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CVS Pharmacology

Cardiovascular system pharmacology- Antihyperlipidemic Drugs

Types of Antihyperlipidemic Drugs Hyperlipidemias Hyperlipoproteinemias Hyperlipemia Hypercholestrolemia
Antihyperlipidemic Drugs have a direct relationship with: Acute pancreatitis Atherosclerosis
What is Niacin? Nicotinic Acid or Vitamin B3 is one of the oldest drugs Water- soluble B-complex vitamin
Function of Niacin: Hypolipidemic effects in large doses Reduces fibrinogen levels Increases plasminogen activator
Niacin increases HDL-C: 35-40%
Niacin lowers triglycerides: 35-45%
Niacin decreases LDL-C production: 20-30%
Mechanism of action of Niacin: In adipose tissue, inhibits the lipolysis of tri-g by inhibiting adenylyl cyclase- reduces transport of free fatty acids to the liver - decreases hepatic tri-g synthesis May inhibit a rate–limiting enzyme of tri-g synthesis DAG acetyltransferase 2
When does the action of Niacin peak? 1 hour
Half life of Niacin: 1 hour
How many times a day is Niacin given? 2 or 3 times
Toxicity of Niacin: Harmless cutaneous vasodilation and sensation of warmth Pruritus, rashes, dry skin or mucus membranes (acanthosis nigricans) Nausea, vomiting, abdominal discomfort, diarrhea
Other names for Fibrates: Fibric Acid Derivatives PPARs Activators
Examples of Fibrates: Clofibrate 1962-1987. Gemfobrozil Fenofibrate Bezafibrate
Action of Fibrates: Stimulate PPAR- α(Peroxisome Proliferator Activated Receptor- α) which stimulates fatty acid oxidation Increases LPL synthesis Reduces expression of apo C-III, Increases apoA-I and apoA-II expression Anticoagulant and fibrinolytic activities
Fibrates are the DOC in: Severe hypertriglyceridemia
Toxicity of fibrates: Rashes Urticaria Hair loss Headache GIT symptoms Impotence Anemia Myalgia Fatigue Myopathy Rhabdomyolysis
Examples of Bile Acid –Binding Resins: Colestipol Chlestyramine Colesevelam
What are these Bile-Acid Binding Resins? These are large polymeric anionic- exchange resins Insoluble in water-binds the negatively charged bile acids in the intestinal lumen and prevent their reabsorption leading to depletion of bile acid pool and increased hepatic synthesis.
What is the function of these Bile-Acid Binding Resins? Hepatic cholesterol content is decreased Stimulate the production of LDL receptors This leads to increased LDL clearance and lowers LDL-C levels
Disadvantage of Bile-Acid Binding Resins: This effect is partially offset by the enhanced cholesterol synthesis caused by upregulation of HMG
Indications of Bile-Acid Binding resins: Lower LDL as much as 25%, but will cause GI side effects Relieve pruritus in cholestasis. Digitalis toxicity, can bind digitoxin and enhance its excretion
Toxicity of Bile-Acid Binding resins: Gritty sensation is unpleasant but can be tolerated Constipation and bloating Heartburn Malabsorption of Vitamin K Gall stones Impaired absorption of many drugs( digitalis, propranolol, thiazides, warfarin, folic acid, statins, aspirin etc)
Examples of Competitive Inhibitors of HMG-CoA Reductase-Statins : Mevastatin Simvastatin Lovastatin Pravastatin Fluvastatin Atorvastatin Rosuvastatin Many Silent Lessons Place Fabulous Apparent Rhythms
What is the most effective drug in lowering LDL? Statins
MOA of statins: Inhibit enzyme in synthesis of cholesterol (3- HMG co-A reductase) Increase expression of the LDL rec. gene Reduced chol. in hepatocytes --> activates protease- will cleave SREBPs- translocated to nucleus enhance LDL receptor transcrip.- remove LDL-C
Higher doses of statins: Reduce triglyceride levels caused by elevated VLDL levels.
Which statins can raise HDL-C? Simvastatin Rosuvastatin
How can statins decrease oxidative stress and vascular inflammation? By enhancing NO production
Effect of statins on platelet aggregations: Reduction
Toxicity of Statins: Elevation of transaminases Elevation of creatine kinase (CK) activity Rhabdomyolysis, causing myoglobinuria and renal injury and failure or even death. It is rare (less than one in 10,000) Lupus-like disorder and peripheral neuropathy
Inhibitor of Sterol Absorption: Ezetimibe
Function of Ezetimibe: Can reduce LDL Inhibitor of a specific transport process in jejunal enterocytes, which takes up cholesterol from the lumen ( NPC1L1)
Can reduce cholesterol absorption by: 54% 60% reduction in LDL-C
Side effects of Ezetimibe: Allergic reactions Reversible impairment of liver function tests Myopathy
Examples of Inhibitors of Cholesteryl Ester Transfer Protein: Torcetrapib JTT-705 CETP
What is CETP? A plasma glycoprotein synthesized by the liver that mediates the transfer of cholesteryl esters from the larger sub-fractions of HDL to triglyceride-rich lipoproteins and LDL in exchange for a molecule of triglyceride
CETP can increase HDL levels by: 45-106%
Created by: Ulaisl



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