bul2011_No1
13
น ย พ ษ ว ท ย า ช น อ ค า ร ว จ ล ว ส ด ก า ร ณ พ ท ย ศ า ส ต ร โ ร ง ย า บ า ล ร า ม า ธ บ ด ถ น พ ร ะ ร า ม า ท ก ท ม 1 0 4 0 ก ร ณ า January-March 2011 Vol.19, No.1 ⌫ ⌫ ⌫ ⌫ ⌫⌫ ⌫ ⌫ ⌫ ⌫ ⌫ ⌫⌫ ⌫ ⌫ ⌫ ⌫ ⌫ ⌫ ⌫ ⌫ ⌫ แนวทางการด แลผ ป วยท ได ร บยากล มต านฤทธ ว ตาม นเคในสถานการณ ท ม ความเส ยงต างๆ ......................................................................... 3 ปฏ ก ร ยาต อก นของยา war farin (dr ug intera cti on of war far in) .................... 4 Warf arin and intr acr ania l haemorrh age. ....................................................... 6 Pheny toin/F osphe nytoin ....... ....... ............. ...... ....... ............. ...... ....... .................. 7 ToxCase Conference Ace taminophen indu ced neph roto xicit y........................................... 10
-
Upload
anuthat-hongprapat -
Category
Documents
-
view
34 -
download
0
description
POISON&DRUG INFORMATION
Transcript of bul2011_No1
-
1 6 . 10400
January-March 2011 Vol.19, No.1
......................................................................... 3 warfarin (drug interaction of warfarin).................... 4Warfarin and intracranial haemorrhage........................................................ 6Phenytoin/Fosphenytoin.................................................................................... 7ToxCase Conference
Acetaminophen induced nephrotoxicity........................................... 10
-
page P&D Information Bulletin / Vol. 19 No. 1, 2011
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
12345678901234567890123456789012123456789012345678901234567
(Ramathibodi Poison Center)
( 24 )
1. Internet
2.
3.
4.
5. (Poison and DrugInformation Bulletin) 3
2
....................................................................................................
.................................................................................................
..............................................................................................
/........................................................
.............................................................................
:
{ 1 100 { 2 150 { 3 250
.
026-4-01398-4
................
()
-
page
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
12345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890123456789012123456789012345678901
3
. ..
French Medical Societies The French National Authority for Health (Haute AutoriteSant HAS) 1979 2007 766 HASwebsite 2008
(vitamin Kantagonists : VKA warfarin ) 3
1. 24 INR (International Normalized Ratio) INR
- INR 3-4 ( INR > 4 )
- INR 4-6 1 INR 2-3 ( 1 INR 1-2 24 )
- INR 6-10 INR 2 ( INR > 6 1 INR 24)
- INR >10 5
2. 1 5
1. 2. systolic BP < 90 mmHg
40 mmHg, MAP
-
page P&D Information Bulletin / Vol. 19 No. 1, 2011
VKA VKA 48-72 VKA endoscopic, endo-vascular procedure intracranial hemorrhage 1-2 bridging therapy [ enoxaparin warfarin] VKA
VKA - VKA (mechanical heart
valve) atrial fibrillation perioperative bridgingtherapy 3
