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Chapter 8. Nonvolatile Anesthetic Agents

Sections in this chapter:

Key Concepts Nonvolatile Anesthetic Agents: Introduction Pharmacological Principles Pharmacokinetics Pharmacodynamics Specific Nonvolatile Anesthetic Agents Barbiturates Benzodiazepines Opioids Ketamine Etomidate Propofol Droperidol Profiles in Anesthetic Practice Case Discussion: Premedication of the Surgical Patient Suggested Reading

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KEY CONCEPTS
As plasma concentration falls, some drug leaves the highly perfused organs to maintain equilibrium. This redistribution from the vessel-rich group is responsible for termination of effect of many anesthetic drugs. For example, awakening from the effects of thiopental is not due to metabolism or excretion but rather to redistribution of the drug from brain to muscle. Nonprotein-bound drugs freely cross from plasma into the glomerular filtrate. The nonionized fraction of drug is reabsorbed in the renal tubules, whereas the ionized portion is excreted in urine. Elimination half-life of a drug is proportional to the volume of distribution and inversely proportional to the rate of clearance. The plasma concentration of a drug with long half-lives may still fall rapidly if distribution accounts for the vast majority of the decline and elimination is a relatively insignificant contributor. Therefore, the rate of clinical recovery from a drug cannot be predicted by its half-lives alone. Repetitive administration of barbiturates saturates the peripheral compartments, so that redistribution cannot occur and the duration of action becomes more dependent on elimination. Barbiturates constrict the cerebral vasculature. This effect may protect the brain from transient episodes of focal ischemia (eg, cerebral embolism) but probably not from global ischemia (eg, cardiac arrest). Although apnea may be less common after benzodiazepine induction than after barbiturate induction, even small intravenous doses of diazepam and midazolam have resulted in respiratory arrest. Ventilation must be monitored in all patients receiving intravenous benzodiazepines, and resuscitation equipment must be immediately available. The accumulation of morphine metabolites (morphine 3-glucuronide and morphine 6glucuronide) in patients with renal failure has been associated with narcosis and ventilatory depression lasting several days. Opioids (particularly fentanyl, sufentanil, and alfentanil) can induce chest wall rigidity

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