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20-September-2008 09:55:49 - Methyldopa Methyldopa Systematic IUPAC name 2S-2-amino-3-3,4-dihydroxyphenyl-2-methyl-propanoic acid Identifiers CAS number 555-30-6 ATC code C02AB01 PubChem 4138 DrugBank APRD01106 Chemical data Formula C10H13NO4 Mol. mass 211.215 g/mol Pharmacokinetic data Bioavailability approximately 50% Metabolism Hepatic Half life 105 minutes Excretion Renal for metabolites Therapeutic considerations Pregnancy cat. a drug of choice in PIH Legal status â„ž Prescription only Routes Oral, 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. Contents 1 Pharmacokinetics 2 Mechanism of action 2.1 Rebound effect 3 History 4 Side effects 5 Footnotes Pharmacokinetics Methyldopa has variable absorption from the gut of approximately 50%. It is metabolized in the intestines and liver; its metabolite alpha-methylnorepineprine acts in the brain to stimulate alpha-adrenergic receptors decreasing total peripheral resistance. It is 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 Rebound effect Rebound hypertension has been reported in some cases when methyldopa has been abruptly withdrawn after extended use1. 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:2 Gastro-intestinal disturbances Dry mouth Bradycardia slow pulse rate Worsening of angina Orthostatic hypotension Postural hypotension Sedation, headaches, dizziness Myalgia muscle pain, arthralgia joint pain or paraesthesia numbness Nightmares, mild psychosis, depression Parkinsonism Bell's palsy Abnormal liver functions tests and hepatitis Pancreatitis Haemolytic anaemia Bone marrow suppresion leading to thrombocytopenia low platelets or 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 ^ Methyldopa PIM 342 ^ British National Formulary 45 March 2003 v d e Adrenergic agonists models/most important in CAPS α α1 METHOXAMINE - Methylnorepinephrine - Oxymetazoline - PHENYLEPHRINE - Metaraminol α2 4-NEMD - CLONIDINE - Guanfacine - Guanabenz - Guanoxabenz - Guanethidine - Xylazine - METHYLDOPA - Apraclonidine - Brimonidine - Detomidine - Dexmedetomidine - Lofexidine - Romifidine - Tizanidine - Xylometazoline Undetermined/ unsorted Amidephrine - Amitraz - Anisodamine - Ergotamine - Indanidine - Medetomidine - Mephentermine - Midodrine - Mivazerol - Naphazoline - Norfenefrine - Octopamine - Phenylpropanolamine - Rilmenidine - Synephrine - Talipexole - Tetrahydrozoline - Xylometazoline β β1 DOBUTAMINE - Dopamine - Denopamine - Xamoterol β2 Short acting β2-agonists: SALBUTAMOL/Levosalbutamol - Fenoterol - TERBUTALINE - Pirbuterol - Procaterol - Bitolterol - Rimiterol - Carbuterol - Tulobuterol - Reproterol - Dopexamine Long acting β2-agonists LABA: Arformoterol - Bambuterol - Clenbuterol - Formoterol - Salmeterol Orciprenaline/metaproterenol - Ritodrine - Hexoprenaline - Indacaterol β3 Amibegron - Solabegron Undetermined/ unsorted Arbutamine - Befunolol - Isoxsuprine - Nylidrin - Oxyfedrine - Prenalterol - Ractopamine - Bromoacetylalprenololmenthane - Broxaterol - Cimaterol - Higenamine - Mabuterol - Methoxyphenamine - Tretoquinol - Zinterol Nonselective β ISOPRENALINE/ISOPROTERENOL α and β Epinephrine α1+2, β1+2 - Norepinephrine α1+2, β1 - Cirazoline - Etilefrine Indirect/ mixed Indirect presynaptic norepinephrine release: Amphetamine - Tyramine Mixed: Ephedrine - Pseudoephedrine Cocaine see also monoamine oxidase inhibitor v d e Antihypertensives C02 and diuretics C03 Sympatholytic agents Centrally acting/antiadrenergics α2 agonist Clonidine, Guanfacine, Methyldopa imidazoline receptor agonist Moxonidine, Rilmenidine adrenergic uptake inhibitor Rescinnamine, Reserpine Ganglion-blocking/nicotinic antagonist Mecamylamine, Trimethaphan Peripherally acting/antiadrenergics α1 blockers: Prazosin Indoramin Trimazosin Doxazosin Urapidil Guanidine derivatives: Betanidine Guanethidine Guanoxan Debrisoquine Guanoclor Guanazodine Guanoxabenz Vasodilators Diazoxide hydrazinophthalazine Hydralazine, Dihydralazine, Endralazine, Cadralazine Minoxidil Nitroprusside Phentolamine Other antihypertensives serotonin antagonist Ketanserin endothelin receptor antagonist Bosentan, Ambrisentan, Sitaxsentan MAOI Pargyline THI Metirosine Diuretics Low ceiling Thiazides at DCT Bendroflumethiazide Hydroflumethiazide Hydrochlorothiazide Chlorothiazide Polythiazide Trichlormethiazide Cyclopenthiazide Methyclothiazide Cyclothiazide Mebutizide Sulfonamides Quinethazone Clopamide Chlortalidone Mefruside Clofenamide Metolazone Meticrane Xipamide Indapamide Clorexolone Fenquizone Other Mersalyl Theobromine Cicletanine osmotic Mannitol, Urea carbonic anhydrase inhibitor at PT Acetazolamide High ceiling Loop diuretic at AL Bumetanide, Furosemide, Torasemide, Ethacrynic acid Potassium-sparing at CD ESC blockers Amiloride, Triamterene aldosterone antagonists Spironolactone, Eplerenone, Potassium canrenoate, Canrenone Retrieved from http://en..org/wiki/Methyldopa Categories: Antihypertensive agents | Hepatitis | Catecholamines Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Español Hrvatski Polski РуÑ?Ñ?кий Svenska This page was last modified on 10 August 2008, at 01:42
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