Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Sep 1996
Differential effects of antiarrhythmic agents on post-pause repolarization in cardiac Purkinje fibres.
1. Marked action potential duration (APD) prolongation with agents such quinidine is often a precursor of early after-depolarizations and triggered activity, thought to be underlying mechanism of torsade de pointes. Episodes of torsade de pointes commonly occur following a pause. 2. ⋯ None of D-sotalol, clofilium or dofetilide exhibits significant sodium channel blockade and, thus, these agents do not manifest post-pause prolongation of repolarization. Disopyramide does produce sodium channel blockade, but recovery from this effect is much slower than for quinidine or amitriptyline (time constant 12-50s). Thus, we propose insufficient recovery occurs during the intervals under study to uncover the action potential-prolonging effect of the unopposed potassium channel blockade for disopyramide.
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1. Recent findings have further helped to elucidate the mechanisms involved in the transmission and modulation of pain. ⋯ In response to these findings, new agents and techniques have been applied in the clinical setting and new approaches have been developed to use existing agents more effectively. This review presents some of the findings from recent studies and the implications they have for the management of pain.
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1. The central nervous system in mammals is able to react to painful stimuli at many levels that are involved in transmission, modulation and sensation of pain. Endogenous opioid peptides and their receptors are located at key points in pain pathways, and response to pain can be modulated by local application of opioids at many sites. ⋯ Noxious stimulation increases neuronal activity and modulates expression of genes, including immediate-early genes and neuropeptide (i.e. opioid) genes at spinal and supraspinal levels of the somatosensory system. Opioid drugs and endogenously released opioid peptides can modulate signal transduction mechanisms and intracellular processes that lead to alterations in protein phosphorylation and gene expression. These effects of opioids at the cellular level may underlie the mechanisms of pre-emptive analgesia and neuroplastic changes such as tolerance, dependence, sensitization, hyperalgesia, adaptation, addiction, and modulation of pain memories.
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Clin. Exp. Pharmacol. Physiol. · Nov 1990
Effects of halothane, ketamine, propofol and alfentanil anaesthesia on circulatory control in rabbits.
1. We have made a within-rabbit comparison of the effects of four general anaesthetic regimens on the haemodynamic response to acute reduction in central blood volume and on baroreflex control of heart rate. 2. Acute haemorrhage was simulated by gradually inflating a cuff on the inferior vena cava in order to cause cardiac output to fall at a constant rate of 8.5%/min while the responses of systemic vascular resistance, arterial pressure and heart rate were measured. ⋯ This effect of alfentanil appeared to be mediated centrally, since it could be reproduced by injecting small doses (1.5-7.5 micrograms) into the fourth ventricle. All four anaesthetic agents and nitrous oxide attenuated the baroreceptor control of heart rate. The effect was least with nitrous oxide and alfentanil, greatest with halothane.
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Clin. Exp. Pharmacol. Physiol. · Dec 1989
In vitro time course studies on train-of-four fade induced by hexamethonium, pancuronium and decamethonium in the rat hemidiaphragm.
1. In vitro time course studies on the effects of hexamethonium (7 mmol/L), pancuronium (5 mumol/L) and decamethonium (220 mumol/L) on nerve-evoked (2 Hz for 2 s every 20 s) maximal twitches (T1, T2, T3, T4) of the rat hemidiaphragm were conducted. All three drugs progressively depressed all four twitches in a given train but at different rates (T4 greater than T3 greater than T2 much greater than T1). 2. ⋯ Thus, for the same degree (i.e. 50%) of twitch (T1) tension depression, the three drugs differed widely in their ability (hexamethonium much greater than pancuronium greater than decamethonium) to produce fade as reflected in the respective train-of-four ratio. 4. Our results therefore show that the train-of-four ratio (T4/T1) at 50% T1-block obtained from such in vitro time course studies is a useful quantitative index of the potential of various drugs to cause train-of-four fade. Based on this index a classification of various compounds already studied is proposed as follows: hexamethonium much greater than pancuronium approximately (+)-tubocurarine greater than decamethonium approximately succinylcholine much greater than alpha-bungarotoxin.