The Antihyperlipidemic The Antihyperlipidemic MedicationsMedications

Classifications of Classifications of LipoproteinsLipoproteins–ChylomicronsChylomicrons

Formed in the mucosal cells Formed in the mucosal cells of the gutof the gut

Protein coated dietary lipidsProtein coated dietary lipids

Carried in the blood to fat Carried in the blood to fat depots and transported depots and transported across the vasculature with across the vasculature with the help of Capillary-Bound the help of Capillary-Bound LPLLPL

Chylomicron remnants goes Chylomicron remnants goes back to the liver to be used back to the liver to be used to synthesize TGsto synthesize TGs

Very Low Density Very Low Density Lipoproteins (VLDL)Lipoproteins (VLDL)–Triglyceride rich particleTriglyceride rich particle–Made in the liverMade in the liver–VLDL is the transport form VLDL is the transport form for TGs made in the liver for TGs made in the liver going to the peripherygoing to the periphery

Cholesterol containing Cholesterol containing particleparticle

LPL transports TGs into LPL transports TGs into fat depotsfat depots

Remainder is a Remainder is a cholesterol rich particle cholesterol rich particle now called LDLnow called LDL

Low Density Lipoprotein Low Density Lipoprotein (LDL)(LDL)

Contains the major portion Contains the major portion of the plasma cholesterolof the plasma cholesterol

Associated with a higher risk Associated with a higher risk for CADfor CAD

In the liver LDL is In the liver LDL is recycled for its recycled for its cholesterol contentcholesterol content

LDL in the liver acts to LDL in the liver acts to regulate liver uptake of regulate liver uptake of additional LDLadditional LDL

High Density Lipoprotein (HDL)High Density Lipoprotein (HDL)These particles scavenge These particles scavenge cholesterol from the peripheral cholesterol from the peripheral vesselsvessels

Carries cholesterol back to the liver Carries cholesterol back to the liver to be used for steroid synthesis, to be used for steroid synthesis, hormone synthesis or the making of hormone synthesis or the making of bile saltsbile salts

Types of Types of hyperlipoproteinemiashyperlipoproteinemias

Type I - Idiopathic Familial Type I - Idiopathic Familial VarietyVariety–Decreased VLDL, LDL, & HDLDecreased VLDL, LDL, & HDL–Elevated TGs, Chylomicrons & Elevated TGs, Chylomicrons & cholesterolcholesterol

Type IIa - Essential Familial Type IIa - Essential Familial VarietyVariety

Elevated LDL, TGs & Elevated LDL, TGs & CholesterolCholesterol

Type IIb - Familial Type IIb - Familial Combined VarietyCombined Variety

Elevated LDL & VLDLElevated LDL & VLDL

Type IV - Endogenous Type IV - Endogenous HypertriglyceridemiaHypertriglyceridemia

Elevated VLDL, TGs, & Elevated VLDL, TGs, & CholesterolCholesterol

Early CADEarly CADPositive family history for Positive family history for an MIan MI

The Antihyperlipidemic The Antihyperlipidemic DrugsDrugs

HMG-CoA Reductase HMG-CoA Reductase InhibitorsInhibitors

The Fibric AcidsThe Fibric Acids Bile Acid Binding ResinsBile Acid Binding Resins Nicotinic AcidNicotinic Acid

HMG-CoA Reductase HMG-CoA Reductase InhibitorsInhibitors

Lovastatin (Mevacor)Lovastatin (Mevacor) Simvastatin (Zocor)Simvastatin (Zocor) Mevastatin (Compactin)Mevastatin (Compactin) PravastatinPravastatin

Mechanism Of ActionMechanism Of Action

HMG-CoA Reductase HMG-CoA Reductase InhibitorsInhibitors

Blocks the synthesis of Blocks the synthesis of cholesterol in the liver by cholesterol in the liver by inhibiting the rate limiting inhibiting the rate limiting enzyme called HMG-CoA enzyme called HMG-CoA ReductaseReductase

There is a compensatory There is a compensatory drop in plasma LDL due drop in plasma LDL due to the up-regulation of to the up-regulation of the LDL receptor and the LDL receptor and enhanced clearance of enhanced clearance of LDL from the plasmaLDL from the plasma

