Table of Contents
Anti-hyperlipidemic drugs
Anti-hyperlipidemic drugs are those drugs which are used in the treatment of hyperlipidemic. It is also known as lipid lowering agents. This drug is decreasing the level of cholesterol and triglycerides in the bloodstream.
Hyperlipidemia
Hyperlipidemia is a condition in which plasma levels of lipids in elevated (increase) in the form of lipoproteins. These lipids include cholesterol and triglycerides, which are essential for various bodily functions but can pose health risks when their levels become elevated. Hyperlipidemia occurs when LDL cholesterol level increases because this excess cholesterol accumulated in the innermost layer of the artery and leads to the formation of plaque which further cause heart disease. Due to this reason, LDL referred as bad cholesterol. Now this hyperlipidemia causes atherosclerotic which further causes heart attack, stroke and many other heart diseases.
Lipid present in the three forms in our body: cholesterol, triglycerides and phospholipids. Cholesterol is a fat-like substance that’s is found in all the cell in your body, it’s major role in hyperlipidemia. Triglycerides are a type of fat that the body uses for energy, it is synthesized by glycerol and fatty acid, and found in the bloodstream. Now, these lipids are insoluble in the blood plasma, so they have to be transported throughout the body in the form of protein complex which is known as lipoproteins.
Classification of lipoproteins
Lipoproteins further divided into four major types:
1. Chylomicrons
It is produced in gastrointestinal tract from dietary lipids. It is composed of mostly triglycerides and small amount of cholesterol. Its main function is delivering energy to cells throughout the body.
2. VLDL-Very low-density lipoprotein
It is mainly produced in the liver. It composed primarily of triglycerides and small amount of cholesterol (more than chylomicrons). It’s also main function is deliver energy to cells throughout the body.
3. LDL-Low density lipoprotein
It is produced from VLDL and contain higher percentage of cholesterol. Its main function is delivering cholesterol to cells throughout the body. Mostly LdL is taken up by liver for the synthesis of bile acid, because LDL contains cholesterol which used in the synthesis of bile acid & steroid hormones.
4. HDL-High density lipoprotein
It is produced in liver and also in small intestine. It is mostly composed of phospholipids, cholesterol and proteins. Its main function is transporting excess cholesterol from the peripheral cells to the liver. It referred as a good cholesterol and LDL referred as a bad cholesterol.
Causes of hyperlipidemia
1. Being overweight
2. Smoking and alcohol
3. Unhealthy lifestyle
4. Diabetes
5. Diet (excessive fat etc)
Classification of anti-hyperlipidemic drug
1. HMG-COA reductase inhibitors
It is also known as statins. They work by inhibiting an enzyme involved in cholesterol production, thus lowering cholesterol levels in the blood.
Mechanism of action
Normally, In liver’s cell HMG-COA reductase converts HMG-COA to mevalonic acid, which is used as a precursor for cholesterol biosynthesis. Now, when LDL is increased in blood circulation, it causes hyperlipidemia.
Now, that time HMG-COA reductase inhibitors introduced into body which give their effect in liver. The reductase inhibitors inhibit the enzyme HMG-COA reductase. So, now mevalonic acid is not synthesized which cause decreasement in the amount of cholesterol in liver.
Cholesterol is used for synthesis of bile acid which is primary work of liver. So, when live sense low levels of cholesterol liver activate the LDLR (Low density lipoprotein receptor).
Now, LDL which is present in excess amount in blood circulation comes near to liver and release cholesterol into liver (because LDL are rich in cholesterol). So, due to this LDL amount in blood circulation is decreases which helps to clear atheroma & plague and directly helps to decrease hyperlipidemia.
Anti-hyperlipidemic drugs
These are some drugs which are known as anti-hyperlipidemic drugs: lovastatin, atorvastatin, pravastatin, rosuvastatin and simvastatin.
1. These are some mostly used drugs as an HMG-COA reductase inhibitors.
2. All have almost similar mechanism of action.
3. They have ability to reduce cholesterol by 20-50% in blood circulation.
4. These drugs also decreases triglycerides levels and may increase HDL levels.
Pharmacokinetics of anti-hyperlipidemic drugs
1. It is mostly given at bedtime for maximum response.
2. Absorption of the statins is variable (30-85%) following oral administration.
3. All statins metabolized in liver.
Adverse effects of HMG-COA reductase inhibitors
1. Mild-GIT disturbance, headache.
2. Risk for liver toxicity.
3. Myopathy in some cases.
4. Contraindicated in pregnancy.
2. Bile acid sequestrants(Resins)
These drugs also give their effect by lowering cholesterol in blood circulation but these are less effective than statins.
