Halothane pharmacokinetics

Levitt, D.G., PKQuest volatile solutes — Application to enflurane, nitrous oxide, halothane, methoxyflurane and toluene pharmacokinetics, BMC Anesthesiol, 2, 5, 2002. 

Older The elderly are at increased risk of adverse drug reactions in general due to altered pharmacokinetics and polypharmacy. For example, reactions to halothane, chlorpromazine, flucloxacillin and co-amoxiclav are more common in elderly patients... 

Caldwell JE, Canfell PC, Castagnoli KP, Lynam DP, Fahey MR, Fisher DM, Miller RD. The influence of renal failure on the pharmacokinetics and duration of action of pipecuronium bromide in patients anesthetized with halothane and nitrous oxide. Anesthesiology 1989 70(1) 7-12. 

Wierda JM, Kleef UW, Lambalk LM, Kloppenburg WD, Agoston S. The pharmacodynamics and pharmacokinetics of Org 9426, a new non-depolarizing neuromuscular blocking agent, in patients anaesthetized with nitrous oxide, halothane and fentanyl. Can J Anaesth 1991 38(4 Pt l) 430-5. 

Muir W W 1995 The haemodynamic effects of milrinone HCI In halothane anaesthetized horses. Equine Veterinary Journal Supplement 19 108-113 Muir W W, Mcguirk S M 1985 Pheirmacology and pharmacokinetics of drugs used to treat cardiac disease in horses. Veterinary Clinics of North America Equine Practice 1 335-352 Muir W W D, Mcguirk S 1987 Cardiovascular drugs. Their pharmacology and use In horses. Veterinary Clinics of North America Equine Practice 3 37-57 Muir W W D, Reed S M, Mcguirk S M 1990 Treatment of atrial fibrillation in horses by intravenous administration of quinidine. Journal of the American Veterinary Medical Association 197 1607-1610... 

Alfentanil pharmacokinetics, analgesic efficacy and behavioral effects have been evaluated in the horse. Alfentanil (0.02-0.04 mg/kg i.v.) produces a significant increase in locomotor activity in horses (Pascoe et al 1991). Electroencephalography (EEG) after alfentanil administration (0.04mg/kg) during halothane anesthesia in the horse shows a reduction in the frequency power... 

Bennett R C, Steffey E P 2002 Use of opioids for pain and anesthetic management in horses. Veterinary Clinics of North America Equine Practice 18 47-60 Bennett R C, Taylor P M, Brearley J C et al 1998 Comparison of detomidine/ketamine and guaiphenesin/thiopentone for induction of anaesthesia in horses maintained with halothane. Veterinary Record 142 541-545 Bettschart-Wolfensberger R, Clarke K W, Vainio O et al 1999 Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation. Research in Veterinary Science 67 41-46 Bettschart-Wolfensberger R, Freeman S L. Jaggin-... 

Hug C G (eds) Pharmacokinetics of anaesthesia. Blackwell, Boston, MA, p. 157 Riedesel D H, Hildebrand S V 1985 Unusual response following use of succinylcholine in a horse anesthetized with halothane. Journal of the American Veterinary Medical Association 187 507-508 Robertson S A, Carter S W, Donovan M et al 1990 Effects of intravenous xylazine hydrochloride on blood glucose, plasma insulin and rectal temperature In neonatal foals. Equine Veterinary Journai 22 43-47 Roger T, Bardon T, Ruckebush Y 1994 Comparative effects of mu and kappa opiate agonists on the cecocolic motility In the pony. Canadian Journal of Veterinary Research 58 163-166... 

Example Inhalation Volatile liquids halothane (Fluothane), Route Inhalation Pregnancy category C Pharmacokinetic Metabolized in liver eliminated via ... 

Table 3.10 Pharmacokinetic parameters showing the influence of halothane anaesthesia on the disposition of gentamicin (4 mg/kg, i.v.) in horses. Results are expressed as mean + SD n = 6.

Pharmacokinetic parameter Gentamicin Gentamicin + halothane Significance3... 

