First-generation antipsychotics — MCQs

10 questions

A 19-year-old woman, accompanied by her parents, presents after a one-week history of abnormal behavior, delusions, and unusual aggression. She denies fever, seizures or illicit drug use. Family history is negative for psychiatric illnesses. She was started on risperidone and sent home with her parents. Three days later, she is brought to the emergency department with fever and confusion. She is not verbally responsive. At the hospital, her temperature is 39.8°C (103.6°F), the blood pressure is 100/60 mm Hg, the pulse rate is 102/min, and the respiratory rate is 16/min. She is extremely diaphoretic and appears stiff. She has spontaneous eye-opening but she is not verbally responsive and she is not following commands. Laboratory studies show: Sodium 142 mmol/L Potassium 5.0 mmol/L Creatinine 1.8 mg/dl Calcium 10.4 mg/dl Creatine kinase 9800 U/L White blood cells 14,500/mm3 Hemoglobin 12.9 g/dl Platelets 175,000/mm3 Urinalysis shows protein 1+, hemoglobin 3+ with occasional leukocytes and no red blood casts. What is the best first step in the management of this condition?

A study is conducted to investigate the relationship between the development of type 2 diabetes mellitus and the use of atypical antipsychotic medications in patients with schizophrenia. 300 patients who received the atypical antipsychotic clozapine and 300 patients who received the typical antipsychotic haloperidol in long-acting injectable form were followed for 2 years. At the end of the observation period, the incidence of type 2 diabetes mellitus was compared between the two groups. Receipt of clozapine was found to be associated with an increased risk of diabetes mellitus relative to haloperidol (RR = 1.43, 95% p<0.01). Developed type 2 diabetes mellitus Did not develop type 2 diabetes mellitus Clozapine 30 270 Haloperidol 21 279 Based on these results, what proportion of patients receiving clozapine would not have been diagnosed with type 2 diabetes mellitus if they had been taking a typical antipsychotic?

A 35-year-old woman comes to the physician accompanied by her husband after he started noticing strange behavior. He first noticed her talking to herself 8 months ago. For the past 6 months, she has refused to eat any packaged foods out of fear that the government is trying to poison her. She has no significant past medical history. She smoked marijuana in college but has not smoked any since. She appears restless. Mental status examination shows a flat affect. Her speech is clear, but her thought process is disorganized with many loose associations. The patient is diagnosed with schizophrenia and started on olanzapine. This patient is most likely to experience which of the following adverse effects?

A 31-year-old man is brought to the emergency department because of fever and increasing confusion for the past day. He has bipolar disorder with psychotic features and hypothyroidism. Current medications are lithium, haloperidol, and levothyroxine. He drinks one beer with dinner every night. His speech is confused and he is oriented to person only. His temperature is 40°C (104°F), pulse is 124/min, and blood pressure is 160/110 mm Hg. He appears acutely ill. Examination shows diaphoresis and muscle rigidity. Deep tendon reflexes are 1+ bilaterally. There is minor rigidity of the neck with full range of motion. His lungs are clear to auscultation. The abdomen is soft and nontender. His leukocyte count is 15,100/mm3 and serum creatine kinase activity is 1100 U/L. Which of the following is the most likely diagnosis?

A 31-year-old woman is brought to the physician because of increasing restlessness over the past 2 weeks. She reports that she continuously paces around the house and is unable to sit still for more than 10 minutes at a time. During this period, she has had multiple episodes of anxiety with chest tightness and shortness of breath. She was diagnosed with a psychotic illness 2 months ago. Her current medications include haloperidol and a multivitamin. She appears agitated. Vital signs are within normal limits. Physical examination shows no abnormalities. The examination was interrupted multiple times when she became restless and began to walk around the room. To reduce the likelihood of the patient developing her current symptoms, a drug with which of the following mechanisms of action should have been prescribed instead of her current medication?

A 24-year-old man with a history of schizophrenia presents for follow-up. The patient says that he is still having paranoia and visual hallucinations on his latest atypical antipsychotic medication. Past medical history is significant for schizophrenia diagnosed 1 year ago that failed to be adequately controlled on 2 separate atypical antipsychotic medications. The patient is switched to a typical antipsychotic medication. Which of the following is the mechanism of action of the medication that was most likely prescribed for this patient?

