Antidepressant and Anxiety drug Q's (part 2)

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A 23-year-old woman arrives in the emergency room complaining of blurry vision, profuse sweating, and headache which developed during a wine and cheese party. Her past medical history is significant for depression for which she takes phenelzine. Vital signs are notable for temperature 37०C (98.6०F) and blood pressure 180/142. EKG shows sinus tachycardia. Patellar tendon reflex is normal and intact. What medication should be used to treat this patient? A. Cyproheptadine B. Epinephrine C. Phentolamine D. Sodium bicarbonate

C. A patient taking an MAOI (e.g. phenelzine) may develop hypertensive crisis after ingesting foods containing tyramine (e.g. wine and aged cheese). In the presence of MAOIs, tyramine enters the circulation and acts as a sympathomimetic agent causing hypertension, blurry vision, and diaphoresis. Phentolamine, a non-selective alpha blocker, can be used to manage TCA-induced hypertensive crisis. A. Cyproheptadine is used to treat serotonin syndrome. Serotonin syndrome presents with hypertension, hyperthermia, and hyperactive reflex (or clonus). Although patients taking MAOI are at risk of developing serotonin syndrome, this patient's diagnosis is most likely hypertensive crisis. B. Epinephrine can be used to treat anaphylaxis which often presents with respiratory compromise, urticaria and hypotension. Adding epinephrine, a sympathomimetic, to a patient already in hypertensive crisis is ill-advised. D. Sodium bicarbonate is used to treat wide QRS complexes in patients with tricyclic antidepressant (TCA) overdose. This patient does not have a history of using TCAs and EKG is significant only for sinus tachycardia. Sodium bicarbonate would not be useful in treating this patient's hypertensive crisis.

Which of the following side effects is most associated with bupropion? A. Erectile dysfunction B. Hypersomnia C. Seizures D. Weight gain

C. Bupropion is known to lower the seizure threshold. As a result, patients with seizure disorder or a history of bulimia or anorexia nervosa should not be prescribed bupropion. A. One of the advantages of bupropion is that it is not associated with sexual dysfunction. Patients who experience negative sexual side effects from SSRIs or tricyclic antidepressants may benefit from switching to bupropion. B. Bupropion exerts CNS activating effects and is a good choice of medication for patient suffering from daytime fatigue and hypersomnia. D. Many antidepressants including SSRIs, tricyclic antidepressants and mirtazapine are associated with weight gain. Bupropion is less likely to cause weight gain compared to many other antidepressant medications.

Which of the following statements is true? A. Mirtazapine is a histamine-2 receptor antagonist B. Mirtazapine is a monoamine oxidase inhibitor C. Mirtazapine is an alpha-2 receptor antagonist D. Mirtazapine is an alpha-2 receptor agonist E. Mirtazapine is an dopamine-2 receptor antagonist

C. Mirtazapine is an alpha-2 receptor antagonist. Blockade of presynaptic alpha-2 receptors leads to an increase in the presynaptic release of serotonin and norepinephrine. A. In addition to antagonizing presynaptic alpha-2 receptors, mirtazapine aslo antagonizes histamine-1 receptors. Diphenhydramine and hydroxyzine are also histamine-1 receptor antagonists. All histamine-1 receptors which cross the blood-brain barrier induce sedation. B. Mirtazapine is an atypical antidepressant, not a monoamine oxidase inhibitor (MAOI). Phenelzine, isocarboxazid, tranylcypromine and selegiline belong to the MAOI class of drugs. D. Its an alpha-2 receptor antagonist (not agonist) E.. Mirtazapine is not a dopamine receptor antagonist. Drugs which treat schizophrenia and nausea frequently target the dopamine receptors.

A patient taking isocarboxazid (a MOAI) unknowingly ingests food containing tyramine. Which of the following clinical findings is most likely to be seen in a patient with tyramine toxicity? A. Anhidrosis B. Bradycardia C. Malignant hypertension D. Orthostatic hypotension

C. Patients taking monoamine oxidase inhibitors (MAOIs) should avoid consumption of tyramine containing food items such as aged cheese, red wine, and cured meat. Tyramine is normally metabolized by monoamine oxidase A (MAO-A) in the gastrointestinal tract. In the presence of MAOIs, excess tyramine enters the circulation and acts as a sympathomimetic agent causing hypertension, tachycardia, blurred vision, and diaphoresis A. When a patient on an MAOI ingests tyramine, there is risk of tyramine toxicity and hypertensive crisis. Patients often present with hypertension and diaphoresis, not anhidrosis. B. Tyramine acts as a sympathomimetic in the presence of MAOIs. As a result, patients are most likely to experience hypertension, tachycardia, and diaphoresis. Bradycardia would not be consistent with tyramine toxicity. D. In the presence of MAOIs, tyramine acts as a sympathomimetic and can cause hypertensive crisis. Patients are most likely to present with hypertension and should be treated with phentolamine.

A young man presents to the emergency department with a painful, involuntary erection which has lasted 5 hours. He started taking a new antidepressant a few weeks ago. His symptoms are most likely caused by the new medication's antagonistic effect on which of the following receptors? A. Alpha-1 receptor B. Alpha-2 receptor C. Histamine-1 receptor D. Histamine-2 receptor

A. "Traz has one long alpha cock" The man in this vignette appears to be suffering from priapism, which is a rare but serious side effect of the antidepressant trazodone. Priapism is a persistent erection lasting more than 4 hours that is not associated with sexual excitement. It is a true urologic emergency that can result in permanent damage to penile tissue and erectile dysfunction if left untreated. Trazodone antagonizes alpha-1 adrenergic receptors which dilates vascular smooth muscle and is responsible for causing both priapism and orthostatic hypotension. Ischemic priapism should be treated with intracavernosal injection of the alpha-adrenergic agonist, phenylephrine. Trazodone should be used with caution in patients with conditions that predispose to priapism (e.g. sickle cell disease, multiple myeloma). B. Alpha-2 adrenergic receptors mediate decreased adrenergic outflow. Alpha-2 receptor antagonists such as mirtazapine are not associated with priapism or orthostatic hypotension. C.H1 histamine receptor antagonists are not associated with priapism or orthostatic hypotension. H1-blockers including mirtazapine and trazodone which can cross the blood brain barrier are associated with fatigue and sedation. D. H2 histamine antagonists such as ranitidine and cimetidine are used to decrease the production of gastric acid. H2-blockers are not associated with priapism or orthostatic hypotension.

