Levodopa is not given alone but always with a peripheral decarboxylase inhibitor.
- Introduced in the late 1960's and made a huge change in the management of patients with PD.
- Therapy becomes less effective with time with side effects.
- In Parkinson's disease there is a deficiency of dopamine in the corpus striatum.
Mode of action
- L-Dopa crosses the Blood-Brain barrier whereas dopamine doesn't. There is a deficiency of dopamine
- L-Dopa is metabolised centrally into the neurotransmitter dopamine by the enzyme decarboxylase.
- L-tyrosine → L-dopa → dopamine → dopamine receptors (D2, D3, D4) → G proteins
- It is given with a peripheral decarboxylase inhibitor which prevents peripheral conversion to dopamine and therefore side effects such as nausea
- Idiopathic Parkinson's disease
- post-encephalitic parkinsonism - Oliver Sacks book/film Awakenings
- Symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication
- Co-beneldopa Madopar 25/100 = 100 Levodopa + 25 Benserazide
- Co-careldopa Sinemet 25/100 = 100 Levodopa + 25 Carbidopa. Start Madopar/ Sinemet 62.5 (50/12.5) mg BD or TDS.
- Aim 400-800 mg Levodopa per day with decarboxylase inhibitor in split doses
- Drug induced Parkinsonism
- Nausea, Hypotension, Confusion/Delirium
- Dopamine induced dyskinesias
- Visual and possibly auditory hallucinations
- Sudden withdrawal can cause the neuroleptic malignant syndrome
- Levodopa is transported as are some other proteins across the gut wall. A protein meal can reduce absorption