A 33-year-old woman comes to the emergency department for the evaluation of a headache and increased sweating for the last two hours. The patient also reports palpitations and nausea. Yesterday, she was started on venlafaxine for treatment-resistant depression. She took citalopram for four weeks, but stopped three days ago because her symptoms of depression did not improve. She does not smoke or drink alcohol. Her temperature is 39°C (102.2°F), pulse is 120/min, and blood pressure is 150/90 mm Hg. On mental status examination, the patient is only oriented to person, but not to place or time. Examination shows tremors in all extremities. She has impaired gait. Deep tendon reflexes are 3+ bilaterally. Which of the following is the most likely cause of this patient's symptoms?

A 26-year-old man is brought to the hospital by his wife who complains that her husband has been behaving oddly for the past few hours. The patient’s wife says that she has known him for only 4 months. The wife is unable to give any past medical history. The patient’s speech is difficult to follow, and he seems very distracted. After 15 minutes, he becomes agitated and starts to bang his head on a nearby pillar. He is admitted to the psychiatric ward and is given an emergency medication, after which he calms down. In the next 2 days, he continues to become agitated at times and required 2 more doses of the same drug. On the 4th day of admission, he appears very weak, confused, and does not respond to questions appropriately. His vital signs include: temperature 40.0°C (104.0°F), blood pressure 160/95 mm Hg, and pulse 114/min. On physical examination, he is profusely diaphoretic. He is unable to stand upright or even get up from his bed. Which of the following is the mechanism of action of the drug which most likely caused this patient’s current condition?

A 16-year-old college student presents to the emergency department with a 3-day history of fever, muscle rigidity, and confusion. He was started on a new medication for schizophrenia 2 months ago. There is no history of sore throat, burning micturition, or loose motions. At the hospital, his temperature is 38.6°C (101.5°F); the blood pressure is 108/62 mm Hg; the pulse is 120/min, and the respiratory rate is 16/min. His urine is cola-colored. On physical examination, he is sweating profusely. Treatment is started with antipyretics and intravenous hydration. Which of the following is most likely responsible for this patient's condition?

Q10

A 36-year-old woman with schizophrenia comes to the office for a follow-up appointment. She has been hospitalized 4 times in the past year, and she has failed to respond to multiple trials of antipsychotic medications. Six weeks ago, she was brought to the emergency department by her husband because of a bizarre behavior, paranoid delusions, and hearing voices that others did not hear. She was started on a new medication, and her symptoms have improved. Laboratory studies show: Hemoglobin 13.8 g/dL Leukocyte count 1,200/mm3 Segmented neutrophils 6% Eosinophils 0% Lymphocytes 92% Monocytes 2% Platelet count 245,000/mm3 This patient was most likely started on which of the following medications?

First-generation antipsychotics US Medical PG Practice Questions and MCQs

Question 1: A 19-year-old woman, accompanied by her parents, presents after a one-week history of abnormal behavior, delusions, and unusual aggression. She denies fever, seizures or illicit drug use. Family history is negative for psychiatric illnesses. She was started on risperidone and sent home with her parents. Three days later, she is brought to the emergency department with fever and confusion. She is not verbally responsive. At the hospital, her temperature is 39.8°C (103.6°F), the blood pressure is 100/60 mm Hg, the pulse rate is 102/min, and the respiratory rate is 16/min. She is extremely diaphoretic and appears stiff. She has spontaneous eye-opening but she is not verbally responsive and she is not following commands. Laboratory studies show: Sodium 142 mmol/L Potassium 5.0 mmol/L Creatinine 1.8 mg/dl Calcium 10.4 mg/dl Creatine kinase 9800 U/L White blood cells 14,500/mm3 Hemoglobin 12.9 g/dl Platelets 175,000/mm3 Urinalysis shows protein 1+, hemoglobin 3+ with occasional leukocytes and no red blood casts. What is the best first step in the management of this condition?

