Safety of Intravenous and Inhalation Anesthetics
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I.I.1 I.I.1.1 I.I.1.2 I.I.2 I.I.2.1 I.I.2.2 I.I.2.3
Determination of Safety of Intravenous Anesthetics . . . . . General Considerations . . . . . . . . . . Tests for Safety of Intravenous Anesthetics . . . . . . . Determination of Safety of Inhalation Anesthetics . . . . . . . General Considerations . . . . . . . . . . Safety Margin of Inhalation Anesthetics . . . . . . . . Determination of Minimal Alveolar Anesthetic Concentration (MAC) . . . . . . . . . . . . . . . . . . . . . . . . . .
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I.I.1 Determination of Safety of Intravenous Anesthetics I.I.1.1 General Considerations PURPOSE AND RATIONALE
The first agents used as intravenous anesthetics were barbiturates. Barbiturates with a duration of action appropriate to the requirements of surgery became available with the introduction of hexobarbital and thiopental (Volwiler and Tabern 1930; Miller et al. 1936). The studies with barbiturates were extended (Butler and Bush 1942; Christensen and Lee 1973). Intravenous anesthetics from other chemical groups were developed, such as acetamido-eugenol (Estil, Domenjoz 1959), steroid derivatives (Presuren=hydroxydione sodium, Laubach et al. 1955, alfaxolone, CT1341, Child et al. 1971), propanidid (Epontol, Goldenthal 1971), ketamine (CI-581, Chen et al. 1966; Reich and Silvay 1989), etomidate (Janssen et al. 1975), propofol (ICI 35868, Glenn 1980), midazolam (Pieri 1983; Reilly and Nimmo 1987). REFERENCES Büch H, Butello W, Neurohr O, Rummel W (1968) Vergleich von Verteilung, narkotischer Wirksamkeit und metabolis-
cher Elimination der optischen Antipoden von Methylphenobarbital. Biochem Pharmacol 17:2391–2398 Büch H, Grund W, Buzello W, Rummel W (1969) Narkotische Wirksamkeit und Gewebsverteilung der optischen Antipoden des Pentobarbitals bei der Ratte. Biochem Pharmacol 18:1995–1009 Butler TC, Bush MT (1942) Anesthetic potency of some new derivatives of barbituric acid. Proc Soc Exp Biol Med 50:232–243 Chen G, Ensor CR, Bohner B (1966) The neuropharmacology of 2-(o-chlorophenyl)-2-methylaminocyclohexanone hydrochloride. J Pharm Exp Ther 152:332–339 Child KJ, Currie JP, Davis B et al. (1971) The pharmacological properties in animals of CT1341 – a new steroid anaesthetic agent. Br J Anaesth 43:2–24 Christensen HD, Lee IS (1973) Anesthetic potency and acute toxicity of optically active di-substituted barbituric acids. Toxicol Appl Pharmacol 26:495–503 Domenjoz R (1959) Anaesthesist 8:16 Glenn JB (1980) Animal studies of the anesthetic activity of ICI 35868. Br J Anaesth 52:731–742 Goldenthal EI (1971) A compilation of LD50 values in newborn and adult animals. Toxicol Appl Pharmacol 18:185–207 Janssen PAJ, Niemegeers CJE, Marsboom RPH (1975) Etomidate, a potent non-barbiturate hypnotic. Intravenous etomidate in mice, rats, guinea pigs, rabbits and dogs. Arch Int Pharmacodyn 214:92–132 Laubach GD, Pan SY, Rudel HW (1955) Steroid anesthetic agent. Science 122:78 Miller E, Munch JC, Crossley FS, Hartung WH (1936) J Am Chem Soc 58:1090 Pieri L (1983) Preclinical pharmacology of midazolam. Br J Cli
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