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abbreviations: iiy2ß, ß phase half-life; CL, clearance; Vss, volume of distribution at steady state; EDTA, ethylenediaminetetraacetic acid; Na-MBS, Na-metabisulfite; PG, propylene glycol; PL, phospholipid.

abbreviations: iiy2ß, ß phase half-life; CL, clearance; Vss, volume of distribution at steady state; EDTA, ethylenediaminetetraacetic acid; Na-MBS, Na-metabisulfite; PG, propylene glycol; PL, phospholipid.

FIGURE 13-2 Context-sensitive half-time of general anesthetics. The duration of action of single intravenous doses of anesthetic/hypnotic drugs is similarly short for all and is determined by redistribution of the drugs away from their active sites. However, after prolonged infusions, drug half-lives and durations of action are dependent on a complex interaction between the rate of redistribution of the drug, the amount of drug accumulated in fat, and the drug's metabolic rate. This phenomenon has been termed the context-sensitive half-time; that is, the half-time of a drug can be estimated only if one knows the context—the total dose and over what time period it has been given. Note that the half-times of some drugs such as etomidate, propofol, and ketamine increase only modestly with prolonged infusions; others (e.g., diazepam and thiopental) increase dramatically.

Infusion Duration (hours)

FIGURE 13-2 Context-sensitive half-time of general anesthetics. The duration of action of single intravenous doses of anesthetic/hypnotic drugs is similarly short for all and is determined by redistribution of the drugs away from their active sites. However, after prolonged infusions, drug half-lives and durations of action are dependent on a complex interaction between the rate of redistribution of the drug, the amount of drug accumulated in fat, and the drug's metabolic rate. This phenomenon has been termed the context-sensitive half-time; that is, the half-time of a drug can be estimated only if one knows the context—the total dose and over what time period it has been given. Note that the half-times of some drugs such as etomidate, propofol, and ketamine increase only modestly with prolonged infusions; others (e.g., diazepam and thiopental) increase dramatically.

All three barbiturates are primarily eliminated by hepatic metabolism and renal excretion of inactive metabolites; a small fraction of thiopental undergoes desulfuration to the longer-acting hypnotic pentobarbital. Each drug is highly protein bound (Table 13-2). Hepatic disease or other conditions that reduce serum protein concentration will decrease the volume of distribution and thereby increase the initial free concentration and hypnotic effect of an induction dose.

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