药品信息:
药物名称
通用名:甲基多巴片
英文名:METHYTDOPA TABLETS
药品类别:抗高血压药
性状:本品为糖衣片，除去糖衣后显白色
药理毒理
1.甲基多巴为芳香氨酸脱羧酶抑制剂。
2.仅α-甲基多巴的左旋异构体对人有抗高血压活性，消旋体（DL-α-甲基多巴）需要2倍剂量方可达到相同的降压作用。其抗高血压作用可能是通过其活性代谢产物α-甲基去甲肾上腺素刺激中枢的抑制性α-肾上腺素受体和假性神经递质，减少血浆肾素活性，从而降低动脉血压。
3.甲基多巴可以降低组织中5-羟色胺、多巴胺、去甲基肾上腺素、甲基肾上腺素浓度。
4.甲基多巴对心脏功能没有直接影响，通常也不减少肾小球滤过率、肾血流量和滤过分数。
5.心输出量在正常心率时保持不变，部分病人出现心率减慢。
6.治疗过程中血浆肾素活性降低。
7.甲基多巴可降低卧位和立位血压，很少出现体位性低血压。罕见日间运动时低血压。致癌、致突变性、生殖毒性 小鼠和大鼠分别服用甲基多巴1800mg/kg/日和240mg/kg/日（分别相当于30 倍和4倍于人用最大剂量），2年无致癌作用。Ames试验甲基多巴未增加染色体畸变和中华仓鼠卵巢生殖细胞姐妹染色单体的交换。雄性和雌性大鼠给予甲基多巴100 mg/kg/日，未见生殖力受到影响。甲基多巴减少精子数量、精子活动性、晚期精子数。雄性大鼠给以甲基多巴200和400 mg/kg/日（按体表面积计算，约为人每日最大剂量的0.5倍和1倍），雄性生殖力指数下降。小鼠口服甲基多巴 1000mg/kg、兔子200mg/kg、大鼠100mg/kg（按体表面积计算，分别相当于人每日剂量的1.4倍、1.1倍和0.2倍），对胎儿未见有害影响。
药代动力学
甲基多巴口服吸收不一，约50%，与血浆蛋白结合不到20% 。单次口服后 4-6小时降压作用达高峰，作用持续12-24小时。多次口服后2-3天达作用高峰，并持续至停药后24-48小时；一旦达到有效降压剂量，大多数人可产生12-24小时平稳降压效应。停药后24-48小时血压恢复。血浆半衰期约为1.7小时，无尿时为3.6小时。药物主要在肝脏代谢，产生??甲基去甲肾上腺素等多种代谢产物，近70%以原形和少量代谢物的形式经尿排泄。正常人肾清除率约130ml/min，肾功能不全时下降。口服36小时后体内基本完全清除。
适应症
高血压。
用法用量
1.成人常用量：口服，250mg/次，分2~3次/日。每2天调整剂量一次，至达预期疗效。一般晚上加量以减少药物的过度镇静作用。若与噻嗪类利尿药合用需减量，起始剂量控制在500mg/日，但利尿药剂量可不变。维持量0.5-2g/日，分2-4次口服，最大剂量不宜超过3g/日。因甲基多巴作用时间较短，停药后48 小时内需给予其它降压治疗。用药2-3个月后可产生耐药性，给利尿剂可恢复疗效。
2.儿童常用量：口服，每日10mg/Kg，或按体表面积300mg/m2给药，分2~4次口服。每2天调整剂量一次，至达到要求疗效。最大剂量不超过65mg/Kg或3g/日。
3.任何疑问，请遵医嘱！
不良反应
1.镇静、头疼和乏力多于开始用药和加量时出现，通常是一过性。
2.较常见的有：水钠潴留所致的下肢浮肿，口干。
3.较少见的有：药物热或嗜酸性粒细胞增多，肝功能变化（可能属免疫性或过敏性），精神改变（抑郁或焦虑、梦呓、失眠），性功能减低，腹泻，乳房增大，恶心，呕吐，晕倒。
4.偶有加重心绞痛和心力衰竭。
