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Heme/Lymph Pharmacology


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Properties - inhibits COX therefore preventing TXA2 synthesis (irreversible inhibition at platelets - life long = 7-10 days) but endo can continue to produce anticoagulant PGI2. Can prolong bleeding time after one dose.
Indications - prevent reinfarct, prevent MI, prevent occlusion in coronary artery bypass grafts. pts with TIAs to prevent stroke.
Why is there a yellow jacket in here?
Cuz mom left the door open for no reason. If I get stung while studying, I'm just not taking the boards.
Properties - inhibits plately aggrecation by irreversibly modifying the platelt ADP receptor.
Indications - reduction of atherosclorotic events in pts with known atherosclorosis.
Properties - inhibits expression of glycoprotein IIb/IIIA receptors on platelets. GPIIb/IIIA has fibrinogen binding sites.
Indications - pts with stroke precursors who can't tolerate aspirin.
SE, Tox - life-threatening blood dyscrasia.
Properties - accelarates antithrombin III (heparin cofactor) binding to thrombin which then inactivates thrombin, Xa, XIa, XIIa, and kallikrein. Given IV/SQ. Prolongs PTT, thrombin time, whole blood clotting time. only anticoagulate that works within minutes.
Met/Excr - liver met by heparinase.
Indications - sq in low doses to prevent clot for pts at high risk, used to stop ongoing thrombosis, in the acute phase of MI, safe in pregnant women because doesn't cross the placenta.
SE, Tox - bleeding - monitor PTT! protamine sulfate reverses the anticoag effect of heparin but too much causes its own anticoagulant effect. so that's helpful. transient and mild thrombocytopenia. hypersensitivity. chonically, osteoporosis. elevation of LFTs.
Low Molecular Weight Heparins
Properties - have more antifactor Xa activity, less inactivation of thrombin, less inhibition of platelets. longer half life than heparin. don't need to be monitored but are not easily reversible.
Indications - hip replacements.
Properties - a coumarin derivative. interferes with vit K-dependent post-translation modifaction (gamma carboxylation) of factors II, VII, IX, and X as well as proteins C and S. Onset delayed 2-3 days until existing factor are depleted. Prolongs PT. Since VII has the shortest half life, the extrinsic pathway is most effective, hence, monitor PT. given PO.
Met/Excr - met in liver. extensively albumin bound.
Indications - similar to heparin but not for acute situations. give concomitant heparin because pro C and S are depleted first causing an initial risk of clotting.
SE, Tox - treat bleeding with vitK or if severe, with concentrates of vitK dependent factors. Pts with vitK deficiency or hepatic insufficiency require lower doses. CI in pregnancy since crosses placenta.
Drug Interactions - barbiturates, glutethimide (substitue barbiturate), rifampin, chronic EtOH ingestin increase hepatic metabolism of warfarin.
Clofibrate increases metabolism of II and X and decreaes platelet adhesiveness therefore it can increase the anticoagulant effect.
Metronidazole, trimethoprim, disulfiram, cimetidine, phenylbutazone, acute EtOH intox, influenza vaccine, sulfonamides decrease metabolism of warfarin. Teratogenic.
Properties - a thrombin inhibitor - binds to the active site and fibrinogen recognition site of thrombing. little bleeding at therapeutic doses. given IV or SQ.
Properties - produced by β-hemolytic strep. forms complexes with plasminogen which can then cleave free plasminogen into plasmin. longest half life of the thrombolytic agents.
Indications - AMI
SE, Tox - bleeding, hypersensitivity-Ag reactions. rare anaphylaxis.
Alteplase (tPA)
Properties - an endogenously produce serine protease. "fibrin selective" - activates only plasminogen bound to fibrin, so V, VIII remain active. Half life of only 5 minutes.
SE, Tox - Hemorrhage with no less incidence than streptokinase.
E Aminocaproic Acid (anistreplase)
Properties - a lysine analog that binds to lysine-binding sites on plasminogen and plasmin to block plasmin's binding to fibrin, inhibiting fibrinolysis.
Indications - Tx of systemic hyperfibrinolysis with surgical commplications following heart surgery and portocaval shunt. or cancer and blah. can reverse the action of thrombolytic agents.
Epoetin alpha
Properties - growth factor produced by the kidney that stimulates RBC production. Given parenterally.
Indications - anemia secondary to renal failure and chemotherapy, secondary to AZT in AIDS pts. used prior to surgery to alleviate potential surgical blood loss and to facilitate autologous blood donation.
Properties - recombinant granulocyte granulocyte-macrophage colony-stimulating factor. Produced by T lymphocytes leads to proliferation of granulocytes, monocytes, macrophages, megakaryocytes.
Indications - neutropenia.
SE, Tox - induration, thrombophlebitis at site, bone pain, fever, rashes, myalgias. limit-dose if pleuritis, pleural effusions, pericarditis.
Properties - recombinant granulocyte colony-stimulating factor. produced by monocytes, fibroblasts, endothelial cells and stimulates the production of neutrophils.
Indications - chemotherapy-induced neutropenia and others.
SE, Tox - less severe than with GM-CSF. bone pain and vascultitis.
Properties - binds to glycoprotein receptor IIb/IIIa on activated platelets.
Indications - acute coronary snydromes, PTCA.
SE, Tox - bleeding, thrombocytopenia.

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