Slavik R S, Rybak M J, Lerner S A
College of Pharmacy and Allied Health, Wayne State University, Detroit, MI, USA.
Ann Pharmacother. 1998 Feb;32(2):189-92. doi: 10.1345/aph.17173.
To report a case of trimethoprim/sulfamethoxazole (TMP/SMX)-induced tremor responsive to a reduction in dosage.
A 55-year-old white man with AIDS and Pneumocystis carinii pneumonia (PCP) developed a tremor after receiving 5 days of therapy with TMP/SMX 19.4 mg/kg/d (TMP). The tremor resolved completely 3 days after a dosage reduction to TMP/SMX 15.1 mg/kg/d.
Central nervous system adverse reactions to TMP/SMX have been reported in both the AIDS and non-AIDS populations. To our knowledge, this is the first reported case of TMP/SMX-induced tremor responsive to a reduction in dosage. Pharmacokinetic and clinical data suggest a concentration-dependent etiology for various adverse effects, including tremor. The mechanism of the tremor is unknown; however, toxic metabolites of SMX and disruptions of biogenic amine neurotransmission by TMP have been hypothesized.
TMP/SMX remains the drug of first choice for treating PCP, but it is clearly not well tolerated by patients with AIDS. Concentration-dependent toxicities such as tremor may lead to premature discontinuation of proven, effective TMP/SMX therapy. Using the lower end of the recommended dosing range for TMP/SMX (TMP 15 mg/kg/d) may reduce the incidence of these toxicities while still achieving acceptable TMP concentrations and antimicrobial efficacy.
报告一例甲氧苄啶/磺胺甲恶唑(TMP/SMX)诱发的震颤,其对剂量减少有反应。
一名55岁患艾滋病和卡氏肺孢子虫肺炎(PCP)的白人男性,在接受5天剂量为19.4mg/kg/d(TMP)的TMP/SMX治疗后出现震颤。在剂量减至15.1mg/kg/d的TMP/SMX 3天后,震颤完全消失。
在艾滋病患者和非艾滋病患者中均有TMP/SMX引起中枢神经系统不良反应的报道。据我们所知,这是首例报道的TMP/SMX诱发的震颤且对剂量减少有反应的病例。药代动力学和临床数据表明,包括震颤在内的各种不良反应存在浓度依赖性病因。震颤的机制尚不清楚;然而,已推测SMX的有毒代谢产物以及TMP对生物胺神经传递的干扰。
TMP/SMX仍然是治疗PCP的首选药物,但艾滋病患者对其耐受性显然不佳。诸如震颤等浓度依赖性毒性可能导致停用已证实有效的TMP/SMX治疗。使用TMP/SMX推荐给药范围的下限(TMP 15mg/kg/d)可能会降低这些毒性的发生率,同时仍能达到可接受的TMP浓度和抗菌效果。