Clinical Pharmacokinetics of the Newer Intravenous Anaesthetic Agents

Abstract

In the last 15 years the role of opioids in anaesthesia management has undergone dramatic change. Initially used as premedicants, or adjuvants to inhalation anaesthetic agents or as analgesics for postoperative pain relief, narcotics have now evolved into primary anaesthetic agents, primarily because of their ability to maintain cardiovascular stability especially in patients with compromised myocardial function. Sufentanil, alfentanil, and lofentanil are 3 new synthetic congeners of fentanyl. Sufentanil and alfentanil afford not only the haemodynamic stability but also the desirable anaesthetic properties of analgesia, and unconsciousness. Their major advantage lies in their pharmacokinetic behaviour; a rapid onset of action and short elimination half-life, allowing for greater flexibility in anaesthetic management. Sufentanil's pharmacokinetic profile is consistent with a 2-compartment model. Its elimination half-life is 149 minutes and its clearance is 11.3 ml/min/kg. Alfentanil's pharmacokinetic profile has been described by both 2- and 3-compartment models. Its distribution and redistribution are rapid, with an elimination half-life of 83 to 137 minutes and a clearance of 4.37 to 6.47 ml/min/kg in adult patients. Lofentanil, however, is an extremely long-acting narcotic analgesic. Presently, its use is justified only when prolonged mechanical ventilation is anticipated. Etomidate, a carboxylated imidazole, is rapidly distributed within a central compartment and then to peripheral compartments; its slow distribution and terminal elimination half-lives are 28 and 273 to 330 minutes, respectively, and its clearance (11.6 to 25 ml/min/kg) is equal to its hepatic plasma flow. Its ability to maintain cardiovascular stability in patients with compromised myocardial function make it a useful induction agent. However, reports of increased mortality and inhibition of steroidogenesis in patients receiving either single injections or constant infusions have created controversies regarding its use. Minaxolone is a water-soluble steroid whose pharmacokinetic profile is consistent with a 2-compartment model. Distribution is rapid with a mean half-life of 2.1 minutes and an elimination half-life of 47 minutes. There do not appear to be any cumulative effects. Plasma levels on recovery were similar in those patients receiving single bolus or continuous infusions. Midazolam and flunitrazepam are two new benzodiazepines. As a class of drugs, benzodiazepines provide the pharmacological properties of anxiolysis, sedation, hypnosis, muscle relaxation, amnesia and anticonvulsant activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Intramuscular Flunitrazepam Versus Intramuscular Haloperidol in the Emergency Treatment of Aggressive Psychotic Behavior

“…slightly longer half-life (19-22 hours versus 10-20 hours), allowing for prolonged antiaggressive action (15,16). It is the unaltered drug, not its metabolites, that is primarily responsible for the clinical effects (10).…”

The determination of total and unbound midazolam in human plasma. A comparison of high performance liquid chromatography, gas chromatography and gas chromatography/mass spectrometry

“…1; Dormicum "), a recently developed 1,4-benzodiazepine derivative is used for sedation, premedication, and intravenous anaesthesia (Dundee et al, 1984;Reves et al, 1985). The compound differs from other benzodiazepines mainly by a short plasma elimination half-life (1.3 to 3.2 h) and high metabolic clearance in healthy subjects (Amrein et al, 1981;Smith et al, 1981;Allonen et al, 1981;Davis and Cook, 1986;Bornemann et a/., 1986;Crevoisier et al, 1986;Heizmann et al, 1983).…”

Activation profiles of opioid ligands in HEK cells expressing δ opioid receptors

“…For example, as reported, etorphine [19] and lofentanil [20] were shown to be highly potent and efficacious at δ opioid receptors.…”