5.少见的有：延长颈动脉窦敏感性和体位性低血压时间，体重增加，窦性心动过缓，肝功能损害，胰腺炎，结肠炎唾液腺炎，舌痛或舌黑，便秘，腹胀，排气，高泌乳素血症，骨髓抑制，血小板减少，溶血性贫血，白细胞减少，抗核抗体、LE细胞、类风湿因子阳性, 直接抗球蛋白(Coombs)试验阳性，心肌炎，心包炎，血管炎，狼疮样综合症，帕金森氏症，震颤麻痹，反应迟钝，不自觉舞蹈症，脑血管供血不足症状，精神混乱如多梦、镇静、衰弱、感觉异常，尿素氮（BUN）升高，关节痛，可伴关节肿胀，肌肉痛，鼻塞，表皮坏死，皮疹，闭经，男性乳腺发育，泌乳。
6.罕见的有：粒细胞减少症，停药后即恢复正常。致命性肝细胞坏死。
禁忌症
1.活动性肝脏疾病，如急性肝炎活动性肝硬化。
2.直接抗球蛋白(Coombs)试验阳性。
注意事项
1.直接抗球蛋白（Coombs）试验阳性、溶血性贫血、肝功能异常可能与服用甲基多巴密切相关，偶可致死亡。因此，用药前和用药过程中应定期检查血常规、Coombs试验和肝功能。若发生溶血性贫血应立即停药，通常贫血很快好转，否则应使用皮质类固醇激素治疗。该类病人不能再次使用甲基多巴。直接抗球蛋白(Coombs)试验阳性在停用甲基多巴数周或数月后可转为正常。
2.如果直接和间接抗球蛋白(Coombs)试验均阳性，主侧交叉配血将出现问题，应请教血液学或输血专家解决。
3.由于甲基多巴主要通过肾脏排除，肾功能不全者慎用。
4.须定期检查肝功能，尤其在用药的头2-3个月内。发现问题立即停药者体温和肝功能可恢复。该类病人不能再次使用甲基多巴。甲基多巴慎用于有肝脏疾病和肝功能不全的病人。
5.服用甲基多巴出现水肿或体重增加的病人，可用利尿剂治疗。一旦水肿进行性加重或有心衰迹象应停服本品。
6.透析过程中甲基多巴被排出体外，将偶有血压回升现象。
7.患有严重双侧脑血管病者，若服药过程中发生不自主性舞蹈症，须立即停药。
8.甲基多巴可以影响下列试验室的检查值：磷酸钨酸盐法测尿酸；苦味酸盐法测肌酐；比色法测SGOT。
9.甲基多巴可使荧光法测定尿样本中的儿茶酚胺假性升高，干扰嗜铬细胞瘤的诊断。
10.嗜铬细胞瘤者慎用。
孕妇及哺乳期妇女用药
本品能通过胎盘。在人体的研究尚不充分。已有的研究显示孕妇服药后对胎儿没有明显有害的影响，因此在必要的情况下甲基多巴可用于孕妇。甲基多巴可排入乳汁，但未有对婴儿影响的报道。尽管如此，哺乳妇女仍应慎用。
儿童用药
对小儿的安全性缺少研究
老年患者用药
老年人对降压作用敏感，且肾功能较差，须酌减药量。
药物相互作用
1.本品可增加口服抗凝药的作用。
2.本品可加强中枢神经抑制剂的作用。
3.三环类抗抑郁药、拟交感胺类药和非甾体抗炎止痛药可减弱本品的降压作用。
4.本品可使血泌乳激素浓度增高并干扰溴隐亭的作用。
5.与其它抗高血压药合用有协同作用。
6.与左旋多巴合用可加强中枢神经毒性作用。
7.与麻醉药合用须减少麻醉药的剂量。
8.与锂剂合用时须防备锂剂的毒性作用。
药物过量
甲基多巴可通过透析排除。药物过量将产生急性低血压伴脑和胃肠道功能紊乱的各种反应，如过度镇静、虚弱、心动过缓、眩晕、反应迟钝、便秘、腹胀、排气、腹泻、恶心、呕吐等。治疗应采取对症疗法。
贮藏
遮光、密闭保存
Drug Name
Common name: methyldopa tablets
English name: METHYTDOPA TABLETS
Drug Category: antihypertensives
Properties: sugar-coated tablet, remove the sugar coating of white
Pharmacology and Toxicology
1. methyldopa aromatic acid decarboxylase inhibitors.
