Halogenated volatile agents

Halogenated volatile agents are inhalational anesthesia gases used during surgeries to provide general anesthesia.

They are metabolized to varying degrees. There is biotransformation in the liver resulting in cleavage and dehalogenation by the specific enzyme P450, which is a haemocytochrome present in the hepatic cell.

Desflurane (CHF2-O-CHFCHF3): It is one of the halogenated volatile agents and is very minimally metabolized (0.1%), its molecule is similar to isoflurane with fluorine atom substituted for chlorine, which makes the molecule resistant to biotransformation. The end products are fluorine and trifluro acetic acid in negligible amounts.

Isoflurane: (CHF,-O-CHCI-CF) It is one from the halogenated volatile agents which is an isomer of enflurane, less than 0.2% is metabolized by oxidation of carbon by hepatic enzymes. The end products are trifluoro acetic acid (TFA), the TFA and protein adducts and a very small amount of organic fluorides.

Enflurane: (CHF2-O-CF2-CHCIF): Another halogenated volatile agents and with 2.5% ofenflurane is metabolized. There is oxidation to difluoro methoxy difluoro acetic acid and fluoride. Isoniazid induces its metabolism significantly.

Sevoflurane: (CH2F-O-CH-(CF3)2): In this halogenated volatile agents , there is oxidation of 5% of sevoflurane to hexafluro isopropanol which conjugates with glycine to form a glucuronide and excreted.

Halothane: (CF3 CHBRCI): Approximately 25% of halothane administered is metabolized by oxidation to trifluoroacetic acid. Less than 1% of halothane metabolises in low oxygen when Br and F are end products.

Trichioroethylene (Trilene) (CCI2=CHCI): about 50% of trichloroethylene is metabolized first to an active intermediate product, chioral hydrate, which also produces sedation. Thereafter, trichioraceticacid and trichloroethanol.

Methoxyflurane: This halogenated volatile agents has the highest metabolism, about 65— 70% is metabolized in the liver by cytochrome P450 to methoxyfluoroacetic acid and dichloracetic acid. Dichloracetic acid is transformed to oxalic acid and then to CO2 and H20. Methoxyfluoracetic acid is acid labile and decomposed to oxalic acid and fluoride; both the reactions produce fluoride ions which are nephrotoxic if greater than 50 µmol/L. There is postoperative polyuric renal insufficiency.

Methoxyflurane is though one of the halogenated volatile agents but is not used clinically anymore.



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