摘要:

Despite recent advances in understanding of the pharmacokinetics and electrophysiologic effects of cardiac glycosides, digitalis toxicity remains distressingly common in clinical practice. Another substantial group of patients is markedly underdigitalized, failing to gain the full therapeutic benefits of optimal use of these drugs. Since cardiac digitalis toxicity is a dose-related phenomenon, and serum or plasma digoxin and digitoxin concentrations rise with increasing doses, at least a statistical correlation between circulating levels and clinical state might be expected. Increasing availability of serum or plasma digitalis concentration measurements thus offers the clinician a potential means of improving the patient's chances of benefiting from treatment with cardiac glycosides. Assay methods in current use include a double-isotope dilution derivative method (digitoxin), red cell86Rb-uptake inhibition (digitoxin and digoxin), Na+-K+ATPase inhibition (digitoxin), ATPase enzymatic displacement (digitoxin and digoxin), gas chromatography (digoxin), and radioimmunoassay (digitoxin, digoxin, and ouabain).The rapidly expanding literature reporting clinical experience with these technics reflects general agreement that mean serum or plasma digoxini and digitoxin levels are significantly higher in patients with clinical evidence of toxicity compared with nontoxic patients. Nevertheless, multiple factors influence individual responses, and blood level data must be interpreted in the overall clinical context. Hypokalemia, hypercalcemia, hypomagnesemia, acid-base disturbances, hypoxemia, and hypothyroidism all tend to decrease tolerance to any given digitalis dose or blood level. Autonomic nervous system tone and other drugs concurrently received must also be considered. Advanced heart disease in general, and coronary artery disease in particular, appear to predispose patients to apparent digitalis toxicity at relatively lower serum or plasma levels.Cardiac glycoside assay technics have also proven useful in various studies of the clinical pharmacology of digoxin, digitoxin, and ouabain. Handling of digoxin by patients on cardiopulmonary bypass has been assessed, and gastrointestinal absorption has been evaluated in normal subjects; poor and erratic absorption of the drug has been documented in patients with malabsorption syndromes. Potentially important drug-drug interactions of agents such as phenobarbital and phenylbutazone with digitoxin have been studied, as well as the effects of steroid-binding resins on digoxin and digitoxin metabolism. Studies of ouabain pharmacokineties by radioimmunoassay have demonstrated a plasma half-life of 21 hours, indicating that, as in the case of digoxin and digitoxin, half-life of serum or plasma concentration after establishment of blood-tissue equilibrium bears a close relationship to duration of clinical effect.

ISSN:0009-7322    

出版商:OVID    

年代:1972

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1972

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1972

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1972

数据来源: OVID