2. Only L-isomer of α- methyldopa of people have antihypertensive activity, racemic (DL-α- methyldopa) 2 times the dose required to achieve the same before the antihypertensive effect. Its antihypertensive effect may be through its active metabolite α- methyl norepinephrine stimulation of central inhibitory α- adrenergic receptor and false neurotransmitters, reducing plasma renin activity, thereby reducing blood pressure.
3. methyldopa can reduce tissue serotonin, dopamine, norepinephrine, norepinephrine concentration.
4. Methyldopa has no direct effect on cardiac function, generally do not reduce glomerular filtration rate, renal blood flow and filtration fraction.
5. cardiac output during normal heart rate remains unchanged, some patients heart rate.
6. The course of treatment reduced plasma renin activity.
7. methyldopa reduce supine and standing blood pressure, orthostatic hypotension is rare. Hypotension rare daytime exercise. Carcinogenicity, mutagenicity, reproductive toxicity in mice and rats were taking methyldopa 1800mg / kg / day and 240mg / kg / day (equivalent to 30 times, respectively, and four times the maximum dose for human use), 2-year carcinogenicity effect. Ames test methyldopa not increase the exchange of chromosomal aberrations and Chinese hamster ovarian germ cell sister chromatids. Male and female rats were given methyldopa 100 mg / kg / day, no fertility affected. Methyldopa reduced sperm count, sperm mobility, late sperm count. Methyldopa male rats given 200 and 400 mg / kg / day (according to body surface area, which is about the maximum daily dose of 0.5 and 1 times), male fertility index fell. Mice by oral methyldopa 1000mg / kg, rabbit 200mg / kg, rat 100mg / kg (based on surface area, respectively, equivalent to 1.4 times the human daily dose, 1.1 times and 0.2 times), and no harmful to the fetus affected.
Pharmacokinetics
Methyldopa oral absorption varies by about 50%, and less than 20% bound to plasma proteins. 4-6 hours after a single oral dose of antihypertensive effect reached the peak, which lasted 12-24 hours. 2-3 days to reach peak effect after repeated oral administration, and continued until 24-48 hours after treatment; once they reach an effective antihypertensive dose, most people can produce stable antihypertensive effect for 12-24 hours. 24-48 hours after treatment to restore blood pressure. Plasma half-life of about 1.7 hours, when no urine was 3.6 hours. Drug metabolism in the liver, to produce a variety of metabolites ?? methyl norepinephrine, nearly 70% in the form of a prototype and a small amount of metabolites excreted in the urine. Normal renal clearance rate of about 130ml / min, decreased renal insufficiency. 36 hours after oral administration of the body substantially completely removed.
Indications
Hypertension.
Dosage
1. The usual dose for adults: oral, 250mg / times 2 to 3 times / day. Once every two days to adjust the dose to achieve the desired effect. General dosage at night to reduce excessive sedation drugs. If thiazide diuretics required reductions, the starting dose control in 500mg / day, but may change the dose of diuretics. Maintenance dose 0.5-2g / day, orally 2-4 times the maximum dose should not exceed 3g / day. Shorter duration of action due to methyldopa, 48 hours after stopping domestic demand given other antihypertensive therapy. 2-3 months after treatment can produce drug resistance, to restore the efficacy of diuretics.
2. Children in common: oral, daily 10mg / Kg, or body surface area of 300mg / m2 administered 2 to 4 times a day orally. Adjust the dose once every two days, to achieve the required effect. The maximum dose does not exceed 65mg / Kg or 3g / day.
3. Any questions, please doctor!
Adverse reactions
Sedation, headache and fatigue than the beginning of treatment and processing volume 1. usually transient.
2. The more common are: lower limb edema induced sodium retention, dry mouth.
3. Less common are: an increase in drug fever or eosinophils, liver function (may belong to autoimmune or allergic), mental changes (depression or anxiety, sleep talking, insomnia), reduced sexual function, diarrhea, breast growth large, nausea, vomiting, fainting.
4. occasional exacerbation of angina and heart failure.
