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Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
Methyldopa chemical structure | |
(2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid IUPAC name | |
CAS number 555-30-6 |
ATC code |
PubChem 4138 |
DrugBank APRD01106 |
Chemical formula | {{{chemical_formula}}} |
Molecular weight | 211.215 g/mol |
Bioavailability | approximately 50% |
Metabolism | Hepatic |
Elimination half-life | 105 minutes |
Excretion | Renal for metabolites |
Pregnancy category | a drug of choice in PIH |
Legal status | Rx-only |
Routes of administration | 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
Pharmacokinetics[edit | edit source]
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[edit | edit source]
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[edit | edit source]
Rebound hypertension has been reported in some cases when methyldopa has been abruptly withdrawn after extended use[1].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.
History[edit | edit source]
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[edit | edit source]
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
See also[edit | edit source]
Footnotes[edit | edit source]
Template:Adrenergic agonists Template:Antihypertensives and diuretics Categor:Drugs with psychosis as a side effect
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