These medications may lower These medications may lower the cholesterol content of the the cholesterol content of the VLDL particle such that when VLDL particle such that when VLDL disposes of its TGs VLDL disposes of its TGs becoming LDL, there is an becoming LDL, there is an enhanced attraction for the enhanced attraction for the cholesterol poor LDL particle and cholesterol poor LDL particle and its receptor - greater LDL its receptor - greater LDL clearanceclearance

Adverse Side EffectsAdverse Side Effects

Flatulence & DiarrheaFlatulence & Diarrhea Dyspepsia (Indigestion)Dyspepsia (Indigestion) HeadachesHeadaches Elevations of the liver Elevations of the liver

enzymes - CPK, LDH, and enzymes - CPK, LDH, and AST - due to hepatotoxicityAST - due to hepatotoxicity

Medical UsesMedical Uses

To treat To treat hypercholesterolemia hypercholesterolemia (>250 mg/dl)(>250 mg/dl)

Patients with elevated Patients with elevated LDL, VLDL & TGsLDL, VLDL & TGs

The Fibric AcidsThe Fibric Acids

Gemfibrozil (Lopid)Gemfibrozil (Lopid) Clofibrate (Atromide-S)Clofibrate (Atromide-S)

Mechanisms of ActionMechanisms of Action

Decrease TG synthesisDecrease TG synthesis Decrease liver Decrease liver

lipoprotein synthesislipoprotein synthesis Decrease the excretion Decrease the excretion

of lipoproteins from the of lipoproteins from the liver, especially VLDLliver, especially VLDL

Decrease the synthesis of Decrease the synthesis of cholesterolcholesterol

Increase the production of Increase the production of sterolssterols

Increases the blood levels Increases the blood levels of HDLof HDL

Medical UsesMedical Uses

Lower cholesterolLower cholesterol Lower serum triglyceridesLower serum triglycerides Lower VLDL levelsLower VLDL levels Lower LDL levelsLower LDL levels These drugs are These drugs are

cardioprotectivecardioprotective

Adverse Side EffectsAdverse Side Effects

GI distress - diarrhea, GI distress - diarrhea, nausea, vomitingnausea, vomiting

Alopecia - loss of hairAlopecia - loss of hair lower testosterone levels lower testosterone levels

and impotenceand impotence

Gall stone formationGall stone formation Hepatotoxic - liver Hepatotoxic - liver

enzymes - LDH, CPK, & enzymes - LDH, CPK, & ASTAST

Bile Acid Binding Bile Acid Binding ResinsResins

Cholestyramine Cholestyramine (Questran)(Questran)

Colestipol (Colestid)Colestipol (Colestid)

Mechanism of ActionMechanism of Action

Bind bile salts in the gutBind bile salts in the gut Bile Acid Binding Resins are Bile Acid Binding Resins are

not absorbed across the not absorbed across the gut into the blood - bile and gut into the blood - bile and cholesterol are irreversibly cholesterol are irreversibly bound in the gut and bound in the gut and disposed of in the fecesdisposed of in the feces

The net effect - causes the The net effect - causes the liver to scavenge more liver to scavenge more cholesterol from the body to cholesterol from the body to make additional bile saltsmake additional bile salts

Liver up-regulates the LDL Liver up-regulates the LDL receptors clearing more LDL receptors clearing more LDL from the bloodfrom the blood

Adverse Side EffectsAdverse Side Effects

Nausea, VomitingNausea, Vomiting IndigestionIndigestion FlatulenceFlatulence ConstipationConstipation Binds to other Binds to other

medicationsmedications

Nicotinic AcidNicotinic Acid

Mechanism of ActionMechanism of ActionInhibits the liver from Inhibits the liver from secreting VLDLsecreting VLDL

Reduces the blood levels Reduces the blood levels of LDLof LDL

Inhibits the destruction Inhibits the destruction of HDL thus allowing a of HDL thus allowing a permissive rise in HDLpermissive rise in HDL

Niacin increases the Niacin increases the excretion of sterols in excretion of sterols in the feces thus using up the feces thus using up more cholesterolmore cholesterol

Adverse Side EffectsAdverse Side Effects

FlushingFlushing VomitingVomiting NauseaNausea DyspepsiaDyspepsia FlatulenceFlatulence

Medical UsesMedical Uses

To reduce VLDLTo reduce VLDL To reduce LDLTo reduce LDL To To increaseincrease HDL HDL Given to most Given to most

hyperlipidemicshyperlipidemics