Class

Dopamine precursor

Pharmacodynamics
  • Dopamine precursor
  • Transported into the CNS where it is decarboxylated to dopamine
  • Also converted to dopamine in periphery (does not enter CNS)
  • Clinical effects are mainly due to stimulation of D2 receptors (substantia nigra), as well as D1 receptors for maximal benefit:
    • Ameliorates all motor symptoms of Parkinson’s
    • Significant peripheral dopaminergic effects
Pharmacokinetics
  • PO administration
  • Rapid absorption
    • Ingestion of food delays absorption
  • Peak plasma concentrations in 1-2 hours
  • Plasma half-life 1-3 hours
  • Only 1-3% reaches brain unaltered when administered alone:
    • Remainder metabolised extra-cerebrally, by decarboxylation to dopamine
    • Carbidopa is a peripheral dopa decarboxylase inhibitor that does not penetrate the blood-brain barrier
    • Co-administration of carbidopa reduces peripheral metabolism, facilitating increased entry into brain, and reducing daily dosage requirements by 75%
  • Metabolised to homovanillic (HVA) and dihydroxyphenylacetic acid (DOPAC)
  • 2/3 excreted in urine as metabolites within 8 hours of an oral dose
Clinical uses
  • Parkinson’s disease:
    • Most efficacious therapy, but not always used as first line due to development of disabling response fluctuations over time
    • Benefits diminish after 3-4 years
    • Does not stop progression of disease but lowers mortality
    • Given in combination with carbidopa (peripheral dopa decarboxylase inhibitor)
    • Response rate is in thirds: one-third respond well, one-third partial response, one-third do not respond or have intolerance
Adverse effects
  • Gastrointestinal disturbance:
    • Nausea/vomiting/anorexia in 80% when given alone
    • 20% in combination with carbidopa
  • Arrhythmias
  • Dyskinesias:
    • 80% in therapy > 10 years
  • Response fluctuations:
    • On-off phenomenon unrelated to dose timing
    • Wearing-off reactions
  • Behavioural disturbances
  • Other:
    • Mydriasis, can precipitate acute angle closure glaucoma (AACG)
    • Positive Coomb’s test
    • Brown urine
Precautions/contraindications
  • Psychosis
  • AACG
  • History of melanoma or suspicious skin lesion
Further reading
References
  • Katzung BG. Basic & Clinical Pharmacology. 14e. 2018: 494-497, 508
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MBBS CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

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