Methyldopa

From Wikipedia, the free encyclopedia

Image:Methyldopa.svg
Methyldopa
Systematic (IUPAC) name
2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid
Identifiers
CAS number	555-30-6
ATC code	C02 AB01
PubChem	4138
DrugBank	APRD01106
Chemical data
Formula	C₁₀H₁₃N O₄
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.

1 Mechanism of action
2 History
3 Side effects
4 Footnotes

[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 If the drug is abruptly withdrawn, the "original" as well as "new" receptors become available and cause a severe reaction to the "normal" SNS activity (which is usually in excess).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:<ref>British National Formulary 45 March 2003</ref>

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

[edit] Footnotes

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