神经系统药理3 2014-10-13.ppt

* * Schematic diagram of a primary afferent neuron mediating pain, its synapse with a secondary afferent in the spinal cord, and the targets for local pain control. The primary afferent neuron cell body is not shown. At least three nociceptors(伤害感受器) are recognized: acid, injury, and heat receptors. The nerve ending also bears opioid receptors, which can inhibit action potential generation. The axon bears sodium channels and potassium channels (not shown), which are essential for action potential propagation. Synaptic transmission involves release of substance P, a neuropeptide (NP) and glutamate and activation of their receptors on the secondary neuron. Alpha2 adrenoceptors and opioid receptors modulate the transmission process. * Effect of repetitive activity on the block of sodium current produced by a local anesthetic in a myelinated axon. A series of 25 pulses was applied, and the resulting sodium currents (downward deflections) are superimposed. Note that the current produced by the pulses rapidly decreased from the first to the 25th pulse. A long rest period after the train resulted in recovery from block, but the block could be reinstated by a subsequent train. nA, nanoamperes. (Modified and reproduced, with permission, from Courtney KR: Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA. J Pharmacol Exp Ther 1975;195:225.) * LAs only bind in the inactive state? * Numbness 麻木 lightheadedness 头晕 Muscular twitching 肌肉震颤 * 收缩性 自律性 节律和传导 * * * * * * T-type Ca2+ channel电流 被认为是丘脑神经元的起搏电流，导致失神发作中产生有节律的皮层放电，抑制此电流可用以解释乙琥胺特殊的治疗作用。 疗效不及氯硝西泮，但副作用及耐受性的产生较少，故为小发作首选。 GI responses， CNS（头疼、头晕、嗜睡等）、精神异常（精神病史患者）、贫血、可导致癫痫大发作。 * GABA合成增加，抑制降解、摄取，增强对GABA的反应性 对小发作的作用优于乙琥胺，但由于其肝脏毒性作用，不做首选。 * Rash、marrow suppression为特异质反应 * 扑米酮：体内转化为苯巴比妥和苯乙基丙二酰胺，用药期间定期查血象，肝肾功能不全者禁用； 美芬妥英：体内容易蓄积、不良反应重，仅用于其他药物不能控制的患者。 乙苯妥英钠：作用和毒性均弱，仅用于辅助用药。 氯硝西泮:对小发作的疗效较地西泮强 * 奥卡西平：过敏反应少，对肝药酶的诱导作用弱。 抗痫灵：桂皮酰胺类药，系我国合成的抗癫痫药物，厌食、恶心头晕嗜睡等，无肝毒性、造血系统损伤； 氟桂