[Methyldopa-induced acute reactive hepatitis in pregnancy, drug-metabolizing capacity of the liver].
Alpha-methyldopa is a regularly used antihypertensive drug during pregnancy. Methyldopa, which decreases the sympathoadrenal system, is the first drug of choice since decades. The reactive hepatitis is not frequent, but known serious side effect of alpha-methyldopa. In non-pregnant women the estimated rate of manifest hepatotoxicity is 2.5-10%. In our case, gestation hypertension developed at the 21st gestation week of a 35 year-old pregnant woman. Oral methyldopa, a central alpha adrenergic blocker therapy was introduced. On the 23rd gestation week acute hepatitis developed. During differential diagnosis of hepatitis, the etiology of methyldopa was taken into account. Viral and autoimmune origin was rolled out. No fetal aberration was found during ultrasound examination. The function of drug metabolizing function from blood was measured by CYP phenotyping (CYP gene expression analysis). CYP3A4 enzyme plays a primary role in the metabolism of nifedipine. Antihypertensive therapy was changed from methyldopa to nifedipine. Nifedipine dosage was based on the value of CYP3A4 gene expression. With the reduced nifedipine therapy (30 mg daily), blood pressure was successfully under control. The diagnosis of alpha-methyldopa induced hepatitis was based on anamnesis, clinical picture and the results of chemical and radiological examination and confirmed by the level of drug-metabolizing capacity. The gestation hepatotoxicity of alpha-methyldopa was reported first in 1969 by Elkington Smith, who suggested the monitoring of serum aminotransferase during alpha-methyldopa therapy in pregnancy in their case report. Our case report confirms that monitoring of serum aminotransferase level is still valuable when treating a pregnant woman with alpha-methyldopa.
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Fejér Megyei Szent György Kórház Infektológiai Osztály Székesfehérvár Seregélyesi út 3. 8000. zsozsvar@mail.fmkorhaz.hu
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D000316:Adrenergic alpha-Agonists / Q000009:adverse effects / Q000493:pharmacokinetics; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism*; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy*; D008750:Methyldopa / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism* / Q000493:pharmacokinetics*; D009543:Nifedipine / Q000008:administration & dosage*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy* / Q000201:enzymology; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D008750:Methyldopa; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; C045793:CYP2C19 protein, human; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010089:Oxidoreductases, N-Demethylating; D000637:Transaminases; D009543:Nifedipine