Drug Interactions of Oral Anticoagulants (Warfarin) PDF

Drug in nteraction ns of oral anticoagu a ulants (warfarin) Dru ugs that potentiate p warfarin Drugs s that inhib...

Drug in nteraction ns of oral anticoagu a ulants (warfarin) Dru ugs that potentiate p warfarin Drugs s that inhib bit warfariin  Mic crosomal enzyme e in nhibitors  Microsomal enzym ers (e.g. me induce (e.g g. cimetidinne, chloram mphenicol)) ↓ phenoba mpin) ↑ arbital, rifam mettabolism of o warfarin. metabolism of warffarin.  Oraal antibiotiics: ↓ vit K synthesiss  Oral con ntraceptive es and vit K. ↑ by kkilling the gut g flora synthesis s of clottin g factors  Liquuid paraffiin: ↓ vit K absorption a  Aluminum hydroxxide: ↓ warffarin  NSA AIDs: disp place warfa arin from p pp. absorptio on █ FIBR RINOLYTIC (THROM MBOLYTIC C) DRUGS S  Norrmally, whe en a fibrin clot is form med, plasm minogen gets g in conntact with this t clot andd becomess activated d into plas smin by th he help off naturally occurring g tissue plassminogen n activatorrs (t-PAs). Plasmin causes c lysis of the clo ot.  Theese endoge enous activators pre eferentially y activate plasminog gen that is s bound to ffibrin, which (in the eory) confiines fibrinolysis to the formeed thromb bus and avooids systemmic activatiion.  Fibrrinolytic drrugs cause rapid ac ctivation of o plasminogen to fo orm plasmmin, but unfoortunately,, they may y activate both fibrin n-bound plasminoge p en and circculating plassminogen thus, bo oth prote ective hemostatic thrombi and path hogenic thro omboembo oli are brok ken down ((→ risk of bleeding). b Strepttokinase  Streeptokinasee is a prote ein (not an n enzyme) that is isoolated from m streptoc cocci; it activates plassminogen into plasmiin non-enzzymaticallyy.  It m may be antigenic (cauuses allergyy) in some people. 213  Urokin nase  Uro okinase is a proteas se originallly isolated d from urinne; the druug is now prepared in recomb binant formm from culttured kidney cells.  It is less antigenic than streptokina s ase. Recommbinant tissue t pla asminoge en activa ators (t- PAs): ((Alteplase e, reteplas se, and ten necteplase e)  Theey are recoombinant human protteins produ uced in cultured cellss.  Theey are mos c to fibrin-b st specific bound pla asminogen; local actiivation of plasmin p at th he thrombus site red duces the incidence of o systemic bleeding g.  Retteplase an nd tenectteplase h have long half-life. The long half-life permits admministrationn as a bolus i.v. injeection rath her than byy continuoous infusio on. (two injections i.v. separatedd by 30 minutes for reteplase, r , one singlle i.v. injec ction for teneecteplase e). Therap peutic use es of throm mbolytic d drugs  Theey are giveen by i.v. route r in ca ases of ac cute myoc arction, is cardial infa schemic stro oke, pulmo onary embo olism, and arterial thrombosis.  In c cases of ac cute MI, th hey should d be givenn within 12 2 h of onseet. The ma aximum bennefit is obta ained if treatment is ggiven within 90 minuutes of the onset of pain. p  Befoore throm mbolysis, care c shouldd be take en to ensu ure there is no liab bility for blee eding in a critical c site e e.g. retina a, CNS, ettc. Advers se effects of thromb bolytic dru ugs – Sysstemic ble eeding is the major adverse effect. The e risk is hhigh with strepto- s kina ase and loww with the recent rec combinant tissue pla asminogen activators s. – Streeptokinasee can cause allergy, fever, and d hypotenssion during g i.v. infusion. █ ANT TIPLATELE ET (ANTIT THROMBO OTIC) DRU UGS Aspirin  Asp pirin inhibit platelet ag ggregation n by: – Irreverssible inhibition of COOX enzyme e → ↓ TXA2 → ↓ plateleet aggregattion. – Irreverssible acetylation of plaatelet cell membrane m s → ↓ platellet adhesio ons. – Decreaase platele et ADP synnthesis → decrease platelet accuumulation.  At h higher dosses (> 325 5 mg/day), aspirin maym decrea ase endothhelial synth hesis of PGII2, which inhibits pla atelet activvity. Low doses d (75-150 mg/daay) ↓ synth hesis of plattelet TXA2 more thann PGI2 in eendothelial cells and avoid this effect.  Othher NSAIDss do not haave compa arable antithrombotic activity. 214