WBR0092

Author	[[PageAuthor::Gonzalo Romero (Reviewed by Yazan Daaboul, Jad Al Danaf, Rim Halaby, M.D. [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Genitourinary
Prompt	[[Prompt::A 35-year-old man presents to the emergency department (ED) for a persistent and painful erection for the past 5 hours. Upon further questioning, he reports he is a single man with no recent sexual activity or trauma to the genitals. The patient also denies any personal or family history of coagulation or hemoglobin disorders. His medical history is only significant for insomnia and major depression for the past 4 months, for which he was prescribed an antidepressant medication whose name he cannot recall. In the ED, the patient's blood pressure is 176/110 mmHg, temperature is 37 °C (98.6 °F), heart rate is 98/minute, and respiratory rate is 20/minute. On physical examination, the patient appears in pain. His penis is fully erect and tender, with no color changes or other signs of necrosis. The physician in the ED suspects the patient's symptoms may be drug-induced. Which of the following is the mechanism of action of the drug responsible for the patient's symptoms?]]
Answer A	AnswerA::Serotonin reuptake inhibitor
Answer A Explanation	[[AnswerAExp::Trazodone is an atypical antidepressant that belongs to the serotonin antagonist and reuptake inhibitor (SARI) class of antidepressants. Trazodone is believed to cause priapism through its antagonistic effect on alpha-1 adrenergic receptors.]]
Answer B	AnswerB::Norepinephrine reuptake inhibitor
Answer B Explanation	[[AnswerBExp::Maprotiline is an atypical antidepressant which inhibits norepinephrine reuptake.]]
Answer C	AnswerC::Serotonin receptor agonist
Answer C Explanation	[[AnswerCExp::Buspirone, which is prescribed for patients with generalized anxiety disorder, stimulates serotonin (5-HT1A) receptors. It may be preferred among a subgroup of patients because it is not associated with sedation, addiction, or tolerance.]]
Answer D	AnswerD::Alpha-2 receptor antagonist
Answer D Explanation	[[AnswerDExp::Mirtazapine is an atypical antidepressant. It blocks alpha-2 receptors in the presynaptic neurons which increases the release of norepinephrine and serotonin. It causes sedation; therefore it may also be prescribed for patients with depression and insomnia. It is also associated with an increase in appetite with weight gain.]]
Answer E	AnswerE::GABA positive allosteric modulators
Answer E Explanation	[[AnswerEExp::Several drugs act by increasing the opening of GABA channels, such as benzodiazepines and barbiturates.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::Trazadone is an atypical antidepressant that belongs to the serotonin antagonist and reuptake inhibitor (SARI) class of antidepressants. It is a "multifunctional" drug because of its varying binding properties at low doses vs. high doses. At low doses, trazodone acts as a 5-HT2A antagonist, and has effects of H1 receptors and alpha-1 adrenergic receptors. At higher doses, trazadone blocks the serotonin transporter (SERT). It is mainly administered to treat depression associated with insomnia due to its antidepressant and sedating effects. Accordingly, trazodone is called a "serotonin antagonist-reuptake inhibitor" (SARI) whose action on both histamine and serotonin is required for appropriate therapeutic effects. An important but rare side effect of trazadone is low-flow priapism, which is a painful sustained penile erection for more than 4 hours. Trazadone also causes sedation, nausea, and postural hypotension. While most cases of priapism are idiopathic, other common causes of priapism include genital trauma, and hemoglobinopathies such as sickle cell disease. Drug-induced priapism accounts for approximately 30% of all cases. Priapism is a clinical diagnosis; differentiation between low-flow and high-flow priapism is important for appropriate management. While most cases are considered low-flow painful ischemic priapisms, high-flow painless priapism due to trauma and fistula formation must be ruled out. Management of priapism must be initiated rapidly to prevent necrosis of the penis. Educational Objective: Trazadone is an atypical antidepressant prescribed for patients with major depression and insomnia. It inhibits serotonin reuptake and may rarely cause low-flow priapism due to its possible antagonistic effect on alpha-1 adrenergic receptors. References: Abber JC, Lue TF, Luo JA, et al. Priapism induced by chlorpromazine and trazodone: mechanism of action. J Urol. 1987;137(5):1039-42 First Aid 2014 page 520]]
Approved	Approved::Yes
Keyword	WBRKeyword::trazodone, WBRKeyword::priapism, WBRKeyword::depression, WBRKeyword::insomnia, WBRKeyword::serotonin reuptake inhibitor
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::

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