Anti-hyperlipidemic agents are medications designed to manage abnormal lipid levels in the blood, thereby reducing the risk of atherosclerosis, coronary artery disease, and related cardiovascular events.
Pathophysiology of Hyperlipidemia
Hyperlipidemia involves elevated levels of lipids (cholesterol and triglycerides) in the blood, which can lead to the formation of fatty deposits (plaques) in arteries.
This process narrows and hardens arteries (atherosclerosis), increasing the risk of heart attacks, strokes, and peripheral vascular disease.
Classification of Anti-Hyperlipidemic Agents
Anti-hyperlipidemic drugs are classified based on their primary mechanism of action:
1) Fibrates
Mechanism of Action:
Fibrates activate peroxisome proliferator-activated receptors (PPAR-α), leading to increased oxidation of fatty acids in the liver and muscle.
This results in decreased triglyceride levels and, to a lesser extent, increased high-density lipoprotein (HDL) cholesterol.
Common Drugs: Clofibrate
Uses:
Primarily used to reduce triglyceride levels.
Can also modestly increase HDL cholesterol.
Side Effects:
Gastrointestinal disturbances (e.g., abdominal pain, nausea).
Increased risk of gallstones.
Myopathy, especially when combined with statins.
2) Statins
Mechanism of Action:
Statins inhibit HMG-CoA reductase, the key enzyme in cholesterol synthesis in the liver.
This leads to decreased low-density lipoprotein (LDL) cholesterol levels and upregulation of LDL receptors, enhancing clearance of LDL from the bloodstream.
Common Drugs: Lovastatin
Uses:
Lowering LDL cholesterol.
Reducing the risk of cardiovascular events (e.g., myocardial infarction, stroke).
Stabilizing atherosclerotic plaques.
Side Effects:
Myalgia and myopathy.
Elevated liver enzymes.
Increased risk of diabetes mellitus.
Gastrointestinal issues (e.g., constipation, diarrhea).
3) Bile Acid Sequestrants
Mechanism of Action:
These agents bind bile acids in the intestine, preventing their reabsorption.
The liver responds by converting more cholesterol into bile acids, thereby lowering circulating cholesterol levels.
Common Drugs: Cholestyramine, Colestipol
Uses:
Lowering LDL cholesterol.
Reducing triglyceride levels.
Increasing HDL cholesterol (to a minor extent).
Side Effects:
Gastrointestinal disturbances (e.g., constipation, bloating).
Interference with the absorption of fat-soluble vitamins (A, D, E, K).
May bind other medications, reducing their efficacy.
Class | Mechanism of Action | Common Drugs | Uses | Side Effects |
Fibrates | Activates PPAR-α, increasing fatty acid oxidation, decreases triglycerides, modestly raises HDL | Clofibrate | Lowers triglycerides, slightly increases HDL | GI disturbances, increased gallstones, risk of myopathy with statins |
Statins | Inhibits HMG-CoA reductase, decreases LDL cholesterol, increases LDL receptor activity | Lovastatin | Lowers LDL, reduces cardiovascular risks, stabilizes plaques | Myalgia, elevated liver enzymes, increased diabetes risk, GI issues |
Bile Acid Sequestrants | Binds bile acids in intestine, prevents reabsorption, liver converts cholesterol to bile acids | Cholestyramine, Colestipol | Lowers LDL, reduces triglycerides, minor HDL increase | GI disturbances, affects fat-soluble vitamin absorption, may bind other medications |