Pharm 101: Levodopa

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 (UWA) CCPU Emergency Medicine Trainee with interests in medical education, ECG interpretation, and the use of point-of-care ultrasound in the undifferentiated patient. Co-author of the LITFL ECG Library | Twitter

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