A. Paracetamol
B. Dantrolene
C. Intravenous hydration
D. Switch risperidone to clozapine
E. Stop risperidone (Correct Answer)

Explanation: ***Stop risperidone*** - The patient's presentation with **fever, altered mental status, muscle rigidity**, and elevated **creatine kinase** after starting risperidone is highly suggestive of **neuroleptic malignant syndrome (NMS)**. - The **first and most critical step** in managing NMS is to **immediately discontinue the offending antipsychotic medication**, as continuation can worsen the severe symptoms and increase mortality. *Paracetamol* - While the patient has a high fever (39.8°C), **paracetamol** (acetaminophen) alone is **insufficient** to address the underlying severe hyperthermia and other systemic effects of NMS. - The fever in NMS is due to **muscle rigidity** and **dysregulation of the hypothalamic thermoregulatory center**, which requires more comprehensive management than antipyretics. *Dantrolene* - **Dantrolene** is a **muscle relaxant** often used in NMS to reduce muscle rigidity and hyperthermia by inhibiting calcium release from the sarcoplasmic reticulum. - However, the **withdrawal of the causative agent** (risperidone) is always the **initial and most crucial management step** before or in conjunction with supportive medications like dantrolene or bromocriptine. *Intravenous hydration* - **Intravenous hydration** is an important **supportive measure** in NMS to manage dehydration, support renal function (due to potential **rhabdomyolysis** from elevated CK), and help with temperature regulation. - While critical, it is **not the *first* step**; discontinuing the causative drug is paramount. *Switch risperidone to clozapine* - Switching to another antipsychotic, even clozapine, is **inappropriate** at this stage because the patient is experiencing a severe adverse reaction to an antipsychotic. - Reintroducing another antipsychotic could **exacerbate NMS** or trigger a similar reaction, and the immediate priority is to stabilize the patient by removing the trigger.

Question 2: A study is conducted to investigate the relationship between the development of type 2 diabetes mellitus and the use of atypical antipsychotic medications in patients with schizophrenia. 300 patients who received the atypical antipsychotic clozapine and 300 patients who received the typical antipsychotic haloperidol in long-acting injectable form were followed for 2 years. At the end of the observation period, the incidence of type 2 diabetes mellitus was compared between the two groups. Receipt of clozapine was found to be associated with an increased risk of diabetes mellitus relative to haloperidol (RR = 1.43, 95% p<0.01). Developed type 2 diabetes mellitus Did not develop type 2 diabetes mellitus Clozapine 30 270 Haloperidol 21 279 Based on these results, what proportion of patients receiving clozapine would not have been diagnosed with type 2 diabetes mellitus if they had been taking a typical antipsychotic?

A. 1.48
B. 0.3 (Correct Answer)
C. 0.43
D. 0.03
E. 33.3

Explanation: ***0.3*** - The question asks for the **proportion of patients** receiving clozapine who *would not have been diagnosed* with type 2 diabetes if they had been taking a **typical antipsychotic (haloperidol)**. This is essentially asking for the **attributable risk proportion** among the exposed. - First, calculate the **incidence of diabetes in the clozapine group**: 30/300 = 0.10. Then, calculate the **incidence of diabetes in the haloperidol group**: 21/300 = 0.07. The difference in incidence (attributable risk) is 0.10 - 0.07 = 0.03. To find the proportion among those exposed, divide this difference by the incidence in the clozapine group: 0.03 / 0.10 = **0.3**. *1.48* - This value is close to the **Relative Risk (RR)** of 1.43, which indicates how many times more likely the clozapine group is to develop diabetes compared to the haloperidol group. It does not represent the proportion of patients who would benefit from switching medications. - The question asks for a proportion that reflects the prevention of diabetes, not a measure of relative risk. *0.43* - This value is close to the **attributable risk fraction** (attributable risk percent / 100), which is calculated as (RR - 1) / RR = (1.43 - 1) / 1.43 = 0.43 / 1.43 ≈ 0.30. It's not a direct proportion of patients. - While related to the increased risk, 0.43 does not directly answer the question about the proportion of patients who would *not* have developed diabetes if they had taken haloperidol. *0.03* - This value represents the **absolute difference in risk (attributable risk)**: 0.10 (clozapine incidence) - 0.07 (haloperidol incidence) = 0.03. - This is the difference in incidence, not the proportion of clozapine users who would avoid diabetes if they were on haloperidol. The question asks for a proportion *among* those receiving clozapine. *33.3* - This value is likely derived from incorrect calculations or misinterpretation of the question as an alternative percentage. - It does not align with any standard epidemiological measure for comparing the impact of switching medications in the context of attributable risk or risk reduction.

