Memantin

Clinical Effects:

MEMANTINE
  • USES: Memantine is indicated in the treatment of moderate to severe dementia of the Alzheimer’s type. PHARMACOLOGY: Memantine hydrochloride is a low to moderate affinity, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist which binds to NMDA receptor-operated cation channels. Memantine also blocks the 5-hydroxytryptamine-3 receptor (at a potency similar to the NMDA receptor) and nicotinic acetylcholine receptors (at one-sixth to one-tenth the potency). However, memantine has low to negligible affinity for gamma-aminobutyric acid, benzodiazepine, dopamine, adrenergic, histamine, and glycine receptors and for voltage-dependent calcium, sodium, or potassium channels. EPIDEMIOLOGY: Overdose is rare. MILD TO MODERATE OVERDOSE: Effects can include agitation, bradycardia, confusion, dizziness, hypertension, lethargy, restlessness, unsteady gait, vertigo, vomiting and weakness. SEVERE OVERDOSE: Can cause nystagmus, hallucinations, psychosis, seizures, and coma. ADVERSE EFFECTS: The following adverse effects have been reported following therapeutic use of memantine (less than 6%): Headache, diarrhea, dizziness, somnolence, fatigue, muscle weakness, akathisia, agitation, increased motor activity, insomnia, tachycardia, bradycardia, hypertension, constipation, seizures, and psychosis.

Range of Toxicity:

MEMANTINE
  • TOXICITY: A specific minimum toxic dose of memantine has not been delineated. A 35-year-old woman developed headache, dizziness, double vision, coma, tachycardia, hypertension, respiratory alkalosis, and seizures after ingesting 2000 mg of memantine. She recovered followed supportive care, including 6 cycles of plasmapheresis. An overdose ingestion of up to 400 mg of memantine resulted in restlessness, psychosis, visual hallucinations, somnolence, stupor, and coma. The patient recovered without permanent neurologic sequelae. One patient developed elevated serum uric acid, elevated serum alkaline phosphatase, and low platelet count after ingesting 112 mg of memantine extended-release daily for 31 days. THERAPEUTIC DOSES: ADULTS: IMMEDIATE-RELEASE: 5 to 20 mg orally once daily or in divided doses; MAX, 20 mg/day. EXTENDED-RELEASE: 7 to 28 mg orally daily; MAX, 28 mg/day. CHILDREN: The safety and efficacy of memantine in children have not been documented.

Treatment:

MEMANTINE
  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. . MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Treat severe agitation with small doses of benzodiazepines. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
  • Decontamination: PREHOSPITAL: Prehospital gastrointestinal decontamination is not recommended because of the potential for CNS depression and subsequent aspiration. HOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
  • Airway management: Ensure adequate ventilation and perform endotracheal intubation early in patients with significant CNS depression or repeated seizures.
  • Antidote: None.
  • Enhanced elimination procedure: Hemodialysis or hemoperfusion are unlikely to be useful because of the large volume of distribution of memantine. Plasmapheresis was used in one patient and was associated with a decrease in memantine concentrations but it is not clear that it affected patient outcome.
  • Monitoring of patient: Plasma concentrations are not readily available or clinically useful in the management of overdose. Monitor vital signs and mental status following significant overdose. ECG changes have been rarely reported with overdose. Obtain an ECG, and institute continuous cardiac monitoring.
  • Patient disposition: HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home. OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for six hours to assess mental status. Patients should be observed for at least 12 hours after overdose of sustained release formulations. Patients that remain asymptomatic can be discharged. ADMISSION CRITERIA: Patients should be admitted for severe agitation, CNS depression or seizures. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
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