1.) Therapeutic subcutaneously low-molecular weightheparin (LMWH)
2.) Therapeutic intravenously unfractionated heparin (UFH)3.) Therapeutic subcutaneously UFH
venous thromboembolism (VTE)
1 1-3 preoperativevena cava filter bridging therapy LMWH UFH 24-48 bridgingtherapy therapeutic heparin doses INR
INR < 1.5
-
page5
Cytochrome P450 CYP mitochondria endoplasmic reticulum
CYP ,
- CYP bilirubin
- CYP 2C9 ( 1A2 3A4) warfarin CYP warfarin CYP warfarin ( 1 2)
1A2 2C9 3A4,5,7cimetidine fluconazole indinavirFQs amiodarone nelfinavir
isoniazid ritonavirclarithromycinitraconazoleetoconazoleerythromycingrapefruitverapamildiltiazemcimetidineamiodaroneNOT azithromycin
2 CYP1A2 2C9 3A4,5,7tobacco rifampin carbamazepine
phenobarbitalphenytoinpioglitazonerifampintroglitazone
1 CYP
( 12)
CYP warfarin
- albumin warfarin - warfarin cholestylamine- cyclic interconversion
second third generationcephalosporins
- coagulation factor thyroxine- flora
sulfonamide, broad spectrum-
NSIADs, high dose penicillin ( 3)
acetaminophen, NSAIDs, allopurinol, antacids, barbiturates, carbamazepine,miodarone, quinidine, cholestyramine, olestipol, corticosteroids,clarithromycin, cephalosporins, erythromycin, griseofulvin, oral contraceptives, phenytoin,metronidazole, quinolones, TMP-SMX, rifampin, vitamin Ktetracycline, fluconazole, isoniazid, dicloxacillin, Q10ketoconazole, anabolic steroids,chloral hydrate, cimetidine, clofibrate,cyclic antidepressants, disulfiram, ethanol,statins, omeprazole, phenytoin, sulfonylureas,tamoxifen, thyroxine, vitamin Ecranberry, gingko, green tea, omega3
3 warfarin
-
page P&D Information Bulletin / Vol. 19 No. 1, 2011
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
Warfarin and intracranial haemorrhage. ..
warfarin 1-5% 8-10 warfarin
warfarin 3 1. embolism
atrial fibrillation2. 3. warfarin
warfarin warfarin , INR , > 80 , Glasgow Coma Score (GSC),, intraventicular hemorrhage
Pathogenesis
warfarin INR Immediate management
pathogenesis warfarin warfarin vitamin K cofactor prothrombin, factor VII, IX, X coagulation factor
4 vitamin K, FFP, PCC,recombinant activated factor VII
1 Options for reversal in warfarin associated intracerebral haemorrhage
Appelboam, R. and E.O. Thomas, Warfarin and intracranial haemorrhage. Blood Rev, 2009. 23(1): p. 5.
6
-
page
CYP1A2
Vitamin K vitamin K ,
Fresh frozen plasma
coagulation factor
Prothrombin complex concentrated
coagulation factor FFP
Recombinant activated factor VIII
hemophilia
vitamin K PCC PCC FFP warfarin
bridging therapy
warfarin (European Societyof Cardiologist/Stroke) 7-14 1. Appelboam R, Thomas EO. Warfarin and intracranialhaemorrhage. Blood Rev 2009; 23(1): 1-9.2. Aguilar MI, Hart RG, Kase CS, Freeman WD, Hoeben MBJ,Garci'a RC, et al. Treatment of Warfarin-Associated IntracerebralHemorrhage: Literature Review and Expert Opinion. MayoClin Proc 2007;82(1):82-92.
7
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
Phenytoin/Fosphenytoin. ..