Question 3: A 35-year-old woman comes to the physician accompanied by her husband after he started noticing strange behavior. He first noticed her talking to herself 8 months ago. For the past 6 months, she has refused to eat any packaged foods out of fear that the government is trying to poison her. She has no significant past medical history. She smoked marijuana in college but has not smoked any since. She appears restless. Mental status examination shows a flat affect. Her speech is clear, but her thought process is disorganized with many loose associations. The patient is diagnosed with schizophrenia and started on olanzapine. This patient is most likely to experience which of the following adverse effects?

A. Dyslipidemia (Correct Answer)
B. Diabetes insipidus
C. Agranulocytosis
D. Myoglobinuria
E. Seizures

Explanation: ***Dyslipidemia*** - **Olanzapine** is a **second-generation antipsychotic** commonly associated with significant **metabolic side effects**, including **weight gain**, **dyslipidemia**, and **insulin resistance**. - These metabolic disturbances increase the risk of cardiovascular disease. *Diabetes insipidus* - This is a rare side effect, not typically associated with **olanzapine** or other **second-generation antipsychotics**. - **Lithium** is an antimanic agent that can cause **nephrogenic diabetes insipidus**, but it is not relevant here. *Agranulocytosis* - While a serious side effect of some antipsychotics, **agranulocytosis** is most notably associated with **clozapine**, - **Olanzapine** has a much lower risk of causing **agranulocytosis** compared to clozapine. *Myoglobinuria* - **Myoglobinuria** is associated with conditions like significant muscle damage (e.g., rhabdomyolysis). - It is not a direct or common adverse effect of **olanzapine** therapy. *Seizures* - While some antipsychotics can lower the **seizure threshold**, **olanzapine** generally has a relatively low risk of inducing seizures. - The risk is higher with certain other antipsychotics, particularly at high doses, or in patients with pre-existing seizure disorders.

Question 4: A 31-year-old man is brought to the emergency department because of fever and increasing confusion for the past day. He has bipolar disorder with psychotic features and hypothyroidism. Current medications are lithium, haloperidol, and levothyroxine. He drinks one beer with dinner every night. His speech is confused and he is oriented to person only. His temperature is 40°C (104°F), pulse is 124/min, and blood pressure is 160/110 mm Hg. He appears acutely ill. Examination shows diaphoresis and muscle rigidity. Deep tendon reflexes are 1+ bilaterally. There is minor rigidity of the neck with full range of motion. His lungs are clear to auscultation. The abdomen is soft and nontender. His leukocyte count is 15,100/mm3 and serum creatine kinase activity is 1100 U/L. Which of the following is the most likely diagnosis?

A. Delirium tremens
B. Neuroleptic malignant syndrome (Correct Answer)
C. Bacterial meningitis
D. Herpes simplex encephalitis
E. Lithium toxicity

