Modification of controlled hypotension induced by nicardipine or nitroprusside in cats pretreated with injectable acetyl salicylic acid

Controlled hypotension is a well established technique to decrease blood loss and improve surgical visibility. Several different pharmacologic agents have been used for controlled hypotension including direct acting vasodilators such as sodium nitroprusside and calcium channel blockers [Testa and Tobias, l995]. This study was designed to assess the effect of non-steroidal anti-inflammatory drug [NSAID] acetyl salicylic acid [ASA] therapy on the efficacy and safety of I.V. infusion of nicardipine compared with the more commonly used agent; sodium nitroprusside. The effect of each drug on blood pressure and ECG pattern of normal"control" cats and cats pretreated with [ASA] was investigated. A target mean arterial pressure [MAP] of 55-65 mmHg was to be achieved. It was found that both nicardipine and nitroprusside achieved a stable controlled hypotensive state in control groups. Comparison between the two drugs revealed a significant increase in [MAP] with nitroprusside after drug discontinuation. Pretreatment with [ASA], attenuated significantly the effect of nicardipine infusion on [MAP]. However, pretreatment with ASA produced insignificant effect on the decrease in MAP caused by nitroprusside except at 4 min. during infusion where ASA pretreatment attenuated its effect. Moreover [ASA] pretreatment decreased nitroprusside dose needed to reach the target blood pressure and increased time of blood pressure to returin to base line. Both nicardipine and nitroprusside infusion caused increase in mean heart rate [HR] without ECG changes in control and pretreated groups.There was a Statistically significant increase in [HR] in the [ASA] pretreated groups of both drugs when compared to that in the control groups. When the increase in [HR] induced by nitroprusside infusion was compared to that induced by nicardipine infusion, there was insignficiant difference in the control groups, while in [ASA] pretreatred groups the difference was significant

Pharmacological interactions between ondansetron, an antiemetic drug, and some neuromuscular blockers, succinyl-choline, mivacurium and atracurium

This study was designed to evaluate the effect of the antiemetic ondansetron [5-hydroxytryptamine subtype 3 receptor antagonist] on the onset, potency and recovery rate of succinylcholine, mivacurium and atracurium induced neuromuscular blocking effect both in vitro and in vivo experiments. The study showed that ondansetron should be administered cautiously to the patients using the muscle relaxants [succinylcholine, mivacurium and atracurium] to protect against its initial depolarizing effect and the possible interference with the potency and the rate of recovery of muscle relaxation during surgical procedures

inotropic drug dopexamine: pharmacodynamic and effect of its interaction with digoxin on blood pressure, electrocardiogram recordings, blood glucose, serum electrolytes content and acute toxicity in experimental animals

Since co-administration of inotropic drugs is frequent in the management of acute heart failure, a possible interaction between these drugs may occur. So, in this study the interaction between dopexarnine and digoxin on arterial blood pressure, ECG pattern. glucose and electrolytes level in the blood of experimental dogs was investigated. The effect of dopexamine alone and Its site of action on these parameters was firstly carried out On blood pressure of anaesthetized dogs, 10 minutes intravenous infusion of dopexarnine [1, 2 and 4 micro g/kg/mini caused a biphasic action: initial vasodilatation and subsequent vasoconstriction. With the aid of selective dopaminerglc receptor antagonists. haloperidol and bulbocapnine, the Initial vasodilatation was shown to be mediated by stimulation of DA2 and DA1 respectively. Prior blockade of uptake l with cocaine prevented the subsequent vasoconstriction suggesting that this effect is mediated by uptakel blockade thus potentiating the effect of endogenous noradrenaline. This explanation was furtherty confirmed when dopexamine administration attenuated the hypertensive effect of tyramine. By contrast, large doses of dopexamine [8 and 16 1micro g/kg/min]. in this work, produced fall in blood pressure which was proved to be mainly due to beta 2 adrenargic agonistic activity. In the present study, prevention of reflex compensation by ganglion block-ads and airopine almost prevented dopexarnine-Induced tachycardia. This demonstrates that the positive chronotropic action of dopexarnine is due to baroreceptor activation which occurs secondary to the drop of blood pressure. Also, we have shown in this work that the tachycardia mediated by dopexamine was reduced after cocaine administration. This suggests that the chronotropic response of the drug may be also due to its blocking effect on neuronal uptake I, thus providing larger concentration of the neurotransmitter to act at the betal adrenoceptors. As regards the effect of dopexamine on glucose and electrolytes level in the blood of dogs, it was found in the present study, that large doses of the drug only produced significant drop of serum potassium and rise of plasma glucose levels in experimental dogs. Dopexamine-digitalis combination, in this work, didn't produce significant changes in the effects of dopexamine on arterial blood pressure, ECG, blood glucose and serum electrolytes content of dogs. Significant potentiation of either dopexamine or digoxin-induced hypokalaemia as well as prolongation of PR interval were noticed by co-administration of digoxin with 16 micro g/kg/min of dopexamine only. In the acute toxicity test, administration of 180 and 720 micro g/kg of dopexamine with digoxin to mice shifted the intraperitoreal median lethal dose [LD50] of digoxin from 5.8 mg/kg to 6.6 and 5.2 mg/kg respectively. In conclusion, the present study has shown that no significant interaction between digoxin and dopexamine on blood pressure, ECG, blood glucose and serum electrolytes content of dogs was observed. However coadministration of digoxin with the large dose of clopexamine accentuated digoxin-Induced hypokalaemia. So patients receiving this combined therapy may require monitoring of their potassium level since hypokalaemia may increase the risk of digoxin intoxication