Spiller Henry A, Sawyer Tama S
Kentucky Regional Poison Center, Louisville, KY 40232-5070, USA.
Am J Health Syst Pharm. 2006 May 15;63(10):929-38. doi: 10.2146/ajhp050500.
The toxicology of oral antidiabetic agents is reviewed.
Type 2 diabetes mellitus is increasing to near epidemic proportions, with a reported 190 million patients worldwide. Use of oral antidiabetic medications is increasing along with a proportional increase in adverse events. Oral antidiabetic medications can be separated by mechanism of action into two groups: hypoglycemics (sulfonylureas and meglitinides) and antihyperglycemics (biguanides and alpha-glucosidase inhibitors). The hypoglycemic agents pose a significant risk of morbidity, mortality, and permanent sequelae secondary to prolonged periods of hypoglycemia. However, outcomes are routinely good if intervention is initiated early, with the primary goal return of euglycemia using supplemental dextrose infusion and octreotide to reduce further insulin secretion. Metformin-associated lactic acidosis (MALA) can occur with both acute and chronic metformin exposure. While MALA is not common, its associated rates of morbidity and mortality can be high. Secondary to MALA, the patient may experience changes in the central nervous system, cardiovascular collapse, renal failure, and death. The primary goals of therapy are restoration of acid-base status and removal of metformin, using hemodialysis and bicarbonate therapy. There is no specific antidote for MALA. The alpha-glucosidase inhibitors and thiazolidinediones pose minimal risk of adverse events in acute overdose. However, acarbose and all thiazolidinediones have been reported to produce hepatic injury with chronic therapy. Cessation of therapy with the offending agent and supportive care are the mainstays of overdose management with these drugs.
The toxicity of oral antidiabetic agents differs widely in clinical manifestations, severity, and treatment.
综述口服抗糖尿病药物的毒理学。
2型糖尿病正呈近乎流行的态势增长，据报道全球有1.9亿患者。随着不良事件的相应增加，口服抗糖尿病药物的使用也在增加。口服抗糖尿病药物可根据作用机制分为两类：降血糖药（磺脲类和格列奈类）和抗高血糖药（双胍类和α-葡萄糖苷酶抑制剂）。降血糖药物会因长时间低血糖导致发病、死亡和永久性后遗症的重大风险。然而，如果早期进行干预，结果通常良好，主要目标是通过补充葡萄糖输注和奥曲肽减少进一步的胰岛素分泌来恢复血糖正常。急性和慢性接触二甲双胍都可能发生二甲双胍相关乳酸酸中毒（MALA）。虽然MALA并不常见，但其相关的发病率和死亡率可能很高。继发于MALA，患者可能会出现中枢神经系统变化、心血管衰竭、肾衰竭和死亡。治疗的主要目标是恢复酸碱平衡状态并清除二甲双胍，采用血液透析和碳酸氢盐治疗。MALA没有特效解毒剂。α-葡萄糖苷酶抑制剂和噻唑烷二酮类药物在急性过量服用时产生不良事件的风险极小。然而，据报道，阿卡波糖和所有噻唑烷二酮类药物在长期治疗时会导致肝损伤。停用致病药物并给予支持性治疗是这些药物过量管理的主要方法。
口服抗糖尿病药物的毒性在临床表现、严重程度和治疗方面差异很大。
