Anaesthesia pharmacokinetics

The ideal intravenous anaesthetic agent Mechanism(s) of intravenous anaesthesia Pharmacokinetics and metabolism Rapidly acting intravenous anaesthetics Non-barbiturate intravenous anaesthetics Slower-acting intravenous anaesthetics Other drugs INTRODUCTION... 

McDonnell CG, Harte S, O DriscollJ, O Loughlin C, Van Pelt FD, Shorten GD. The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam. Anaesthesia 2003 58 899-904. 

Gepts E 1998 Pharmacokinetic concepts for TCI anaesthesia. Anaesthesia 53 (SI) 4-12 Harper N 2001 Inhalational anaesthetics. 

Holley, F.O. van Steennis, C. Postoperative analgesia with fentanyl pharmacokinetics and pharmacodynamics of constant-rate IV and transdermal delivery. Br. J. Anaesthesia. 1988, 60, 608-613. 

Knibbe CA, Voortman HJ, Aarts LP, Kuks PF, Lange R, Langemeijer HJ, Danhof M. Pharmacokinetics, induction of anaesthesia and safety characteristics of propofol 6% SAZN vs propofol 1% SAZN and Diprivan-10 after bolus injection. Br J Clin Pharmacol 1999 47(6) 653-60. 

Cooper RA, Maddineni VR, Mirakhur RK, Wierda JM, Brady M, Fitzpatrick KT. Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure. Br J Anaesth 1993 71(2) 222-6. 

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-... 

Krasowski M D, Nishikawa K, Nikolaeva N et al 2001 Methionine 286 in transmembrane domain 3 of the GABAa receptor beta subunit controls a binding cavity for propofol and other alkylphenol general anesthetics. Neuropharmacology 41 952-964 Kristinsson J, Thordarson T H, Johannesson T 1996 Pharmacokinetics of lignocaine in Icelandic horses after infiltration anaesthesia. Veterinary Record 138 111-112... 

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... 

Wan P Y, Trim C M, Mueller P O 1992 Xylazine-ketamine and detomidine-tiletamine-zolazepam anesthesia in horses. Veterinary Surgery 21 312-318 Waterman A E, Amin A 1992 The influence of surgery and anaesthesia on the pharmacokinetics of pethidine in the horse. Equine Veterinary Journai Suppiement 11 56-58 Waterman A E, Robertson S A, Lane J G 1987 Pharmacokinetics of intravenously administered ketamine in the horse. Research in Veterinary Science 42 162-166... 

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.

Several studies have similarly found that the use of esmolol reduced the required dose of isoflurane or propofol, or resulted in a deeper anaesthesia (as measured by BIS), but only in the presence of an opioid. " As there appears to be no pharmacokinetic interaction between esmolol and propofol it has been suggested that esmolol could be interacting with the opioid. ... 

Two reviews have discussed the use of opioids and propofol in anaesthesia, their pharmacokinetic and pharmacodynamic interactions, and administration and monitoring techniques. ... 

Lichtenbelt B-J, Mertens M, Vuyk J. Strategies to optimise propofol-opioid anaesthesia. Chn Pharmacokinet (2004) 43, 577-93. 

The evidence for an interaction between sulfafurazole and thiopental is limited, but it appears to be strong. Less thiopental than usual may be required to achieve adequate anaesthesia, but since the awakening time is shortened repeated doses may be needed. Phenobarbital does not appear to affect the pharmacokinetics of the sulfonamides. 

A study on the use of chloroprocaine 3%, bupivacaine 0.5% or a mixture of chloroprocaine 1.5% with bupivacaine 0.375% in obstetric epidural anaesthesia found that time to onset of analgesia, time to maximum analgesia, and effectiveness of analgesia were similar irrespective of the treatment regimen. Bupivacaine 0.5% alone had a longer duration of action than chloroprocaine or the mixture of anaesthetics. Another study found that lidocaine did not affect the pharmacokinetics of bupivacaine. ... 

Pretreatment with eimetidine 300 mg intramuseularly 1 to 4 hours before epidural anaesthesia with 0.5% bupivaeaine (for eaesarean section) had no effect on the pharmacokinetics of bupivacaine in 16 women or their foetuses when compared with 20 control women, although the maternal unbound bupivacaine plasma levels rose by 22%. These findings were confirmed in two similar studies in which women were pretreated with cimetidine before caesarean section, and a further study in 7 healthy subjects (6 women and one man) given two oral doses of cimetidine 400 mg before intramuscular bupivacaine. However, the AUC of bupivacaine in 4 healthy male subjects was increased by 40% (when compared to placebo) by cimetidine 400 mg at 10 pm the previous evening and 8 am on the study day, followed by a 50-mg infusion of bupivacaine at 11 am. ... 

In 7 women given epidural anaesthesia for caesarean section the pharmacokinetics of 400 mg of lidocaine 2%, (given with adrenaline (epinephrine) 1 200 000) were unchanged after a single 150-mg oral dose of ranitidine given about 2 hours preoperatively. A similar study in 8 women also found no statistically significant rises in whole blood lidocaine levels in the presence of ranitidine 150 mg given orally at least 2 hours preoperatively. ... 

One man receiving intravenous lidocaine had a seizure about two days after starting treatment with amiodarone, and another man with sick sinus syndrome taking amiodarone had a sinoatrial arrest during placement of a pacemaker under local anaesthesia with lidocaine. There is conflicting evidence as to whether or not amiodarone affects the pharmacokinetics of intravenous lido-... 

---