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[[Rebound effect|Rebound]] hypertension has been reported in some cases when methyldopa has been abruptly withdrawn after extended use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]]
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