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CVS Pharmacology
Cardiovascular system pharmacology- Antihyperlipidemic Drugs
Term | Definition |
---|---|
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% |