Methyldopa (L-α-Methyl-3,4-dihydroxyphenylalanine; Aldomet, Aldoril, Dopamet, Dopegyt, etc.) is an alpha-adrenergic agonist (selective for α2-adrenergic receptors) psychoactive drug used as a sympatholytic or antihypertensive. Its use is now mostly deprecated following the introduction of alternative safer classes of agents. However, it continues to have a role in otherwise difficult to treat hypertension and gestational hypertension (previously known as pregnancy-induced hypertension (PIH)).
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[1]
Medical uses[edit]
Methyldopa is used in the clinical treatment of the following disorders:
Hypertension (or high blood pressure)
Gestational hypertension (or pregnancy-induced hypertension) and pre-eclampsia
Side effects[edit]
Methyldopa is capable of inducing a number of adverse side effects, which range from mild to severe. Nevertheless, they are generally mild when the dose is less than 1 gram per day.[2] Side effects may include:
Psychological
Depression and/or even suicidal ideation, as well as nightmares
Apathy and/or anhedonia, as well as dysphoria
Anxiety, especially of the social anxiety variant
Decreased alertness, awareness, and wakefulness
Impaired attention, focus, and concentration
Decreased desire, drive, and motivation
Fatigue or lethargy and/or malaise or lassitude
Sedation or drowsiness and/or somnolence or sleepiness
Agitation or restlessness
Cognitive and memory impairment
Derealization and/or depersonalization, as well as mild psychosis
Sexual dysfunction including impaired libido, desire, and drive
Physiological
Dizziness, lightheadedness, or vertigo
Miosis or pupil constriction
Xerostomia or dry mouth
Gastrointestinal disturbances such as diarrhea and/or constipation
Headache or migraine
Myalgia or muscle aches, arthralgia or joint pain, and/or paresthesia ("pins and needles")
Restless legs syndrome (RLS)
Parkinsonian symptoms such as muscle tremors, rigidity, hypokinesia, and/or balance or postural instability
Akathisia, ataxia, dyskinesia as well as even tardive dyskinesia, and/or dystonia
Bell's palsy or facial paralysis
Sexual dysfunction consisting of impaired erectile dysfunction and/or anorgasmia
Hyperprolactinemia or excess prolactin, gynecomastia/breast enlargement in males, and/or amenorrhoea or absence of menstrual cycles in females
Bradycardia or decreased heart rate
Hypotension or decreased blood pressure (though this may also be considered a therapeutic benefit)
Orthostatic hypotension (also known as postural hypotension)
Hepatitis, hepatotoxicity, or liver dysfunction or damage
Pancreatitis or inflammation of the pancreas
Haemolytic anaemia or deficiency in red blood cells (RBCs)
Myelotoxicity or bone marrow suppression, potentially leading to thrombocytopenia or blood platelet deficiency and/or leukopenia or white blood cell (WBC) deficiency
Hypersensitivity such as lupus erythematosus, myocarditis, and/or pericarditis
Lichenoid reactions such as skin lesions and/or rashes
Pallor
Rebound/withdrawal[edit]
Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.[3]
See also[edit]
Difluoromethyldopa
D-DOPA (Dextrodopa)
L-DOPA (Levodopa; Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc.)
L-DOPS (Droxidopa)
Dopamine (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.)
Norepinephrine (Noradrenaline; Levophed, etc.)
Epinephrine (Adrenaline; Adrenalin, EpiPed, Twinject, etc.)
Mechanism of Action[edit]
Methyldopa has a dual mechanism of action:
It is a competitive inhibitor of the enzyme DOPA decarboxylase, also known as aromatic L-amino acid decarboxylase, which converts L-DOPA into dopamine. Dopamine is a precursor for norepinephrine (noradrenaline) and subsequently epinephrine (adrenaline). This inhibition results in reduced dopaminergic and adrenergic neurotransmission in the peripheral nervous system. This effect may lower blood pressure and cause central nervous system effects such as depression, anxiety, apathy, anhedonia, and parkinsonism. In addition, decreased dopamine may reduce its inhibitory effect on prolactin leading to signs and symptoms of hyperprolactinemia.
It is converted to α-methylnorepinephrine by dopamine beta-hydroxylase (DBH). α-methylnorepinephrine is an agonist of presynaptic central nervous system α2-adrenergic receptors. Activation of these receptors in the brainstem appears to inhibit sympathetic nervous system output and lower blood pressure. This is also the mechanism of action of clonidine.
Pharmacokinetics[edit]
Methyldopa exhibits variable absorption from the gastrointestinal tract. It is metabolized in the liver and intestines and is excreted in urine.
