 |
|
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|
Anesthesia Anesthesia during delivery was more frequent in autistic children who developed tardive (TD) and withdrawal dyskinesias (WD) than in those who did not (Armenteros et al, 1995). The agent used by Armenteros was Haloperidol, yet another fluorinated drug (4-fluorophenyl metabolite, see Fang et al, 2001). Most anesthetic agents are fluorinated. Other examples are halothane, sevoflurane, isoflurane, alyrane, etc. All easily cross the placenta. Organic fluoride compounds undergo extensive transformation in the liver, mainly via a process called oxidative demethylation, involving the thyroid hormone (T3) mediated P-450 enzyme system. In many instances the resulting metabolites may have higher activity and/or greater toxicity than the original compound. Ironically, an example often used as textbook case to demonstrate of how more-toxic metabolites are produced after passing through the liver, is Sevoflurane. Inorganic fluoride is a normal metabolite of Sevoflurane and thought to be responsible for the accompanying renal failure observed. see also: F- in Drugs ----------------------------------------------------- SEROFLURANE PACKAGE INSERT ALYRANE Monograph Armenteros JL, Adams PB, Campbell M, Eisenberg ZW - "Haloperidol-related dyskinesias and pre- and perinatal complications in autistic children" Psychopharmacol Bull 31(2):363-9 (1995) Fang J, McKay G, Song J, Remillrd A, Li X, Midha K - “In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomes” Drug Metab Dispos 29(12):1638-43 (2001) Frink EJ Jr, Ghantous H, Malan TP, Morgan S, Fernando J, Gandolfi AJ, Brown BR Jr - "Plasma inorganic fluoride with sevoflurane anesthesia: correlation with indices of hepatic and renal function." Anesth Analg 74(2):231-5 (1992) Nishiyama T, Hanaoka K -"Inorganic fluoride kinetics and renal and hepatic function after repeated sevoflurane anesthesia" Anesth Analg 87(2):468-73 (1998) Nishiyama T, Yokoyama T, Hanaoka K - "Effects of sevoflurane and isoflurane anesthesia on arterial ketone body ratio and liver function" Acta Anaesthesiol Scand 43(3):347-51 (1999)
|