5. rare: prolonged carotid sinus sensitivity and time orthostatic hypotension, weight gain, sinus bradycardia, liver damage, pancreatitis, colitis salivary gland inflammation, pain, or tongue black tongue, constipation, bloating, exhaust, hyperprolactinemia, myelosuppression, thrombocytopenia, hemolytic anemia, leukopenia, antinuclear antibody, LE cells, rheumatoid factor positive direct antiglobulin (Coombs) test was positive, myocarditis, pericarditis, vascular arthritis, lupus-like syndrome, Parkinson's disease, Parkinsonism, unresponsive, unconscious chorea, cerebral vascular insufficiency symptoms such as mental confusion dreams, sedation, weakness, paresthesia, blood urea nitrogen (BUN) increased, joint pain, may be associated with joint swelling, muscle pain, nasal congestion, skin necrosis, skin rash, amenorrhea, gynecomastia, lactation.
6. There are rare: neutropenia, returned to normal after discontinuation. Fatal hepatic necrosis.
Contraindications
1. Active liver disease, such as acute hepatitis, active cirrhosis.
2. Direct antiglobulin (Coombs) test was positive.
Precautions
1. Direct antiglobulin (Coombs) test was positive, hemolytic anemia, abnormal liver function may be related to taking methyldopa, and even can cause death. Therefore, before treatment and medication should regularly check blood, Coombs test and liver function. In case of hemolytic anemia should be discontinued immediately, usually anemic better soon, or should use corticosteroid therapy. These patients can not be used again methyldopa. Direct antiglobulin (Coombs) test positive discontinuation methyldopa few weeks or months later can be converted to normal.
2. If the direct and indirect antiglobulin (Coombs) tests were positive, the main side of crossmatch will have problems, you should consult an expert to solve hematology or blood transfusion.
3. Since methyldopa exclude primarily through the kidneys, renal insufficiency caution.
4. Liver function should be checked regularly, especially during the first 2-3 months of medication. Found the problem immediately discontinued restore body temperature and liver function. These patients can not be used again methyldopa. Methyldopa used with caution in patients with liver disease and liver dysfunction.
5. taking methyldopa edema or weight gain in patients with available diuretics. Once aggravated sexual edema or signs of heart failure should stop taking the product.
6. dialysis process methyldopa is excreted, the occasional blood pressure rise phenomenon.
7. suffering from severe bilateral cerebrovascular disease, if they occur chorea involuntary medication process, should be discontinued immediately.
8. methyldopa may affect the value of the following laboratory examination: phosphoric acid measured tungstate; Picrates measured creatinine; colorimetry SGOT.
9. methyldopa can Fluorescence Spectrometry urine sample in falsely elevated catecholamine interference addicted diagnosis of pheochromocytoma.
10. pheochromocytoma caution.
Pregnant and lactating women
The goods through the placenta. Studies in humans is not sufficient. Previous studies show no significant deleterious effect in pregnant women after administration of the fetus, so if necessary methyldopa may be used in pregnant women. Methyldopa can be discharged into the milk, but no impact on infant reported. However, breast-feeding women should still be used with caution.
Pediatric
For the lack of research in children's safety
Elderly patients
Elderly sensitive to antihypertensive effect and poor kidney function, the dose required to reduce it.
Drug Interactions
1. It can be used to increase the role of oral anticoagulation.
2. It can be used to strengthen the role of central nervous system depressants.
3. tricyclic antidepressants, sympathomimetic amines, nonsteroidal anti-inflammatory drugs and painkillers can weaken the antihypertensive effect of this product.
4. It can be used to make blood prolactin concentration increased and interference effects of bromocriptine.
5. with other antihypertensive drugs have a synergistic effect.
6. combined with levodopa may strengthen the central nervous system toxicity.
7. anesthetic combined with the need to reduce the dose of anesthetic.
Require protection against the toxic effects of lithium and lithium agents 8. agent combination.
Overdose
Methyldopa can be excluded by dialysis. The excessive production of a variety of drug reactions associated with acute hypotension, brain and gastrointestinal disorders, such as excessive sedation, weakness, bradycardia, dizziness, unresponsive, constipation, bloating, exhaust, diarrhea, nausea, and vomiting. Allopathic treatment should be taken.
Storage
Shading, sealed
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