Which of the following electrocardiogram abnormalities is LEAST likely to be seen in a patient with tricyclic antidepressant overdose? A. Depressed, "sagging" ST segment B. QRS interval prolongation C. QT interval prolongation D. Sinus tachycardia

A. An ST segment which is "slurred", "scooped", or "sagging" (or resembles Salvador Dali's moustache!) is suggestive of digoxin toxicity. Digoxin toxicity may also induce premature ventricular contractions and sinus bradycardia. A sagging ST segment is not seen in tricyclic antidepressant overdose. B. QRS interval prolongation is a hallmark of tricyclic antidepressant toxicity. A QRS interval greater than 100 msec is suggestive of cardiotoxicity and the patient should be treated with sodium bicarbonate in an effort to reduce the wide QRS interval and prevent ventricular arrhythmias. C. Tricyclic antidepressants block cardiac fast sodium channels and may cause prolongation of the QT interval. D. Sinus tachycardia is the most common arrhythmia seen in tricyclic antidepressant overdose. Tricyclic antidepressants inhibit muscarinic acetylcholine receptors which cause dry mouth, constipation, blurred vision, urinary retention as well as sinus tachycardia.

Which of the following antidepressants is LEAST likely to cause sedation? A. Bupropion B. Imipramine C. Mirtazapine D. Trazodone

A. Bupropion inhibits reuptake of dopamine and norepinephrine and is more likely to act as a neurostimulant than most other antidepressants. Bupropion is also less likely to cause weight gain or sexual dysfunction when compared to many other antidepressants. These properties make bupropion a good choice as first-line medication for patients with major depressive disorder. However, patients with bulimia and anorexia nervosa should not take bupropion due to increase risk of seizures. B. Imipramine is a tricyclic antidepressant with anticholinergic and antihistaminic properties, known to cause drowsiness and sedation. C. Mirtazapine antagonizes H1 histamine receptors causing sedation. Mirtazapine is also associated with weight gain and can be a good choice of medication in depressed patients who also suffer from insomnia and anorexia. D. Trazodone antagonizes H1 histamine receptors, resulting in sedation as an adverse effect. Trazodone can be an effective choice in patients suffering from insomnia alongside their depressive symptoms.

Many patients with eating disorders such as anorexia and bulimia also suffer from comorbid depression and anxiety. When treating these patients for depression, which of the following drugs should NOT be used? A. Bupropion B. Fluoxetine C. Mirtazapine D. Trazodone

A. Bupropion is a selective reuptake inhibitor of catecholamines (noradrenaline and dopamine). It is contraindicated in patients with bulimia (uncontrolled episodes of overeating) or anorexia nervosa as it may increase the risk of seizures. Bupropion is also contraindicated in patients with seizure disorders for the same reason. B. Fluoxetine is an SSRI used to treat depression and various forms of anxiety. SSRIs are actually first-line agents for treating bulimia; however, these agents are not effective for treating anorexia. C. Mirtazapine is an antidepressant which is known to increase appetite and promote weight gain. Mirtazapine can be especially useful in patients with anorexia to promote weight gain. D. Trazodone is not contraindicated in patients with eating disorders such as bulimia or anorexia. However, trazodone is generally not used as a first line agent due to its adverse effect profile.

A man with treatment resistant depression is started on imipramine after failing trials of SSRIs and SNRIs. On his follow up visit, he states that he feels lightheaded and dizzy more often. This feeling usually occurs if he stands up too quickly after prolonged periods of sitting or lying down. Sometimes his vision blurs for a moment after standing up too quickly. This patient's symptoms are most likely attributed to the interaction between imipramine and which receptor? A. Alpha-1 B. Beta-1 C. Histamine-1 D. Muscarinic

A. Imipramine is a tricyclic antidepressant (TCA) used for treatment resistant depression and childhood enuresis. Imipramine blocks alpha-1, histamine-1 and muscarinic acetylcholine receptors. Alpha-adrenergic blockade is most likely responsible for this patient's orthostatic hypotension. An impaired ability to contract vascular smooth muscle results in temporary pooling of the blood in the lower extremities. As a result, this patient experiences transiently decreased cerebral perfusion when he stands up too quickly. Clinically, this manifests as dizziness, lightheadedness and blurred vision. B. The beta-1 adrenergic receptor mediates cardiac contractility and chronotropy. Excessive beta-1 blockade may lead to dizziness due to hypotension and bradycardia C. Imipramine blocks histamine-1 (H1) receptors. H1 antagonists can cause sedation and weight gain. H1 blockers are also used to decrease vascular permeability and nasal mucus production. Alpha-1 adrenergic blockade, rather than histamine-1 blockade, is responsible for causing orthostatic hypotension. D. Tricyclic antidepressants (TCAs) including imipramine are often poorly tolerated due to its adverse effect profile. TCAs are known to cause dry mouth, constipation, urinary retention and blurred vision as a results of muscarinic receptor antagonism.

Monoamine oxidase B (MAO-B) selectively targets which of the following molecules? A. Dopamine B. Norepinephrine C. Serotonin D. Tyrosine

A. MAO-B selectively degrades dopamine. B. Norepinephrine, serotonin and dopamine are all degraded by MAO-A. C. Serotonin undergoes oxidative deamination through a chemical reaction catalyzed by monoamine oxidase A (MAO-A). D. Tyrosine hydroxylase can convert tyrosine to L-DOPA, the precursor of dopamine.