Phenytoin : ..1938 (alcoholwithdrawal syndrome )
Fosphenytoin : .. 1997 phenytoin
Phenytoin or 5,5-diphenyl-2,4-imidazolidinedione barbiturates five membered ring
Fosphenytoin disodium phosphate ester of pheny-toin phenytoin phosphatases,
1 phenytoin fosphenytoin
- (block of sodium
channels)- (inhibit calcium
channels)- Na+/K+ ATPase pump
-
page P&D Information Bulletin / Vol. 19 No. 1, 2011
Phenytoin conc = observed concentration (mg/L)
(mg/L) [0.2 x serum albumin (g/dl)] + 0.1
albumin 90%
(volume of distribution ,Vd) 0.6 L/Kg (free drug) 10% albumin albumin free drug 15% free drug 50% metabolized free drug distribution freedrug peripheral tissue free drug drug interaction albumin total form bound form albumin phenytoin
free drug
- free drug-Neonate-Elderly-Hypoalbuminemia-Hyperbilirubinemia-Uremic patient-Combination therapy with VPA,salicylates,
sulfonamides-Metabolized primarily by CYP450
2C9 parahydroxylphenyl derivative secondarilyby CYP450 2C19 5% phenytoin (inhibit) CYP450 2C9 amiodarone, fluconazole, fluoxetine, metronidazole orzafirlukast phenytoin (inducer) CYP450 2C9 phenobabital, rifampicin
CYP450 2C19 cimetidine,felbamate, fluvoxamine, ketoconazole, lanzoprazole,omeprazole, paroxetine, ticlopidine phenytoin CYP450 2C19 carbamazepine rifampicin metabolism phenytoin dose dependent concentration 10 mg/L: first order elimination metabolism half life 6-24 concentration metabolism saturated (elimination) zeroorder half life 20-60
-Fosphenytoin : phenytoinequivalents 1.5 mg fosphenytoin 1 mg phenytoin phenytoin 6-16 IV (intravenous) 150 mgPE/minAcute phenytoin toxicity [overdose]
cerebellar vestibular
15 mg/L nystagmus, 30 mg/L ataxia, 50 mg/L pyramidal extrapyramidal chorea opisthotonic posturing cardiovascularChronic phenytoin toxicity zero order, free drug , hepatic metabolismAdverse effect
gingival hyperplasia, folic acid deficiency,agranulocytosis, anticonvulsant hypersensitivity syndrome (AHS)
AHS : aromatic anticonvulsant phenytoin,carbamazepine, phenobarbital, primidone 2 toxic arene oxide metabolites
8
-
page
multiorgan involvement hepatitis, leukocytosis (atypical lymphocytes, eosinophils), admit, methylprednisolone 0.5-1 mg/kg/d 6
-Serum phenytoin concentration zero
elimination Therapeutic serum concentration : 10-20 mg/L-Free phenytoin fraction gas chromatography enzyme-multiplied
immunoassay technique (EMIT)Therapeutic free phenytoin concentration : 1-2 mg/L
- (supportive care)- 1
(NG lavage)-Multiple-dose-activated charcoal (MDAC) half
life -Hemodialysis or hemoperfusion
(90%)- IV benzodiazepine,
barbiturate admit ICU
-- (coingestion)-Coma- ataxia
discharge ICU
--No coma-
phenytoin - 3-5 - 100 mg 1.2
mg/L- propylene glycol (40%)
ethanol (10%) propylene glycol (depress myocardial tissue)
(decrease peripheral vascularresistance) , , (EKG) show increase PR interval, widened QRSinterval, ST-T wave change (Intramuscular;IM) hematoma,sterile abscess, myonecrosis (Extravasation) purple hand syndrome edema, erythema,vesicle, bullae, local tissue ischemia, gangrene, compartmentsyndrome, rhabdomyolysis, death
- 50 : 4-10mg /ml NSS 50 mg/ml
- 50 : 4 mg/ml NSS 25 mg/ml
- cardiac monitoring -
- Marked bradycardia- Second or third degree heart block- Severe arteriosclerotic heart disease- Hypotension
30-60 bolus 0.9%NSS 250-500 ml, atropine,temporary cardiac pacing if symptomatic bradycardia vascular or soft tissue injury orthopedic plastic surgeon
1. LoVecchio F. Phenytoin. In: Brent J, Wallance KL, BurkhartKK, Philips SD, Donovan JW. Critical care toxicology : diag-nosis and management of critical poisoned patient. Philadel-phia: Mosby;2005.p.553-8.2. Goldfrank LR, Flomenbaum N, Hoffman RS, Howland MA,Lewin NA, Nelson LS. Anticonvulsants. In: Goldfrank's manualof toxicologic. New York: McGraw Hill;2007. p.403-13.
