Inhibition of paracetamol induced reduction in hepatic glutathione level by INH of rifampin coadministration in mice

Repated administration of paracetamol induces hepatotoxicity due to depletion of the liver tissue from its glutathione contents. As paracetamol may be currently used in combination with INH and rifampin it was notworthy to explore the effect of these drugs on hepatic glutathione contents. Paracetamol, INH and rifampin were given either alone or in combination. After certain period of drug treatment, the animals were sacrificed and their livers were homogenized to determine its glutathione contents. It was observed that paracetamol significantly decreased while either INH or rifampin significantly increased the glutathione contents of the liver. When given in combination, both INH and rifampin could prevent the decrease in glutathione level when paracetamol was given with either of them for 2 days and only partially when it was given for 7 days. How much this effect can be benificial ? this needs thorough clinical investigation

relationship between cyclic AMP elevating agents and neuromuscular blockers

The effects of aminophylline, papaverine and forskolin on the neuromuscular transmission were studied using isolated rat phrenic nerve-diaphragm preparation. These cyclic AMP elevating agents were found to be capable of enhancing the diaphragmatic contractions elicited by indirect electrical stimulation. The paralysis of the indirectly stimulated rat diaphragm induced by d-tubocurarine was inhibited by aminophylline, papaverine and forskolin, while that induced by succinylcholine was deepened. Pretreatment with adenosine inhibited the enhancement effect of aminophylline, papaverine and forskolin on the contractions of the indirectly stimulated rat diaphragm. Doubling the concentration of calcium in the bathing fluid potentiated the effects of the three compounds on the rat phrenic nerve-diaphragm preparations-while doubling the concentration of external magnesium inhibited their effects. The pretreatment with aminophylline, papaverine and forskolin reduced the toxicity of d-tubocuranine in mice. These results suggest that aminophylline, papaverine and forskolin promote neuromuscular transmission, obviously by facilitating the release of acetylcholine. This finding is compatible with the hypothesis that the intracellular accumulation of cyclic AMP may facilitate the calcium influx and transmitter release from the mammalian motor nerve endings

Effect of GABA, GABA agonists and antagonists on gastric ulcer in rats

In the present investigation the effect of gamma-aminobutyric acid [GABA] on indomethacin [IM] [25 mg/kg orally] induced gastric ulcer in rats was studied. Results revealed that GABA at doses of 75 mg/kg [I.P.] and 150 mg/kg [I.P.] were devoid of significant effect on IM-induced ulceration, mean while higher doses of GABA 300 mg/kg [I.P.] and [450 mg/kg [I.P.] potentiated IM-ulceration. Regarding the effect of GABA antagonists, data proved that picrotoxin [2.5 mg/kg I.P] bicuculline [2.5 mg/kg I.P.] and pentylenetetrazole [PTZ] [25 mg/kg I.P.] blocked the aggravating effect of GABA on IM-induced gastric ulceration. It was noticed that GABA antagonists produced no significant changes on IM-ulceration. Also diazepam [0.5 mg/kg I.P.] and pentobarbital [5 mg/kg I.P.] potentiated the exacerbating effect of GABA on IM-induced gastric ulceration. At the same time both diazepam and pentobarbital were devoid of significant effect on IM-ulceration. In contrast GABA agonist muscimol [6 mg/kg orally] had cytoprotective effect against IM-induced gastric ulceration, while GABA agonist baclofen [6 mg/kg orally] showed no significant effect on IM- ulceration However, atropine [1 mg/kg I.P.] was protective against both IM-induced gastric ulceration and the GABA potentiating effect of IM -ulceration. The results suggested that GABA induced exacerbation of IM -ulceration might be due to the activation of peripheral muscarinic receptors in the stomach. This effect was mediated by stimulation of GABA[A] .-receptors and not GABA receptors in the stomach

Effect of midazolam and diazepam on either spontaneous or oxytocin induced contractions of isolated pregnant mouse uterus near term

