Anti-hyperlipidemic
Hypolipidemic agents, cholesterol-lowering drugs or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of high levels of fats (lipids), such as cholesterol, in the blood (hyperlipidemia). They are called lipid-lowering drugs.
SYMPTOMS:
Hyperlipidaemia doesn't cause any symptoms. Consult a doctor for medical advice
CLASSIFICATION
1. HMG CoA reductase Ingibitors
Lovastatin
Simvastatin
Metastatin
Pravastatin
Fluvastatin
Atorvastatin
Pitavastatin
Rosuvastatin
2. Fibric accid derivatives
Clofibrate
Fenofibrate
Gemfibrozil
Ciprofibrate
Benzaffibrate
Fluvastatin
3. Bile acid sequestrants
Cholestyramine
Colestipol
4. Pyridine derivative
Nicotinic acid (NIACIN)
Nicotinamide
5. Cholesterol absorption inhibitors
Ezetimibe
6. PCSK9 inhibitors
Evolocumab
Alirocumab
7. Omega-3 fatty acids
Docosahexaenoic acid(DHA)
Eicosapentaenoic acid(EPA)
Evolocumab
Alirocumab
7. Omega-3 fatty acids
Docosahexaenoic acid(DHA)
Eicosapentaenoic acid(EPA)
MECHANISM OF ACTION
1. HMG CoA Reductase Ingibitors
Liver cell where HMG-CoA reductase enzyme converts HMG-CoA into mevalonic acid which is a cholesterol precursor. So inhibiting this enzyme statins effectively reduce concentration of cholesterol within the liver cell. Liver cells sense the reduced level of cholesterol production and begin to compensate by synthesizing more LDL receptors which in turn bind and internalize LDL that is circulating in in the blood. additionally low intracellular cholesterol level lead to decrease secretion of VLD which also contributes in lowering of triglyceride level.
DOSE:
Lovastatin: 20 mg orally OD with the evening, Maintenance dose: 10 to 80 mg orally OD
SIDE EFFECTS:
pain in your stomach area
nausea
heartburn
constipation
headache
muscle pain
memory loss/forgetfulness
2. Fibric acid derivatives
Fibrates work primarily by activating nuclear transcription receptor called peroxisome proliferator-activated receptor-𝛼(PPAR_alpha). PPAR-𝛼 if found in metabolically active tissue such as liver and adipose tissue. The bind of fibrates to PPAR-𝛼 induces activation and inhibition of certain genes that code for proteins involved in lipid metabolism.
The main effects induced by fibrates is increased expression of lipoprotein lipase which in turn increase the removal triglycerides from circulation and their breakdown to fatty acid. furthermore fibrates decrease expression of protein called APO-CⅢ which inhibits lipoprotein lipase activity and lastly fibrates also increase APO-AⅠ and APO-AⅡ which are major component of HDL, thus leading to increase in it's concentration.
Dose:
Clofibrate: 500 mg orally QID
Fenofibrate: Maximum dose: 1 tablet or capsule orally once a day
Lipofen (capsules): 150 mg, Fenoglide (tablet): 120 mg
Fluvastatin: 40 mg orally OD or BD
SIDE EFFECTS:
headache
nausea
vomiting
rash
constipation
diarrhea
muscle pain
3. Bile acid sequestrants
Bile acids are produced in the liver, stored in the gallbladder and they are excreated into the gut where they facilitate digestion and absorption of lipid.
Bile acid sequestrants serve as an ion exchange resins that bind negatively charged bile acids and salts in the small intestine. the formation of this insoluble complex prevents the reabsorption of bile acids and thus leads to their excretion. this is in turn creates increase demand for their production.
since bile acids are made from cholesterol, liver cells increase their number of LDL receptors to bring in more LDL cholesterol in order to meet this new demand. so the end result is decrease levels of circulating LDL
DOSE:
Cholestyraminen
Initial dose: 4 g orally OD or BD
Maintenance dose: 8 to 16 g orally
Colestipol:
Initial dose: 4 g orally OD or BD
Maintenance dose: 8 to 16 g orally
SIDE EFFECTS:
Constipation
Diarrhea
Gas
Stomach pain
Nausea
Vomiting
4. Pyridine derivative
Nicotinic acid(NIACIN):
Nicotinic acid works on adipose tissue, where it inhibits enzyme called hormone-sensitive lipase which is responsible for breakdown of triglycerides to free fatty acid.
by reducing level of free fatty acid available for transport to the liver, nicotinic acid effectively decrease hepatic VLDL synthesis which in turn leads to decrease level of LDL
DOSE:
Children: Between 1-16 mg daily, depending on Age
Men: 14 mg daily
Women (pregnant): 18 mg daily
Women (breastfeeding): 17 mg daily
Maximum daily intake for adults of all ages: 35 mg daily
SIDE EFFECTS:
Skin Flushing
redness and itching occurs on the face, neck, chest, and back
rash
nausea
vomiting
5. Cholesterol absorption inhibitors
Ezetimibe
Free cholesterol that comes either from bile or dietary sources, first binds to protein abbreviated NPC1L1 which is located in the plasma membrane of cells known as enterocytes that line the intestinal walls. this binding then triggers endocytosis which utilizes protein complex called AP2 that works on the cell membrane to internalize the cholesterol cargo upon endocytosis the cholesterl is released and the NPC1L1 returns back to the plasma membrane.
The cholesterol absorption inhibitor binds to NPC1L1 and inhibit it's ability to interact with clathrin AP2 complex that is necessary for endocytosis. this leads to decrease delivery of intestinal cholesterol to the liver which is turn cause decrease in hepatic cholesterol level and ultimately increased clearance of LDLcholesterol from the circulation.
DOSE:
Ezetimibe: 10 mg orally OD
SIDE EFFECTS:
Abdominal fullness
Abdominal fullness
Black tarry stool
Darkened urine
Blood in urine or stool
Skin rash
vomiting
6. PCSK9 inhibitors
Evolocumab
Alirocumab
PCSK9 is an abbreviated name of enzyme circulating in the blood that binds to LDL receptors on the surface of liver cells and promotes their degradation in other word the activity of PCSK9 reduces the removal of LDL from the circulation.
PCSK9 inhibitors are monoclonal antibodiesthat binds and inactivate PCSK9. In the absence of PCSK9 there is more LDL receptor available to bind and clear LDL from the circulation leading to decreased level of of LDL cholesterol.
DOSE:
Evolocumab: 140 mg/ml subcutaneously every 2 week OR 420 mg/3.5ml subcutaneously Once a month.
Alirocumab:
Initial dose: 75 mg/ml subcutaneously every 2 week
Maximum dose: 150 mg/ml subcutaneously every 2 week
SIDE EFFECTS:
fever
rash
nausea
neurocognitive problem
7. Omega-3 fatty acids
Omega-3 fatty acids are used primarily for their Triglyceride lowering effects which are thought to be caused by inhibiting of VLDL and triglyceride synthesis in the liver.
DOSE:
(high enough doses there appears to be some increased risk of bleeding)
SIDE EFFECTS:
Abdominal pain
nausea
diarrhea
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