Fluoxetine is LEAST likely to help improve the symptoms of which of the following patients? A. 20-year-old woman with BMI 16 who severely restricts her caloric intake B. 21-year-old man with BMI 18 who exercises intensely after binge eating C. 22-year-old woman with BMI 20 who induces self vomiting after large meals D. 23-year-old man with BMI 22 who regularly uses laxatives to achieve a goal weight

A. Patients with a BMI below 17 kg/m2 who restrict caloric intake, have a fear of weight gain, and have an unhealthy sense of their own body weight/shape meet the DSM-5 diagnostic criteria for anorexia nervosa. There are few studies demonstrating the effectiveness of fluoxetine or other SSRIs in the treatment of anorexia nervosa. B. Recurrent episodes of binge eating followed by compensatory mechanisms such as intense exercise in a patient with normal BMI is suggestive of bulimia nervosa. Fluoxetine is the first line treatment option for bulimia nervosa. C. This woman likely has bulimia nervosa as she has a normal BMI and recurrent episodes of binge eating followed by self induced vomiting. Fluoxetine and other SSRIs including citalopram, fluvoxamine and sertraline are also effective in treating bulimia. D. Patients with bulimia nervosa frequently binge eat followed by compensatory behaviors to avoid weight gain (e.g using laxatives, diuretics, fasting and/or exercise). SSRIs such as fluoxetine are effective in treating bulimia. However, patients should also be offered psychotherapy in addition to medical therapy.

SSRIs are associated with all of the following side effects EXCEPT: A. Hypertension B. Sexual dysfunction and decreased libido C. Sleep disturbance D. Weight gain

A. SNRIs increase noradrenergic transmission and are therefore associated with increased blood pressure and hypertension. (SSRIs are not associated with increased blood pressure or hypertension) B. SSRIs may cause sexual dysfunction, anorgasmia, impotence as well as decreased libido. Patients who cannot tolerate these side effects may be switched to the atypical antidepressant bupropion which is associated with lower levels of sexual dysfunction. C. Sleep disturbance is one of the common adverse effects associated with SSRIs. Patients may complain of insomnia or drowsiness and sedation. Patients may be advised to take the medication before bedtime to alleviate symptoms of daytime sedation, or take the medication in the morning to combat symptoms of insomnia. D. SSRIs are associated with weight gain. Within the SSRI drug class, fluoxetine is the least likely to cause weight gain while paroxetine is the most likely to cause weight gain. If this side effect is unacceptable to the patient, bupropion may be used as it is not associated with weight gain.

Which of the following medications is LEAST likely to precipitate serotonin syndrome? A. Bupropion B. Mirtazapine C. Paroxetine D. Trazodone

A. Serotonin syndrome is usually caused by taking drugs which increase the level of serotonin at the neuronal synapse. Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) are all associated with increased risk of serotonin syndrome. Bupropion inhibits the reuptake of norepinephrine and dopamine and has little effect on serotonin. Bupropion alone has not been reported to cause serotonin syndrome. B. Mirtazapine is an antidepressant that antagonizes serotonin receptors and alpha-2 adrenergic receptors. Antagonism of alpha-2 adrenergic receptors increases presynaptic release of norepinephrine and serotonin. Use of mirtazapine increases the risk of serotonin syndrome especially when used together with SSRIs, TCAs, or MAOIs. C. Paroxetine is an SSRI and can be used to treat many conditions including major depressive disorder and generalized anxiety disorder. SSRIs inhibit reuptake of serotonin and are associated with serotonin syndrome. D. Trazodone is an antidepressant that antagonises the 5HT-2 receptor and also inhibits serotonin reuptake. Trazodone, especially when taken with another drug which increases serotonin in the synapse, can increase the risk of developing serotonin syndrome.

A man is brought to the emergency room due to acute onset of uncontrollable tremor, muscle rigidity, severe diaphoresis and diarrhea. He has social anxiety disorder for which he takes sertraline. He also has fibromyalgia for which he takes duloxetine and tramadol. His dose of tramadol was recently increased. On physical exam, the medical student is able to elicit clonus from the ankle. Which of the following medications is most appropriate for treating this patient's condition? A. Cyproheptadine B. Dantrolene C. Imipramine D. Linezolid

A. Sertraline is a SSRIs Duloxentine is a SRIs This patient is most likely has serotonin syndrome due to polypharmacy of drugs that increase the level of serotonin. SSRIs, SNRIs, MAOIs, TCAs and tramadol are all risk factors for developing serotonin syndrome. On clinical exam, serotonin syndrome is characterized by hyperthermia, hypertension and neuromuscular hyperactivity including clonus. Cyproheptadine is a serotonin receptor antagonist and can be used to treat serotonin syndrome. B. Dantrolene is a muscle relaxant used in the treatment of neuroleptic malignant syndrome and malignant hyperthermia. However, this patient likely has serotonin syndrome due to polypharmacy of drugs that increase the level of serotonin. C. Imipramine is a tricyclic antidepressant which inhibits the reuptake of norepinephrine and serotonin. As a result, imipramine is associated with serotonin syndrome. D. Linezolid is an antibiotic with gram positive coverage including MRSA. Linezolid may cause serotonin syndrome as it inhibits monoamine oxidase A and B resulting in increased levels of serotonin within the neuronal synapse.

A patient taking paroxetine is diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH). Which of the following findings would be expected in a patient with SIADH? A. Euvolemia B. Hypernatremia C. Low urine osmolality D. Low urine sodium

A. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) may be a side effect of taking SSRIs, cyclophosphamide or carbamazepine. SIADH may also be found in patients with small cell lung cancer, head trauma or pneumonia. Patients with SIADH present with euvolemic hyponatremia. B. SIADH is characterized by euvolemic hyponatremia. Patients may present with symptoms of hyponatremia including nausea, vomiting, muscle cramps, and in severe instances, seizures. C. Patients with SIADH are expected to have elevated urine sodium and elevated urine osmolality. Low urine osmolality may be indicative of psychogenic polydipsia or a low solute diet ("tea and toast" or "beer potomania") as well as diabetes insipidus. D. Patients with SIADH are expected to have elevated urine sodium and elevated urine osmolality. Very low urine sodium may be caused by prerenal azotemia, nephrotic syndrome, hyperaldosteronism, gastrointestinal losses, and hypovolemic hyponatremia.

