The rational pharmacology of digoxin.

Although digoxin remains one of the most widely prescribed drugs in the United States, potential pharmacodynamic and pharmacokinetic interactions between this compound and other drugs, diseases, and events commonly encountered in the perioperative period remain largely unappreciated. Furthermore, the therapeutic benefit of discontinuing or initiating digoxin treatment preoperatively remains unclear. We present a basic review of current knowledge regarding digoxin pharmacology and examine those concepts from the perspective of clinical anesthesiologists.

Isoniazid-induced enflurane defluorination in humans.

Serum inorganic fluoride (F-) levels were measured in 20 surgical patients treated with 300 mg isoniazid per day for periods of up to one year, prior to anesthesia with enflurane. Thirty-six control patients anesthetized with enflurane, but taking no drugs, also were studied. Regression lines for peak serum fluoride were plotted against enflurane exposure in MAC-hours. Nine isoniazid-treated patients had fluoride levels significantly (P less than 0.001) higher (y = 22.2x + 12.0) than either the 11 other isoniazid-treated patients (y = 5.0x + 8.2) or the 36 control patients (y = 5.4x + 6.3). Peak serum fluoride values in three patients exceeded 100 microM but in no patient did values exceed 10 microM by 48 h after anesthesia. It was concluded that isoniazid treatment resulted in enzyme induction in the nine patients with high peak fluoride levels. This pattern, i.e., induction occurring in approximately one-half the patients, probably is related to the genetically determined bimodal distribution of rapid and slow acetylation of isoniazid.