Explanation: ***Neuroleptic malignant syndrome*** - The patient presents with **fever (40°C)**, **muscle rigidity**, **altered mental status (confusion)**, **autonomic instability (tachycardia, hypertension, diaphoresis)**, and **elevated creatine kinase**, all classic features of **Neuroleptic Malignant Syndrome (NMS)**. - The use of **haloperidol**, a high-potency antipsychotic, is a significant risk factor for NMS. *Delirium tremens* - While delirium tremens can cause altered mental status, autonomic instability, and fever, it is typically preceded by a history of **heavy chronic alcohol intake** followed by acute withdrawal, which is not indicated by "one beer with dinner every night." - **Muscle rigidity** and **marked elevation of creatine kinase** are not typical features of delirium tremens. *Bacterial meningitis* - Although bacterial meningitis presents with fever and altered mental status, it would typically involve **nuchal rigidity** that limits range of motion, which is not fully present here, and **CSF findings** (e.g., pleocytosis, low glucose) would be diagnostic. - **Profound muscle rigidity** and **markedly elevated creatine kinase** are not characteristic features of bacterial meningitis. *Herpes simplex encephalitis* - This condition presents with fever, altered mental status, and often **focal neurological deficits** or **seizures**, which are not described. - Diagnosis relies on **characteristic MRI findings** and **CSF PCR for HSV DNA**, and it would not typically cause diffuse **muscle rigidity** or **elevated creatine kinase**. *Lithium toxicity* - **Lithium toxicity** typically presents with neurological symptoms like **tremors**, **ataxia**, **nystagmus**, and altered mental status, but it is less commonly associated with **severe muscle rigidity**, **very high fever (40°C)**, or **markedly elevated creatine kinase** unless complicated by severe dehydration or NMS-like features. - A **high lithium level** would be expected, which is not mentioned as present.

Question 5: A 31-year-old woman is brought to the physician because of increasing restlessness over the past 2 weeks. She reports that she continuously paces around the house and is unable to sit still for more than 10 minutes at a time. During this period, she has had multiple episodes of anxiety with chest tightness and shortness of breath. She was diagnosed with a psychotic illness 2 months ago. Her current medications include haloperidol and a multivitamin. She appears agitated. Vital signs are within normal limits. Physical examination shows no abnormalities. The examination was interrupted multiple times when she became restless and began to walk around the room. To reduce the likelihood of the patient developing her current symptoms, a drug with which of the following mechanisms of action should have been prescribed instead of her current medication?

A. H2 receptor antagonism
B. 5-HT2A receptor antagonism (Correct Answer)
C. α2 receptor antagonism
D. NMDA receptor antagonism
E. GABA receptor antagonism

Explanation: ***5-HT2A receptor antagonism*** - The patient is experiencing **akathisia**, a common extrapyramidal side effect of **typical antipsychotics** like haloperidol, characterized by subjective or objective motor restlessness. - Atypical antipsychotics, which exert their antipsychotic effects primarily through **5-HT2A receptor antagonism** along with D2 receptor antagonism, have a lower propensity to cause extrapyramidal symptoms, including akathisia, compared to typical antipsychotics. *H2 receptor antagonism* - **H2 receptor antagonists** are primarily used to reduce gastric acid secretion in conditions like peptic ulcer disease and GERD. - They have no direct role in treating psychosis or preventing extrapyramidal side effects. *α2 receptor antagonism* - **Alpha-2 receptor antagonists** (e.g., mirtazapine) are typically used as antidepressants; their mechanism involves increasing norepinephrine and serotonin release. - This mechanism is not directly therapeutic for psychosis and would not prevent akathisia caused by D2 receptor blockade. *NMDA receptor antagonism* - **NMDA receptor antagonists** (e.g., ketamine, memantine) are studied for various neurological and psychiatric conditions, but their primary use is not in typical psychosis treatment, nor do they prevent akathisia from antipsychotics. - Instead, NMDA receptor hypofunction is hypothesized in schizophrenia, and antagonism could potentially worsen psychotic symptoms. *GABA receptor antagonism* - **GABA receptor antagonists** (e.g., flumazenil) block the effects of inhibitory neurotransmitter GABA and can cause seizures and increased anxiety, which would be detrimental in a patient with psychosis and anxiety. - Medications that *enhance* GABAergic transmission (e.g., benzodiazepines) are sometimes used to treat acute akathisia or anxiety, but long-term antagonism would be contra-indicated.

Question 6: A 24-year-old man with a history of schizophrenia presents for follow-up. The patient says that he is still having paranoia and visual hallucinations on his latest atypical antipsychotic medication. Past medical history is significant for schizophrenia diagnosed 1 year ago that failed to be adequately controlled on 2 separate atypical antipsychotic medications. The patient is switched to a typical antipsychotic medication. Which of the following is the mechanism of action of the medication that was most likely prescribed for this patient?

