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TOXICOLOGY

COMPLICATIONS

■ Hypersensitivity reactionsmay occur 1–6 weeks after starting phenytoin
therapy, eg, SLE, TEN, erythema multiforme.
■ Gingival hyperplasiacan be seen with chronic phenytoin therapy.
■ Chronic ingestion of valproic acid: Hepatic failure

ANTIPARKINSONISM DRUGS

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).

Acute overdose of antiparkinsonism drugs is rare.

MECHANISM/TOXICITY

■ Dopamine agonists: Excessive activation of dopaminergic neurons. Activa-
tion 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 Agonism

■ Acute toxicity: Anxiety, confusion, agitation, insomnia, tachycardia,
hypotension
■ Chronic toxicity: Dystonia, hallucinations, hypersexuality, delusions

Anticholinergics

■ Anticholinergic toxidrome

TABLE 6.10. Drugs Used in the Treatment of Parkinson Disease

DRUG MECHANISM OFACTION

Dopamine Agonists

Levodopa Converts to dopamine

Catechol-O-methytransferase (COMT) Extend the duration of effect of levodopa

inhibitors

Selegiline Selective monoamine oxidase inhibitor, blocks

reuptake of dopamine

Bromocriptine Dopamine receptor agonist

Anticholintergics

Benztropine (and others) Inhibit the excess central muscarinic activity

caused by dopamine deficiency