9
-
page P&D Information Bulletin / Vol. 19 No. 1, 201110
CYP3A4,5,7CYP2E11234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
1234567890123456789012345678901212345678901234567890123456789012123456789012345678901234567890121234567890123456789012345678901212345678901234567890
Acetaminophen induced nephrotoxicity
AST 21,960 U/L, ALT 5,415 U/L transaminase enzyme 1,000 U/L
1. viral hepatitis2. shock liver, ischemic hepatitis3. toxin or drug induced hepatotoxicity
5 / 2030 / fulminant hepatitis acetaminophen induced hepatotoxicity creatinine (2.8 mg/dl) (nephrotoxicity) Acetaminophen induced nephrotoxicity acetaminophen (APAP) (extrahepatic tissue) extra-hepatic tissue renal functionabnormality (1,2) renal insufficiency
12 % APAP overdose (2) 25% significant hepatotoxicity(3,4) 50% hepartic failure (5,6)
retrospective case series APAP nephrotoxicity (7) APAP-induced nephrotoxicity 8.9% APAP (7)
prospective study 275 encephalo-pathy coagulopathy APAPinduced fulminanthepatic failure 43-57% creatininine > 2 mg/dl (8)
APAP-induced fulminant hepaticfailure hepatic failure (6) APAPoverdose renal damage hepatoxicity (9 11)Pathophysiology Primary toxicity APAP drug metabolism (12) 1%
. ..
47 .: 1 : 1-2 (500 .) 10 4-6
1 : A Thai female with marked icteric sclera:
Liver function test: AST 21,960 U/L ALT 5,415 U/LALP 122 U/L TB/DB 10.9/5.7 mg/dlBUN 27.8 mg/dl Cr 2.8 mg/dl
-
page 11
toxic intermediate, N-acetylimidoquinone cytochrome P450 pathway cellularmacromolecules cell injury cell death cytochrome P450 activity phenobarbital, phenytoin APAP-induced nephotoxicity (13)
Acute kidney injury:
1. Renal impairment 2% 2. 5% 3. 10 % 4. 53 % fulminant hepatic failure (14-15)
Histopathology histopathology acute tubular necrosis(ATN) (16) urinary analysis APAPinduced nephrotoxicity renal insufficiency hepatorenal syndrome (HRS) prerenal azotemia 1 (14,17)1 Urinalysis Findings Acute Renal Failure (14,17)
organ failure medical comorbidity renal dyfunction (17)Management and the role of N-Acetylcysteine (NAC)
BUN, Cr renalinsufficiency ATN prerenal azotemia hepatorenal syndrome 1
NAC APAP -induced livernecrosis APAP-induced nephrotoxicity NAC NAC (24,25) NAC NAC isolatedrenal function NAC peritoneum APAP (26) NAC (22)Summary
APAP induced nephropathy APAP isolated renaltoxicity multisystem organ failure APAP induced nephropathy recover NAC APAP
NAC supportive care, serial monitoring of urine output, bloodpressure markers of glomerular filtration
Manifestation
glutathione starvation,alcoholism cytochrome P450 enzyme intermediatemetabolite (18) renal insufficiency 1-8 2-5 creatinine 7 316 renal function 1 1% multisystem
Parameter ATN Prerenal Azotemia HRSSediment Granular casts +/-cells None NoneOsmolality Same as plasma Greater than plasma Greater than plasmaUrine sodium >20 mmol/L
-
page P&D Information Bulletin / Vol. 19 No. 1, 2011 12