Midazolam is a water soluble member of the benzodiazepine group of drugs which were thoroughly investigated as sedative hypnotics and anticonvulsant drugs. However its effect on the uterus was not yet sufficiently explored. Therefore the present study was carried on to investigate the effect of midazolam and diazepam on the isolated uterus of pregnant mouse near term. Doth midazolam and diazepam were added to the organ bath either alone or after oxytocin. The effects of these drugs on the uterus were recorded and compared with the effect of magnesium sulfate as a tocolytic agent. Diazepam produced significant decrease in the spontaneous uterine activities. Neither midazolam nor diazepam could produce any effect on the oxytocin induced uterine contractions compared to magnesium sulfate which could inhibit both spontaneous as well as oxytocin induced uterine activities. It was concluded that midazolam and diazepam can be used therapeuticaly as an alternative for magnesium sulfate to control eclamptic fits without interference with the effect of oxytocin if it is indicated to induce labour

effect of the simultaneous use of acetylsalicylic acid and propranolol on dogs with experimentally induced hypertension

The effect of aspirin on the antihypertensive effect of propranolol was investigated. Experimental renal hypertension was induced by bilateral partial ligation of the renal arteries. Propranolol was given either alone into one group of animals or combined with aspirin into other group. The mean BP, heart rate, blood electrolytes, urea and creatinine were determined. Aspirin could obtund the antihypertensive effect of propranolol. The possible mechanisms for these were discussed. It can be concluded that propranolol may act through stimulation of prostaglandin synthesis therefore, its effect could be attenuated by co-administration of aspirin

Potentiation of the neuromuscular blocking effects of both atracurium and pancuronium by propofal an in vitro study

The possible interaction between propofol and the non-depolarizing muscle relaxants is still debatable. This study was carried out to clarify the effect of propofol on the skeletal muscle and its possible interactions with atracurium and pancuronium. The isolated rat phrenic-nerve diaphragm preparation bathed in krebs solution was used in this study. Propofol alone produced concentration dependent muscle relaxation. Moreover it potentiated the neuromuscular blockade of atracurium and pancuronium. The ED50 was significantly reduced from 39.60 [ +/- 1.3] to 26.20 [ +/- 0.72] and from 1.86 [ +/- 0.06] to 1.01 [ +/- 0.04] ug/ml for atracurium and dpancuronium respectively. Although the dose response curves of either atracurium or pancuronium with propofol as fitted by regression line analysis were shifted to the left, there was no difference in their slopes compared to the slope of their curves when they were given : alone. In conclusion, the present study suggests that propofol can potentiate the effect of either atracurium or pancuronium. This should be taken in consideration in therapeutic use of propofol. However this needs further clinical assessment

Some cardiovascular responses elicited by beta-adrenergic antagonists, calcium-entry blockers and their combinations

The present study was carried out on both intact rabbits and isolated perfused rabbit's heart for the assessment of the cardiovascular actions of Ca++ - entery blockers, beta blockers and their combinations. The results indicated that the Ca++ blockers, verapamil and nifedipine and the non selective beta blocker propranolol have a negative inotropic and chronotropic effects on the isolated heart preparation. The selective B-blocker atenolol, depressed the myocardium only in very high dose which is much greater than the therapeutic dose. The combinations of the two groups have an additive negative inotropic and chronotropic actions. The combinations of verapamil with the beta blockers, specially propranolol produced much more negative inotropic effect than when nifedipine was used instead of verapamil. The individual drugs of both groups have a hypotensive effect on the blood pressure [B.P.] of rabbits. The combinations of both groups of the drugs have no additive effect on the B.P. of rabbits. Electrocardiographic monitoring indicated that each verapamil, propranolol, atenolol and their combinations produced bradycardia and prolongation of both P-R and Q-T intervals. Nifedipine caused tachycardia and shortening of Q-T interval. The two groups of drugs produced insignificant changes in the electrolyte levels in serum and cardiac tissue except for Ca++ ion level in the cardiac tissue which was significantly reduced by the individual Ca++ blocking drugs and by their combination with the B-blockers