A 34-year-old man presents with poor mood, daytime fatigue, loss of interest, feelings of guilt, poor concentration and increased appetite. He has no other medical conditions. He smokes 3 packs of cigarettes a day and has tried unsuccessfully to quit cold turkey. He does not use alcohol or illicit drugs. Which of the following medications would be most appropriate for this patient? A. Bupropion B. Mirtazapine C. Trazodone D. Varenicline

A. This man is presenting with symptoms of major depressive disorder (MDD). Bupropion is an atypical antidepressant which can be used as first line therapy for treatment of MDD. Bupropion would be well suited for this man because it exerts CNS activating effects, is less likely to cause weight gain, and may be used to treat tobacco dependence. B. Mirtazapine is an atypical antidepressant that blocks alpha-2, 5HT-2, 5HT-3 and H1 receptors. Mirtazapine can cause sedation and weight gain and would not be the best choice of medication in this patient with daytime fatigue and increased appetite. C. Trazodone is a serotonin modulator and is used to treat depression. However, trazodone is not used as first line therapy due to its possible adverse effects including priapism, sedation, orthostatic hypotension and sexual dysfunction. The patient would likely tolerate bupropion much better. Additionally, bupropion can be used to treat nicotine dependence from cigarette use. D. Varenicline is a partial nicotinic receptor agonist used to treat nicotine addiction. Although this patient may benefit from pharmacological aid in his quest to stop smoking, he should also be treated for major depressive disorder. Bupropion can be used to treat nicotine addiction as well as depression.

Which of the following medications is most likely to cause urinary retention? A. Amitriptyline B. Desipramine C. Nortriptyline D. Paroxetine

A. Tricyclic antidepressants are categorized into tertiary amines and secondary amines. Tertiary amines include amitriptyline, imipramine, and clomipramine; these drugs have increased affinity for the muscarinic acetylcholine receptor. Secondary amines such as nortriptyline and desipramine have less affinity for the muscarinic receptors. As a result, tertiary amines including amitriptyline are more likely to precipitate anticholinergic effects such as urinary retention, dry mouth, and constipation. B. Desipramine and nortriptyline are both secondary amines. Anticholinergic effects including urinary retention, dry mouth, and constipation are more likely to occur with tertiary amines such as amitriptyline. C. Secondary amines (e.g. nortriptyline and desipramine) are associated with less anticholinergic effects than tertiary amines (e.g. amitriptyline and imipramine). D. Paroxetine is a selective serotonin reuptake inhibitor (SSRI). Unlike tricyclic antidepressants, SSRIs do interact with the muscarinic receptor and do not cause anticholinergic side effects such as urinary retention.

A woman has been experiencing fatigue, poor concentration, anhedonia, early morning awakening, and poor appetite for the past month. She denies suicidal ideation. She is prescribed sertraline. Ten days later, she returns to report no improvement in her symptoms. Which of the following steps in management is most appropriate for this patient? A. Add citalopram B. Continuation of sertraline under close observation C. Hospitalization for electroconvulsive therapy D. Replace sertraline with duloxetine

B. "SIG-E-CAPS" stands for sleep, interest, guilt, energy, concentration, appetite, psychomotor and suicidal ideation. This patient has major depressive disorder (MDD) as she endorses 5 of the 9 "SIG-E-CAPS" symptoms for at least two weeks. SSRI medications such sertraline can be used as first line treatment for MDD but response to the medication may take 4-8 weeks. This patient should take sertraline for at least 4-8 weeks before any modifications are made to her treatment regimen. A. This patient is suffering from major depressive disorder (MDD). Both sertraline and citalopram are SSRIs and can be used to treat MDD. It typically takes 4-8 weeks to achieve maximal treatment response with use of SSRIs. This patient has only been taking sertraline for 10 days and should continue taking the drug for at least 4-8 weeks before starting an additional agent or increasing the dose of sertraline. C. Electroconvulsive therapy (ECT) is indicated in patients with severe suicidality, severe psychosis or catatonia. This patient does not endorse suicidal ideation and has no other indications for immediate hospitalization. She should continue the trial of sertraline as an outpatient to treat major depressive disorder. D. SSRIs like sertraline typically take 4-8 weeks to achieve maximal effect. Treatment failure cannot be determined after only 10 days. Patients should be counseled on this timeline prior to starting the medication. Substitution of alternative drugs should take place only after a sufficient trial period on the initial agent.

A patient prescribed fluoxetine for major depressive disorder can no longer tolerate the medication due to anorgasmia and impotence. Which of the following medications can treat major depressive disorder without causing sexual dysfunction? A. Amitriptyline B. Mirtazapine C. Phentolamine D. Trazodone

B. Between 15%-80% of patients treated with SSRIs experience some form of sexual dysfunction. Patients who cannot tolerate SSRIs due to sexual dysfunction may prefer mirtazapine, which is not associated with sexual dysfunction. However, patients should be counseled that mirtazapine comes with other side effects such as weight gain and sedation. Bupropion is another atypical antidepressant that is not associated with sexual dysfunction. A. Amitriptyline is a tricyclic antidepressant. Tricyclic antidepressants are associated with sexual dysfunction C. Phentolamine is a non-specific alpha adrenergic receptor blocker used to treat hypertensive symptoms of tyramine toxicity. Phentolamine is not used to treat depression. D. Trazodone is associated with sexual dysfunction. Trazodone can also cause sedation, orthostatic hypotension, priapism and serotonin syndrome.

Fluoxetine is relatively contraindicated in which of the following conditions? A. Agoraphobia B. Bipolar disorder C. Bulimia D. Social anxiety disorder

B. Bipolar disorder is characterized by the switching between manic or hypomanic episodes and depressive episodes. Patients with bipolar disorder should not be treated with SSRI monotherapy due to the risk of precipitating a hypomanic or manic episode. Patients with major depressive disorder as well as bipolar disorder may be carefully treated with an antidepressant if the patient is also placed on a mood stabilizing medication such as lithium, valproate or carbamazepine. A. Agoraphobia is an anxiety disorder characterized by fear of public spaces. SSRIs like fluoxetine have proven effective in treating agoraphobia and other forms of anxiety such as social phobia and obsessive-compulsive disorder. C. Bulimia is an eating disorder that involves alternating periods of binging and purging. SSRIs such as fluoxetine are useful for treating bulimia. Bupropion, an atypical antidepressant, is contraindicated in patients with bulimia due to risk of seizures. D. Social anxiety disorder typically responds well to treatment with cognitive behavioral therapy and SSRIs. Fluoxetine, an SSRI, would be a good choice for treatment of social anxiety disorder.

