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MECHANISM / ACTION Reverses hypocoagulability Factors 2, 7, 9, 10, and Protein C require Vit. K for carboxlyation to bind Ca+ to for clotting (once oxidized, Vit. K is reduced by epoxide reductase for use again)
Desmopressin (DDAVP)
INDICATIONS Deficiency caused by: Liver problems(HIV, Hepatitis, EtOH) Malabsorption syndromes ~ CF ~ sprue ~ short bowel syndrome ~ blind loop syndrome Hemorrhagic dz in neonates mild-mod HemA & vWF minor surgery ( bld loss) plt defect
CONTRAINDICATIONS
SE
vWF type IIb precipitate thrombosis & produce thrombocytopenia patients with heart dz
Aprotinin
Serine proteinase inhibitor Complexes w/ plasmin, kallikreins inhibit fibrinolysis Doesnt cross BBB competitively inhibit plasminogen activation (fibrinolytic inhibitor)
High risk coronary bypass surgery lower bleeding & transfusion need hemophilia adjunct post op bleeding bladder hemorrhage intracranial aneurysms primary & secondary MI px DIC Renal/ureteral bleeding pregnancy intravasc thrombosis hypotension myopathy abdominal discomfort diarrhea Too much is bad b/c it inhibits PGI2(which has anti-aggregatory effects) coagulation
blocks cyclooxygenase blocks TXA2 formation effect on plt in circulation = irrev relieved only by new plt formation PDE inhibitor Inhibit plt fxn by: ~ increasing cAMP ~ stim PCI2 ADP receptor antagonist that prevents dec. in cAMP=prevents aggregation on plt by dec. expression of IIb/IIIa
coag defect
Ticlopidine antiplt
With aspirin: more complete effect on plt With warfarin: decrease embolism with prosthetic heart valve TIA Thrombotic strokes With aspirin: angioplasty patients & stents reduce secondary thrombosis
Coag defects
Hemopoietic hemostatic disorders severe liver dz hypersensitivity Drug interactions: cimetidine: lower clearance theophylline: t1/2 & clearance antacids: lower plasma level
similar to ticlopidine MECHANISM / ACTION glycoprotein IIb/IIIa antibody inhibitor INDICATIONS Conjuction w/angioplasty inhibit coronary thromboses CONTRAINDICATIONS Coag defects
Eptifibatide antiplt Tirofiban antiplt Recomb tPA 2nd g thrombolytic DRUG Heparin anticoag
Fab fragment of human Ab to glycoprotein oppose glycoprotein IIb/IIIa receptor activation glycoprotein IIb/IIIa inhibitor minimizes allergic rxn expensive
coag defects hemostatic thrombi & thromboemboli lysed bleed less than other thrombolytics
MECHANISM / ACTION rev binds antithrombin III (tx DIC) decreases 2,7,9,10 immediate effect no effect on pre-existing clots; works to prevent new clots Unfractionated is a scaffold to promote binding of thrombin to antithrombin LMWH: enoxaparin ~ longer half life ~ more predictable ~ Not attacked by Ab ~ able to activate antithrombin III hirudin direct thrombin inhibitor in salivary gland of leech inhibits epoxide reductase and depletes reduced Vit. K.blocks synthesis of 2, 7, 9, 10 lag time btwn admin & PT affect 99% bound to serum albumin
INDICATIONS LMW: THR DVT Venous thrombosis Pulm emoblism Initial management: unstable angina or acute MI Coronary angioplasty Stent placement Cardiopulm bypass surgery Pregnancy ~ does not cross placenta
CONTRAINDICATIONS Coag disorders Liver dz Prolonged admin osteoporosis antidote: protamine sulfate
HIT
No antidote antidote is Vit. K Fetal Warfarin syndrome - Hypoplastic nose, low nasal bridge, altered bone growth
long term in DVT, heart valves, post MI Increased Response vit K def liver dz alcoholism Decreased Response Pregnancy ~ crosses placenta ~ secreted in milk
ACTION INHIBITED (PT shorten) enhance degradation barbiturates phenytoin rifampin ACTION POTENTIATED (PT long) displace from protein / lower metab cimetidine
Binding of ADP inhibits adenylyl cyclase which dec. cAMP(aggregation) and dec. PKA= platelet activation, also cAMP is metabilized to AMP by PDE(aggregation) Protein C(activated by thrombomodulin) is anti-coagulant that inhibits Va and VIIIa and dec .inhibitor of plasminogen activation, and inhibits release of TNF from monocytes during septic shock(r-APC)