History[edit]
When methyldopa was first introduced, it was the mainstay of antihypertensive treatment, but its use has declined on account of relatively severe adverse side effects, with increased use of other safer and more tolerable agents such as alpha blockers, beta blockers, and calcium channel blockers. Nonetheless, one of methyldopa's still current indications is in the management of pregnancy-induced hypertension (PIH), as it is relatively safe in pregnancy compared to many other antihypertensives which may affect the fetus.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[1]
Medical uses[edit]
Methyldopa is used in the clinical treatment of the following disorders:
Hypertension (or high blood pressure)
Gestational hypertension (or pregnancy-induced hypertension) and pre-eclampsia
Side effects[edit]
Methyldopa is capable of inducing a number of adverse side effects, which range from mild to severe. Nevertheless, they are generally mild when the dose is less than 1 gram per day.[2] Side effects may include:
Psychological
Depression and/or even suicidal ideation, as well as nightmares
Apathy and/or anhedonia, as well as dysphoria
Anxiety, especially of the social anxiety variant
Decreased alertness, awareness, and wakefulness
Impaired attention, focus, and concentration
Decreased desire, drive, and motivation
Fatigue or lethargy and/or malaise or lassitude
Sedation or drowsiness and/or somnolence or sleepiness
Agitation or restlessness
Cognitive and memory impairment
Derealization and/or depersonalization, as well as mild psychosis
Sexual dysfunction including impaired libido, desire, and drive
Physiological
Dizziness, lightheadedness, or vertigo
Miosis or pupil constriction
Xerostomia or dry mouth
Gastrointestinal disturbances such as diarrhea and/or constipation
Headache or migraine
Myalgia or muscle aches, arthralgia or joint pain, and/or paresthesia ("pins and needles")
Restless legs syndrome (RLS)
Parkinsonian symptoms such as muscle tremors, rigidity, hypokinesia, and/or balance or postural instability
Akathisia, ataxia, dyskinesia as well as even tardive dyskinesia, and/or dystonia
Bell's palsy or facial paralysis
Sexual dysfunction consisting of impaired erectile dysfunction and/or anorgasmia
Hyperprolactinemia or excess prolactin, gynecomastia/breast enlargement in males, and/or amenorrhoea or absence of menstrual cycles in females
Bradycardia or decreased heart rate
Hypotension or decreased blood pressure (though this may also be considered a therapeutic benefit)
Orthostatic hypotension (also known as postural hypotension)
Hepatitis, hepatotoxicity, or liver dysfunction or damage
Pancreatitis or inflammation of the pancreas
Haemolytic anaemia or deficiency in red blood cells (RBCs)
Myelotoxicity or bone marrow suppression, potentially leading to thrombocytopenia or blood platelet deficiency and/or leukopenia or white blood cell (WBC) deficiency
Hypersensitivity such as lupus erythematosus, myocarditis, and/or pericarditis
Lichenoid reactions such as skin lesions and/or rashes
Pallor
Rebound/withdrawal[edit]
Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.[3]
See also[edit]
Difluoromethyldopa
D-DOPA (Dextrodopa)
L-DOPA (Levodopa; Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc.)
L-DOPS (Droxidopa)
Dopamine (Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc.)
Norepinephrine (Noradrenaline; Levophed, etc.)
Epinephrine (Adrenaline; Adrenalin, EpiPed, Twinject, etc.)
Mechanism of Action[edit]
Methyldopa has a dual mechanism of action:
It is a competitive inhibitor of the enzyme DOPA decarboxylase, also known as aromatic L-amino acid decarboxylase, which converts L-DOPA into dopamine. Dopamine is a precursor for norepinephrine (noradrenaline) and subsequently epinephrine (adrenaline). This inhibition results in reduced dopaminergic and adrenergic neurotransmission in the peripheral nervous system. This effect may lower blood pressure and cause central nervous system effects such as depression, anxiety, apathy, anhedonia, and parkinsonism. In addition, decreased dopamine may reduce its inhibitory effect on prolactin leading to signs and symptoms of hyperprolactinemia.
It is converted to α-methylnorepinephrine by dopamine beta-hydroxylase (DBH). α-methylnorepinephrine is an agonist of presynaptic central nervous system α2-adrenergic receptors. Activation of these receptors in the brainstem appears to inhibit sympathetic nervous system output and lower blood pressure. This is also the mechanism of action of clonidine.
Pharmacokinetics[edit]
Methyldopa exhibits variable absorption from the gastrointestinal tract. It is metabolized in the liver and intestines and is excreted in urine.
History[edit]
When methyldopa was first introduced, it was the mainstay of antihypertensive treatment, but its use has declined on account of relatively severe adverse side effects, with increased use of other safer and more tolerable agents such as alpha blockers, beta blockers, and calcium channel blockers. Nonetheless, one of methyldopa's still current indications is in the management of pregnancy-induced hypertension (PIH), as it is relatively safe in pregnancy compared to many other antihypertensives which may affect the fetus.
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