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127-5-第五节 四环素类药物的副作用和毒性
严重影响生命的副作用不常见,低剂量或停药后,轻的副作用是可逆的。在二甲胺四环素控制RA的治疗中,副作用很少见,导致停药的只有7%。& D. k1 Y" W, K
' z2 H* n9 y7 q& N4 G2 X5 A% \' t$ d 一、对骨、牙生长的影响 $ @4 _/ O. B+ h" A) G" l
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四环素可与新形成的骨、牙中所沉积的钙相结合。妊娠5个月以上的妇女服用这类抗生素时,出生的幼儿乳牙可出现荧光、变色、牙釉质发育不全,畸形和生长抑制。幼儿,尤其是出生后第1年,由于肾发育不全,药物不能充分排泄,即使短期用药,也极易引起乳牙的色素沉着和牙釉质发育不全,易于造成龋齿,牙染色由黄转为棕黄。剂量越大,黄染越深,牙釉质发育不全也更加显著。因此,年龄小于7-8岁儿童、怀孕5个月以上和哺乳的妇女等慎用或禁用。
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二、胃肠道紊乱
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% |: b5 X! X! \) }2 @ 恶心、呕吐、上腹部不适、腹胀、腹泻、舌炎、口腔炎和肛门炎等。减少剂量至50mg,每天1次或2次,或与食物同服,可以减轻症状。在RA病人中,因为 RA本身有关节和全身的症状,同时又用其他有潜在肝脏毒性的药物,因此这些副作用不容易及时发现。为此,要求开始治疗 1个月后每 3个月检查全血细胞计数和肝、肾功能。
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三、头晕或轻度头痛6 o4 G; K$ L5 |1 x
2 V% I) O5 h0 D( [" Q6 ]) d 妇女更加多见。减少开始剂量(50mg,每天1次或2次)可减轻其副作用,在2-4周逐渐增加剂量。
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四、其他+ b7 p& y9 W2 o& t8 U6 H+ C
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有关于服用二甲胺四环素产生光敏反应的报道,服药1年或更长会产生灰黑色素沉着,在身体的任何部位都会有,特别在腿胫部。国外报道二甲胺四环素引起可逆性前庭副作用,包括恶心、呕吐、头晕、眩晕及运动失调。前庭反应妇女较男性多见,发生率与剂量高低无明显关系。脱氧土霉素的皮疹少见。因为四环素降低血浆抗凝活性,所以接受抗凝治疗的病人应该减少抗凝药物的剂量。 9 p; L2 J8 w" ~) e
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近年来,国外学者在用米诺环素治疗RA的研究过程中,还发现了该药可诱发类狼疮样症状,并称之为“米诺环素诱导自身免疫综合征(minocycline-induced autoimmune syndrome)”,其特点主要有可逆性的关节痛、关节炎、发热、晨僵、皮肤损害,偶有慢性活动性肝炎表现,同时出现抗核抗体阳性及p-ANCA抗体滴度增高。
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五、菌群失调
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* Z6 ~- R0 V4 A5 r2 k _- ? 长期用四环素后,使正常菌群的分布发生改变,敏感菌受到抑制,耐药细菌、真菌(主要是白色念珠菌)等乘机在体内繁殖,发生消化道、呼吸道和泌尿道等感染。如果发生这种情况,应当马上停药,改用其他药物。脱氧土霉素的肠道二重感染少见。 6 q8 v1 \2 w- S+ @3 q$ d j7 A# Z+ x
9 O3 |2 H* \& L8 ?* m 综上所述,脱氧土霉素和二甲胺四环素对RA、反应性关节炎、骨关节炎和骨质疏松都有一定的疗效,且有副作用低的优点,尤其适用于肾功能不良的病人,这是一个有潜力的抗风湿药物。 ! n3 U' a$ i E4 k& D0 j$ @! ?
( 叶益新 李小霞 张如峰 )
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