1. Hamlyn AN, Douglas AP, James O. The spectrum of(acetaminophen) overdose: Clinical and epidemiologicalstudies. Postgrad Med J 1978;54:400-4.2. Prescott LF. Paracetamol overdosage: Pharmacologicalconsiderations and clinical management. Drugs 1983;25:290-314.3. Davenport A, Finn R: Paracetamol (acetaminophen) poisoningresulting in acute renal failure without hepatic coma. Nephron1988;50:55-56.4. Prescott LF, Proudfoot AT, Cregeen RJ. Paracetamol-induced acute renal failure in the absence of fulminant liverdamage.Br Med J (Clin Res Ed) 1982 Feb 6;284(6313):421-2.5. Makin A, Williams R. The current management of paracetamoloverdosage. Br J Clin Pract 1994;48:144-8.6. Wilkinson SP, Moodie H, Arroyo VA, Williams R. Frequencyof renal impairment in paracetamol overdose compared withother causes of acute liver damage. J Clin Pathol 1977Feb;30(2):141-37. Boutis, K, Shannon M. Nephrotoxicity after acute severeacetaminophen poisoning in adolescents. Clin Toxicol2001;39:41-445.8. Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E,Hynan. LS, et al. Acetaminophen-induced acute liver failure:results of a. United States multi-center, prospective study.Hepatology. 2005;42:(6)1364-72.9. Cobden I, Record CO, Ward MK, Kerr DN. Paracetamol-induced acute renal failure in the absence of fulminant liverdamage. Br Med J (Clin Res Ed) 1982; 284:21-2. 10 . Kher K, Makker S. Acute renal failure due to acetaminopheningestion without concurrent hepatotoxicity. Am J Med 1987;82:1280-1.11.Ozkaya O, Genc G, Bek K, Sullu Y. A case of acetaminophen(paracetamol) causing renal failure without liver damage in achild and review of literature. Ren Fail 2010; 32(9):1125-7.12 . Gu J, Cui H, Behr M, Zhang L, Zhang QY, Yang W et al.In vivo mechanisms of tissue-selective drug toxicity: effectsof liver-specific knockout of the NADPH-cytochrome P-450reductase gene on acetaminophen toxicity in kidney, lung, andnasal mucosa. Mol Pharmacol 2005;67:62330.
13. Rose BD, Post TW. Acetaminophen (paracetamol)-inducedacute kidney injury (acute renal failure).UpToDate online 18.3[cited 2010 dec 20] Available from:http://www. uptodate.com/ o n l i n e / c o n t e n t / t o p i c . d o ? t o p i c K e y= r e n l f a i l /7856&selectedTitle=2%7E150& source=search_result14. Blakely P, McDonald BR. Acute renal failure due toacetaminophen ingestion: a case report and review of theliterature. J Am Soc Nephrol 1995 Jul;6(1):48-53.15. Wilkinson SP, Moodie H, Arroyo VA, Williams R. Frequencyof renal impairment in paracetamol overdose compared withother causes of acute liver damage. J Clin Pathol 1977; 30:141-3. 16. Blantz RC. Acetaminophen: acute and chronic effects onrenal function. Am J Kidney Dis. 1996 Jul;28(1 Suppl 1):S3-6.17 .Mazer M, Perrone J. Acetaminophen-induced nephrotoxicity:pathophysiology, clinical manifestations, and management. JMed Toxicol. 2008 Mar;4(1):2-6.18. Bray GP, Harrison PM, O'Grady JG, Tredger JM, WilliamsR. Long-term anticonvulsant therapy worsens outcome inparacetamol-induced fulminant hepatic failure. Hum ExpToxicol 1992; 11: 265-70.19. Eguia L, Materson BJ. Acetaminophen-related acuterenal failure without fulminant liver failure. Pharmacotherapy1997 Mar-Apr;17(2):363-70.20. Slitt AL, Dominick PK, Roberts JC, Cohen SD. Standardof care may not protect against acetaminophen-inducednephrotoxicity. Basic & Clinical Pharmacology & Toxicology2004;95:2478.
( warfarin(drug interaction of warfarin))1. Su M, Hoffman RS.Anticoagulants.In:Goldfrank LR,Flomenbaum NE, Hoffman RS, Howland MA, Lewin NA,Nelson LS, editors. Goldfranks Toxicologic Emergences. 8thed. New York: McGraw-Hill;2007.p 887-902.2. Indiana university department of medicine school ofmedicine. Cytochrome P450 Drug Interaction Table. Version5.0 released on January 12, 2009. [cite 2010 July 1].Availablefrom:URL http://www.drug-interactions.com.
