Injectable Anesthetics

Substances from different chemical classes suspend consciousness when given intravenously and can be used as injectable anesthetics (B). Unlike inha-lational agents, most of these drugs affect consciousness only and are devoid of analgesic activity (exception: keta-mine). The effect cannot be ascribed to nonselective binding to neuronal cell membranes, although this may hold for propofol.

Most injectable anesthetics are characterized by a short duration of action. The rapid cessation of action is largely due to redistribution: after intravenous injection, brain concentration climbs rapidly to anesthetic levels because of the high cerebral blood flow; the drug then distributes evenly in the body, i.e., concentration rises in the periphery, but falls in the brain—redistribution and cessation of anesthesia (A). Thus, the effect subsides before the drug has left the body. A second injection of the same dose, given immediately after recovery from the preceding dose, can therefore produce a more intense and longer effect. Usually, a single injection is administered. However, etomidate and propofol may be given by infusion over a longer time period to maintain unconsciousness.

Thiopental and methohexital belong to the barbiturates which, depending on dose, produce sedation, sleepiness, or anesthesia. Barbiturates lower the pain threshold and thereby facilitate defensive reflex movements; they also depress the respiratory center. Barbiturates are frequently used for induction of anesthesia.

Ketamine has analgesic activity that persists beyond the period of unconsciousness up to 1 h after injection. On regaining consciousness, the patient may experience a disconnection between outside reality and inner mental state (dissociative anesthesia). Frequently there is memory loss for the duration of the recovery period; however, adults in particular complain about dis-Lullmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license.

tressing dream-like experiences. These can be counteracted by administration of a benzodiazepine (e.g., midazolam). The CNS effects of ketamine arise, in part, from an interference with excitatory glutamatergic transmission via li-gand-gated cation channels of the NMDA subtype, at which ketamine acts as a channel blocker. The non-natural excitatory amino acid N-methyl-D-aspartate is a selective agonist at this receptor. Release of catecholamines with a resultant increase in heart rate and blood pressure is another unrelated action of ketamine.

Propofol has a remarkably simple structure. Its effect has a rapid onset and decays quickly, being experienced by the patient as fairly pleasant. The intensity of the effect can be well controlled during prolonged administration.

Etomidate hardly affects the auto-nomic nervous system. Since it inhibits cortisol synthesis, it can be used in the treatment of adrenocortical overactivity (Cushing's disease).

Midazolam is a rapidly metabolized benzodiazepine (p. 228) that is used for induction of anesthesia. The longer-acting lorazepam is preferred as adjunct anesthetic in prolonged cardiac surgery with cardiopulmonary bypass; its am-nesiogenic effect is pronounced.

Periphery: relatively

CNS:

relatively high blood flow

Periphery: relatively low flow blood g tissue

Initial situation

Initial situation

concentration

Redistribution

High concentration in tissue

High concentration in tissue i.v. injection

tively small unt of drug mg drug x g tissue i.v. injection tively small unt of drug mg drug x g tissue

Low concentration in tissue

Preferential accumulation of drug in brain concentration concentration

Lorazepam Injection Preparation
Steady-state of distribution
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