CLINICAL USE Halothane is a potent, nonpungent and well-tolerated agent that usually is used for maintenance of anesthesia and is well tolerated for inhalation induction of anesthesia, most commonly in children, in whom preoperative placement of an intravenous catheter can be difficult. Anesthesia is produced by halothane at end-tidal concentrations of 0.7-1%. The use of halothane in the U.S. has diminished substantially since the introduction of newer inhalational agents with better pharmacokinetic and side-effect profiles. 

Halothane reduces splanchnic and hepatic blood flow. Halothane can produce fulminant hepatic necrosis in a small number of patients, a syndrome characterized by fever, anorexia, nausea, and vomiting, developing several days after anesthesia and sometimes accompanied by a rash and peripheral eosinophilia. There is a rapid progression to hepatic failure, with a fatality rate of -50%. This syndrome occurs in about 1 in 10,000 patients receiving halothane and is referred to as halothane hepatitis. Halothane hepatitis may be the result of an immune response to hepatic proteins that become trifluoroacetylated as a consequence of halothane metabolism see Pharmacokinetics, above). 

A. Classification and Pharmacokinetics The agents currently used in inhalation anesthesia are nitrous oxide (a gas) and several easily vaporized liquid halogenated hydrocarbons, including halothane, desflurane. enflurane, isoflurane, sevoflurane, and methoxyflurane. They are administered as gases their partial pressure, or tension, in the inhaled air or in blood or other tissue is a measure of them concentration. Since the standard pressure of the total inhaled mixture is atmospheric pressure (760 mm Hg at sea level), the partial pressure may also be expressed as a percentage. Thus 50% nitrous oxide in the inhaled air would have a partial pressure of 380 mm Hg. The speed of induetion of anesthetic effects depends on several factors ... 

In addition to pharmacokinetic drug-drug interactions, pharmacodynamic effects have been reported as well. Halothane increases the susceptibility to ventricular arrhythmias under theophylline therapy as a result of increased sensitivity of the myocardium to endogenous catecholamine release by theophylUne. Ketamine lowers the theophyUine seizure threshold. Benzodiazepines Uke midazolam, diazepam, lorazepam, and Uurazepam increase the central nervous system concentration of adenosine, a potent central nervous system depressant. As theophyUine also blocks adenosine receptors, it counteracts benzodiazepine-induced sedation, resulting in increased dosage requirements for these compounds. ... 

The pharmacokinetics of (+)-tubocurarine in man with and without renal failure, and anaesthetized with halothane and nitrous oxide, have been studied. Other studies with (+)-tubocurarine include investigations of its effects on neurally evoked compound electromyograms, its actions at hyperbaric pressures, the effects of circulating residue of the ED50 dose five minutes after injection on unexposed neuromuscular junctions, the uptake of (+)-tubo-curarine by liver lysosomes, the potentiation of (+)-tubocurarine neuromuscular blockade by lithium chloride in cats, effects on the heart and on ocular function, and the distribution of the alkaloid in cerebrospinal fluid after intravenous injection. The clinical pharmacology of dimethyl-(+)-tubocurarine (metocurine) has also been studied. ... 

Most of the F NMR studies are related to anaesthetic, psychoactive and antineoplastic drugs. The distribution of anaesthetics in the brain and the pharmacokinetics of their elimination are still a subject of controversy. The feasibility of in vivo F NMR studies of halothane in humans has been recently demonstrated. Resonances attributable to this compound were observed up to 90 min after withdrawal of the anaesthetic agent in eight patients. 

In vivo F MRS has also been used to study the pharmacokinetics and metabolism of anaesthetic agents such as halothane, isoflurane and desflurane in experimental animals. It has also been shown that anaesthetic agents can be observed noninvasively in the brains of patients immediately following surgery. The principal aim of these studies was to elucidate the mechanism of action of these compounds and eventually help in the development of more effective and selective anaesthetics. Unfortunately, factors such as sensitivity and localization of the region of interest (which are particularly relevant to the study of anaesthetics) have greatly limited the impact of this research. 

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