Lec 1 Drugs Used in Hyperlipidemia Final

7/31/2019 Lec 1 Drugs Used in Hyperlipidemia Final

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Dr Heethal Jaiprakash 1


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Intestinal

cell Extra hepatic

tissue

Metabolism of Chylomicron

B48Intestine


Liver

B48

Adipose tissue


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Extra hepatictissue

Functions of VLDL, LDL & HDL

VLDL

LDL

B100LDL

HDL

LACT

v


LiverAdipose tissue

Muscle

E, C,

B100 IDL HDL

A1

LCAT

HDL


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Type I ( Familial Hyperchylomicronemia)

Deficiency of lipoprotein lipase or of normal apolipoprotein CII

Low fat diet. No drug therapy

Type IIA(Familial Hypercholesterolemia)

Defects in synthesis or processing of LDL receptor

Diet , cholestyramine, niacin or statins

Type IIB( Familial combined Hyperlipidemia)

over production of VLDL by the liver

Diet , drugs similar to that for Type II A

VLDL

chylo

micro

LDL

LDL


Type III( Familial dysbetalipoproteinemia)Due to over production or underutilisation of IDL

Diet , drugs like niacin, fenofibrate or statins

Type IV(Familial Hypertriglyceridemia)

Over production and/or decreased removal of VDL and TGDiet , drugs like niacin and fenofibrate

Type V( Familial mixed Hypertriglyceridemia)

Increased production or decreased clearance of VLDL and chylo

Diet , drugs like niacin, fenofibrate or statins

IDL

VLDL

chylo

microVLDL


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Classification of

Hyperlipoproteinaemias

Single gene defect- monogenic or

genetic Mutliple genetic, dietary ,

physical activity- polygenic or

multifactorial

Primary


Diabetes, myxodema, nephrotic

syndrome, chronic alcoholism,

drugsSecondary


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Classification of Hypolipidemic drugs

Atorvastatin, Simvastatin, LevostatinHMG- Co A

Reductaseinhibitors


Fenofibrate, GemfibrozilFibrates

Nicotinic acid

( Niacin)


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Classification of Hypolipidemic drugs-

Contd

Cholestyramine, ColestipolBile acidSequestrants


EzetimibeCholestrol

absorptioninhibitors


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HMG-CoA Reductase inhibitorsThey primarily reduce the LDL levelsMost efficacious and best tolerated

Mechanism:

1. Inhibition of HMG Co A reductase


.

Pharmacokinetics:

Administered orally

Biotransformed

Excreted primarily through bile and faeces


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HMG CoA Reductase

Statins



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Adverse effects:

Liver- abnormality in liver functions

Muscle- Myopathy, Rhabdomyolysis

Contraindications Pregnancy and lactation


Uses:All types of hyperlipidemias- less with familial

hypercholesterolemia


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Fi rates i ric aci erivatives

MechanismActivates PPAR

Lipoprotein lipase synthesis


Degradation of Triglycerides

Lowering of circulating TGs


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They primarily decrease the triglyceride levels

Also increase HDL levelsPharmacokinetics:

Absorbed orally

Biotransformed

Excreted in urine

Adverse effects:


LithiasisMyositis

Contraindications- severe liver or renal

dysfunctionUses:

Treatment of Type III, Type IV, V


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Niacin

It is a B group vitamin

Higher doses reduces plasma lipids

Most effective drug in increasing HDL-CH


Pharmacokinetics:Administered orally

Excreted in urine


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Triacylglycerol

Fatty Acids

NiacinNiacin

Mechanism of action of niacin

Adipose tissue is the storage site offats

Fats in the form of triacylglycerol is

converted to Fatty acids by Lipolytic

enzymes

These fatty acids are transported tothe liver in the blood stream where

they are converted back to

triacylglycerol


Fatty Acids

Triacylglycerol

VLDL

These TGs are packed in VLDL

lipoproteins and are released into to

the circulation becoming a potential

threat

Niacin inhibits the process of

lipolysis in the adipose tissue.

This eventually reduces the

amount of Fatty acids entering the

circulation.


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Adverse effects:

Intense cutaneous pruritis- due to

prostaglandin release

Nausea, abdominal painHyperuricemia


u

Hepatotoxicity

Uses :

Type III,IV,V


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Bile acid binding resins

Bind to negatively chargedbile acids and bile salts in

the Small intestine

Resin+ bile acid complex

Decreased total plasmacholesterol

Activates Increased hepaticuptake of cholesterol containingLDL particles-fall in plasma LDL


Excreted in feaces

Prevent enterohepaticcirculation

Decreased intracellularcholesterol concentration

Increased conversion ofcholesterol to bile acids


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Pharmacokinetics :

Taken orallyTotally excreted in faeces

Adverse effects:

-


Impaired absorption- Vitamin A,D,E,K

Uses:

Type IIa and IIb hyperlipidemias


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Cholesterol absorption inhibitors:

Inhibits intestinal absorption of dietary and biliary

cholesterol in small intestine


Decreased delivery of intestinal cholesterol to theliver

Decreased hepatic cholesterol stores and increased

clearance from the blood


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Ezetimibe is generally Combined with statins

Pharmacokinetics :

Biotransformed

Undergoes enterohepatic circulation


Excreted in faeces

Adverse effects:

Reversible hepatic dysfunction

Documents

Lec 1 Drugs Used in Hyperlipidemia Final