Chapter 8

• 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.
• Non–protein-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 6-glucuronide) 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 severe enough to prevent adequate ventilation.
• The stress response to surgical stimulation is measured in terms of the secretion of specific hormones, including catecholamines, antidiuretic hormone, and cortisol. Opioids block the release of these hormones more completely than volatile anesthetics.
• In sharp contrast to other anesthetic agents, ketamine increases arterial blood pressure, heart rate, and cardiac output. These indirect cardiovascular effects are due to central stimulation of the sympathetic nervous system and inhibition of the reuptake of norepinephrine.
• Induction doses of etomidate transiently inhibit enzymes involved in cortisol and aldosterone synthesis. Long-term infusions lead to adrenocortical suppression that may be associated with an increased mortality rate in critically ill patients.
• Propofol formulations can support the growth of bacteria, so good sterile technique must be observed in preparation and handling. Sepsis and death have been linked to contaminated propofol preparations.
• Droperidol is a potent antiemetic; however, delayed awakening limits its intraoperative use to low doses (0.05 mg/kg, to a maximum of 2.5 mg). The antidopaminergic activity of droperidol rarely precipitates extrapyramidal reactions (eg, oculogyric crises, torticollis, agitation), which can be treated with diphenhydramine. Nonetheless, droperidol should be avoided in patients with Parkinson disease.

General anesthesia is not limited to the use of inhalation agents. Numerous drugs that are administered orally, intramuscularly, ...

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