Methyldopa 995108 221688201 2008-06-25T17:07:24Z Arcadian 104523 [[WP:UNDO|Undid]] revision 210993326 by [[Special:Contributions/58.165.12.85|58.165.12.85]] ([[User talk:58.165.12.85|talk]]) {{drugbox | | IUPAC_name = 2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid | image = Methyldopa.svg | CAS_number = 555-30-6 | ATC_prefix = C02 | ATC_suffix = AB01 | PubChem = 4138 | DrugBank = APRD01106 | C = 10 | H = 13 | N = 1 | O = 4 | molecular_weight = 211.215 g/mol | bioavailability = approximately 50% | metabolism = [[Liver|Hepatic]] | elimination_half-life = 105 minutes | excretion = [[Kidney|Renal]] for metabolites | pregnancy_category = a drug of choice in [[Pregnancy-induced hypertension|PIH]] | legal_status = Rx-only | routes_of_administration = Oral, [[intravenous|IV]] }} '''Methyldopa''' or '''alpha-methyldopa''' (brand names '''Aldomet''', '''Apo-Methyldopa''', '''Dopamet''', '''Novomedopa''') is a centrally-acting adrenergic [[antihypertensive]] medication. Its use is now deprecated following introduction of alternative safer classes of agents. However it continues to have a role in otherwise difficult to treat hypertension and [[pregnancy-induced hypertension]]. ==Pharmacokinetics== Methyldopa has variable absorption from the gut of approximately 50%. It is metabolized in the [[intestine]]s and [[liver]]; its metabolite alpha-methylnorepineprine acts in the [[brain]] to stimulate [[alpha-adrenergic receptor]]s decreasing [[total peripheral resistance]]. It is [[excretion|excreted]] in [[urine]]. ==Mechanism of action== Methyldopa, in its active metabolite form, is a central alpha-2 receptor agonist. Using methyldopa leads to [[alpha-2 receptor]]-negative feedback to [[sympathetic nervous system]] (SNS) (centrally and peripherally), allowing peripheral sympathetic nervous system (PSNS) tone to decrease. Such activity leads to a decrease in [[total peripheral resistance]] (TPR) and [[cardiac output]]. ===Rebound effect=== [[Rebound effect|Rebound]] hypertension has been reported in some cases when methyldopa has been abruptly withdrawn after extended use<ref>http://www.inchem.org/documents/pims/pharm/methyldo.htm</ref>. This results because the long term use of methyldopa lowers the sensitivity of [[presynaptic]] alpha 2 receptors: the release of [[norepinephrine]] (NE) from sympathetic nerve endings is modulated by NE itself acting on the presynaptic alpha 2 autoreceptors thus inhibiting its own release. The discontinuation of methyldopa removes the inhibition on NE release leading to excessive NE release from the SNS and the rebound hypertension. ==History== When introduced it was a mainstay of antihypertensive therapy, but its use has declined, with increased use of other safer classes of agents. One of its important present-day uses is in the management of [[pregnancy-induced hypertension]], as it is relatively safe in pregnancy compared to other antihypertensive drugs. ==Side effects== There are many possible reported side-effects with some, whilst rare, being serious. Side effects are usually fewer if the dose is less than 1 g per day:<!-- --><ref>[[British National Formulary]] ''45'' March 2003</ref> * Gastro-intestinal disturbances * Dry mouth * [[Bradycardia]] (slow pulse rate) * Worsening of [[Angina pectoris|angina]] * [[Orthostatic hypotension]] (Postural hypotension) * Sedation, headaches, dizziness * [[Myalgia]] (muscle pain), [[arthralgia]] (joint pain) or [[paraesthesia]] (numbness) * Nightmares, mild [[psychosis]], [[depression (mood)|depression]] * [[Parkinsonism]] * [[Bell's palsy]] * Abnormal liver functions tests and [[hepatitis]] * [[Pancreatitis]] * [[Haemolytic anaemia]] * Bone marrow suppresion leading to [[thrombocytopenia]] (low platelets) or [[leukopenia|leucopenia]] (low white blood cells) * Hypersensitivity reactions including [[lupus erythematosus]]-like syndrome, myocarditis (heart muscle inflammation), [[pericarditis]] and rashes * Ejaculatory failure, Impotence, decreased libido, [[gynecomastia]] (breast enlargement in men), [[hyperprolactinaemia]] and [[amenorrhoea]] * '''Note that if used in pregnant women, it may cause a positive [[Coombs test]]''' ==Footnotes== <references/> {{Antihypertensives and diuretics}} [[Category:Antihypertensive agents]] [[Category:Hepatitis]] [[de:Methyldopa]] [[es:Metildopa]] [[hr:Metildopa]] [[pl:Metyldopa]] [[ru:Метилдопа]] [[sv:Metyldopa]]