Methyldopa is a centrally acting sympatholytic agent used in the treatment of hypertension.
Since its introduction in 1960, the drug quickly became a leading antihypertensive, but its use has decreased markedly, replaced by better-tolerated alternatives. It is still in use in developing countries due to its low cost.
This drug is also useful in pregnancy because it has no teratogenic effects.
Alpha-methyldopa is converted to methyl norepinephrine centrally to decrease the adrenergic outflow by alpha-2 agonistic action from the central nervous system, leading to reduced total peripheral resistance and decreased systemic blood pressure. Alpha-2 agonistic activity does not affect cardiac output or renal blood flow.; hence, this drug is useful in hypertensive patients with renal insufficiency.
Methyldopa is generically available as 125, 250, or 500 mg tablets.
Fixed-dose combinations with thiazides are also on the market.
The recommended dose in adults is 500 mg to 2 g daily. Clinicians should discontinue the drug if any side effects manifest in the patient.
IV infusion in the form of methyldopa hydrochloride is available.
The drug gets diluted in 5% dextrose, and the required dose is added to 100 mL of 5% dextrose in water injection and administered slowly over 30 to 60 minutes.
Despite its popularity during the 70s, other alternatives have replaced methyldopa as mainstays for the treatment of hypertension. Methyldopa remains a second-line treatment to be used safely during pregnancy.
Common adverse effects include:
Rare, yet clinically fatal adverse effects include:
Information about the adverse effects and pharmacokinetic principles of the drug is crucial in therapeutic monitoring.
After initiation of treatment, periodic testing of hemoglobin, hematocrit, and the red blood cell count is necessary to rule out hemolytic anemia.
Direct Coombs test is reported positive, usually after 6 to 12 months of therapy, but rarely results in fatal hemolytic anemia. Discontinuance of drug reverses results within weeks to months.
Liver function tests are necessary for increased serum concentrations of alkaline phosphatase, aminotransferases, and bilirubin.
Hepatic dysfunction may represent a hypersensitivity reaction.
A periodic assessment of hepatic function is important during the first 6 to 12 weeks of therapy. Abnormal liver function test results require discontinuation of the drug.
The drug is contraindicated in active hepatic disease.
Methyldopa overdose reports are exceedingly rare.
Clinical manifestations include coma, hypothermia, hypotension, bradycardia, and dry mouth.
Prolonged, severe hypotension, along with marked renal potassium loss necessitating IV infusion of norepinephrine and vigorous potassium replacement therapy for almost two days, was reported.
Management of drug overdose requires an interprofessional team of healthcare professionals that includes pharmacists, nurses, laboratory technologists, and several physicians in different specialties. Absent proper management, morbidity, and mortality from methyldopa overdose are high. The moment the triage nurse has admitted an overdose, the emergency department clinician is responsible for coordinating the care which includes the following:
The management of methyldopa overdose does not stop in the emergency department. Following patient stabilization, one has to determine how and why the patient overdosed. Consult with a mental health counselor if this was an intentional act and assess risk factors for-self harm. Only by functioning as an interprofessional team can the morbidity of methyldopa overdose be decreased. The long-term outcomes for drug therapy include prescribing better-tolerated drugs within a therapeutic range. [Level 2]
Patients should understand the importance of informing clinicians of existing or contemplated concomitant therapy or concurrent diseases.
Importance of informing clinicians about a current or planned pregnancy plays a vital role in improving outcomes. WIth an interprofessional team approach to methyldopa therapy, successful results with minimal adverse events are achievable. [Level 5]
|||Molvi SN,Mir S,Rana VS,Jabeen F,Malik AR, Role of antihypertensive therapy in mild to moderate pregnancy-induced hypertension: a prospective randomized study comparing labetalol with alpha methyldopa. Archives of gynecology and obstetrics. 2012 Jun [PubMed PMID: 22249781]|
|||Mah GT,Tejani AM,Musini VM, Methyldopa for primary hypertension. The Cochrane database of systematic reviews. 2009 Oct 7 [PubMed PMID: 19821316]|
|||Whelton PK,Carey RM,Aronow WS,Casey DE Jr,Collins KJ,Dennison Himmelfarb C,DePalma SM,Gidding S,Jamerson KA,Jones DW,MacLaughlin EJ,Muntner P,Ovbiagele B,Smith SC Jr,Spencer CC,Stafford RS,Taler SJ,Thomas RJ,Williams KA Sr,Williamson JD,Wright JT Jr, 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension (Dallas, Tex. : 1979). 2018 Jun; [PubMed PMID: 29133356]|
|||Taler SJ, Initial Treatment of Hypertension. The New England journal of medicine. 2018 Feb 15; [PubMed PMID: 29443671]|
|||Folic MM,Jankovic SM,Varjacic MR,Folic MD, Effects of methyldopa and nifedipine on uteroplacental and fetal hemodynamics in gestational hypertension. Hypertension in pregnancy. 2012 [PubMed PMID: 21219124]|
|||Khalil A,Muttukrishna S,Harrington K,Jauniaux E, Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders. PloS one. 2008 Jul 23 [PubMed PMID: 18648513]|
|||Methyldopa 2012; [PubMed PMID: 31643501]|
|||Myhre E,Rugstad HE,Hansen T, Clinical pharmacokinetics of methyldopa. Clinical pharmacokinetics. 1982 May-Jun [PubMed PMID: 7047042]|
|||Chan TY,Gomersall CD,Cheng CA,Woo J, Overdose of methyldopa, indapamide and theophylline resulting in prolonged hypotension, marked diuresis and hypokalaemia in an elderly patient. Pharmacoepidemiology and drug safety. 2009 Oct; [PubMed PMID: 19623566]|