Fill in the blank: Trazodone and mirtazapine BOTH antagonize _______. A. 5HT-1 serotonin receptors B. 5HT-2 serotonin receptors C. Alpha-1 adrenergic receptors D. Alpha-2 adrenergic receptors

B. Both trazodone and mirtazapine antagonize 5HT-2 serotonin receptors. Mirtazapine and trazodone also both inhibit H1 histamine receptors and cause sedation. A. Neither trazodone nor mirtazapine antagonize 5HT-1 serotonin receptors. Vilazodone and vortioxetine are atypical antidepressants which act as 5HT-1 receptor agonists. C. Trazodone, but not mirtazapine, antagonizes alpha-1 adrenergic receptors. Alpha-1 blockade results in vasodilation and may cause orthostatic hypotension and priapism. D. Mirtazapine, not trazodone, antagonizes presynaptic alpha-2 adrenergic receptors, thereby increasing release of the neurotransmitters serotonin and norepinephrine

Which of the following tricyclic antidepressants should be used to treat obsessive-compulsive disorder? A. Amitriptyline B. Clomipramine C. Imipramine D. Nortriptyline

B. Clomipramine is a tricyclic antidepressant that is used to treat obsessive compulsive disorder (OCD). SSRIs are generally used as first line treatment for OCD due to a more preferable side effect profile. Additionally, adding cognitive-behavioral therapy to pharmacotherapy can improve treatment response. C. Imipramine, a tricyclic antidepressant, is used to treat childhood nocturnal enuresis. However, due to the adverse effects of tricyclic antidepressants, desmopressin is the preferred medication for treatment of enuresis (loss of bladder control) A. Amitriptyline is used as a second-line agent for treating major depressive disorder. It may also be used to treat chronic neuropathic pain and fibromyalgia. D. Nortriptyline is used as a second-line agent for treating major depressive disorder. It may also be used to treat neuropathic pain such as postherpetic neuralgia.

Isocarboxazid is ______, with inhibitory effects against ______ . A. Irreversible, MAO-B only B. Non-selective, MAO-A and MAO-B C. Reversible, MAO-A and MAO-B D. Selective, MAO-A only

B. Isocarboxazid is an irreversible, non-selective monoamine oxidase inhibitor which has activity against both MAO-A and MAO-B. MAO-A degrades serotonin, norepinephrine and dopamine while MAO-B only degrades dopamine. Isocarboxazid raises synaptic concentration of serotonin, norepinephrine, and dopamine and is used to treat depression A. Selegiline is an irreversible MAO inhibitor, specific for MAO-B.

Sodium bicarbonate is used to reverse which of the following adverse effects caused by tricyclic antidepressants? A. Alpha-1 receptor blockade B. QRS prolongation C. Seizure D. Weight gain

B. Overdose of tricyclic antidepressants can result in dangerous prolongation of the QRS complex due to blockade of the fast sodium channels. Sodium bicarbonate increases the serum pH and decreases the availability of ionized or active drug to bind to sodium channels. Sodium bicarb also increases extracellular Na+ which helps overcome the competitive rapid sodium channel blockade induced by TCAs. When the QRS complex is widened as a result of TCA overdose, sodium bicarbonate should be administered to prevent deterioration to ventricular arrhythmias. C. Tricyclic antidepressants lower the threshold for development of seizures. In patients with TCA-induced seizures, benzodiazepines such as lorazepam and diazepam should be used to abort the seizures. Sodium bicarbonate is used to treat wide QRS complex, not abort or reverse TCA-induced seizures.

What is the mechanism of action of phentolamine? A. Alpha-2 adrenergic receptor agonist B. Non-selective alpha receptor blocker C. Selective alpha-1 receptor blocker D. Selective alpha-2 receptor blocker

B. Phentolamine is a reversible non-selective alpha receptor blocker which targets both alpha-1 and alpha-2 adrenergic receptors. Phentolamine can be used to lower blood pressure in patients with hypertensive crisis secondary to tyramine toxicity as well as cocaine overdose. Phenoxybenzamine is an irreversible non-selective alpha blocker which is used preoperatively in patients with pheochromocytoma to prevent hypertensive crisis. A. Clonidine and alpha-methyldopa are both alpha-2 adrenergic receptor agonist which can be used to treat hypertension. Clonidine may also be used to treat ADHD and Tourette syndrome. C. Prazosin, terazosin and tamsulosin are all selective alpha-1 receptor blockers. Alpha-1 receptor blockers are used to relieve symptoms of benign prostatic hypertension. Prazosin can also be used to treat PTSD. D. Mirtazapine is a selective alpha-2 blocker and is used as an antidepressant. Mirtazapine is also used to increase appetite and induce somnolence.

Which of the following best characterizes the mechanism of action of tricyclic antidepressants (TCAs) in treating depression? A. Block the alpha-2 adrenergic receptor B. Inhibit presynaptic uptake of serotonin and norepinephrine C. Inhibit presynaptic uptake of serotonin only D. Prevent the degradation of serotonin and norepinephrine

B. TCAs such as imipramine, clomipramine, amitriptyline and nortriptyline act by inhibiting the presynaptic uptake of both serotonin and norepinephrine. TCAs have a similar mechanism of action as SNRIs which also inhibit presynaptic uptake of serotonin and norepinephrine. A. Mirtazapine block alpha-2 adrenergic receptor. Alpha-2 inhibition increases presynaptic release of serotonin and norepinephrine. C. SSRIs (such as Fluoxetine, paroxetine, sertraline, and citalopram) inhibit presynaptic uptake of serotonin only. D. Monoamine oxidase (MAO) inhibitors, inhibit the degradation of serotonin and norepinephrine. MAO inhibitors including phenelzine and tranylcypromine increase the amount of amine transmitters in the synaptic cleft by preventing it from being metabolised in the presynaptic neurons.

