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Lipid Lowering Drugs. Pharma

Pharmacology

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5 views35 pages

Lipid Lowering Drugs. Pharma

Pharmacology

Uploaded by

Saniya00
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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 Over View of Cholesterol

 Introduction to dyslipidemia
 Treatment Goals and Strategies
 Classification of Lipid Lowering Drugs
 Pharmacokinetics and dynamics of Statin
 Pharmacokinetics and dynamics of Statin
 Pharmacokinetics and dynamics of Niacin
 Pharmacokinetics and dynamics of Fibrates
 Cholesterol is carried in combination with
specific proteins in the plasma in the form of
lipoproteins. These are
 LDL-C (Bad cholesterol) <150mg/dl
 VLDL-C
 HDL-C (Good Cholesterol)>36mg/dl
 Triglyceride <200mg/dl
 Chylomicrons
 Type I (Familial hyper chylomironemia).
cause is the deficiency of lipoprotein lipase ,TGs are
increased,
Treatment: No drug except low fat.
 Type IIA (Familial hypercholesterolemia).
Cause is defect in LDL receptor synthesis, ↑ LDL-
C but normal TGs, treated by Cholestyramine
and Niacin/statins
 Type IIB(Familial combined
Hyperlipidemia).
Cause is over production of VLDL by the
liver, ↑VLDL and TGs treatment same
as IIA.
 Type III (Familial dys beta lipoproteinemia)
Cause is ↑ production/ ↓ utilization of IDL-C due
to mutation of apolipoprotein E so ↑ IDL-C and
TGs. Treatment is
Niacin
Fenofibrates
statins.
 Type IV(Familial hypertriglyceridemia)
Cause is ↑ production/↓ removal of VLDL and
TGs resulting in ↑VLDL and TGs with normal
or ↓LDL
 Type V(Familial mixed hypertriglyceridemia).
Cause is ↑ production/↓ removal of VLDL and
Chylomicron, ↑VLDL,TGs and chylomicrons.
 To reduce the LDL-Cholesterol levels
 To increase the HDL-Cholesterol levels
 Diet low in saturated fats
 Exercise
 Weight reduction
 Proper selection of drugs
 Drug combination if required
 STATINS: (HMG-Co-A Reductase Inhibitors)
Simvastatin , Atorvastatin
 NIACIN: (Vitamin B3, Nicotinic Acid )
 FIBRATES: Gimfebrozil , Fenofibrate
 BILE ACID SEQUESTRANTS: Cholestyramine
 CHOLESTEROL ABSORPTION INHIBITORS:
Ezetimibe, Orlistat
 OMEGA-3-FATTY ACIDS:
Docosahexaenoic Acid, Eicosapentaenoic Acid
 Atorvastatin
 Simvastatin
 Rovastatin
 Absorption: 35%-85% absorbed
 Distribution:
 Metabolism: Simvastatin and Rovastatin are
prodrugs all other statins are active drugs,
metabolized by liver
 Half-Life:
 Excretion: Excreted mainly in bile and feces.
 Mechanism of Action:
 They competitively inhibit HMG-Co A
Reductase a rate limiting enzyme in
Cholesterol synthesis that results in ↓LDL-C,
VLDL-C,TGs, ↑LDL Receptors
 Hyperlipidemia
 Atherosclerosis
 Cardiovascular disease associated with
raised lipids
 Hyperlipidemia associated with diabetes
 Statins

 Fibrates

 Niacin
FIBRIC ACID DERIVATIVES (FIBRATES)
 Bezafibrate
 Ciprofibrate
 Fenofibrate
 Gemfibrozil
 Derivatives of Fibric Acid

 Lowers serum TG

 Increase HDL levels.


Agonists at PPAR (peroxisome proliferator-
activated receptor) →
expression of genes responsible for increased
activity of plasma lipoprotein lipase enzyme
→
hydrolysis of VLDL and chylomicrons→
↓serum TGs.
↑ clearance of LDL by liver
↑ HDL.
Secretion
Not excretion
 Gemfibrozil & Fenofibrate are completely
absorbed after oral administration.
 Widely distributed
 Extensively bound to plasma Albumin proteins
 Fenofibrate is a Prodrug which is converted to
the active drug i.e. Fenofibric acid.
 Both drugs undergo extensive Biotransformation.

 Excreted in the urine as glucuronide conjugates


❑ Hypertriglyceridemia
(The most effective in reduction TGs)

❑ Dysbetalipoproteinemia(IDL Accumulation)

❑ Combined Hyperlipidemia (If statins are contraindicated)


❑ Mild Gastrointestinal Disturbance.

❑ Formation of Gallstones (Lithiasis)

❑ Myositis(at high doses)

❑ Myopathy & Rhabdomyolysis reported in


patients taking Gemfibrozil and statin
together.
❑ Should not be given with Simvastatin

Fibrates should not be used in patients with

❑ Severe hepatic dysfunction

❑ Renal dysfunction

❑ Preexisting gallbladder diseases.


 It has low effect on LDL-C (10% to 20%)

 But most effective agent in increasing HDL-C.

 It also lowers the TG.(20 to 35%)

 Mostly these drugs are used in combination


with statins.
 Mostly combine with Lovastatin.
 It works just at small doses in grams about 1.5 to 3
grams/day.
 At very small doses it strongly inhibit lipolysis in adipose
tissue.
 Inhibition of lipolysis production of free fatty acid.

Note-(in the liver free fatty acids as a major precursor for TG synthesis)
Reduced production of triglyceride in Liver
Reduction in Hepatic VLDL production

Which in turn reduces LDL-C


 Administered orally
 Niacin in body is converted to Nicotinamide.
 Which is converted in Nicotinamide adenine
dinucleotide(NAD)
 Nicotinamide & Other metabolites are excreted
in the urine.

(Nicotinamide alone can not reduce plasma lipid levels)


 It lowers plasma levels of Cholesterol & TG.

 Familial Hyperlipidemia.( VLDL LDL)

 Severe Hypercholesterolemias. ( LDL)

 But this drug alone can not produce as better


effect.
 Hence combination therapy is needed.
ADVERSE EFFECTS
severe itching of the skin
3-Some patients may produce Nausea & Vomiting.

4-Hyperuricemia (niacin (–) tubular secretion of Uric Acid)

5-Gout

6-Hepatotoxicity
Hepatic Failure
Gout

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