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Academic Guideline for MBBS Students Seeking FCPS, MD, MS and Other PG Admission

Lipid Lowering Agents

Hyperlipidemia:

Hypelipidemias are a complex group of diseases that can be designated either primary or secondary depending on their causes.

Primary: Result from single inherited gene defect or combination of genetic and environmental factor.

Secondary: Result of more generalized metabolic disorder e.g. DM, excessive alcohol intake, hypothyroidism or primary billiary cirrhosis.

 

Drugs used in the treatment of elevated serum lipids generally targeted to –

  • Decreased production of a lipoprotein by the tissues
  • Increased catabolism of a lipoprotein in the plasma
  • Increased removal as cholesterol and triglycerides from the body

 

Lipid such as cholesterol and triglycerides are transported in the plasma as lipoprotein of which there are 4 classes:

I. Chylomicrons: Transport triglycerides and cholesterol from the GIT to the tissues, where they are split by lipoprotein lipase, to FFA and then they are taken up.

 

Chylomicron remnants are taken up in the liver where cholesterol is oxidized to bile acids or released into –

 

II. Very low density lipoprotein (VLDL) : which transport cholesterol and newly synthesized triglyceride to the tissue.

III. Low density lipoprotein (LDL): with a large component of cholesterol some of which is taken up by the tissue and some by the liver, by endocytosis via specific LDL receptors.

 

IV. High density lipoprotein (HDL): which absorbed and derived from cell breakdown in tissues (including arteries) and transfer to VLDL & LDL.

 

WHO classification of Hyperlipoproteinaemia:

Type Lipoprotein elevated Cholesterol ( C ) TG Atherosclerosis risk Drug (Rx)
I Chylomicrons + +++ NE None
IIa LDL ++ NE High HMG-CoA reductase
IIb LDL + VLDL ++ ++ High Fibrates, HMG-CoA
III β VLDL ++ ++ Moderate Fibrates
IV VLDL + ++ Moderate Fibrates (+ Fisnoil)
V Chylomicron + VLDL + ++ NE None (+ Fisnoil)

 

Classification of Lipid lowering agent

1. HMG-CoA reductase inhibitors (3-hydroxy-3-methylglutaryl-coenzyme A)
  • Simvastatin
  • Pravastatin
  • Lovastatin
  • Atorvastatin
  • Fluvastatin
2. The fibrates (activator of plasma lipoprotein lipase)
  • Gemfibrozil
  • Bezafibrate
  • Fenofibrate
  • Clofibrate
  • Ciprofibrate
3. Bile acid binding resins
  • Cholestyramine
  • Colestipol
  • Colesevelam
4. Inhibition of lipolysis
  • Nicotinic acid
  • Acipimase derivatives of nicotinic acid
5. Increased non receptor mediated cholesterol clearance
  • Probucol
6. Others: Antiatherosclerotic drugs:
  • Aspirin
  • Ca++ channel blockers (nifedipine, Nicardipine)
  • β –blocker only Carvedilol
  • ACE inhibitors Captopril
7. Natural antiatherosclerotic agents:
  • Oestrogen in case of female
  • Dietary antioxidant
  • Tea (dietary flavinoid) – only in green tea
  • Physical exercise
8. Inhibitors of intestinal sterol absorption
  • Ezetimibe

 

SIMVASTATIN

It is a prodrug which enzymatically hydrolyzed to its active form. It is the drug of 1st choice.

 

Mechanism of action:

It acts by competitively inhibition of HMG-CoA reductase and by increasing LDL receptors which increases removal of LDL from the blood and thereby lowering LDL levels. This drug is highly effective in reducing total and LDL cholesterol level.

 

Dose: 5 -10 mg once daily in the evening

 

Clinical use:

Effective in lowering plasma cholesterol level in all types of hyperlipidemias

 

Side effects:

  • Biochemical abnormality in liver function and serum transaminase levels.
  • Muscle – myopathy and rhabdomyolysis
  • Renal insufficiency may occur, so plasma creatinine kinase level should be measured
  • Paresthesia

Contraindications:

  • Pregnancy
  • Nursing mother
  • Children

 

Drug interaction:

Drug interaction occurs with coumarin derivatives.

 

Secondary causes of hypelipoproteinaemia:        

Hypertriglyceridemia

Hypercholesterolemia

Diabetes mellitus

Alcohol ingestion

Severe nephrosis

Estrogen

Uremia

Corticosteroid excess

Hypothyroidism

Glycogen storage disease

Hypopituitarism

Acromegaly

Immunoglobulin lipoprotein complex disorder

 

 

Hypothyroidism

Early nephrosis

Resolving lipemia

Immunoglobulin lipoprotein complex disorder

Anorexia nervosa

Cholestasis

Hypopituitarism

Corticosteroid excess

Ref: Katzung

 

Lipid lowering drugs: Summary of actions

Drugs Major mechanisms LDL HDL Triglycerides
HMG-CoA reductase inhibitor Competitive inhibition of cholesterol biosynthetic enzyme induces LDL expression & enhanced LDL clearance ↓↓
Fibrates Enhance VLDL catabolism (Apo C) and increase HDL cholesterol content (Apo Al/II)
Bile acid sequestrant resins Increase intestinal clearance of cholesterol

Others

Nicotinic acid (niacin) Decrease fatty acid flux from adipose tissue
Probucol Decrease VLDL production

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