Levodopa is an indirect central dopamine agonist due to its central conversion to dopamine. Levodopa is used in combination with carbidopa, which is a decarboxylase inhibitor that prevents peripheral destruction of levodopa. These drugs are most often used in the symptomatic treatment of Parkinson’s disease.
0.2.1) SUMMARY OF EXPOSURE
B) PHARMACOLOGY: Levodopa, the metabolic precursor of dopamine, has the capacity to cross the blood brain barrier thus providing dopamine to the corpus striatum. Carbidopa is an inhibitor of aromatic acid decarboxylation which prevents the rapid decarboxylation of levodopa in extracerebral tissues making more levodopa available for transport to the brain.
C) TOXICOLOGY: Cardiovascular and CNS effects are probably due to levodopa’s immediate metabolite dopamine. This compound at low serum levels causes hypotension and tachycardia due to stimulation of the dopaminergic and beta receptors. At higher levels alpha receptor stimulation overrides and hypertension is the result. Dysrhythmias may occur due to stimulation of beta receptors in the heart. CNS effects due to excessive dopamine may be expected to include dyskinesias.
D) EPIDEMIOLOGY: Overdose is rare.
E) WITH THERAPEUTIC USE
F) WITH POISONING/EXPOSURE
0.2.3) VITAL SIGNS
B) THERAPEUTIC DOSES: IMMEDIATE RELEASE TABLETS: Initial, 1 carbidopa/levodopa combination tablet (10 mg/100 mg, 25 mg/100 mg, 25 mg/250 mg) orally 3 to 4 times daily; titrated up to 8 tablets daily. SUSTAINED RELEASE TABLETS: Initial, 1 carbidopa/levodopa combination tablet (50 mg/200 mg) orally twice daily; titrated to 400 to 1600 mg of levodopa daily.
B) MANAGEMENT OF SEVERE TOXICITY
2) HOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
D) AIRWAY MANAGEMENT
G) HYPERTENSIVE EPISODE
H) HYPOTENSIVE EPISODE
I) PSYCHOMOTOR AGITATION
J) NEUROLEPTIC MALIGNANT SYNDROME
L) ENHANCED ELIMINATION PROCEDURES
M) PATIENT DISPOSITION
2) OBSERVATION CRITERIA: Symptomatic patients and those with deliberate ingestions should be sent to a medical facility for evaluation and treatment. Peak concentrations of sustained-release formulation is reached 2 hours after ingestion as compared with 0.5 hours after an immediate-release formulation. Patients that have ingested a sustained-release product have the potential to manifest symptoms in a delayed/prolonged fashion and should be observed for 4 to 8 hours.
3) ADMISSION CRITERIA: Patients with deliberate ingestions demonstrating cardiotoxicity or persistent neurotoxicity should be admitted.
4) CONSULT CRITERIA: Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
P) DIFFERENTIAL DIAGNOSIS
B) Monitor vital signs and mental status following significant overdose.
C) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea.
D) Monitor CK, renal function, and urine output in patients with rhabdomyolysis.
E) Serum concentrations are not widely available or clinically useful in managing overdose.