Prior to the discovery of SSRIs, tricyclic antidepressants (TCA) were used as first line treatment for major depressive disorder. Today, TCAs are usually reserved as second or third line agents for all of the following reasons EXCEPT: A. Cardiotoxicity including torsades de pointes B. Decreased efficacy due to weak serotonin reuptake inhibition C. Poor drug tolerance D. Unsafe to use in elderly patients

B. Tricyclic antidepressants effectively inhibit reuptake of both norepinephrine and serotonin via blockade of the serotonin transporter (SERT) and norepinephrine transporter (NET). TCAs have comparable efficacy with SSRIs in studies examining treatment of major depressive disorder. The primary reason that TCAs are used as second or third line medications is due to the risk of severe adverse events (with low threshold for drug overdose and death), poor drug tolerance and risk of drug interactions. A. Tricyclic antidepressant induced cardiotoxicity is the most common cause of death in overdose. There is a much lower threshold for toxic overdose of TCAs than SSRIs (10 times the daily dose can be fatal). TCAs can prolong the QT segment, widen the QRS complex and in rare instances cause torsades de pointes. C. Tricyclic antidepressants are associated with myriad adverse effects, including cardiotoxicity, seizures, sedation, and hypotension. Although SSRIs are also associated with adverse effects (e.g. sexual dysfunction, nausea and SIADH), SSRIs are generally much better tolerated and safer to use than TCAs. D. Tricyclic antidepressants are used primarily to increase the levels of serotonin and norepinephrine in neuronal synapses. However, TCAs have additional undesirable properties such as histamine receptor antagonism, muscarinic acetylcholine receptor antagonism and alpha-1 receptor blockade. For these reasons, TCAs are relatively contraindicated in elderly patients. In contrast, SSRIs can be safely administered to older patients and do not have antihistamine or anticholinergic effects.

A 22-year-old woman presents to her physician because of excessive sleepiness and depressed mood. She endorses symptoms consistent with the DSM-5 criteria for major depressive disorder. In particular, she states that she now sleeps 20 hours a day as a result of her depressed mood. She endorses binge eating episodes but denies purging or inappropriate use of laxatives. Her BMI is 23. Physical exam shows parotitis and calluses on the dorsum of the right hand. Which of the following medications should be prescribed for this patient? A. Bupropion B. Fluoxetine C. Mirtazapine D. Trazodone

B. This patient with depression has signs and symptoms concerning for bulimia nervosa so bupropion should not be used. (Dental caries, parotitis, and hand trauma/Russell's sign should raise suspicion for purging activity). Since her chief complaint is hypersomnia, a sedating medication like mirtazapine, trazodone or tricyclic antidepressants may worsen her symptoms. Fluoxetine is an SSRI and is often used as the first line agent for treating depression. SSRIs can also be used to treat bulimia. A. This patient endorses habits (e.g. binging food) and has physical exam findings (e.g. parotitis and Russell's sign/callouses) concerning for bulimia nervosa. Bupropion is contraindicated in patients with bulimia due to risk of seizures. This patient should be treated for major depressive disorder but her eating habits should also be examined further to determine if treatment for bulimia nervosa should also be initiated. C. Mirtazapine is an antidepressant associated with sedation and weight gain. In this patient who already sleeps 20 hours a day, a sedating antidepressant would not be the best choice of first line medication. D. Trazodone is a serotonin modulator and can be used to treat depression. However, its adverse effects including orthostatic hypotension, sedation and sexual dysfunction make it difficult for most patients to tolerate. An SSRI, SNRI or atypical antidepressant should usually be used as a first line agent before using trazodone.

Which of the following pairs of medications can be safely prescribed together? A. Isocarboxazid, tramadol B. Phenelzine, amitriptyline C. Selegiline, levodopa D. Tranylcypromine, fluoxetine

C. Selegiline a selective MAOI which increases synaptic concentration of dopamine. Levodopa is a dopamine analog used to treat Parkinson disease. This combination of medication is often used to improve the symptoms of Parkinson disease. Drugs which increase the synaptic concentration of serotonin (e.g. non-selective MAOI, SSRIs, SNRIs and tricyclic antidepressants) should not be prescribed together due to the risk of precipitating serotonin syndrome. A. Isocarboxazid is a non-selective MAOI and tramadol is a weak opioid agonist which also inhibits serotonin and norepinephrine reuptake. When used together, there is increased risk of serotonin syndrome. B. Phenelzine is a non-selective monoamine oxidase inhibitor (MAOI) that inhibits degradation of norepinephrine, dopamine, and serotonin. Amitriptyline is a tricyclic antidepressant (TCA) that inhibits reuptake of serotonin and norepinephrine. MAOIs should not be used in combination with TCAs due to the risk of precipitating serotonin syndrome D. Tranylcypromine is an MAOI and fluoxetine is an SSRI. Both agents increase synaptic concentration of serotonin and may precipitate serotonin syndrome when used together. When switching from an SSRI to an MAOI, the SSRI should be allowed to completely wash out before initiating the MAOI.

Which of the following monoamine oxidase inhibitors (MAOI) is a selective MAO-B inhibitor? A. Isocarboxazid B. Phenelzine C. Selegiline D. Tranylcypromine

C. Selegiline specifically inhibits monoamine oxidase B (MAO-B) and not MAO-A. MAO-B metabolizes dopamine. Selegiline is sometimes administered to patients with Parkinson disease due to its ability to increase dopamine concentration in the central nervous system. A. Isocarboxazid is a non-selective, irreversible inhibitor of both MAO-A and MAO-B. Non-selective MAOIs increase the concentration of norepinephrine, serotonin, and dopamine in the central nervous system. B. Phenelzine is a non-selective, irreversible MAO-A and MAO-B inhibitor. Phenelzine is used to treat atypical or treatment resistant depression. D. Tranylcypromine is a non-selective, irreversible MAO-A and MAO-B inhibitor. Tranylcypromine is used as a second or third line agent to treat depression due to its adverse effect profile and dietary limitations.

