Methyldopa

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Methyldopa chemical structure
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. weight 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. It 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

[edit] Mechanism of action

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.

Methyldopa, in its active metabolite form, leads to increased alpha-2 receptor-mediated inhibition of SNS (centrally and peripherally), allowing PSNS tone to increase. Such activity leads to a decrease in total peripheral resistance (TPR) and cardiac output.

All drugs in this class can cause "rebound" hypertension due to an up-regulation of alpha-2 receptors while under the influence of the drug. If the drug is abruptly withdrawn, the "original" as well as "new" receptors become available and cause a severe reaction to the "normal" SNS activity (which is usually in excess). In other words, the SNS typically releases more norepinephrine (NE) than is needed to activate receptors (leading to a sustained response), and extra receptors leads to an over-response (in this case mediated by alpha-2 receptors leading to vascular smooth muscle constriction = 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:[1]

[edit] Footnotes

  1. ^ British National Formulary 45 March 2003


Antihypertensives (C02) and diuretics (C03) edit
Antiadrenergic agents (including alpha):

Clonidine, Doxazosin, Guanethidine, Guanfacine, Lofexidine, Mecamylamine, Methyldopa, Moxonidine, Prazosin, Rescinnamine, Reserpine
Vasodilators:

Diazoxide, Hydralazine, Minoxidil, Nitroprusside, Phentolamine
Other antihypertensives:

Bosentan, Ketanserin
Low ceiling diuretics:

Bendroflumethiazide, Chlorothiazide, Chlortalidone, Hydrochlorothiazide, Indapamide, Quinethazone, Mersalyl, Metolazone, Theobromine
High ceiling diuretics:

Bumetanide, Furosemide, Torasemide
Potassium-sparing diuretics:

Amiloride, Eplerenone, Spironolactone, Triamterene


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