Pharm Exam 1 Post-cardio Flashcards
Statins
- Drugs of choice for LDLreduction.
- Reduce cardiovascular mortality.
- Lower LDLlevels in all types of hyperlipidemias.
- Homozygotes for familial hypercholesterolemia lack functional LDL receptors and thus benefit much less from treatment with statins.
- Contraindicated in pregnancy.
OTHER EFFECTS
• Improve endothelial function.
• Decrease platelet aggregation
• Reduce inflammation.
• Decrease plasma levels of C-reactive protein.
ADVERSE
• Elevation of aminotransferases. Usually not associated with other evidence of liver toxicity.
• Myopathy and rhabdomyolysis. Rare.
• Creatine kinase levels should be determined
regularly.
• Rhabdomyolysis may cause myoglobinuria, leading to renal injury.
Niacin (nicotinic acid)
- Niacin favorably affects virtually all lipid parameters.
- Decreases VLDL, LDL and Lp(a) levels.
- It often increases HDL levels significantly.
- Niacin is the most effective agent for increasing HDL and the only agent that may reduce Lp(a).
MOA
• Activates Gi protein -> decreased cAMP -> decreased TAG lipase inactive
• Blocks hormone sensitive lipase -> decreased plasma free fatty acids
• Decreased TAG and FA synthesis -> decreased VLDL and LDL
• Stimulates lipoprotein lipase
• The catabolic rate for HDL is decreased -> HDL increases.
ADVERSE
• Intense cutaneous flush after each dose of niacin when the drug is started or the dose increased.
• Administration of aspirin prior to niacin decreases the flush, which is prostaglandin- mediated.
• Pruritus, rashes, dry skin and acanthosis nigricans.
• Hepatotoxicity is manifested as elevated serum transaminases.
• Niacin should be used cautiously in patients with diabetes mellitus, since niacin-induced insulin resistance can cause severe hyperglycemia.
• Niacin elevates uric acid levels and may precipitate gout.
Gemfibrozil Fenofibrate
- Fibrates lower VLDL levels and increase HDL levels.
- Fibrates activate peroxisome proliferator- activated receptor-a (PPAR-a).
- PPAR-a receptors are expressed primarily in liver and brown adipose tissue.
- Activation of PPAR-a by fibrates leads to a decrease in plasma TG levels and increase in plasma HDL levels.
- Only modest reductions of LDL occur in most patients.
- In patients with combined hyperlipidemia, LDL often increases as TGs are reduced.
- HDL increases moderately.
USES
• Hypertryglyceridemias and dysbetalipoproteinemia.
ADVERSE
• Mild GI disturbances.
• Myositis. Patients with renal insufficiency may be at risk. Rhabdomyolysis has occurred rarely.
• Lithiasis. Fibrates increase biliary cholesterol excretion, therefore they may cause gallstones.
Cholestyramine Colestipol Colesevelam
- Useful only in hyperlipidemias involving isolated increases in LDL.
- In patients who have hypertriglyceridemiaas well as elevated LDL levels, VLDL levels may increase.
- Bind to anionic bile acids in the intestinal lumen and prevent their reabsorption
- Up-regulation of LDL receptors in the liver.
- Liver uptake of LDLincreases, leading to a decrease in plasma LDL levels.
- HDL rises modestly.
USES
• Used with statins or niacin to increase LDL reduction.
• Drugs of choice for pregnant women and for children.
ADVERSE
• GI adverse effects: bloating, nausea, cramping and constipation.
• Colesevelam produces fewer GI adverse effects than cholestyramine or colestipol.
• They may increase TGs: contraindicated in hypertryglyceridemia.
• Cholestyramine and colestipol reduce absorption of several drugs and liposoluble vitamins.
Ezetimibe
- Inhibits intestinal absorption of cholesterol and phytosterols.
- Its primary clinical effect is to lower LDL.
- It also causes small increases in HDL and a mild decrease in TGs.
- Cholesterol synthesis increases.
- There is a decrease in the incorporation of cholesterol into chylomicrons. Less cholesterol is delivered to the liver by chylomicron remnants.
- This leads to upregulation of LDL receptors, enhancing LDL clearance from plasma.
Complementary to statins
ADVERSE
• Low incidence of reversible impaired hepatic function.
• Small increase in incidence when ezetimibe is given with a statin.
• Myositis has been reported rarely.
Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)
- w-3 fatty acids. Reduce TG biosynthesis and increase fatty acid oxidation in the liver.
