A 60-year-old man is found by his daughter to be confused at home. Emergency medical services are called and he is brought to the emergency department by ambulance. The patient's daughter, who accompanies him, says that she found an empty bottle of amitriptyline next to his bed. He has not been taking any other medications. In the emergency department, the patient is delirious and says that he sees small animals running around in the corner of the room. He appears flushed. The patient has a brief seizure and becomes unconscious. Temperature is 37.2 C (99 F), blood pressure is 90/62 mm Hg, and pulse is 120/min. Both pupils are dilated and equally reactive to light, and his skin and mucous membranes are dry. Initial ECG shows QRS widening and QTc prolongation. He is transferred to the intensive care unit but dies despite resuscitation attempts. Which of the following pharmacological effects most likely contributed to the patient's death?

Question

A 60-year-old man is found by his daughter to be confused at home.  Emergency medical services are called and he is brought to the emergency department by ambulance.  The patient's daughter, who accompanies him, says that she found an empty bottle of amitriptyline next to his bed.  He has not been taking any other medications.  In the emergency department, the patient is delirious and says that he sees small animals running around in the corner of the room.  He appears flushed.  The patient has a brief seizure and becomes unconscious.  Temperature is 37.2 C (99 F), blood pressure is 90/62 mm Hg, and pulse is 120/min.  Both pupils are dilated and equally reactive to light, and his skin and mucous membranes are dry.  Initial ECG shows QRS widening and QTc prolongation.  He is transferred to the intensive care unit but dies despite resuscitation attempts.  Which of the following pharmacological effects most likely contributed to the patient's death?

Quizplus · Accepted Answer

11ec160b_3c5a_1358_9249_753422194294_MD0001_00 Tricyclic antidepressants (TCAs), such as amitriptyline, inhibit the reuptake of norepinephrine and serotonin and are used in the treatment of depression. They also inhibit fast sodium channel conduction, slowing down myocardial depolarization and potentially leading to cardiac arrhythmias in overdose. Refractory hypotension results from decreased cardiac contractility and direct peripheral vasodilation (from peripheral alpha-1 adrenergic receptor antagonism). Most deaths from TCA overdose are due to cardiac arrhythmias and refractory hypotension. Treatment of TCA overdose involves sodium bicarbonate (NaHCO₃) therapy. NaHCO₃ increases serum pH, promoting TCA dissociation from sodium channels, and increases extracellular sodium concentration. These effects help overcome the sodium channel blockade induced by TCAs. (Choice A) TCAs cause antihistaminic effects by antagonizing histamine (H1) receptors. This can cause increased sedation and appetite but is not implicated in death from TCAs. (Choice C) TCAs block the amine reuptake pumps within the synaptic cleft, which normally terminate amine transmission. This permits a longer interaction between the neurotransmitter and the receptor, which is thought to account for TCA antidepressant properties. However, synaptic norepinephrine accumulation is not the mechanism by which death occurs following TCA overdose. (Choice D) Serotonin syndrome must be considered in suspected antidepressant overdose. Patients with serotonin syndrome have hyperthermia, autonomic instability, hyperreflexia, myoclonus, and diaphoresis. Cardiac changes are not usually indicative of serotonin syndrome. Although symptoms of excess serotonin may be present after TCA overdose, most deaths are due to cardiac toxicity. (Choice E) TCAs do not increase presynaptic release of dopamine. Amphetamines increase the release of dopamine (and norepinephrine) by vesicles in presynaptic neurons. Educational objective: Tricyclic antidepressant overdose can cause fatal cardiac arrhythmias and refractory hypotension due to inhibition of fast sodium channels in cardiac myocytes. Sodium bicarbonate is used to treat associated cardiac toxicity and works by increasing serum pH and extracellular sodium (alleviating fast sodium channel blockade). __________ References: Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. (http://www.ncbi.nlm.nih.gov/pubmed/21436332) The return of an old nemesis: survival after severe tricyclic antidepressant toxicity, a case report. (http://www.ncbi.nlm.nih.gov/pubmed/29854605) Tricyclic antidepressant poisoning: cardiovascular toxicity. (http://www.ncbi.nlm.nih.gov/pubmed/16390222)

A 60-Year-Old Man Is Found by His Daughter to Be