Warfarin resistance with nafcillin therapy.

Drug-induced warfarin resistance may be mediated by the direct effect of a drug on warfarin's absorption, excretion, distribution, or metabolism. A 29-year-old man on long-term stable anticoagulation therapy with warfarin sodium developed resistance to warfarin while receiving nafcillin. His prothrombin time ranged between 14 and 17 s (control, 12 s) despite an increase in his warfarin dosage to 25 mg/d. Pharmacokinetic studies showed that the decreased hypoprothrombinemic effect of warfarin was most likely due to rapid metabolism of the anticoagulant induced by nafcillin. Warfarin's half-life was 11 hours when the patient was on nafcillin therapy and 44 hours when he was off nafcillin therapy. This interaction may be clinically important in patients requiring concomitant administration of nafcillin and warfarin.

Importance of time-related parameters of pre-optic electrical stimulation in the release of LH in the pentobarbital-blocked pro-oestrous rat.

The effectiveness of pre-optic stimulation in overcoming the pentobarbital blockade of ovulation in the rat has long been recognized and employed in neuroendocrine investigations. Although some reports have appeared comparing certain aspects of electrical stimulation in effectiveness in releasing LH, no complete study in female rats has been reported. The present study utilized regularly cycling rats of the Charles River CD strain in which ovulation was blocked by the injection of sodium pentobarbital on the afternoon of pro-oestrus. Electrical stimulation was delivered through bipolar platinum electrodes stereotaxically positioned in the preoptic area, and LH was measured in plasma samples obtained at the onset of stimulation and 10, 20, 30, 45, 60, 80, 120 and 150 min thereafter. LH release was established in response to a baseline set of parameters: 15 HZ, 1.5 mA and 1.5 ms per phase, 30 s on/off for 60 min. Stimulations employing equi-coulombic increments of 1/3 introduced in each parameter in turn were compared in groups of 4-6 animals. Use of small increments in each parameter allowed the detection of those parameters to which the pre-optico-hypothalamo-pituitary system is most sensitive over the range studied, namely duration: of each pulse and of the overall stimulation period. This observation may be explained in terms of characteristics of the pituitary responsiveness.