Tricyclic antidepressants would be expected to worsen all of the following conditions EXCEPT for: A. Congenital long QT syndrome B. Epilepsy C. Essential hypertension D. Narrow angle glaucoma

C. Tricyclic antidepressants are alpha-1 adrenergic receptor antagonists. As a result, tricyclic antidepressants may cause postural hypotension. Tricyclic antidepressants would not be expected to worsen hypertension. However, patients with hypertension who are taking antihypertensive medications should be carefully monitored for hypotension and orthostasis. A. Tricyclic antidepressants are known to block cardiac sodium channels in a similar manner to Class IA antiarrhythmics. As a result, tricyclic antidepressants may cause prolongation of the QT interval. Patients with congenital long QT syndrome, those already taking other QT prolonging agents, and patients taking high doses of tricyclic antidepressants should be carefully monitored or find an alternative medication with less cardiotoxic effects. B. Cardiotoxicity, coma, and convulsions ("3 C's" tricyclic) are a good way to recall some of the more serious adverse effects associated with use of tricyclic antidepressants. Tricyclic antidepressants are known to lower the seizure threshold and should not be used in patients with epilepsy. D. Tricyclic antidepressants have anticholinergic properties which can precipitate acute glaucoma crisis in patients with narrow angle glaucoma

A man with major depressive disorder achieves remission after 6 months of treatment with tranylcypromine as well as psychotherapy. His psychiatrist advises stopping pharmacotherapy but continuing psychotherapy. The next day, he goes out to dinner to celebrate the end of taking medication and the end of his dietary limitations. Which of the following menu items is now safe for him to eat? A. Red wine B. Cheese appetizer C. Grilled fresh salmon with dill D. Purple potatoes with fermented sausage

C. Most fresh meats, fish, fruits and vegetables do not contain tyramine. This patient should be able to enjoy grilled salmon safely. A. Patients who stop MAOI therapy need to wait two weeks before stopping the low tyramine diet. Red wines, beers, and cured or preserved foods are high in tyramine. B. The tyramine associated hypertensive crisis is often called the "cheese reaction". Cheeses have high tyramine content and may precipitate tyramine toxicity in patients who are taking or have recently stopped taking an MAOI. This patient should wait two more weeks after stopping his medication before enjoying this delicious appetizer. D. Fermented, aged, pickled and smoked meats are high in tyramine and should not be consumed by a patient taking MAOIs. Furthermore, even after a patient stops taking an MAOI, he or she must wait an additional 2-4 weeks before consuming tyramine-rich foods. Although the half-life of MAOIs is relatively short (2-3 hours for tranylcypromine), the irreversible effects may last for weeks. Until the body can generate new MAO enzymes, patients are still at increased risk of tyramine toxicity. This patient should wait another 2-4 weeks after stopping his MAO therapy before enjoying fermented sausages.

Amitriptyline and Venlafaxine can both be used to treat all the following conditions EXCEPT: A. Major depressive disorder B. Migraine headaches C. Neuropathic pain D. Obsessive compulsive disorde

D. Neither amitriptyline nor venlafaxine have been approved for treating obsessive compulsive disorder (OCD). SSRIs and cognitive behavioral therapy are first line therapy for OCD. Clomipramine, a tricyclic antidepressant, can be used as second line medications for OCD. Neither tricyclic antidepressants including amitriptyline nor the SNRI drug class has been well studied for treating OCD. A. Both amitriptyline (a tricyclic antidepressant) and venlafaxine (an SNRI) can be used to treat major depressive disorder. SSRIs and SNRIs are first-line therapy while TCAs are reserved for treatment resistant depression due to increased risk of adverse effects. B. Amitriptyline is a tricyclic antidepressant (TCA) and venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI). Both drugs inhibit reuptake of serotonin and norepinephrine. Amitriptyline and venlafaxine have both been shown to be effective as migraine prophylaxis. Antihypertensives, anticonvulsants and botulinum toxin injections can also prevent the development of migraine headaches. C. Both tricyclic antidepressants like amitriptyline and SNRIs like venlafaxine can be used to treat chronic neuropathic pain including diabetic neuropathy.

A man is brought into the emergency room due to altered mental status. He cannot name his medications and has no medical records on file. His vital signs are notable for fever and hypertension. Physical exam reveals diaphoresis, dry mucous membranes and spontaneous muscle clonus. Which of the following findings would suggest that this patient is suffering from serotonin syndrome rather than neuroleptic malignant syndrome (NMS)? A. Altered mental status B. Diaphoresis C. Fever D. Muscle clonus

D. Neuroleptic malignant syndrome (NMS) and serotonin syndrome present similarly with hyperthermia, hypertension, altered mental status and muscle rigidity. NMS is precipitated by dopamine antagonists whereas serotonin syndrome is caused by serotonin agonists. In the absence of knowing a patient's medical history, testing neuromuscular reflexes can be very helpful in making a diagnosis. NMS is characterized by hyporeflexia whereas serotonin syndrome is characterized by hyperreflexia and clonus. Additionally, dilated pupils (mydriasis) is a feature of serotonin syndrome, whereas pupillary diameter is normal in NMS. A. Both NMS and serotonin syndrome cause patients to develop altered mental status. Patients with both conditions may present with anxiety, agitation or delirium. B. Diaphoresis is a feature of both NMS and serotonin syndrome. Diaphoresis alone would not suggest the diagnosis of serotonin syndrome over neuroleptic malignant syndrome. C. Both NMS and serotonin syndrome precipitate autonomic instability including hyperthermia, tachycardia and hypertension. Fever is known to occur in both syndromes and would not necessarily favor one diagnosis over the other.

Venlafaxine can be used to treat all of the following conditions EXCEPT: A. Generalized anxiety disorder B. Major depressive disorder C. Neuropathic pain D. Obsessive compulsive disorder

D. Obsessive compulsive disorder (OCD) is characterized by repetitive, intrusive thoughts and compulsions. SSRIs (especially Clomipramine) are the preferred medication for treating OCD. SNRIs are not approved by the FDA to treat OCD A. Venlafaxine, an SNRI, can be effective in treating generalized anxiety disorder (GAD). SSRIs and buspirone are also effective in decreasing baseline symptoms of anxiety in patients with GAD. Benzodiazepines may be used as adjunct therapy to treat acute episodes of anxiety. B. Venlafaxine is an SNRI. SSRI and SNRI class of drugs can be used as first line medications in the treatment of major depressive disorder. SNRIs are also useful in the treatment of fibromyalgia, PTSD, panic disorder, and generalized anxiety disorder. C. SNRIs such as venlafaxine and duloxetine may be used to treat chronic neuropathic pain including diabetic neuropathy. Other options for treating neuropathic pain include gabapentin, tricyclic antidepressants, and topical lidocaine or topical capsaicin.

