Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure.[1] It is one of the preferred treatments for high blood pressure in pregnancy.[1] For other types of high blood pressure including very high blood pressure resulting in symptoms other medications are typically preferred.[1] It can be given by mouth or injection into a vein.[1] Onset of effects is around 5 hours and they last about a day.[1]
Common side effects include sleepiness.[1] More severe side effects include red blood cell breakdown, liver problems, and allergic reactions.[1] Methyldopa is in the alpha-2 adrenergic receptor agonist family of medication.[1] It works by stimulating the brain to decrease the activity of the sympathetic nervous system.[1]
Methyldopa was discovered in 1960.[2] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] The wholesale cost in the developing world is about 4.31 to 9.48 USD per month.[4] In the United States it costs less than 25 USD per month.[5]
Contents
1Medical uses
2Side effects
2.1Rebound/withdrawal
3Mechanism of action
4Pharmacokinetics
5History
6See also
7References
8External links
Medical uses
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
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.[6] Side effects may include:
Psychological
Depression or even suicidal ideation, as well as nightmares
Apathy 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 or malaise or lassitude
Sedation or drowsiness or somnolence or sleepiness
Agitation or restlessness
Cognitive and memory impairment
Derealization 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 or constipation
Headache or migraine
Myalgia or muscle aches, arthralgia or joint pain, or paresthesia ("pins and needles")
Restless legs syndrome (RLS)
Parkinsonian symptoms such as muscle tremors, rigidity, hypokinesia, or balance or postural instability
Akathisia, ataxia, dyskinesia as well as even tardive dyskinesia, or dystonia
Bell's palsy or facial paralysis
Sexual dysfunction consisting of impaired erectile dysfunction or anorgasmia
Hyperprolactinemia or excess prolactin, gynecomastia/breast enlargement in males, 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
Warm autoimmune hemolytic anemia or deficiency in red blood cells (RBCs)
Myelotoxicity or bone marrow suppression, potentially leading to thrombocytopenia or blood platelet deficiency or leukopenia or white blood cell (WBC) deficiency
Hypersensitivity such as lupus erythematosus, myocarditis, or pericarditis
Lichenoid reactions such as skin lesions or rashes
Pallor
Rebound/withdrawal
Rebound hypertension via withdrawal on account of tolerance upon the abrupt discontinuation of methyldopa has been reported.[7]
Mechanism of action
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
Methyldopa exhibits variable absorption from the gastrointestinal tract. It is metabolized in the liver and intestines and is excreted in urine.
History
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. Additionally, it has yet to be associated with reducing adverse cardiovascular events including myocardial infarction and stroke, or overall all-cause mortality reduction in clinical trials.[8] 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.
^ abcdefghijk"Methyldopa". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
^Walker, S. R. (2012). Trends and Changes in Drug Research and Development. Springer Science & Business Media. p. 109. ISBN 9789400926592. Archived from the original on 2016-09-14.
^"WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
^"Methyldopa". International Drug Price Indicator Guide. Retrieved 8 December 2016.
^Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 140. ISBN 9781284057560.
^British National Formulary 56. September 2008. pp. 95–96. ISBN 978-0-85369-778-7.
^Methyldopa (PIM 342) Archived 2008-03-13 at the Wayback Machine.
…most widely used medications (labetalol, nifedipine, and methyldopa) have not been examined in comparative effectiveness trials. Methyldopa has been widely used in pregnant women and its long-term …
…necrosis factor (TNF) alpha therapy (most commonly with infliximab and etanercept), interferon-alfa, methyldopa, chlorpromazine, and practolol . The frequency of clinical disease is generally lower with …
…the small risk of continued therapy. The centrally acting sympatholytic drugs (eg, clonidine, methyldopa, and guanfacine) and the beta blockers are associated with acute withdrawal syndromes that can …
…mechanism. The antihypertensive drug methyldopa, which is not commonly used now, increases prolactin secretion by a similar mechanism to the gastric motility drugs. Methyldopa inhibits dopamine synthesis . …
…past, was widely used for the prevention of migraine headaches), bromocriptine, beta blockers, methyldopa, hydralazine, analgesics; Biological agents such as etanercept, a soluble receptor that acts as …
English Journal
Layered double hydroxide nanoparticles as an appealing nanoparticle in gene/plasmid and drug delivery system in C2C12 myoblast cells.
Yazdani P, Mansouri E, Eyvazi S, Yousefi V, Kahroba H, Hejazi MS, Mesbahi A, Tarhriz V, Abolghasemi MM.
Artificial cells, nanomedicine, and biotechnology. 2019 Dec;47(1)436-442.
Gene and drug delivery systems need crucial update in the issue of nanocarriers. Layered double hydroxides (LDHs) are known as biocompatible inorganic lamellar nanomaterials with versatile properties. In the present study, Zn/Al-LDH nanoparticle was synthesized and characterized by FTIR, XRD, SEM, T
Treatment and Prevention of Hypertensive Disorders During Pregnancy.
Leavitt K, Običan S, Yankowitz J.
Clinics in perinatology. 2019 06;46(2)173-185.
This article reviews the pharmacology of the most commonly used antihypertensive medications during pregnancy; their mechanism of action; and the effects on the mother, the fetus, and lactation. Each class of antihypertensive pharmacologic agents have specific mechanisms of action by which they exer
Trypsin mediated one-pot reaction for the synthesis of red fluorescent gold nanoclusters: Sensing of multiple analytes (carbidopa, dopamine, Cu, Co and Hg ions).
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy. 2019 May;215()209-217.
Herein, we fabricated fluorescent gold nanoclusters (Au NCs) by using trypsin as a ligand. The fabricated trypsin-Au NCs emit bright red color fluorescence upon the exposure of 365 nm UV light. The trypsin-Au NCs are stable and well dispersed in water, which exhibited strong red emission peak at 6
Induction of metamorphosis of pediveliger larvae of the mussel Mytilus galloprovincialis Lamarck, 1819 using neuroactive compounds, KCl, NH4Cl and organic solvents.
Yang Jin-Long,Satuito Cyril Glenn,Bao Wei-Yang,Kitamura Hitoshi
Biofouling 24(6), 461-470, 2008-08-12
… In 24-h exposure assays, alpha-methyldopa at 5 x 10(-5) M and methoxyphenamine at 5 x 10(-5)-10(-4) M induced 55-94% metamorphosis. …
… Test drugs were benzylpenicillin, procainamide, hydralazine, isoniazid, α-methyldopa, D-penicillamine, captopril, sulfamethoxazole and 2, 4-dinitrochlorobenzene (DNCB), which are known to induce allergic responses in man including hypersensitivity reactions and drug-induced auto-immune responses. …
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 ...
methyldopa /meth·yl·do·pa/ (-do´pah) a phenylalanine derivative used in the treatment of hypertension. meth·yl·do·pa (m th l-d p ). n. A drug used in the treatment of high blood pressure. methyldopa. [-dō′pə]. an alpha2 receptor agonist that ...
