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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor=Gonzalo Romero (reviewed by [[user: Jad Al Danaf|Jad Al Danaf]], {{Rim}})
|QuestionAuthor=Gonzalo Romero (Reviewed by Yazan Daaboul, [[user: Jad Al Danaf|Jad Al Danaf]], {{Rim}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Pharmacology
|MainCategory=Pharmacology
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|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Genitourinary
|SubCategory=Genitourinary
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
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|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Genitourinary
|SubCategory=Genitourinary
|Prompt=A 35 year-old male presents to the emergency room for persistent and painful erection of 5 hours duration. The patient usually has erections throughout the night and in the morning, but they only last for a couple of minutes.  He denies any sexual encounter the previous night or any erectile dysfunction for which he takes medications.
|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?
The patient has a history of depression for which he is on medical therapy. He also reports the use of a medication to help him sleep for the last 6 weeks. 
|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.  
 
His vitals are the following: blood pressure of 126/70 mmHg, regular heart rate of 87 beats/minute, respiratory rate of 16 per minute, and temperature of 37 C.
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]].
The emergency medicine doctor is concerned that the sleep medication is associated with his prolonged painful erection. Which of the following is the mechanism of action of the drug that is most likely prescribed to this patient?
 
|Explanation=[[Trazadone]] is an atypical antidepressant used mainly to treat insomnia. With high doses it can be used to treat depression. An important but rare side effect is priapism, which is a painful sustained penile erection of more than 4 hours. It also causes sedation, nausea, and postural hypotension. It acts by inhibiting serotonin reuptake and belongs to the serotonin antagonist and reuptake inhibitor (SARI) class.
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.
|AnswerA=Inhibits serotonin reuptake
|AnswerA=Serotonin reuptake inhibitor
|AnswerAExp=The new drug that has been prescribed for the patient is most likely to be [[Trazodone]]. It is an atypical antidepressant that belongs to the serotonin antagonist and reuptake inhibitor (SARI) class of antidepressants. It is usually prescribed to treat insomnia in patients with major depressive symptoms, and has also been shown to have anxiolytic properties.
|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.
|AnswerB=Inhibits NE reuptake
|AnswerB=Norepinephrine reuptake inhibitor
|AnswerBExp=[[Maprotiline]] is an atypical antidepressant which blocks [[neuroepinephrine]] reuptake.  It can cause [[sedation]] as a side effect.
|AnswerBExp=[[Maprotiline]] is an atypical antidepressant which inhibits [[norepinephrine]] reuptake.  
|AnswerC=Serotonin receptor agonist
|AnswerC=Serotonin receptor agonist
|AnswerCExp=[[Buspirone]], which is used to treat general anxiety disorder, stimulates [[serononin]] (5-HT1a) receptors. It does not cause [[sedation]], [[addiction]] or [[tolerance]].
|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]].
|AnswerD=Alpha-2 receptor antagonist
|AnswerD=Alpha-2 receptor antagonist
|AnswerDExp=[[Mirtazapine]] is an atypical antidepressant, which blocks alpha-2 receptors in the presynaptic neurons which increases the release of [[norepinephrine]] and [[serotonin]].  It causes [[sedation]]; therefore, it can be used in depressed patients with [[insomnia]]. It might also cause an increase in appetite with possible weight gain.
|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.
[[Trazodone]] is thought to cause [[priapism]] through its antagonistic effect on alpha adrenergic receptors.
|AnswerE=GABA positive allosteric modulators
|AnswerE=modulating GABA receptors
|AnswerEExp=Several drugs act by increasing the opening of [[GABA]] channels, such as [[benzodiazepines]] and [[barbiturates]].
|AnswerEExp=Different drugs act by increasing the opening of [[GABA]] channels such as [[benzodiazepines]] and [[barbiturates]].
|EducationalObjectives=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.
|EducationalObjectives=Trazadone is an atypical antidepressant used to treat [[insomnia]] in patients with [[depression]]. Its inhibits [[serotonin]] reuptake and can cause priapism, on rare occasions, due to its possible antagonistic effect on alpha 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
|References=First Aid 2013, page 476;
First Aid 2014 page 520
Abber RE et al. (1987). "Priapism induced by chlorpromazine and trazodone: mechanism of action". J. Urol 137 (5): 1039–1042.
 
|RightAnswer=A
|RightAnswer=A
|WBRKeyword=trazodone, priapism, depression, insomnia, serotonin reuptake inhibitor
|WBRKeyword=trazodone, priapism, depression, insomnia, serotonin reuptake inhibitor
|Approved=Yes
|Approved=Yes
}}
}}
{{WBRImage|||Explanation}}
{{WBRImage|||Explanation}}

Latest revision as of 23:19, 27 October 2020

 
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::


Image [[WBRImage::|]] Caption WBRImageCaption::no-display Position [[WBRImagePlace::Explanation|]]