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Antihyperlipidemic Drugs hFERN (Niacin (Nicotinic acid, vitamin B3) oral…
Antihyperlipidemic Drugs hFERN
Niacin (Nicotinic acid, vitamin B3)
oral administration, converted to nicotinamide
Inhibits lipolysis in
adipose tissue
. Thus, both plasma triglyceride (in VLDL) and cholesterol (in VLDL and LDL) are lowered.
Niacin treatment increases (good) HDL-cholesterol levels.
(Most potent effect)
Decrease secretion of lipoprotein
Antithrombotic
(by
decreasing circulating fibrinogen
and
increasing tissue plasminogen activator
, niacin can reverse thrombosis associated with hypercholesterolemia and atherosclerosis)
Reduces vascular inflammation, improves endothelial function and stabilizes plaques.
Adverse effects:
an intense cutaneous flush and pruritus (administer with aspirin to prevent prostaglandin mediated flush)
hyperuricemia and gout
Fibrates (Gemfibrozil)
Increase peripheral clearance
Ligands for the peroxisome proliferators-activated receptor-alpha (PPAR-α) protein. The interaction with PPAR-α results in increased activity of
lipoprotein lipase (LPL)
, decreasing plasma TG
Levels of VLDL decrease, due to decreased secretion by the liver.
HDL levels rise moderately
treatment of hypertriglyceridemias with VLDL elevation, especially for dysbetalipoproteinemia.
Adverse effects:
Nausea, rashes, gall-stones, myositis
Resins (Cholestyramine)
oral administration
Reduce fat absorption
Anion exchange resins bind negatively charged bile acids and bile salts in the small intestine.
Lowering the bile acid concentration causes hepatocytes to
increase conversion of cholesterol to bile acids
. Therefore, the intracellular cholesterol concentration decreases
Increased LDL receptor
produces increased hepatic uptake of cholesterol-containing LDL particles, leading to a fall in plasma LDL.
May increase VLDL, but has little effect on HDL.
Treatment of patients with primary hypercholesterolemia (IIa)
+Niacin: treat LDL elevations in persons with combined hyperlipidemia (IIb)
Adverse Effects
GI effects: constipation, nausea and flatulence
impaired absorptions: vitamins A, D, E,
K (bleeding)
Decreased absorption of other drugs,
Give one hour before or two hours after bile acid resins
HMG-CoA Reductase
Inhibitors (Lovastatin)
oral administration
Increase peripheral clearance
Inhibition of HMG-CoA reductase
: Their strong affinity for the enzyme compete effectively to inhibit HMG-CoA reductase, the rate-limiting step in
cholesterol synthesis
Increase in LDL receptors
These drugs are effective in lowering plasma cholesterol levels in all types of hyperlipidemias
Given in the evening
due to diurnal regulation, cholesterol synthesis mainly occurs during sleep
Adverse effects
Liver dysfunction (H)
Muscle: myopathy and rhabdomyolysis (M)
Contraindications:
pregnancy
, nursing mothers (G), children or teenagers
Cholesterol is required for normal development of the placenta, fetus, development, eg neural since cholesterol is required for the formation of the myelin sheath
Fatty acids are absorbed by the apical microvilli of mucosal cells.
Apo B48 is the structural protein of the chylomicron.
Then it reaches the blood where it receives Apo C II and Apo E from HDL.
Apo C II stimulates lipoprotein lipase enzyme.
Lipoprotein lipase digest the triglyceride in the chylomicron transforming chylomicron to chylomicron remnants.
Chylomicron remnants enter the hepatocyte by Apo E receptor in the hepatocyte.
VLDL from liver is secreted with Apo B100 instead of Apo B48
Ezetimibe
Reduce intestinal cholesterol absorption
A selective
inhibitor of cholesterol transport protein
, critical for absorption, NPC1L1, located in the
GIT and hepatocytes, effective in absence of dietary cholesterol
since reabsorption in the liver is by the same receptor.
Primary effect is reduction of LDL
• Vytorin: Ezetimibe + simvastatin
Resins decrease absorption
Generally safe, low incidence hepatic dysfunction