Introduction
Hyperlipidemia means abnormally high levels of lipids such as cholesterol and triglycerides in the blood. It is one of the major risk factors for atherosclerosis, coronary artery disease and stroke. The condition occurs due to faulty lipid metabolism, hereditary factors or lifestyle problems like obesity, lack of exercise and high-fat diet. Treatment involves diet modification and use of lipid-lowering medicines.
Plasma Lipids and Lipoproteins
Lipids such as cholesterol, triglycerides and phospholipids cannot travel freely in blood because blood is water-based. They need special carrier particles called lipoproteins. Each lipoprotein contains lipid plus a protein component called apolipoprotein.
Types of Lipoproteins
- Chylomicrons – carry dietary triglycerides.
- VLDL – carry triglycerides from liver to tissues.
- LDL – “bad cholesterol”; responsible for plaque formation.
- HDL – “good cholesterol”; removes cholesterol from blood.
High LDL and high triglycerides increase cardiovascular risk, while high HDL protects the heart.
Major Drug Classes Used in Hyperlipidemias
- HMG-CoA reductase inhibitors (Statins)
- Fibrates
- Bile acid sequestrants
- Cholesterol absorption inhibitor (Ezetimibe)
- Nicotinic acid (Niacin)
- LDL oxidation inhibitor (Probucol)
- Plant sterols (β-Sitosterol)
1. HMG-CoA Reductase Inhibitors (Statins)
Examples: Lovastatin, Simvastatin, Pravastatin, Atorvastatin, Fluvastatin
Statins block the enzyme HMG-CoA reductase, which is required for cholesterol synthesis in the liver. This causes the liver to pull more LDL out of the blood, lowering LDL levels significantly.
Main Benefits
- Strong reduction in LDL cholesterol
- Mild reduction in triglycerides
- Slight increase in HDL
- Decreased risk of heart attack and stroke
Side Effects
- Muscle pain or weakness
- Liver enzyme elevation
- Digestive discomfort
2. Fibrates
Examples: Gemfibrozil, Fenofibrate, Bezafibrate
Fibrates activate PPAR-α receptors, which increase fatty acid oxidation and reduce VLDL production. They strongly lower triglycerides and increase HDL levels.
Key Actions
- Lower triglycerides by reducing VLDL
- Increase HDL cholesterol
- Useful in mixed dyslipidemia and hypertriglyceridemia
Side Effects
- Dyspepsia
- Gallstones
- Muscle toxicity (higher when combined with statins)
3. Bile Acid Sequestrants
Examples: Cholestyramine, Colestipol, Colesevelam
These agents bind bile acids in the intestine and prevent their reabsorption. The liver then uses more cholesterol to make new bile acids, lowering blood LDL.
Uses
- Moderately lower LDL
- Safe for children and pregnancy (non-absorbed)
Side Effects
- Constipation
- Bloating
- Reduced absorption of fat-soluble vitamins (A, D, E, K)
4. Cholesterol Absorption Inhibitor
Example: Ezetimibe
Ezetimibe selectively blocks cholesterol absorption from the intestine. This reduces cholesterol delivery to the liver and increases LDL clearance from blood.
Advantages
- Useful in combination with statins
- Does not interfere with absorption of triglycerides or fat-soluble vitamins
Uses
- Elevated LDL cholesterol
- Familial hypercholesterolemia (with statins)
5. Nicotinic Acid (Niacin, Vitamin B3)
Niacin in high doses acts as a lipid-lowering agent. It reduces VLDL and LDL production and increases HDL.
Actions
- Lowers LDL
- Lowers triglycerides
- Raises HDL
Side Effects
- Flushing (common)
- Itching
- GI upset
- Liver dysfunction (high doses)
6. LDL Oxidation Inhibitor
Example: Probucol
Probucol lowers LDL and has strong antioxidant properties. It reduces LDL oxidation, a key step in plaque formation.
Limitations
- Reduces HDL levels
- GI disturbances
- Prolongs QT interval
7. Plant Sterols
Example: β-Sitosterol
Plant sterols compete with cholesterol for intestinal absorption, reducing dietary cholesterol uptake.
Uses
- Mild LDL lowering
- Supportive therapy for high cholesterol
Side Effects
- GI discomfort
- Diarrhoea or constipation
Detailed Notes:
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