Amanita phalloides poisoning is the most common cause of lethal mushroom poisoning (lethality >20% in adults, >50% in children). However, there is no standard treatment strategy and no antidote against the ensuing hepatic failure. This review of 14 investigations published over the last 20 years shows that the introduction of detoxification techniques, in particular the use of plasmapheresis, in combination with supportive therapy to prevent the absorption of aminitine toxins into blood, produced a substantial reduction in mortality. The main complications in using these techniques include infections and coagulation disorders. Because of the latency period in the development of symptoms, treatment should begin on the first suspicion that an intoxication is present. The best therapeutic results can be expected when the detoxification techniques are applied in combination with conservative therapies within the first 36–48 h. Using this approach, mortality rates in some recent studies have been below 10%.

SUMMARYCyclo-oxygenase-2-selective inhibitors produce less gastric damage than conventional non-steroidal antiinflammatory drugs. Valdecoxib is a new orally administered cyclo-oxygenase-2-selective inhibitor, recently approved for use in osteoarthritis, rheumatoid arthritis and primary dysmenorrhoea in the USA. The drug has been evaluated in more than 60 clinical studies involving more than 14 000 patients and healthy volunteers. The analgesic efficacy of valdecoxib at a dose of 10 mg once daily in both osteoarthritis and rheumatoid arthritis is superior to that of placebo and similar to that of traditional non-steroidal anti-inflammatory drugs. Valdecoxib is effective in single doses of up to 40 mg for the alleviation of acute menstrual pain and has a rapid onset of action (within 30 min) and a long duration of analgesia (up to 24 h). Valdecoxib is well tolerated and has safety advantages compared with traditional non-steroidal anti-inflammatory drugs in terms of less gastrointestinal toxicity and a lack of an effect on platelet function. The incidence of adverse effects involving the kidney (fluid retention, oedema and hypertension) is similar to that of non-selective, nonsteroidal anti-inflammatory drugs.

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1 A search for patient variables relevant to digoxin dose requirements was made in forty-three patients with a wide range of renal and hepatic function. The daily dose of digoxin to achieve a mean serum concentration of 1.5 ng/ml, the standardized dose, was calculated for each patient. 2 The standardized dose correlated significantly with the following variables, in descending order of correlation coefficient; creatinine clearance, serum creatinine concentration, body weight and serum albumin concentration. An equation containing the two independent variables, creatinine clearance and serum albumin concentration, had a significantly stronger correlation with standardized dose than creatinine clearance alone. 3 Attempts were made in each patient to predict the standardized dose using both empirical prescribing methods and the published nomograms. Although a maximum of 70% of the variance of the standardized dose was explained, this corresponded approximately to one patient in three having a predicted dose outside the 95% confidence limits for the standardized dose. 4 There remain important sources of individual variation in digoxin dose requirements yet to be identified. Future application of empirical prescribing methods, such as multiple linear regression and Bayes' theorem, to prescription for large, defined patient groups may improve dose prediction for individual patients.

Verapamil kinetics have been determined in liver disease (mainly in cirrhotic patients), in intensive-care patients, and in healthy control subjects. Areas under the concentration-time curves (AUCs) after intravenous 5-mg and oral 80-mg doses were used to calculate systemic blood clearance, intrinsic blood clearance, and bioavailability of verapamil in patients and to calculate apparent hepatic blood flow. Intravenous data showed that verapamil clearance was reduced in all patients with liver disease (mean = -66%), but intensive-care patients were a more heterogenous group in which some patients had increases (five patients; mean = +72%) and others had decreases (two patients; mean = 6-57%) in verapamil clearance. The changes in clearance corresponded to changes in the half-time for the beta-phase (t1/2 beta). Verapamil bioavailability is low, and the intensive-care patients and healthy subjects examined it ranged from 13% to 21%. There was considerable variation in liver disease subjects, in whom verapamil bioavailability ranged from 3.8% to 64%. THe systemic clearance of verapamil correlated linearly with calculated apparent hepatic blood flow (r = 0.99; regression coefficient = 0.87). In the case of one liver patient the kinetic results could be used to confirm the clinical diagnosis of hepatic shunts. It is concluded that there are clinically significant changes in verapamil elimination in liver disease and in intensive-care patients. For patients with normal hepatic vascular anatomy, these changes can be explained in terms of differences in hepatic blood flow.

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