Effect of the H2 antagonist cimetidine versus famotidine on serum theophylline level and theophylline induced hypokalemia in rats

The effect of the H[2] antagonists on serum theophylline level was determined both directly by measuring serum theophylline concentrations at 0.5 - 1 - 2 - 4 and 6 hours after a single therapeutic dose of the drug [l0mg/kg intraperitoneally [IP]] in control [untreated] rats and in rats pretreated with Cimetidine [100 mg/kg] or famotidine [4 mg/kg] orally for 1 week and indirectly by determining the influence of these H[2] antagonists [in the above doses] on the degree of hypokalemia induced by a single high dose of theophylline [25 mg/kg Ip] [theophylline induced hypokalemia is believed to correlate well with serum theophylline level]. The results showed that Cimetidine consistently induced a statistically significant increase in serum theophylline level starting 1 hour after injection [10.3% [P<0.05] and thereafter [40.6 - 41.6 and 45.2% at 2-4 and 6 hours respectively [P<.0005]]. In contrast famotidine did not induce significant changes in serum theophylline level [P>.05] during the total duration of the experiment. Moreover, high dose theophylline induced a statistically significant reduction [P<.0005] in serum K+ from a control value of 3.9 +/- .06 to 3.5 +/- .047 mEq/L [10.25%]; pretreatment with Cimetidine resulted in a further reduction in serum K+ from 3.5 +/- .047 to 3.2 +/- 0.04 mEq/L [8.5% P<.0005] whereas pretreatment with famotidine resulted in an insignificant change [3.5 +/- .047 versus 3.4 +/- 0.07 mEq/L 2.8%P>.05]. Since H [2] receptor antagonists and theophylline may be given concurrently in more than one clinical setting [prophylactic against development of gastrointestinal symptoms of theophylline, in reflux oesophagitis occurring in as many as 30-60% of asthmatics or in patients with upper gastrointestinal bleeding who are intubated and maximally bronchodilated], clinicians should be alert to the significant interaction. Serum theophylline concentration should be measured periodically, measurement of serum potassium could also assist indirectly in prediction of serum theophylline level. Finally famotidine could be a safer alternative to cimetidine whenever H[2] antagonists are given concurrently with theophylline

Assessment of the hypnotic activity of etomidate alone and in combination with either diazepam or thiopentone-sodium in mice

The effect of etomidate alone and in combination with either thiopentone sodium or diazepam was assessed on the sleeping time and muscle strength. The drug was injected intraperitoneally in therapeutic doses in adult albino mice of both sexes and the time for loss and recovery of the righting reflex [R.R.] were recorded. Both drug combinations, according to the results obtained, would give excellent intravenous anaesthesia. However, etomidate-diazeparn would be superior to etomidate-thiopentone, in view of the additive hypno-sedative and myorelaxant properties of diazepam, and the cardio-respiratory depressant potential of thiopentone

cardiotoxicity of the tetracyclic antidepressant mianserin HCl in guinea pigs

Mianserin hydrochloride is a newly introduced antidepressant of the tetracyclic series. Unlike imipramine and other tricyclic antidepressants, mianserin was reported to be free of cardiotoxicity. In the present study the effect of the drug on the ECG pattern in anaesthetized guinea pigs was investigated in gradually increasing doses up to the toxic level. Prior to these experiments, the L.D[50] of the drug was determined in mice by the intraperitoneal route over 24 hours and 5 days. The results obtained are discussed and compared with previous findings for tricyclic drugs

curative and prophylactic propertics of sotalol and propranolol on adrenaline induced arrhysthmia

Sotalol is a non selective beta adrenoceptor blocking agent that differs from propranolol in having no membrane stabilising properties. In the present study the antiarrysthmic, effect of sotalol was shown when injected immediately after, or 2 minutes before adrenaline injection in anaesthetised dogs. 2mg/ Kg b.w. sotalol prevented as well as cured arrhythmic effect of even large dose of adrenaline while 0.2mg/ Kg b.w. propranolol was needed to produce the same effect. Sotalol was also evaluated clinically as regards its usefulness against the cardiac arrhythmia that may arise in patients after infiltration of adrenaline in the presence of halothane anaesthesia

Comparative study of the analeptic-respirogenic agents doxapram HCl and nikethamide: I - the acute toxicity and analeptic activity in mice

LD50 determinations showed that both Doxapram HCl and Nikethamide fall in the category of moderate toxicity; but Doxapram HCl was the less toxic. Assessment of the arousal capacity of Doxapram HCl against sleeping doses of pentobarbitone sodium in mice demonstrated that the drug has a high therapeutic index. Assessment of the restorative activity of Doxapram HCl and of Nikethamide against toxic doses of pentobarbitone sodium as percentage survival in mice, demonstrated the higher potency of Doxapram HCl

Comparative study of the analeptic-respirogenic agents doxapram HCl and nikethamide: II - respirogenic and cardiovascular pharmacodynamic activites in dogs

Experiments in pentobarbitone-sodium anesthetized dogs revealed that Doxapram HCl was a more potent respirogenic agent than Nikethamide; but at higher doses tachyphylaxis develops. Further assessments of its respirogenic activity in halothane-anesthetized dogs, by calculation of the minutevolume demonstrated a significant increase in ventilatic. These respirogenic effects were accompanied by transientrise in blood pressure at lower doses, and by bradycardia at higher doses. Nikethamide lowered the blood pressure at all dose levels, while it produced no ECG changes. Both drugs produced a dose-related direct myocardial depression of the isolated heart. The site of the respirogenic and cardiovascular effects of Doxapram HCl, was investigated after vagotomy, by intravertebral injection and in the spinal dog. The results demonstrated that the drug acts by central and peripheral mechnisms; and that its action may be partly through sympathetic influence