THERAPEUTICS

Brands

• Sinemet, Sinemet CR, Parcopa, Laradopa (levodopa), Lodosyn (carbidopa), Atamet, Caramet, Co-careldopa, Rytary, Duopa

Generic?

• Yes

Class

• Antiparkinson agent

Commonly Prescribed for

(FDA approved in bold)

• Treating symptoms of idiopathic Parkinson's disease (PD), post-encephalitic parkinsonism, symptomatic parkinsonism

• Dopa-responsive dystonia (DRD)

• Restless legs syndrome (RLS)

How the Drug Works

• Levodopa, the metabolic precursor of dopamine, crosses the BBB and is converted by dopa decarboxylase to dopamine in the brain

• Carbidopa is a peripheral decarboxylase inhibitor that prevents levodopa from being metabolized in the gut, increasing CNS dopamine

• In PD, there is a loss of dopaminergic neurons in the substantia nigra and relative excess of cholinergic input. In DRD, there is a deficiency of tetrahydrobiopterin, a cofactor for tyrosine hydroxylase, the ratelimiting enzyme in dopamine synthesis

How Long Until It Works

• PD: hours, but may take 4–8 weeks to receive maximal benefit from a particular dose level when starting

• DRD: usually improves within days or weeks

• RLS: days to weeks

If It Works

• PD: may require dose adjustments over time or augmentation with other agents

• DRD: effective at low doses

If It Doesn't Work

• PD: bradykinesia, gait, and tremor should improve. Non-motor symptoms, including autonomic symptoms such as postural hypotension, depression, and bladder dysfunction, do not improve with carbidopa/ levodopa. If the response is poor, reconsider the diagnosis of idiopathic PD and consider drug-induced parkinsonism or atypical parkinsonism syndromes

• RLS: rule out peripheral neuropathy, iron deficiency, thyroid disease. Change to dopamine agonist or another drug

Best Augmenting Combos for Partial Response or Treatment-Resistance

• For end-of-dose failure (wearing-off), early morning or nocturnal akinesia, and end-of-dose dystonia: increase frequency and decrease amount of each dose of medication, add a dopamine agonist with a longer half-life, add a monoamine oxidase (MAO)-B or catechol-O-methyltransferase (COMT) inhibitor

• Amantadine may help suppress dyskinesias, although benefit is often short-lived