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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor=Gonzalo Romero
|QuestionAuthor=Gonzalo Romero (Reviewed by Yazan Daaboul, [[user: Jad Al Danaf|Jad Al Danaf]],  {{Rim}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|MainCategory=Pharmacology
|SubCategory=Neurology
|SubCategory=Genitourinary
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|MainCategory=Pharmacology
|SubCategory=Neurology
|SubCategory=Genitourinary
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|MainCategory=Pharmacology
|SubCategory=Neurology
|SubCategory=Genitourinary
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|MainCategory=Pharmacology
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|MainCategory=Pharmacology
|SubCategory=Neurology
|MainCategory=Pharmacology
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|SubCategory=Genitourinary
|SubCategory=Neurology
|MainCategory=Pharmacology
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|SubCategory=Genitourinary
|SubCategory=Neurology
|MainCategory=Pharmacology
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|SubCategory=Genitourinary
|SubCategory=Neurology
|MainCategory=Pharmacology
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|SubCategory=Genitourinary
|MainCategory=Behavioral Science/Psychiatry, Pharmacology
|MainCategory=Pharmacology
|SubCategory=Neurology
|MainCategory=Pharmacology
|Prompt=A 35 year-old male comes to the emergency room for acute medical care due to a persistent erection, which he thought it would go away. He is very concerned because this  erection has lasted more than 6 hours. He usually has erections throughout the night and in the morning, but normally last a couple of minute. He denies any sexual encounter the night before. The nurse practitioner meets the patient in the ER and starts asking health relevant questions.  Upon interrogation, he states he has an intense pain over his penis.  He recently was prescribed a medication to aid with sleep, which he has been taking for the last 6 weeks.  He has a history of depression.  His vitals are BP=126/70 mmHg, HR=87, RR=16, T=37 C. The nurse practitioner communicates the information to the medical team. They team is concerned that the drug prescribed to this patient to “aid with his sleep” is associated with his symptoms.   Which of the following is the mechanism of action of the drug most likely prescribed to this patient?
|SubCategory=Genitourinary
|Explanation=[[Trazadone]] is an atypical antidepressant used mainly to treat insomnia. With high doses it can be used to treat depression. An important side effect is priapism, which is a painful sustained penile erection. It also causes sedation, nausea, and postural hypotension. It acts by inhibiting serotonin reuptake primarily
|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?
<br>
|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.  
<font color="MediumBlue"><font size="4">'''Educational Objective:''' </font></font> Trazadone is an atypical antidepressant, which is used to treat insomnia. It acts by inhibiting serotonin reuptake primarily. Its typical side effect is [http://www.wikidoc.org/index.php/Priapism priapism]
 
'''References:''' First Aid 2013, page 476
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]].  
|AnswerA=Inhibits serotonin reuptake
 
|AnswerAExp=Correct
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.
|AnswerB=<font color="Green">'''Correct.'''</font> Inhibits NE reuptake
|AnswerA=Serotonin reuptake inhibitor
|AnswerBExp=<font color="red">'''Incorrect.'''</font> [[Maprotiline]] is an atypical antidepressant which acts by blocking NE reuptake.  It can cause sedation as a side effect.
|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=Norepinephrine reuptake inhibitor
|AnswerBExp=[[Maprotiline]] is an atypical antidepressant which inhibits [[norepinephrine]] reuptake.  
|AnswerC=Serotonin receptor agonist
|AnswerC=Serotonin receptor agonist
|AnswerCExp=<font color="red">'''Incorrect.'''</font> [[Buspirone]] used to treat general anxiety disorder, acts by stimulating setononin (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=<font color="red">'''Incorrect.'''</font> [[Mirtazapine]] is an atypical antidepressant, which acts blocking the alpha-2 receptors in the presynaptic neurons increasing the release of NE and serotonin.  It causes sedation; therefore it can be used in depressed patients with insomnia. Also causes an increase in the appetite leading to weight gain (this could be beneficial in elderly or anorexic patients).
|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.
|AnswerE=GABA receptor moduling
|AnswerE=GABA positive allosteric modulators
|AnswerEExp=<font color="red">'''Incorrect.'''</font> Different drugs act by increasing the opening of GABA channels such as [[benzodiazepines]] and [[barbiturates]].
|AnswerEExp=Several 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.
|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
 
|RightAnswer=A
|RightAnswer=A
|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|]]