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Duloksetin (Cymbalta)

Clinical Effects:

DULOXETINE
  • USES: Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, and fibromyalgia. PHARMACOLOGY: The exact mechanism of action is unknown but is believed to be related to the potentiation of serotonergic and noradrenergic activity in the CNS. EPIDEMIOLOGY: Overdose of duloxetine is rare. MILD TO MODERATE TOXICITY: Somnolence, syncope, tachycardia, vomiting, diarrhea, headaches, diaphoresis, agitation, confusion, and hypertension. SEVERE TOXICITY: Serotonin syndrome (altered mental status, neuromuscular abnormalities and autonomic instability), seizures, hypotension, and coma. Fatalities have occurred. ADVERSE EFFECTS: COMMON: Nausea, dry mouth, constipation, fatigue, dizziness, somnolence, and hyperhidrosis. LESS COMMON: Slight increases in blood pressure and heart rate with therapeutic use. Withdrawal symptoms, following abrupt cessation of duloxetine therapy, may include dizziness, nausea, headache, paresthesias, vomiting, irritability, and nightmares. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) with hyponatremia have been reported in patients receiving duloxetine.

Rane of Toxicity:

DULOXETINE
  • TOXICITY: Death has been reported following ingestions of duloxetine doses as low as 1000 mg. In premarketing clinical trials, four patients recovered following acute ingestions of 300 to 1400 mg of duloxetine, as either sole therapy or in combination with other drugs. Somnolence, coma, serotonin syndrome, seizures, syncope, tachycardia, hypotension, hypertension, and vomiting have been reported in patients taking duloxetine (alone or with mixed drugs) doses as low as 1000 mg. INFANT: Drowsiness was the only reported symptom in a 1-year-old child following an unintentional duloxetine ingestion of 7.4 mg/kg. THERAPEUTIC DOSE: The recommended dosage range for duloxetine is 30 to 120 mg daily.

Treatment:

DULOXETINE
  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Most patients require only supportive care. Control agitation with either benzodiazepines. Serotonin syndrome generally responds to benzodiazepines, although a serotonin antagonist such as cyproheptadine may also be considered. Hypertension and tachycardia are generally mild and well tolerated, and do not require specific treatment. MANAGEMENT OR SEVERE TOXICITY: Aggressive use of benzodiazepines and serotonin antagonists is required for more severe serotonin syndrome. Early intubation, neuromuscular paralysis, ventilation assistance, and aggressive cooling should be performed if the patient presents with severe muscle rigidity, and severe hyperthermia. Treat hypotension initially with IV fluids, add vasopressors if necessary. Treat seizures with benzodiazepines; use barbiturates or propofol for recurrent seizures. Patients with wide-complex dysrhythmias should be treated with sodium bicarbonate boluses (1 to 2 mEq/kg, monitor arterial blood gases, target pH 7.45 to 7.55). Although QTc interval prolongation is well described, torsade de pointes is rare. If torsade de pointes occurs, patients should be treated using standard interventions (magnesium sulfate 2 g IV, external or internal cardiac pacing).
  • Decontamination: PREHOSPITAL: Activated charcoal can be considered within the first hour after large ingestion, if the patient has an appropriate level of consciousness, has a patent airway, and is able to drink the charcoal. HOSPITAL: Administer activated charcoal if the patient presents early after large ingestion, if the patient has an appropriate level of consciousness, patent airway and can drink the charcoal, or if the patient is intubated. Severe toxicity is rare; gastric lavage is rarely, if ever, warranted.
  • Airway management: Perform early with neuromuscular paralysis if the patient presents with respiratory or CNS depression, severe muscle rigidity, or severe hyperthermia.
  • Antidote: There is no antidote.
  • Seizure: IV benzodiazepines, barbiturates, or propofol for recurrent seizures.
  • Serotonin syndrome: IV benzodiazepines, cooling measures. Cyproheptadine may be considered (ADULT: 12 mg orally or nasogastric (NG) tube, followed by 4 to 8 mg orally or NG tube every 4 to 6 hours if symptoms persist, up to a maximum of 32 mg in 24 hours. CHILD: 0.25 mg/kg/day divided every 6 hours, maximum dose 12 mg/day). Severe cases have been managed with benzodiazepine sedation and neuromuscular paralysis with nondepolarizing agents.
  • Torsades de pointes: Hemodynamically unstable patients require electrical cardioversion. Emergent treatment with magnesium, isoproterenol, or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities.
  • Monitoring of patient: Monitor vital signs (including temperature) and mental status. Monitor serum electrolytes (including potassium, bicarbonate) following significant overdose. Obtain baseline ECG, continuous cardiac monitoring, and serial ECGs following a significant exposure. Plasma concentration is not readily available and does not correlate well with therapeutic or adverse effects. Monitor liver enzyme concentrations in symptomatic patients.
  • Enhanced elimination procedure: Hemodialysis and hemoperfusion are NOT of value due to the large volume of distribution.
  • Patient disposition: HOME CRITERIA: Asymptomatic children with acute inadvertent ingestions may be monitored at home. Asymptomatic patients or those with mild toxicity following an isolated unintentional acute ingestion of up to 5 times an initial adult therapeutic dose (ie, duloxetine 150 mg) can be observed at home with instructions to call the poison center back if symptoms develop. For patients already on duloxetine with ingestions of up to 5 times their own single therapeutic dose can be observed at home with instructions to call the poison center back if symptoms develop. OBSERVATION CRITERIA: Symptomatic patients, those with deliberate ingestions, and those with ingestions of more than 5 times their therapeutic dose should be evaluated in a healthcare facility and observed for 6 to 12 hours. ADMISSION CRITERIA: Patients with severe toxicity need to be admitted to an intensive care unit. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or if the diagnosis is unclear.
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