Hypolipidemic drugs - SRM · PDF fileHYPOLIPIDEMIC DRUGS • HMG CoA reductase inhibitors. • LPL activity increasers • Adiposo tissue lipolysis inhibitors(PPAR alpha agonists)

• Hypolipidemic drugs

CONTENTS• Brief introduction about lipids.• Lipoproteins.• Lipoprotein metabolisn.• Classification of Hyper (Dys)lipidemias.• Management of Hyper (Dys)lipidemias.• Antidyslipidemic drugs.• Combination therapy.• Antioxidants and other non pharmacological

measures.• Duty of a primary care physician.

Major Plasma lipids are• Cholesterol-Free & esterified.• Phospholipids.• Triglycerides-TGL.• Free fatty acids FFA.

• Lipids-water insoluble.• Carrier-Protein.• Lipid+ protein complex = Lipoprotein.• The protein moiety of a lipoprotein is called

apolipoprotein.• Apolipoprotein+ TG+Ch+Phospholipids.

Plasma lipoproteins-Classification• Chylomicrons(CM).• Very Low Density Lipoprotein (VLDL).• Low Density Lipoprotein (LDL).• Intermediate Density Lipoprotein (IDL).• High Density Lipoprotein (HDL).

Cholesterol pathway• Exogenous-Diet• Endogenous-Liver.

KEY WORDS• LPL-Lipoprotein lipase.• CM & VLDL contains chiefly TGL.• LDL contains Cholesterol.

IntestineDIET

TGL-Ch.

Capillary ET-LPL

CM

CM

CM-RFFA

VLDL

IDL

LDL

LDL-Recep

MacrophagesExtra

hep tis

Risk Factors• Total Cholesterol >

220mg/ 100ml.• Plasma LDL > 150mg%.• Plasma TGL >

150mg/100ml.• Plasma HDL< 35mg%.

Dyslipidemias• Primary- Familial

Hypercholesterolemia.• Familial Combined

Hyperlipidemia.• Secondary-CRF, DM,

Hypothyroidism…..

Treatment strategies• Life style modification.• Diet.• Restrict intake of saturated fat.• Regular exercise.• Obesity reduction.• Fish intake-oily sea fish.• Eg-Tuna & Mackarel.• Plenty of fruits & vegetebles.• Stop smoking & alcoholism.• TREAT THE UNDERLYING CAUSE.

HYPOLIPIDEMIC DRUGS• HMG CoA reductase inhibitors.• LPL activity increasers• Adiposo tissue lipolysis inhibitors(PPAR

alpha agonists).• Bile acid binding resins.• Antioxidants and others.

Pleomorphic effects of statins• Antiinflammatory• Rx of Osteoporosis• Plaque stabiliser• Inhibit platelet thrombus formation• Improvement of coronary endothelial

function

Drug MOA Uses Adverse effectsStatins HMG CoA reductase

Inhibition.Pleomorphic effectsOf statins???

Hyperlipidemias-alltypes.

HMG?↑↑↑ liver enzymes.C/I-Pregnancy,lactation,Children.

Niacin Lipolysis inhibition in adipose tissue.↓ FFA,↓TGL& ↓ LDL.↑HDL.↑ tPA ↓ pl.fibrinogen. Reverse ET dysfn.

Most potent antihyperlipidemicdrug to elevate HDL.FamilialHyperlipidemias.

Cutaneousflush,pruritus&warmth.IGT.Livertoxicity,nausea,abdominal pain.Gout.

Fibrates PPAR agonists.↑Genes coding expression of LPL.↓apoCII.↑HDL by ↑ apo AI and apoAII.

Hyper TGL emias.Types III, IV & V.

LMG?CI-Severe liver,GB & renal disease.

Bile-acid binding resins

Bind bile acids(-vely) in SI.↑↑Excretion in feces.>>Cholesterol-bile acids.LDL-receptor upregulation.

Types IIa/ IIbHyp.lip.Along with Niacin.

GI(MC),ADEK absorption inhibitor.DI-↓↓ OBA of co administered drugs.

EzetimibeT ½ 22 hrs.

SI-absorption inhibitor.molecular target as the Niemann-Pick C1-like

Hypercholesterolemia

CI-Hepatic insufficiency.

My dream is to see you practice as an efficient primary care physician.

Type of Drug Effect on LDL Effect on HDL Effect on Triacylglycerols

HMG CoA reductaseinhibitors (statins)

↓↓↓↓ ↑↑ ↓↓

Fibrates ↓ ↑↑↑ ↓↓↓↓

Niacin ↓↓ ↑↑↑↑ ↓↓↓

Bile acid sequestrants ↓↓↓ ↑ Minimal

Cholesterol absorptioninhibitor

↓ ↑ ↓