Efectividad de la morfina por vía subaracnoidea versus tramadol más ketorolaco por vía intravenoso en el control del dolor postquirúrgico en cirugías ortopédicas de miembros inferiores / Effects of morphine by more subarachnoid tramadol versus intravenous ketorolac in controlling postoperative pain in orthopedic surgery of the lower limbs

Se realizó un ensayo clínico, ciego simple, aleatorizado, con intención a tratar. EL objetivo fue valorar la efectividad analgésica postquirúrgica de cirugias de miembros inferiores y los efectos secundarios del sulfato de morfina administrado por vía subaracnoidea versus el tramadol más Ketorolaco por vía intravenosa. La muestra fue de 122 sujetos, divididos en dos grupo A (n=60) a quienes se les administró 500 microgramos de morfina más bupivacaína hiperbárica vía subaracnoidea y al grupo B (n=60) a los que se les administro tramadol 100 mg más ketorolaco 60 mg vía intravenosa, los resultados fueron que la morfina más bupivacaina fue más efectiva que el tramadol más ketorolaco para el control del dolor postquirúrgico. Con un efecto análgesico de 23 horas versus 12 horas del grupo B valor de p menor 0.005. Las reacciones adversas más frecuentes fueron: prurito, náuseas y retención urinaria...

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease) can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2). In the other experiment, apneic threshold PaC0(2) was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit.

Behavioral changes of Wistar rats with experimentally-induced painful diabetic neuropathy

With the purpose of studying data on spontaneous customary changes in diabetic rats, we induced diabetes in 28 Wistar rats with streptozotocin. The animals were observed for 27 weeks in an attempt to characterize spontaneous customary chages that could suggest signs of chronic pain. Morphine, as a central-acting potent analgesic and its specific antagonist naloxone, were used. Our results evidenced in the animals a clinical syndrome similar to human diabetes. Long-term customary analysis revealed a significant (p<0.05) increase of scratching and resting/sleeping behaviors, but diminished motor, eating and grooming customs. Moreover, the thermal tests revealed hyperalgesia in 43 per cent of the animals, what may corroborate the meaning of scratching as a sign of pain. Pharmacological tests with morphine showed a significant (p<0.05) inhibition of scratch, with concomitant increase of motor and eating activities and diminished rest/sleep capacity. Naloxone antagonized the effects induced by morphine. Such results suggest that these animals exhibit evoked behavior of hyperalgesia and that scratch may possibly be a spontaneous manifestation of chronic pain also in Wistar rats with this experimental model of painful diabetic neuropathy.

Pharmacological analysis of acute morphine dependence in infant rats: close molecular relationship of head-shaking precipitated by opiate antagonists and cholinergic neurotransmission

The influence of drugs affecting different neurotransmitter systems on an acute abstinence heanshaking (AHS) model induced by nalorphine or naloxone was studied in 9-day-old rat pups pretreated (3 h before) with morphine (10mg/kg, i.p.). One hour after the injection of nalorphine (10 mg/kg, i.p.) AHS was stopped by a second dose of morphine (10 mg/kg, i.p.) and reinitiated 1 h later by a higher dose of nalorphine (20 mg/kg, i.p.). In other groups AHS was blocked by spiroperidol (0.1 mg/kg, i.p.), clonidine (0.01 mg/kg, i.p.) or scopolamine (50 mg/kg, i.p.). In these groups a second injection of nalorphine did not reinitiate AHS. In dose-effect curve experiments the AHS induced by naloxone or nalorphine was significantly reduced by previous injections of scopolamine, spiroperidol, metergoline or phentolamine in the corresponding groups. Scopolamine was the only antagonist which displaced the AHS dose-effect curves to the right without affecting the maximal response. Since no common receptors exist for a direct competitive interaction between opiate antagonists and scopolamine, these experiments suggest that a direct molecular relationship exists between the tissue concentration of nalorphine (or naloxone) and the endogenous ACh release during abstinence. Thus, the AHS model in 9-day-old rats clearly differentiates specific from non-specific blockade of the abstinence syndrome, and confirms a distinct or primary role of cholinergic neurotransmission in morphine abstinence

El empleo de la morfina y de otros narcóticos en el dolor por cáncer / The use of morphine and other drugs to relieve cancer pain

Exponemos los conocimientos que debemos concientizar sobre el dolor por cáncer y el empleo de la analgesia opioidea en los pacientes que lo requieren. Para ello abarcamos una breve reseña histórica del origen de la morfina, lugar de acción, mención de algunos morfínicos, sus efectos adversos, las actuales vías de administración, y añadimos los agonistas tipo morfina y los antagonistas.

Role of dopaminergic system in opioid-induced cardiovascular responses in dogs.

A study was carried out to determine the involvement of dopaminergic system in opioid-induced cardiovascular responses in the dogs. The study population consisted of 32 mongrel dogs of either sexes. The results show that morphine given in small dose (2 mg/kg I.V.) causes significant fall in blood pressure. The results also show that there is involvement of dopaminergic system in opioid-induced vasomotor responses in dogs. Partial blockade of the parenterally induced hypotensive response of morphine by haloperidol given centrally induced hypotensive responses of morphine by haloperidol given centrally in doses, which are too low to be effective by the peripheral route, strongly favours the involvement of central dopaminergic system in the morphine-induced hypotensive responses. The results also show that the hypotensive response of morphine was almost completely blocked after naloxone pretreatment by central route.

Morphine analgesia and its modification by drugs altering serotonin (5-HT) and dopamine levels in the brain.

Morphine analgesia in mice was significantly potentiated by pretreatment with 5-hydroxytryptophan (5-HTP), especially with higher dose of morphine. Morphine analgesia was antagonised by reserpine. With l-dopa it was antogonised when the dose of morphine was minimal but with increased dosage of morphine, there was no significant effect.

Studies on morphine analgesia.

Several agents with specific action on biologically active substances in brain were investigated for their influence on morphine analgesia. It was observed that imipramine, chlorpheniramine, and haloperidol antagonized morphine analgesia. The probable mechanism of action has been discussed.

On the Effect of Morphine Hydrochloride on the Mesenteric Mast cells of Albino Rats

Histological studies were carried out on the degranulation of mesenteric mast cells of white rats caused by injections of morphine and nalorphine hydrochloride intravenously and the following conclusions were obtained. 1. By the injection of morphine hydrochloride fairly significant degranulation of the mesenteric mast cell was observed. 2. In various experimental doses of morphine hydrochloride the cytological change of the degranulation was not proportional to the doses of it in cases given more than 12mg./kg. of body weight. 3. The degranulating effect of the mesenteric mast cell by the injection of morphine hydrochloride was significantly inhibited by an adrenalectomy.