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  • Image not available. Repetitive administration of barbiturates (eg, infusion of thiopental for “barbiturate coma” and brain protection) saturates the peripheral compartments, minimizing any effect of redistribution, and rendering the duration of action more dependent on elimination. This is an example of context sensitivity.
  • Image not available. Barbiturates constrict the cerebral vasculature, causing a decrease in cerebral blood flow, cerebral blood volume, and intracranial pressure.
  • Image not available. Although apnea may be relatively uncommon after benzodiazepine induction, even small intravenous doses of diazepam and midazolam have resulted in respiratory arrest.
  • Image not available. In contrast to other anesthetic agents, ketamine increases arterial blood pressure, heart rate, and cardiac output, particularly after rapid bolus injections.
  • Image not available. Induction doses of etomidate transiently inhibit enzymes involved in cortisol and aldosterone synthesis. Etomidate was often used in the past for ICU sedation before reports of its consistent ability to produce adrenocortical suppression in that circumstance appeared.
  • Image not available. Propofol formulations can support the growth of bacteria, so sterile technique must be observed in preparation and handling. Propofol should be administered within 6 h of opening the ampule.


General anesthesia began with inhaled agents but now can be induced and maintained with drugs that enter the patient through a wide range of routes. Drug administration can be oral, rectal, transdermal, transmucosal, intramuscular, or intravenous for the purpose of producing or enhancing an anesthetic state. Preoperative sedation of adults is usually accomplished by way of oral or intravenous routes. Induction of general anesthesia in adults usually includes intravenous drug administration. Effective topical anesthesia with EMLA (eutectic mixture of local anesthetic) cream, LMX (plain lidocaine cream 4% and 5%), or 2% lidocaine jelly has increased the ease of intravenous inductions in children. Maintenance of general anesthesia is feasible with a total intravenous anesthesia (TIVA) technique. This chapter focuses on the intravenous agents used to produce hypnosis, including barbiturates, benzodiazepines, ketamine, etomidate, and propofol.


Mechanisms of Action


Barbiturates depress the reticular activating system in the brainstem, which controls multiple vital functions, including consciousness. In clinical concentrations, barbiturates more potently affect the function of nerve synapses than axons. Their primary mechanism of action is believed to be through binding to the γ-aminobutyric acid type A (GABAA) receptor. Barbiturates potentiate the action of GABA in increasing the duration of openings of a chloride-specific ion channel.


Structure-Activity Relationships


Barbiturates are derived from barbituric acid (Figure 9-1). Substitution at carbon C5 determines hypnotic potency and anticonvulsant activity. A long-branched chain conveys more potency than does a short straight chain. Likewise, the phenyl group in phenobarbital is anticonvulsive, whereas the methyl group in methohexital is not. Replacing the oxygen at C2 (oxybarbiturates) with a sulfur atom (thiobarbiturates) increases lipid solubility. As a result, thiopental and thiamylal have a greater potency, more rapid onset of action, and shorter durations of action (after a single “sleep dose”) than pentobarbital. The sodium salts of the barbiturates are water soluble but markedly alkaline ...

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