- With long-term intake, they may increase HDL.
- w-3 fatty acids may increase total LDL as they lower TAG levels.
Lovaza
- FDA-approved w-3 product. Ethyl esters of w-3 fatty acids.
- Adjunct to diet to reduce TG levels in adult patients with very high (> 500 mg/dL) TG levels.
Antihyperlipidemic drugs in pregnancy
- Statins: absolutely contraindicated in pregnancy. Category X.
- Fibrates: Category C.
- Niacin: Category C.
- Ezetimibe: Category C.
- Cholestyramine & colestipol: might interfere with absorption of nutrients. Category C.
- Colesevelam: Category B. Should be used during pregnancy only if clearly needed.
Aspirin
- Aspirin inhibits TXA2 synthesis by irreversible acetylation of the enzyme COX.
- The anuclear platelet can’t synthesize new proteins.
- Therefore it can’t synthesise new enzyme during its 10-day lifetime.
USES
• Prophylactic treatment of transient cerebral ischemia
• To reduce the incidence of recurrent MI
• To decrease mortality in post MI patients.
Clopidogrel Ticlopidine
• Irreversible inhibitors of P2Y12, one of the two
subtypes of ADP receptor on the platelet surface.
• Clopidogrel has fewer adverse effects than ticlopidine.
• Clopidogrel is preferred over ticlopidine.
USES
• Indicated to reduce the rate of stroke, MI, and death in patients with recent MI or stroke or acute coronary syndrome.
- Clopidogrel is a prodrug converted to an active metabolite, mainly by CYP2C19.
- Alternative treatments should be considered for CYP2C19 poor metabolizers
- Concomitant use of clopidogrel and CYP2C19 inhibitors should be avoided.
- Omeprazole, a CYP2C19 inhibitor, reduces plasma levels of the active metabolite of clopidogrel.
- Concurrent use of clopidogrel and omeprazole should be avoided.
Dipyridamole
- PDE inhibitor. Coronary vasodilator.
- Used to prophylactically treat angina pectoris.
USES
• Dipyridamole by itself has little beneficial effect.
• Used in combination with warfarin or aspirin.
Abciximab Eptifibatide Tirofiban
ABCIXIMAB
• Monoclonal antibody against the GPIIb/IIIa receptor.
EPTIFIBATIDE
• Cyclic peptide reversible antagonist of the GPIIb/IIIa receptor.
TIROFIBAN
• Nonpeptide reversible antagonist of the GPIIb/IIIa receptor.
Heparin
MOA
• Antithrombin III inhibits serine proteases, including several of the clotting factors, eg thrombin.
• In the absence of heparin, antithrombin III inhibitis thrombin very slowly.
• Binding of heparin to antithrombin III accelerates inhibition of thrombin.
MONITORING
• Monitoring is performed with the activated partial thromboplastin time (aPTT) assay.
• The aPTT is a test of the integrity of the intrinsic and common pathways of coagulation.
• Dosing of LMWH results in predictable plasma levels.
• It is not usually necessary to monitor LMWH blood levels.
USES
• DVT
• Pulmonary embolism
• MI
• DOC during pregnancy
ADVERSE
• Bleeding
• Hypersensitivity reactions
• Heparin-induced Thrombocytopenia (HIT)
Heparin-induced thrombocytopenia type II
• Antibodies recognize complexes of heparin and a platelet protein, Platelet Factor 4.
• This leads to platelet aggregation and release of platelet contents.
• This can result in thrombocytopenia and thrombosis that can be life-threatening.
• Therapy: Discontinuance of heparin and administration of a DTI or fondaparinux.
REVERSAL OF HEPARIN
• Excessive anticoagulant action of heparinis treated by discontinuance of the drug.
• If bleeding occurs, protamine sulfate is given.
LMWH
- Heterogeneous compounds produced by chemical or enzymatic depolymerization of UFH.
- LMWH inhibit Xa but have less effect on thrombin than UFH. (Ternary complex not needed to accelerate ATIII inhibition of Xa, but is needed for thrombin)
- LMWH have equal efficacy to UFH, higher bioavailability, longer half-life, and less frequent dosing requirements.
- LMWH are replacing UFH in many clinical situations.
Fondaparinux
- Selective Xa inhibitor. Sequence of five carbohydrates that bind to antithrombin III.
- Negligible antithrombin activity.
- Approved for prevention and treatment of DVT.
