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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
Dr Heethal Jaiprakash 3
Liver
B48
Adipose tissue
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Extra hepatictissue
Functions of VLDL, LDL & HDL
VLDL
LDL
B100LDL
HDL
LACT
v
Dr Heethal Jaiprakash 4
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
Dr Heethal Jaiprakash 6
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
Dr Heethal Jaiprakash 7
Diabetes, myxodema, nephrotic
syndrome, chronic alcoholism,
drugsSecondary
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Classification of Hypolipidemic drugs
Atorvastatin, Simvastatin, LevostatinHMG- Co A
Reductaseinhibitors
Dr Heethal Jaiprakash 8
Fenofibrate, GemfibrozilFibrates
Nicotinic acid
( Niacin)
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Classification of Hypolipidemic drugs-
Contd
Cholestyramine, ColestipolBile acidSequestrants
Dr Heethal Jaiprakash 9
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
Dr Heethal Jaiprakash 10
.
Pharmacokinetics:
Administered orally
Biotransformed
Excreted primarily through bile and faeces
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HMG CoA Reductase
Statins
Dr Heethal Jaiprakash 11
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Adverse effects:
Liver- abnormality in liver functions
Muscle- Myopathy, Rhabdomyolysis
Contraindications Pregnancy and lactation
Dr Heethal Jaiprakash 13
Uses:All types of hyperlipidemias- less with familial
hypercholesterolemia
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Fi rates i ric aci erivatives
MechanismActivates PPAR
Lipoprotein lipase synthesis
Dr Heethal Jaiprakash 14
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:
Dr Heethal Jaiprakash 16
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
Dr Heethal Jaiprakash 17
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
Dr Heethal Jaiprakash 18
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
Dr Heethal Jaiprakash 19
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
Dr Heethal Jaiprakash 20
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:
-
Dr Heethal Jaiprakash 22
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
Dr Heethal Jaiprakash 23
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
Dr Heethal Jaiprakash 24
Excreted in faeces
Adverse effects:
Reversible hepatic dysfunction
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