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Methyldopa: Uses, Dosage Side Effect and Interactions

Description and Composition

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Methyldopa is a phenylalanine derivative and an aromatic amino acid decarboxylase inhibitor with antihypertensive activity. Methyldopa is a prodrug and is metabolized in the central nervous system into alpha-methylnorepinephrine, a potent alpha-2 adrenergic agonist. Alpha-2 adrenergic agonist binds to and stimulates potent central inhibitory alpha-2 adrenergic receptors.

Mechanism of Actions and Pharmacology

The exact mechanism of antihypertensive action of methyldopa is unknown. However, it is thought to involve stimulation of central alpha-adrenergic receptors by a metabolite, alpha-methylnorepinephrine, thus inhibiting sympathetic outflow to the heart, kidneys and peripheral vasculature. Reduced peripheral resistance and plasma renin activity levels may also contribute to its effect.

Pharmacokinetics

Absorption:

Absorption of methyldopa from the gastrointestinal tract is variable but averages approximately 50%.

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Protein Binding:

Methyldopa – Low (less than 20%)

Its sulphate conjugate – Moderate

Biotransformation:

It is extensively metabolised and is converted to alpha-methyinorepinephrine in central adrenergic neurons; methyldopate hydrochloride is hydrolysed to methyldopa.

Sulphate conjugation occurs to a greater extent after orat than after intravenous administration

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Half-life:

Normal – Alpha: 1.7 hours

Anuric – Alpha: 3.6 hours

Time to peak effect:

Single dose – 4 to 6 hours

Multiple doses – 2 to 3 days

Duration of action:

Single dose – 12 to 24 hours

Multiple doses – 24 to 48 hours

Excretion:

Renal, approximately 70% of absorbed drug is excreted in urine as methyldopa and its mono-O-sulfate metabolite.

Unabsorbed oral methyldopa is excreted unchanged in the feces

Indications and Uses

Methyldopa is used in treatment of:

  1. Moderate to severe hypertension.
  2. Gestational hypertension (or pregnancy-induced hypertension)
  3. Pre-eclampsia

Contraindication

Not recommended for patients with acute liver disease or phaeochromocytoma

Precautions

  • Evidence of hemolytic anaemia is an indication for discontinuing the drug.
  • Positive Coombs’ tests may indicate an incompatible cross-match when transfusion is required and an indirect Coombs test should be carried out
  • Safety for use in pregnancy and lactation has not been established.
  • Caution if any kind of surgery or dialysis is required.

Pregnancy and Lactation

Safety for use in pregnancy and lactation has not been established

Side Effects

  • Drowsiness
  • Edema
  • Dry mouth
  •  Geadache.

Other side effects other than those listed above can occur.

Report to your healthcare provider if you experience severe side effects while taking this drug.

Drug Interactions

Concurrent use with the following drugs is not recommended.

  • Monoamine oxidase (MAO) inhibitors,
  • Levodopa
  • Methotrimeprazine.

Concurrent use with the following drugs requires careful monitoring

  • Alcohol,
  • Antihypertensives
  • General anaesthetics
  • Norepinephrine.

Overdosage

Clinical features:

  • Dizziness
  • Drowsiness
  • Hypotension
  • Tachycardia or bradycardia,
  • Hypothermia
  • Extra-pyramidal signs
  • Coma.

Treat overdosage by emesis or gastric lavage, if appropriate; and IV 1-2 mg benztropine if extrapyramidal signs are present

Dosage and Adminstration

Adults:

Initial – Oral, 250 mg two or three times a day for two days, the dosage then being adjusted as directed.

Maintenance – Oral, 500 mg to 2 g a day, divided into two to four doses, not exceeding 3 g daily.

Children:

Oral, initially 10 mg per kg of body weight daily, divided into two to four doses, the dosage then being adjusted as directed, not exceeding 65 mg per kg of body weight or 3 g daily, whichever is less.

 

Chemical structure of Methyldopa

 

Storage

Store below 25°C. Protect from light. Keep all medicines away from the reach of children.

Manufactured by: HOVID Bhd.

121, Jalan Tunku Abdul Rahman, 30010 Ipoh, Malaysia,

References

  1. https://pubchem.ncbi.nlm.nih.gov/compound/methyldopa
  2. Dopatab drug leaflet: Hovid brand of methyldopa
  3. https://www.sciencedirect.com/topics/neuroscience/methyldopa
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