hypolipidemic drugs - srm · pdf filehypolipidemic drugs • hmg coa reductase inhibitors....
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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).
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.
Type of Drug Effect on LDL Effect on HDL Effect on Triacylglycerols
HMG CoA reductaseinhibitors (statins)
↓↓↓↓ ↑↑ ↓↓
Fibrates ↓ ↑↑↑ ↓↓↓↓
Niacin ↓↓ ↑↑↑↑ ↓↓↓
Bile acid sequestrants ↓↓↓ ↑ Minimal
Cholesterol absorptioninhibitor
↓ ↑ ↓