Mechanism of action
All drugs of this class are anion-exchange resins which binds with negatively charged bile acids and bile salts in small intestine and forms insoluble complex. Now these insoluble complex does not get reabsorbs through intestine to liver and excreted.
It lowers the bile acid concentration in liver. Now, liver sense this lower amount and activates LDLR, which further get the cholesterol rich LDL from blood circulation because liver want more cholesterol to synthesize bile acid. Due to this LDL (cholesterol) level in blood circulation is decreases and helps in treatment of hyperlipidemia.
Drugs used as bile acid sequestrants
These are some drugs which are used as resins: cholestyramine, colestipol and colesevelam. These drugs are not so popular because do not have potent effects and also required in large amount.
Uses of Resins
1. It is used in the treatment of hyperlipidemia.
2. It is reducing the level of cholesterol.
3. Cholestyramine can also relieve pruritus caused by accumulation by bile acids.
3. Lipoprotein lipase activators (fibrates)
These drugs are the derivatives of fibric acid and these drugs give their action by decreasing the triglycerides and by increasing HDL levels.
Mechanism of action
Normally we get triglycerides from diet or other important methods. Now, liver use this triglyceride to synthesize the lipids, LDL, VLDL in liver. If concentration of VLDL & LDL increases then it causes hyperlipidemia.
Now, introduced fibrates in body which further binds with PPARs (peroxisome proliferator activated receptor) which the members of the nuclear receptor family that regulated lipids metabolism. Then, it activates PPAR which further increases the expression of lipoprotein lipase enzymes and it is responsible for the degradation of triglycerides, which helps to treat hyperlipidemia.
Drugs used as fibrates
These are some drugs which are used as fibrates: fenofibrates, gemfibrozil and bezafibrate. These drugs lower about 20-50% of TGS, almost similar mechanism of action.
Pharmacokinetics of fibrates
1. It is completely absorbed through oral administration.
2. Fenofibrate (prodrug) converted to active moiety fenofibric acid.
3. Excreted in urine.
Adverse effect of fibrates
1. Nausea
2. Liver toxicity
3. Muscle pain
4. GIT disturbance
4. Nicotinic acid (Niacin)
These drugs give their effects by decreasing triglycerides in liver and also these drugs can increase HDL.
Mechanism of action
These drugs work in adipose tissue. In adipose tissue, triglycerides converted into free fatty acids through hormone sensitive lipase enzymes. Now, liver use these free fatty acids and make their own triglycerides which further used in synthesis of VLDL, LDL.
Now, introduced this nicotinic acid. This niacin inhibits hormone sensitive lipase enzyme and decrease in the concentration of free fatty acid, which decreases the production of this in liver then it decreases in the amount of LDL in plasma concentration.
Uses of nicotinic acid
1. It is used in the treatment of hyperlipidemia & also effective in hypercholesterolemia’s.
2. It is also help in reduce the level of LDL by 10-20%.
3. It is also help in increase the HDL.
4. It is used in combination with statins (more effective).
Pharmacokinetics of nicotinic acid
1. Administered orally
2. Excreted in the urine
Adverse effects
1. Flushing
2. Risk of hyperuricemia
3. Cause liver toxicity.
5. Cholesterol absorption inhibitors
It is also known as sterol absorption inhibitors. These drugs give their action by inhibiting dietary and cholesterol in the small intestine.
Mechanism of action
Give their action in small intestine, cholesterol which we get through dietary and bike acid are reabsorb into small intestine and get back to liver.
Now, in case of hyperlipidemia cholesterol absorption inhibitors introduced into body which blocks the NPC1LI receptor on which cholesterol bind.
Now cholesterol does not bind and not get reabsorbed and decreases in the amount of cholesterol in liver. When liver sense it, it activates LDL receptor and excess amount of LDL (rich cholesterol) from blood circulation & helps to treat hyperlipidemia.
Adverse effect
1. Nausea
2. Liver toxicity
3. Muscle pain
4. GIT disturbance