Methyldopa

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Methyldopa
Systematic (IUPAC) name
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	℞ 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

[edit] 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.

[edit] 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.

[edit] Rebound effect

Rebound hypertension has been reported in some cases when methyldopa has been abruptly withdrawn after extended use^[1]. 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.

[edit] 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.

[edit] 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

YISSS

[edit] Footnotes

1. ^ http://www.inchem.org/documents/pims/pharm/methyldo.htm
2. ^ British National Formulary 45 March 2003

v • d • e Antihypertensives (C02) and diuretics (C03) Sympatholytic agents (including alpha) centrally acting/antiadrenergics: Clonidine • Guanfacine • Methyldopa • Moxonidine • Rilmenidine • adrenergic uptake inhibitor (Rescinnamine, Reserpine) ganglion-blocking/nicotinic antagonist (Mecamylamine, Trimethaphan) peripherally acting/antiadrenergics (Prazosin, Guanethidine, Indoramin, Doxazosin) Vasodilators Diazoxide • Hydralazine • Minoxidil • Nitroprusside • Phentolamine Other antihypertensives serotonin antagonist (Ketanserin) • endothelin receptor antagonist (Bosentan, Ambrisentan, Sitaxsentan) Low ceiling diuretics Thiazide (Bendroflumethiazide, Chlorothiazide, Hydrochlorothiazide) • Chlortalidone • Indapamide • Quinethazone • Mersalyl • Metolazone • Theobromine • Cicletanine High ceiling diuretics Loop diuretic (Bumetanide, Furosemide, Torasemide) Potassium-sparing diuretics ESC blockers (Amiloride, Triamterene) • aldosterone antagonists (Spironolactone, Eplerenone, Potassium canrenoate, Canrenone)