Cellular and molecular mechanisms of drug dependence.

The molecular and cellular actions of three classes of abused drugs--opiates, psychostimulants, and ethanol--are reviewed in the context of behavioral studies of drug dependence. The immediate effects of drugs are compared to those observed after long-term exposure. A neurobiological basis for drug dependence is proposed from the linkage between the cellular and behavioral effects of these drugs.

Toxins.

Exposures to toxins are prevalent, frequently complicate surgical emergencies, and impact critical care. A fundamental understanding of pathophysiologic principles and management strategies is essential for the anesthesiologist frequently responsible for the acute care of patients who have toxicologic exposures. Given their pervasiveness and ability to confound the clinical presentations in the perioperative or intensive care setting, substances of abuse and asphyxiants warrant particular attention and a high degree of vigilance.

Muscarinic receptor inhibition and other effects of pancuronium in the rabbit ear artery preparation.

The effect of pancuronium in the rabbit ear artery was investigated in order to measure the inhibition it produces at the prejunctional muscarinic receptor on sympathetic nerve endings in this tissue. Pancuronium (0.1-0.2 mmol/l) produced an enhancement of responses to transmural electrical stimulation but this effect was absent in experiments conducted in the presence of cocaine (10 mumol/l) suggesting that an inhibition of the uptake1 mechanism occurs with pancuronium in this tissue. Pancuronium (10 mumol/l) in the presence of cocaine (10 mumol/l) and yohimbine (1 mumol/l) caused a small transient increase in resting output of tritium from arteries preincubated with 3H-noradrenaline but did not affect stimulated output of tritium nor the perfusion pressure in perfused preparations. Pancuronium in the presence of cocaine or cocaine plus yohimbine caused a parallel shift of the concentration-response curve for the inhibitory effect of carbachol (CCh) on the increase in perfusion pressure induced by nervous stimulation. An Arunlakshana-Schild plot of the data was linear but the slopes of 0.92 and 0.95 respectively, were significantly different from unity (P less than 0.05). The calculated pKB value suggests that pancuronium has a different affinity for prejunctional muscarinic receptors on sympathetic nerve endings in this tissue compared to that previously reported in cardiac or ileal smooth muscle.

Selective inhibition of responses to carbachol and McN-A-343 in the rabbit vas deferens.

1. The effect of several selective muscarine receptor antagonists were evaluated on the responses of carbachol (CCh) and McN-A-343 (McN) during sympathetic nerve stimulation in the rabbit vas deferens. 2. The muscarine M1 receptor antagonist pirenzepine exhibited similar apparent pKB values for antagonism of the prejunctional inhibitory response of either CCh (pKB, 8.2) or McN (pKB, 8.5) on sympathetic nerve stimulation. 3. The muscarine M2 receptor antagonists, pancuronium and the bisalkyl ammonium compound 'C7/3-phth' were selective inhibitors of the postjunctional facilitatory response produced by CCh on sympathetic nerve stimulation. They were also 17- and three-fold, respectively, less potent against the inhibitory responses of McN on sympathetic nerve stimulation. The apparent pKB value of pancuronium on the inhibitory response produced by CCh did not differ significantly (P greater than 0.05) from that using McN. A similar finding was made for C7/3-phth. 4. Selective blockade of the inhibitory response to CCh with pirenzepine (0.03 or 0.5 mumol/L) did not significantly (P greater than 0.05) modify the apparent pKB value for pancuronium on the facilitatory response of CCh. 5. Selective blockade of the facilitatory response to CCh with a low concentration of pancuronium (0.5 mumol/L) did not significantly (P greater than 0.05) modify the apparent pKB value for pancuronium (30 mumol/L) on the inhibitory response of CCh. 6. It is suggested that CCh and McN activate the same prejunctional M1 muscarine receptor and that pancuronium is the most selective of the muscarine M2 receptor antagonists presently tested in this preparation for distinguishing between muscarine M1 and M2 receptors.

[Drugs and sexual behavior]. / Droga e condotte sessuali.

The abundant scientific literature on the addictions does not unclude many papers on the subject of sexual behaviors under the effect of self-administration of drugs. The results of the studies and of the experiments carried out in this field do not allow a classification of drugs in homogeneous groups according to their specific actions on sexual behavior. For each of the most common drugs the most reliable existing data have been examined. Final conclusions cannot be reached for each drug, since several substances may often act, according to many variables, in different cases as depressants or stimulants. The need to study this aspect of drug addiction has been underlined with the aim to improve our knowledge both in the field of the new sexual therapies and of the prevention and control of drug addiction.

Drogas en el Perú / Drugs in Peru

Bajo el título de drogas en el Perú se presenta un apretado resumen de la farmacología de las drogas ilícitas de uso más extendido en el país. No se ha considerado pertinente presentar en esta oportunidad la gran familia de las drogas de las que se abusa frecuentemente pero que por razones epidemiológicas y de manejo de los aspectos preventivos se clasifican como drogas sociales, productos industriales o drogas folclóricas. El libro ha sido diseñado como un auxiliar práctico para público general, maestros y alumnos que requieran obtener información farmacológica acerca de las drogas en un lenguaje accesible al público general. Ramiro Castro de la Mata, médico farmacólogo especialista en drogas y miembro fundador de CEDRO, presenta en esta obra, una apretada síntesis de los principales aspectos de la farmacología de las principales drogas ilícitas cuyo consumo viene aquejando a la población peruana o de aquellas como el opio que amenazan a las futuras generaciones