Pharmacokinetic parameters of morphine after ocular instillation versus intravenous administration

The route of administration of morphine, other than parenteral administration may be promising in increasing the compliance in patients that continuously need morphine for its analgesic effect. Morphine systemic penetration was investigated after ocular instillation. Its pharmacokinetic parameters and its bioavailability after ocular instillation compared to its intravenous administration were determined in healthy New Zealand albino rabbits. A cross over design was performed with an eight days wash-out period between the ocular and intravenous administrations. After ocular instillation, morphine was rapidly absorbed and attained serum levels compatible with effective concentration for its analgesic effect. Ocular bioavailability of morphine was high [66%]. Ocular administration of morphine could provide prolonged high serum levels and prolonged systemic pharmacologic effect. Ocular administration of morphine should be considered for its systemic pharmacologic effect

Pharmacodynamics of pipecuronium neuromuscular blockade under peripheral hypothermia in child and cat: a combined clinical and pharmacological study

20 ASA class I or II children subjected to elective surgery were studied. Their mean + SD age was 3.4 + 1.4 year [range: 10 months-7 years], body weight: 15.6 + 4.8 kg [range: 10-25 kg]. Male/female ratio: 13/7. Anaesthesia was induced with thiopental 33.5 mg kg-1. Intubation was facilitated by topical Xylocaine 4% without a muscle relaxant. Peripheral hypothermia [30C] was induced in the right arm using ice bags. Body core and left arm temperature was given a ED95 [50 mu kg-1]. Neuromuscular function analyzer NS252 was used to deliver TOF stimulation at 12 second intervals. Onset of action of pipecuronium, duration of blockade and reversal time were recorded in minutes. Experimental study was conducted on intact anesthitized cat gastrocnemius sciatic nerve prepartion using an electronic square pulse stimulator and a platinum electrode. ED95 of pipecuronium was first estimate. Onset of action duration and reversal time of pipecuronium induced and the same parameters were recorded. It was found that peripheral hypothermal has significantly delayed the onset of action of pipecuronium from 2.4 + 1 to 5.5 + 1.3 min. In child and from 5 2 to 8 2.5 min. in cat [p < 0.001 and p < 0.05 respectively]. The duration of blockade was significantly increased form 35 + 6.5 to 46 + 8 min. in child and from 35 + 8 to 55 10 min. in cat [p < 0.01 and p < 0,05 respectively]. Reversal time was also significantly increased from 3.3 + 1 to 5.2 + 1.2 min. In child and form 5 + 3 to 13 + 4.4 min. In cat [p < 0.001]. Hypothermia has also reduced the cat gastrocnemius evoked twitch tension to 50% of its normothermic value. In conclusion peripheral hypothermia [30C] has markedly delayed the onset of action of pipecuronium in both child and cat. It augmented the duration of blockade. Reversal with neostigmine was hindered. These findings can be valuable if this drug is used in children during hypothermic cardiopulmonary bypass or in those subjected to inadvertent hypothermia

Infarct size reduction by timolol and prenylamine

The ability of the B-receptor blocker, timolol and the Ca[2+] channel antagonist prenylamine to limit infarct size [I.S.] was assessed in cats, 5 hours after ligation of the left anterior descending coronary artery [LAD]. In control untreated cats, the S-T segment was raised significantly 30 min. after ligation to reach a value of 0.7 +/- 0.09 MV and was maintained significantly elevated [0.67 +/- 0.07 MV] to the end of the experiment. Ventricular dysrhythmia occurred in 3 out of 6 cats and ended in one of them by ventricular fibrillation and death. Serum CPK level increased significantly from a pre-occlusion level of 94 +/- 5 U/L to reach 724 +/- 60, 5 hours later. The I.S., measured by planimetry in serial cardiac sections, stained by triphenyl tetrazolium stain, was found to measure 315 +/- 34 mm[2] representing 31.67% of the heart. Timolol, given in a dose of 25 ug/kg i.v., 15 min. before ligation of LAD, induced hypotension, sinus bradycardia and decreased S-T segment elevation significantly to 0.13 +/- 0.04 MV. It prevented ventricular dysrhythmia and fibrillation. Timolol also reduced significantly serum CPK level to 195 +/- 17 U/L and I.S. to 9.18%. I.V. administration of prenylamine in a dose of 3 mg/kg was accompanied by sinus bradycardia, and hypotension. The S-T segment was significantly lowered [0.15 +/- 0.04 MV] and ventricular fibrillation was prevented. Both serum CPK level [193 =/- 25 U/L] and I.S. [12.93] were significantly reduced when compared with the corresponding levels in coronary ligated untreated cats. It is concluded that, both timolol and prenylamine could protect the heart against extension of infarct size and its complication. An effect which might be due to decrease in free cytosolic Ca[2+] or through their haemodynamic effects which reduce the cardiac work

Cardioprotective effect of captopril on the catecholamine-induced myocardial necrosis

The cardioprotective effect of captopril, a converting enzyme inhibitor, was studied on the isoprenaline-induced myocardial necrosis [M.N.] in rats. The degree of protection was assessed biochemically by measuring variations in level of serum CPK and histopathologically by estimating infarct size [I.S.]% i.e. surface area of injured myocardium to area of heart sections, after being stained with haematoxylin basic fuchcin picric acid stain. Also, injury currents in ECG were looked for. Pretreatment with captopril in a dose of 100 ug/kg i.p., 15 min. before injection of a necrotizing dose of isoprenaline [300 mg/kg] s.c., was found to be highly protective. The serum CPK and I.S. of rats pretreated with captopril were markedly decreased. Moreover, the injury currents, which were observed in ECG of rats treated with isoprenaline, disappeared in captopril treated rats. Injected 15 min. after isoprenaline, captopril was found to be protective but less effective than if it was administered before isoprenaline although used in the same dose level. The mean values of serum CPK and I.S. of post-treated rats were significantly lower than the corresponding values in isoprenaline-treated rats. Further reduction of the cardioprotective effect of captopril was noticed on increasing the post-treatment interval to 30 min. Captopril protects the heart effectively against catecholamine-induced myocardial necrosis. This protective effect proved to be time-related, the earlier the intervention, the better the results

Some possible mechanisms underlying the hypotensive action of clonidine

Intravenously injected clonidine HCL in a dose of 20 ug/kg in cats has produced a biphasic effect on the arterial blood pressure. There was an initial limited pressor response followed by a significant, gradual long lasting vasodepressor effect. Such hypotensive action was completely abolished in spinal cat preparation, with preservation of the initial pressor effect. Also, the hypotensive action was blocked by the H[2]-receptor blocker, cimetidine, opioid antagonist, naloxone, proper atropinization and by the cycloxygenaze enzyme inhibitor, indomethacin. This work supports that such hypotensive effect of clonidine is mainly central through inhibition of noradrenaline release. An effect which is suggested to be under multi-receptor control involving alpha 2 adrenergic, cholinergic, opioid, H[2] and prostaglandin receptors