Antihyperlipidemic agents are drugs used to lower high levels of lipids (fats) such as cholesterol and triglycerides in the blood. These drugs work either by reducing the production of lipoproteins or by increasing their removal from the bloodstream. The main goal of therapy is to reduce LDL (“bad cholesterol”) and improve HDL (“good cholesterol”) levels.
What Is Hyperlipidemia?
Hyperlipidemia, also called hyperlipoproteinemia, is a condition where blood levels of cholesterol, triglycerides, or both are elevated. This imbalance in lipid levels is a major risk factor for atherosclerosis, a disease where fatty plaques form inside blood vessels, leading to heart attack and stroke.
- LDL & VLDL – lipoproteins that promote plaque formation (atherogenic)
- HDL – protective lipoprotein that carries cholesterol away from tissues
- Normal cutoffs: Cholesterol > 240 mg/dL, Triglycerides > 150 mg/dL
Classification of Antihyperlipidemic Agents
There are five major groups of lipid-lowering drugs:
- HMG CoA Reductase Inhibitors (Statins)
- Fibrates / Fibric Acid Derivatives
- Bile Acid Sequestrants
- Inhibitors of Lipolysis (Nicotinic Acid)
- Cholesterol Absorption Inhibitors (Ezetimibe)
1. HMG CoA Reductase Inhibitors (Statins)
Statins are the most widely used antihyperlipidemic drugs. They are fungal-derived products that competitively inhibit the enzyme HMG-CoA reductase—the rate-limiting step in cholesterol synthesis in the liver.
Mechanism of Action
- Statins block HMG-CoA reductase → decrease cholesterol synthesis
- Reduced cholesterol levels stimulate liver cells to produce more LDL receptors
- More LDL receptors increase clearance of LDL from the blood
- Overall effect: ↓ LDL, ↓ triglycerides, ↑ HDL
Examples
- Atorvastatin
- Simvastatin
- Rosuvastatin
- Lovastatin
- Pravastatin
Therapeutic Uses
Effective in most hyperlipidemias except familial Type-IIA (where LDL receptors are absent).
Adverse Effects
- Increased liver enzymes (monitor regularly)
- Myopathy and muscle pain
- Reduced production of Coenzyme Q10 leading to fatigue
2. Fibrates (Fibric Acid Derivatives)
These drugs mainly lower triglycerides by activating the enzyme lipoprotein lipase.
Examples
- Fenofibrate
- Gemfibrozil
- Clofibrate
Mechanism
- Increase breakdown of VLDL and triglycerides
- Increase HDL production
3. Bile Acid Sequestrants
These agents bind bile acids in the intestine and prevent their reabsorption. The liver then uses more cholesterol to make new bile acids, thereby reducing blood cholesterol levels.
Examples
- Cholestyramine
- Colesevelam
- Colestipol
Features
- Non-absorbable resins
- Useful in combination with statins
4. Inhibitors of Lipolysis — Nicotinic Acid (Niacin)
Nicotinic acid reduces breakdown of fats in adipose tissues, decreasing free fatty acids delivered to the liver.
Effects
- ↓ VLDL synthesis
- ↓ LDL
- ↑ HDL (one of the best agents for raising HDL)
5. Cholesterol Absorption Inhibitors
These drugs block intestinal absorption of dietary cholesterol.
Example
- Ezetimibe
Mechanism
- Inhibits cholesterol transport protein (NPC1L1) in small intestine
- Reduces total cholesterol and LDL
Summary Table
| Class | Main Action | Examples |
|---|---|---|
| Statins | Block cholesterol synthesis | Atorvastatin, Simvastatin |
| Fibrates | Reduce triglycerides | Fenofibrate, Gemfibrozil |
| Bile Acid Sequestrants | Bind bile acids | Cholestyramine |
| Niacin | Reduce lipolysis and VLDL | Nicotinic acid |
| Absorption Inhibitors | Block cholesterol absorption | Ezetimibe |
Detailed Notes:
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