

Alak abuse

Pregnant or lactating (teratogenic)

<7 y/o

Statins w CYP3A4 interaction

Atorva

Losuva

Simva

Statins metabolized by CYP2C9

Fluva

Rosuva

Fibric Acid derivatives are ligands for

PPAR-alpha protein (peroxisome proliferator-activated receptor alpha)

Fibrates MOA

Upregulates:

Lipoprotein Lipase mainly in skeletal ms.

Apo AI and AII increasing HDL

Downregulates liver ApoCIII

Gemfibrozil PK

Abs improved w food

Tightly bound to plasma prot

Gemfibrozil HL

1.5hrs

Fenofibrate PK

Hydrolized completely in intestine

Fenofibrate HL

19-27 hrs

Fibrates excretion

Urine

Gemfibrozil dosage

300-600mg capsule BID oral w food

Fenofibrate dose

160-300mg oral QD

Fibrates precautions

Myopathy in combo w statins

Pregnancy category C

Avoid in hepatorenal dysfunction

Caution biliary tract dx

Potentiates anticoagulant aktion