Antihyperlipidemic.pdf

Introduction
Classification
Structure and MOA of drugs

1. Antihyperlipidemicdrugs
Dr. Jasmine Chaudhary
Associate Professor
MMCP

2. Introduction
Drugsusedtotreathyperlipidemia.
Alsoknownaslipidloweringdrugsorhypolipidemic.
Hyperlipidemiaisanincreaseinlipidswhichareagroupoffatsorfat
likesubstancesintheblood(duetoabnormalityinlipidmetabolism.
Cholesterolandthetriglyceridesaretwolipidsintheblood.Elevationof
oneorbothoftheselipidsisseeninhyperlipidemia.Soaccordingly
classifiedas
•Hyperlipoproteinemia(Increasedconcentrationsoflipoproteins)/
•Hypercholesterolemic(highconcentrationofcholesterol)/
•Hypertriglyceridemia(highconcentrationoftriglyceride)

3. Serumcholesterollevelsabove240mg/dLandtriglyceride
levelsabove150mg/dLareassociatedwithatherosclerosis.
Atherosclerosisisadisorderinwhichlipiddepositsaccumulate
ontheliningofbloodvessels,eventuallyproducing
degenerativechangesandobstructionofbloodflow.
Atherosclerosisisconsideredtobeamajorcontributorinthe
developmentofheartdisease.

4. Lipidsarewaterinsolublewhereasbloodandotherbodyfluids
arewaterysotheyneedaspecialtransportwhichiscarried
throughproteinandthiscomplexiscalledlipoproteinandthe
proteinmoietyofalipoproteiniscalledapolipoproteinwhich
allowfatstomovethroughthewaterinsideandoutsidecells.

5. Therearedifferenttypesoflipoproteinswhichdiffer
fromeachotherw.r.ttosize,densityandrelative
proportionoftriglyceridesandcholesterol
Chylomicrons(CM).
•VeryLowDensityLipoprotein(VLDL).
•LowDensityLipoprotein(LDL).
•IntermediateDensityLipoprotein(IDL).
•HighDensityLipoprotein(HDL)

6. HDLstandsforhigh-densitylipoproteins.Itiscalledthe
"good"cholesterolbecauseitcarriescholesterolfrom
otherpartsofyourbodybacktoliver.Liverthen
removesthecholesterolfrombody.
LDLstandsforlow-densitylipoproteins.Itiscalledthe
"bad"cholesterolbecauseahighLDLlevelleadstoa
buildupofcholesterolinarteries.

7. Causes
•Lifestylehabits(notexercising,andsmoking)
•Obesity,diabetes,kidneydisease,pregnancy,andan
underactivethyroidgland.
•Inherithyperlipidemia

8. Classification of
AntihyperlipidemicDrugs
•HMG-CoA-reductaseInhibitor: e.g. Lovastatin, Simvastatin,
Pravastatin
•Fibricacid derivatives: e.g. Clofibrate, Fenofibrate, Ciprofibrate,
Benzafibrate, Gemfibrozil
•Bile-acid sequestrants: e.g. Cholestyramine, Colestipol
•Inhibition of LDL oxidation: e.g. Probucol
•Cholestrolabsorption inhibitor: Ezetimibe
•Miscellaneous Agents: e.g. Nicotinic acid, Neomycin, β-Sitosterol,
Acipimox, Metformin, Dextrothyroxine.

