THERAPEUTICS

Brands

• Artane, Tremin (discontinued)

Generic?

• Yes

Class

• Antiparkinson agent, anticholinergic

Commonly Prescribed for

(FDA approved in bold)

• Extrapyramidal disorders

• Parkinsonism

• Idiopathic generalized dystonia

• Focal dystonias

• Dopa-responsive dystonia

• Cerebral palsy

• Tardive dyskinesia

How the Drug Works

• Trihexyphenidyl is a synthetic anticholinergic with relatively greater CNS activity than most other anticholinergics

• May also inhibit the reuptake and storage of dopamine at dopamine neurons and transporters, prolonging dopamine action

• In Parkinson's disease (PD), it works presumably by restoration of the striatal dopamine-acetylcholine balance through blockade of postsynaptic muscarinic receptors; this may benefit from denervation hypersensitivity caused by loss of the ascending cholinergic input to that region from the basal forebrain

How Long Until It Works

• PD/extrapyramidal disorders: minutes to hours

• Dystonia: days to weeks

If It Works

• PD: do not abruptly discontinue or change doses of other PD treatments. Usually most effective in combination with other medications

If It Doesn't Work

• PD: generally trihexyphenidyl is an adjunctive medication for common PD symptoms, such as tremor, rigidity, and drooling. Other cardinal PD symptoms, such as bradykinesia and gait difficulties, are most likely to improve with other PD treatments, such as levodopa, dopamine agonists, amantadine, or monoamine oxidase (MAO)-B inhibitors

• Extrapyramidal disorders: increase to highest tolerated dose. Long-standing disorders are less likely to respond to treatment

Best Augmenting Combos for Partial Response or Treatment-Resistance

• For bradykinesia or gait disturbances causing significant functional disturbance, levodopa is most effective. For idiopathic PD patients, especially younger patients with normal cognition and milder disability, dopamine agonists are also a good first choice. Amantadine and MAO-B inhibitors may also be useful

• Depression is common in PD and may respond to low-dose SSRIs

Tests

• None

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Prevents the action of acetylcholine on related receptors

Notable AEs

• Constipation, urinary retention, behavioral, dry mouth, tachycardia, palpitations, hypotension, disorientation, confusion, hallucinations, nausea/vomiting, dilation of colon, rash, blurred vision, diplopia, elevated temperature, decreased sweating, erectile dysfunction