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过量吸入氟替卡松可抑制肾上腺功能弊大于利
在加拿大卫生部门数据库中，1996年1月1日至2002年9月30日期间，怀疑与吸入性皮质类固醇类药物有关的内分泌紊乱不良反应报告中，尚未发现怀疑与布地奈德和倍氯米松有关的肾上腺皮质功能不全病例报告。与氟替卡松有关的报告共9例，5例为4～13岁儿童，给药剂量为250～1100μg/d；4例剂量超过1000μg/d。2例患者出现肾上腺危象，1例为男孩（年龄不详），另1例为72岁男性。
肾上腺皮质功能不全可因吸入性皮质类固醇类药物而发生，因为皮质类固醇的系统吸收必然导致内源性糖皮质素抑制；肾上腺皮质功能不全也可由突然停止治疗或不依从治疗而导致急性类固醇缺乏。肾上腺抑制及肾上腺危象的体征和症状是非特异性的，包括：食欲缺乏、腹痛、体重下降、疲劳、头痛、恶心、呕吐、意识模糊、低血糖和癫痫发作等。
加拿大哮喘指南推荐，一旦达到最佳治疗结果，给药剂量可以通过适当延长给药间隔来减少剂量，最终达到能持续控制哮喘的最小给药剂量。此外，不同的吸入方法和推进剂也可影响吸入药量和生物利用度。
有关专家提醒，医师应该告知患者和及患儿父母有关吸入性皮质类固醇类药物的不良反应危险，以及有关的指征和症状。肾上腺功能抑制可以通过减少药物剂量而逆转，然而，也要注意由于突然停药而引起的严重不良反应。
Fluticasone and adrenal suppression
Inhaled corticosteroids are highly effective for the control of asthma and the prevention of exacerbations. Recently, there have been several reports worldwide of adrenal insufficiency in adults and children using inhaled corticosteroids. Although adrenal insufficiency can occur with any inhaled corticosteroid, it may be more common with fluticasone because of the drug's pharmacologic and pharmacokinetic properties, including its greater potency and hence lower equivalent dose (half the dose of either budesonide or beclomethasone ). In addition, this may result from higher-than-licensed doses of fluticasone being more widely prescribed in children than other inhaled corticosteroids.
The Health Canada database was searched for suspected adverse reactions involving endocrine disorders reported from Jan. 1, 1996, to Sept. 30, 2002, associated with fluticasone, budesonide and beclomethasone. There were no Canadian case reports of suspected adrenal insufficiency associated with the use of budesonide or beclomethasone.
There were 9 reports involving fluticasone, 5 of which involved children aged 4-13 years (where specified). Dosages (where specified) ranged from 250 to 1100 μg/d; in 4 cases the dose exceeded 1000 μg/d. Two patients experienced adrenal crisis; one was a boy (age unspecified), and the other was a 72-year-old man.
Adrenal insufficiency associated with inhaled corticosteroid use can occur because of systemic absorption of the corticosteroid and consequent suppression of endogenous glucocorticoids, which leaves insufficient adrenal reserve to respond to stressful stimuli (e.g., surgery, trauma and infection). Adrenal insufficiency may also result from abrupt discontinuation or noncompliance with treatment, which leads to acute steroid deficiency. Signs and symptoms of adrenal suppression and crisis are nonspecific and include anorexia, abdominal pain, weight loss, fatigue, headache, nausea, vomiting, decreased level of consciousness, hypoglycemia and seizures.
Clinicians are reminded that, beyond a certain limit, increasing the dose of inhaled corticosteroids offers minimal benefit but increases the risk of systemic adverse effects. Canadian asthma consensus guidelines recommend that, once best results are achieved, the dose should be reduced at appropriate intervals to determine the minimum dose required to maintain control. In addition, different inhalation techniques (e.g., chambers, inhalers and spacers) and propellants (e.g., chlorofluorocarbon v. hydrofluoroalkane preparations) can influence the portion of inhaled drug, and thus systemic bioavailability.
Patients and parents should be informed of the risk as well as the signs and symptoms of adrenal suppression associated with the use of inhaled corticosteroids. Adrenal suppression can be reversed upon reduction of dosage. However, patients and parents should also be cautioned about the risk of serious adverse reactions from abruptly stopping treatment.
Canadian Adverse Reaction Newsletter. 2003,13:4 [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-04-07 05:11
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