9. HMG CoA-reductaseInhibitors:
Most effective and best tolerated drugs
Thesedrugsbringaboutspecific,reversibleandcompetitive
blockageofHMG-CoAreductase(3-Hydroxy-3-methyl-glutaryl-
CoAreductase),theenzymethatcatalyzestheconversionofHMG-
CoAtomevanolate.Thisreactionistherate-determiningstepinthe
syntheticpathwayofcholesterolleadingtodecreasedhepatic
cholesterolsynthesis.
HMG-CoAreductase
HMG-CoA Mevalonicacid Cholesterol
There are two classes of statins:
•Natural Statins:Lovastatin, Compactin, Pravastatin, Simvastatin
•Synthetic Statins: Atorvastatin, Fluvastatin

10. Lovastatin
8-{2-[4-Hydroxy-6-oxo-oxan-2-yl]ethyl}-3,7-dimethyl-
hexahydronaphthalenyl-2-methylbutanoate

11. Lovastatin is aprodrug, an inactive lactone in its native
form. It is hydrolysed in vivo to the β-hydroxy acid open
ring form; which is the active form.
Adverse effects
Mild, transient GI disturbances
Rash
Headache
Myopathy (muscle pain)
Elevations in liver enzymes or liver disease

12. Fibricacid derivatives
•Fibratesare2-phenoxy-2-methylpropanoicacidderivatives.These
drugsstimulateβ-oxidationoffattyacidsinmitochondria.
ModeofAction
•DecreaseplasmaTGslevelsmorethancholesterollevels
•Fibrateslowerbloodtriglyceridelevelsbyreducingtheliver's
productionofVLDL(thetriglyceride-carryingparticlethatcirculates
intheblood)bystimulatingenzymelipaseandbyspeedingupthe
removalofTGsfromtheblood.
•FibratesalsoaremodestlyeffectiveinincreasingbloodHDL
cholesterol;however,fibratesarenoteffectiveinloweringLDL
cholesterol.
e.g:Clofibrate,Fenofibrate,Gemfibrozil

13. Adverse effects
•Abdominal discomfort, diarrhea, nausea
•Blurred vision, headache
•Increased risk of gallstones
•Malignancy
Ethyl-2-(4-chlorophenoxy)-2-methyl propanoate

14. Bile acid Sequesterents
AlsocalledBileacid–bindingresinsandion-exchangeresins.E.g.
cholestyramineandcolestipol.
Bileacidsarethemetabolicend-productsofcholesterolwhichare
releasedintotheintestineandaidindissolutionandabsorptionof
lipids.Majorfraction(about98%)ofbileacidsreleasedintothegut
isreabsorbedthroughenterohepaticcirculationandsuppressesthe
microsomalhydroxylaseenzymeinvolvedintheconversionof
cholesteroltothebileacids.Thusduetoenterohepaticreabsorption
ofthebileacidsfurthercholesterolmetabolismissuppressed.

15. Cholestyramineandcolestipolaretheexamplesofbileacid-bindingresins
whichformasortofnon-absorbablecomplexwithbileacidsduetothe
presenceofquaternarynitrogen.Thusthesedrugspromotetheirelimination
fromthegutandinhibittheirreabsorptionintothecirculation.
ADR:
•Constipation
•Heartburn,nausea,bloating
[4-[3-(4-ethylphenyl)butyl]phenyl]-trimethylazanium

16. Cholestipol
Side effects include: Gastrointestinal tractdisturbances

17. InhibitionofLDLoxidation:
Theantioxidanteffectsofagentsofthisgroupinhibittheoxidationof
LDL,thereby,preventingitsuptakebymacrophages.Thismayhelp
preventdevelopmentofatherosclerosis.E.gProbucol
Cholestrolabsorptioninhibitor:Ezetimibe
Itisadrugthatlowersplasmacholesterollevelsbydecreasing
cholesterolabsorptionintheintestine.

18. Miscellaneous
Niacin(AwatersolublevitaminoftheBfamily)
•Increasesactivityoflipase,whichbreaksdownlipids
•Reducesthemetabolismofcholesterolandtriglycerides
Adverseeffects
•Flushing(duetohistaminerelease)
•Pruritus
•GIdistress

19. β –Sitotsterol: It is a plant sterol.
Due to the structural similarity with cholesterol, this agent
impedestheabsorptionofdietarycholesterolandproducesa
moderatereductionincholesterollevel.Itslowefficacyand
highcostdecreaseitspopularityaslipidloweringagent.