Selegiline is sometimes used as adjuvant treatment for which of the following neurodegenerative conditions? A. Alzheimer dementia B. Amyotrophic lateral sclerosis C. Huntington disease D. Parkinson disease

D. Parkinson disease is a movement disorder associated with loss of dopaminergic neurons from the nigrostriatal pathway. Selegiline, a selective monoamine oxidase type B inhibitor, increases the amount of dopamine available in the central nervous system and may be used to improve motor function as an adjunctive treatment to levodopa in patients with Parkinson disease.

Which of the following statements regarding treatment of major depressive disorder (MDD) is true? A. Patients taking SNRIs may achieve response rates in as soon as 1-2 days B. Patients taking SSRIs should give the drug an 8-12 month trial before declaring treatment failure C. Sudden withdrawal from SSRIs may cause myoclonus D. Sudden withdrawal of SNRI will result in a flu-like syndrome

D. Sudden withdrawal from either an SNRI or SSRI may result in an uncomfortable flu-like syndrome. Patients may experience nausea, headache, sleep disturbance and gastrointestinal distress. When switching or stopping an SNRI or SSRI, the drug should be slowly tapered over 1-2 weeks to avoid symptoms of withdrawal. A. Patients taking SSRIs or SNRIs for MDD may achieve a positive response in as soon as 1-2 weeks, not 1-2 days. However, one study on citalopram showed that the majority of patients required at least 8 weeks to achieve either response or remission B. Patients treated with either an SSRI or SNRI should be allowed a 6-12 week trial period before declaring treatment failure. Generally, it takes 4-8 weeks for SSRIs and SNRIs to achieve maximal effect. If 8-12 weeks has passed and the patient has not experienced significant improvement, it is appropriate to switch to another medication in the same class, begin combination therapy or switch to another drug class. C. Myoclonus (involuntary muscle spasms or twitches) can be a sign of serotonin syndrome. A careful tapering schedule should be used to prevent SSRI "discontinuation syndrome". Sudden withdrawal from SSRIs may result in flu-like syndrome. Patients may complain of headache, fatigue, chills, nausea and myalgias

A man diagnosed with major depressive disorder presents for follow-up after 12 weeks on fluoxetine. He reports that his mood is unchanged along with having an excessive appetite, hypersomnia and "heaviness" in his limbs. Which of the following treatment plans would be most appropriate for this patient? A. Fluoxetine should be discontinued immediately B. Prescribe phenelzine in addition to fluoxetine C. Recommend avoiding intake of tyramine to increase the efficacy of fluoxetine D. Recommend tapering off fluoxetine and starting tranylcypromine

D. This patient presents with symptoms suggestive of atypical depression, which is characterized mood reactivity (improved mood with positive events), hypersomnia, hyperphagia and leaden paralysis. Some studies suggest that monoamine oxidase inhibitors (MAOIs) such as tranylcypromine can be beneficial in treating atypical depression. At least 2 weeks should elapse between the last dose of SSRI and the first dose of the MAOI in order to avoid precipitating serotonin syndrome. Another reasonable option for this patient who failed his first trial of an SSRI is to switch to another agent within the same class. A. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). Although this patient has failed a trial of fluoxetine and should discontinue the medication, SSRIs need to be slowly tapered over a period of weeks to avoid precipitating withdrawal symptoms or "discontinuation syndrome." B. Fluoxetine is an SSRI and phenelzine is an MAOI. Both drug classes are associated with increase in serotonin levels and the combination of these medications may increase the risk of serotonin syndrome. MAOIs should not be taken with any medications which raise synaptic concentration of serotonin including tricyclic antidepressants, SNRIs, linezolid and triptans. C. There is no contraindication to tyramine containing foods for patients taking fluoxetine. However, patients taking MAOIs should avoid tyramine-rich foods due to risk of hypertensive crisis.

A 55-year-old woman with painful diabetic neuropathy is prescribed nortriptyline. She returns for a follow-up visit 2 months later and reports partial improvement in neuropathy symptoms She is concerned because ever since she started taking nortriptyline she has been experiencing severe fatigue, constipation and blurry vision. Which of the following treatment options would be most appropriate for this patient? A. Continue a trial period of 6-8 months before switching to another drug class B. Increase the dose of nortriptyline C. Switch to amitriptyline to reduce muscarinic side effects D. Switch to another drug class

D. Tricyclic antidepressants like nortriptyline can be used to treat neuropathic pain, but often patients are unable to tolerate the associated side effects. Tricyclic antidepressants may cause anticholinergic symptoms (dry mouth, constipation, blurred vision and urinary retention), somnolence, weight gain, sexual dysfunction, cardiac arrhythmias and seizures) As a result, other medications such as gabapentin, SNRIs and anticonvulsants are often used as first line therapies for neuropathic pain. This patient should be switched to another drug class which may be as effective but with a more tolerable side effect profile. C. Nortriptyline is a secondary amine with fewer anticholinergic side effects than tertiary amines like amitriptyline. Since this patient is already complaining of anticholinergic side effects like blurry vision and constipation, switching to a tertiary amine would likely exacerbate her symptoms

Which of the following drugs is correctly paired with its mechanism of action? A. Citalopram; inhibits the breakdown of serotonin B. Duloxetine; inhibits the breakdown of dopamine C. Fluoxetine; inhibits the presynaptic reuptake of serotonin and norepinephrine D. Venlafaxine; inhibits the presynaptic reuptake of norepinephrine and serotonin

D. Venlafaxine, duloxetine, desvenlafaxine and milnacipran are all serotonin-norepinephrine reuptake inhibitors (SNRI). SNRIs inhibit the presynaptic reuptake of norepinephrine and serotonin which increases the availability of these neurotransmitters at the postsynaptic site. A. Citalopram, fluoxetine, sertraline, and paroxetine are all selective serotonin reuptake inhibitors (SSRI). SSRIs act by inhibiting the reuptake of serotonin rather than inhibiting the breakdown of serotonin. B. Duloxetine is an SNRI which inhibits the reuptake of serotonin and norepinephrine. Duloxetine does not inhibit the breakdown of dopamine. Selegiline is a selective monoamine oxidase B inhibitor which prevents the degradation of dopamine. C. Fluoxetine is a serotonin reuptake inhibitors (SSRI) which inhibits the presynaptic reuptake of serotonin, not norepinephrine. SSRIs can be used to treat obsessive compulsive disorder, generalized anxiety disorder, panic disorder, PTSD and social anxiety disorder.


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