Anti-Parkinsonism Drug Toxicity


In Parkinson disease, cells in the substantia nigra degenerate, reducing the production of dopamine, an essential neurotransmitter for the control of movement and coordination.

The drugs used in the treatment of Parkinson disease can be divided into two main groups: Dopamine agonists and anticholinergics (see Table 6.10).
Drugs Used in the Treatment of Parkinson Disease
DRUG MECHANISM OF ACTION
Levodopa/Cabidopa


 
Converts to dopamine
Extend the duration of effect of levodopa
Carbidopa
Benserazide
DOPA decarboxylase agonist
Bromocriptine
Cabergoline
Pergolide
Pramipexole
Ropinirole
Apomophine
Dopamine receptor agonist.
Amantadine Stimulates release of dopamine
Inhibits Dopamine reuptake
Entacapone
Tolcapone
Catechol-O-methytransferase (COMT) inhibitors
Selegiline
Rasagiline
Monoamine oxidase inhibitor
Benztropine
Orphenadine
Procyclidine
Trihexyphenidyl
Anticholinergics
Inhibit the excess central muscarinic activity caused by dopamine deficiency

MECHANISM/TOXICITY

  • Dopamine agonists: Excessive activation of dopaminergic neurons. Activation of serotonergic systems may also occur.
  • Anticholinergics: Inhibition of central and peripheral muscarinic receptors
  • Monoamine oxidase inhibition (selegiline): May become nonselective at high doses → excessive circulating catecholamines.

SYMPTOMS/EXAM

  • Dopamine Agonist
    • Acute toxicity: Anxiety, confusion, agitation, insomnia, tachycardia, hypotension
    • Chronic toxicity: Dystonia, hallucinations, hypersexuality, delusions
  • Anticholinergics
    • Anticholinergic toxidrome Selegiline
    • Limited data, may see classic MAOI toxicity

DIAGNOSIS

  • Clinical diagnosis is based on history and examination.
  • Selegiline is metabolized to L-methamphetamine, which can be detected on urine toxicology screening.

TREATMENT

  • Supportive care
  • Cessation of medication
  • Sedation with benzodiazepines, as needed