Allopurinol influences aminophenazone elimination

The authors observed an interaction between allopurinol and both theophylline and warfarin in 2 patients. To determine the possible effect of allopurinol on hepatic oxidative metabolism a [14C]-aminophenazone (aminopyrine) breath test was performed before and during treatment with allopurinol 100mg daily in 5 patients with hyperuricaemia. Allopurinol prolonged the [14CO2]-aminophenazone half-life from 72 +/- 13 to 104 +/- 16 minutes (mean +/- SEM, p less than 0.05). It is possible that allopurinol may produce clinically significant drug interactions through an inhibitory effect not only on xanthine oxidase metabolism but also on oxidative metabolism.     

Uhthoff's symptom in multiple sclerosis

A case report is presented in which a patient's initial complaint is of blurred vision after exercise (Uhthoffs symptom). Visual acuity and colour vision were found to be reduced after exercise. Additional neurological signs included homonymous scotomata and delayed visual evoked and somatosensory responses. Magnetic resonance imaging demonstrated multiple abnormal lesions in the brain. The significance of this symptom and its relationship to multiple sclerosis are discussed.     

Analgesic profile of the sodium salt of pemedolac

Pemedolac Na, 1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b] indole-1-acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED₅₀ values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall-Selitto model, the ED₅₀ o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ-induced writing in mice with an ED₅₀ of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley-Liss, Inc.     

VASOCONSTRICTION IN THE RENAL VASCULAR BED DURING EXERCISE: STUDIES IN CONTROL AND HEART FAILURE RABBITS

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.