书城养生烟草工业与人类健康
2808900000045

第45章 戒烟的治疗(4)

α4β2尼古丁乙酰胆碱能受体部分激动剂[如司巴丁(金雀花碱)、伐尼克兰]具有激动和拮抗的双重作用,因而具有良好的治疗效果。临床试验显示,伐尼克兰的戒断率大约是安慰剂的3倍,是安非他酮的1.5~1.9倍。Ⅲ期临床试验显示,它可能比尼古丁替代疗法和安非他酮更有效。伐尼克兰的常见不良反应有恶心等消化道症状,但较轻微,戒烟者多数可以忍受。但此药上市后有报告患者出现焦虑、抑郁和自杀的案例,故伐尼克兰在使用说明中添加进了新的安全性警告。不过到目前为止,这些神经精神不良反应与服用伐尼克兰的因果关系尚未被证实。

4.尼古丁依赖的其他临床可行的药物治疗方案

(1)间接的单胺激动剂:既往有研究证据表明,尼古丁依赖的神经生物学涉及单胺类。几种抑制NA和5羟色胺再摄取的三环类抗抑郁药(TCA),如去甲替林和多塞平(多虑平)联合治疗,可能强化戒烟效果。然而,TCA有明显的不良反应,如抗胆碱能毒性,大剂量经常致死。

(2)5羟色胺类药:一类耐受性更好、更安全的抗抑郁药,选择性5羟色胺再摄取抑制剂(SSRI)已研制成功,在调节吸烟行为中发挥5HT的作用,对一部分有抑郁病史的吸烟者有益。丁螺环酮(buspar)是一种用来治疗焦虑性不适的抗焦虑药,是5HT1A受体部分激动剂。5HT1A受体是突触前和突触后的抑制性自主受体。因此,用丁螺环酮刺激5HT1A受体导致突触前5HT释放减少,似乎是发挥它的抗焦虑效应。丁螺环酮不产生躯体依赖,这一点使其成为治疗尼古丁依赖的强有力的替补,尤其是针对焦虑性吸烟者。

(3)α2肾上腺素能受体激动剂:可乐定是一种最初证实用来治疗高血压的α2肾上腺素能受体激动剂,现已经发现在治疗阿片戒断中有作用,这与中枢神经系统肾上腺素能受体的超活性有关。1985—1993年开展的几项临床试验证实,可乐定在戒烟试验中有微弱的效能,但是由于可乐定有严重的副作用,如镇静、便秘和直立性低血压,而限制了它的使用。大量经皮和口服试验证明该药的轻微效能,因此可乐定可当作二线戒烟药物应用于临床。

(4)烟碱受体拮抗剂:神经节阻滞剂美卡拉明(美加明)是高亲和力nAchR离子通道的非竞争性拮抗剂,具有与安非他酮、TCA和SSRI相似的疗效。它可减少与吸烟有关的满足感和迫切性。其不良反应包括腹痛、便秘、口干和头痛。两项研究暗示美卡拉明联合TNP比TNP加安慰剂有更好的治疗效果。虽然联合激动剂(TNP)和拮抗剂(美卡拉明)看起来是相反的,但长期使用可下调nAchR,也可能对高亲和力nAchR亚单位复合体有明显的作用。

尼古丁依赖至吸烟成瘾,是一个慢性反复发作的过程,只有从其病理机制着手,找出原因和影响因素,有针对性地采取药物治疗和非药物治疗,才能循序渐进、行之有效地进行戒烟。

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