Methyldopa (left-handed)

L-methyldopa is an active ingredient mainly used as a second-line agent in the treatment of hypertension. In gestational hypertension, L-methyldopa is the drug of choice. In this case, it is usually taken orally. In addition, it can be administered intravenously in hypertensive crisis.

L-methyldopa was developed in the 1960s and was originally the drug of choice for hypertension. It was slowly superseded by the advent of newer and better tolerated agents.

Pharmacodynamics and mechanism of action

(S)-α-Methyldopa is a syhnthetic amino acid that can cross the blood-brain barrier. It is decarboxylated in the body to α-methyldopamine and subsequently hydroxylated to α-methylnorepinephrine. This substance has an agonistic effect at α2-adrenoceptors and leads to vasodilation of blood vessels, resulting in a decrease in systemic blood pressure.

Pharmacokinetics

Methyldopa is incompletely absorbed from the gastrointestinal tract after oral administration. Bioavailability is approximately 25%. Methyldopa is less than 15% bound to plasma proteins. Approximately 70% of absorbed methyldopa is excreted unchanged by the kidneys. Unabsorbed portions are excreted unchanged in the stool. After oral administration, elimination is essentially complete within 36 hours.

Drug Interactions

Interactions may occur with the following drugs:

• Ferrous sulfates and other drugs containing iron.
• Lithium
• Other antihypertensives (excessive blood pressure lowering).

Side effects

Methyldopa can cause a number of adverse side effects, ranging from mild to severe. It is generally considered to be a rather poorly tolerated drug. The possible side effects can be physiological, as well as psychological.

The possible side effects include:

• Depression or suicidal thoughts
• Nightmares
• apathy or anhedonia
• Anxiety, especially of the social anxiety variety
• Clouding of consciousness
• Impaired ability to concentrate
• Decreased drive and motivation
• Fatigue or lethargy
• Agitation or restlessness
• Memory impairment
• Depersonalization
• mild psychosis
• impaired libido or loss of libido
• dizziness or lightheadedness
• miosis or pupillary constriction
• xerostomia or dry mouth
• gastrointestinal disturbances such as diarrhea or constipation
• headache or migraine
• myalgia or muscle pain
• Arthralgia or paresthesias ("pins and needles")
• restless legs syndrome (RLS)
• Parkinsonian symptoms such as muscle tremor, rigidity, or hypokinesia
• Bell's palsy or facial paralysis
• Hyperprolactinemia
• Gynecomastia/breast enlargement in men
• Absence of menstrual cycles in women
• Bradycardia
• Hypotension
• Orthostatic hypotension (postural hypotension)
• Hepatitis
• Pancreatitis
• Myelotoxicity or bone marrow suppression

Contraindications and precautions

Use of methyldopa is contraindicated in patients with pheochromocytoma or acute liver disease.