Medicine & USMLE

Levodopa, Carbidopa

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  9. Levodopa, Carbidopa
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Levodopa and Carbidopa are drugs used in the treatment of Parkinson's disease. Levodopa is a pharmacologic form of L-DOPA, a precursor to dopamine.  Levodopa can cross the blood brain barrier, after which it is converted into dopamine. This increase in dopamine in the brain helps stimulate motor control of body movements, treating Parkinson’s disease. 

In contrast, carbidopa works by blocking or inhibiting the enzyme DOPA decarboxylase, thereby preventing the conversion of L-DOPA into dopamine. Since Carbidopa cannot cross the blood brain barrier, it only works peripherally.  When given in conjunction with Levodopa, carbidopa reduces peripheral conversion of dopamine and increases the availability of central L-DOPA.

Side effects of levodopa are mainly caused by its peripheral conversion into dopamine, leading to nausea and vomiting, as well as arrhythmias and hypotension.  These peripheral effects can be largely minimized by the use of carbidopa. Other adverse effects of levodopa are central effects of dopamine, including anxiety, agitation, and hallucinations. Since these are central effects, they do not respond to carbidopa use.

Key Points

  • Levodopa/Carbidopa 
    • Mechanism
      • Levodopa (L-DOPA) is a dopamine precursor 
        • L-DOPA is a dopamine precursor that can cross the blood brain barrier (BBB) and be converted into dopamine (Dopamine cannot directly cross the BBB)
      • Carbidopa blocks peripheral conversion of L-DOPA to dopamine by inhibiting DOPA decarboxylase
        • Given in conjunction with Levodopa (L-DOPA) to increase central L-DOPA availability
        • Also reduces side effects of peripheral L-DOPA conversion into dopamine (nausea/vomiting, see below)
    • Clinical Use
      • Parkinson disease
    • Adverse effects
      • “On-off” phenomenon with long-term use
        • Improved mobility during “on” periods with bradykinesia/rigidity during “off” times when medication “wears off”
        • Therapeutic windows narrows over time with use of levodopa
      • Nausea/vomiting 
        • Peripheral effect of dopamine (a catecholamine)
          • Dopamine stimulates the emetic center located in the brainstem (outside of the BBB.
        • Minimalized by carbidopa (peripheral DOPA decarboxylase inhibitor)
      • Tachyarrhythmias
        • Peripheral effect of dopamine
        • Minimized by carbidopa
      • Anxiety, agitation, and hallucinations
        • Central effects of dopamine
        • Unaffected by carbidopa (peripheral only)
      • Postural hypotension