A. Dopaminergic receptor antagonist (Correct Answer)
B. Dopaminergic partial agonist
C. Serotonergic receptor agonist
D. Serotonergic receptor antagonist
E. Cholinergic receptor agonist

Explanation: ***Dopaminergic receptor antagonist*** - The patient has **treatment-resistant schizophrenia**, indicated by failure to respond to two different atypical antipsychotics. - Typical antipsychotics like **haloperidol** or **fluphenazine** are primarily **D2 dopamine receptor antagonists**, which may be used when a patient has not responded to atypical agents. - The **primary mechanism** of typical (first-generation) antipsychotics is **potent D2 receptor blockade** in the mesolimbic pathway, which reduces positive symptoms of schizophrenia. - Note: Clozapine would be the preferred choice for true treatment-resistant schizophrenia, but typical antipsychotics may still be considered in some clinical scenarios. *Dopaminergic partial agonist* - **Dopamine partial agonists**, such as **aripiprazole** or **brexpiprazole**, are **atypical antipsychotics** used for schizophrenia. - The patient has failed to respond to atypical antipsychotics already, making it unlikely that another atypical agent would be the next choice. - The question specifically states the patient is switched to a **typical antipsychotic**. *Serotonergic receptor agonist* - **Serotonin receptor agonists**, like LSD or psilocybin, are **not used** in the treatment of schizophrenia; they can, in fact, **induce psychotic symptoms**. - While some antipsychotics modulate serotonin receptors, their therapeutic effect is not through agonism of these receptors. *Serotonergic receptor antagonist* - Many **atypical antipsychotics** have significant **serotonin 5-HT2A receptor antagonist** activity, in addition to D2 antagonism. - However, the question states that the patient is being switched to a **typical antipsychotic**, whose primary and defining mechanism is **D2 antagonism**, not combined serotonin-dopamine antagonism. *Cholinergic receptor agonist* - **Cholinergic receptor agonists** are **not used** to treat schizophrenia and would likely worsen symptoms or cause significant side effects. - These agents would have no therapeutic benefit in psychosis and are not part of the antipsychotic drug class.

Question 7: A 33-year-old woman comes to the emergency department for the evaluation of a headache and increased sweating for the last two hours. The patient also reports palpitations and nausea. Yesterday, she was started on venlafaxine for treatment-resistant depression. She took citalopram for four weeks, but stopped three days ago because her symptoms of depression did not improve. She does not smoke or drink alcohol. Her temperature is 39°C (102.2°F), pulse is 120/min, and blood pressure is 150/90 mm Hg. On mental status examination, the patient is only oriented to person, but not to place or time. Examination shows tremors in all extremities. She has impaired gait. Deep tendon reflexes are 3+ bilaterally. Which of the following is the most likely cause of this patient's symptoms?

A. Increased CNS serotonergic activity (Correct Answer)
B. Anticholinergic toxicity
C. Dopamine receptor blockade
D. Abnormal ryanodine receptor
E. Suspected amphetamine intake

Explanation: ***Increased CNS serotonergic activity*** - The patient's symptoms, including **headache**, **sweating**, **palpitations**, **nausea**, **fever (39°C)**, **tachycardia**, **hypertension**, **disorientation**, **tremors**, **impaired gait**, and **hyperreflexia**, are classic signs of **serotonin syndrome**. - This syndrome is precipitated by the recent initiation of **venlafaxine** (an SNRI) after stopping **citalopram** (an SSRI) just three days prior, leading to an excessive buildup of **serotonin** in the central nervous system. *Anticholinergic toxicity* - This condition presents with symptoms such as **dry mouth**, **dilated pupils**, **blurred vision**, **urinary retention**, and **constipation**, which are not seen in this patient. - While it can cause **confusion** and **tachycardia**, the prominent **sweating**, **hyperreflexia**, and **tremors** are inconsistent with anticholinergic overdose. *Dopamine receptor blockade* - This is typically associated with **extrapyramidal symptoms** such as **dystonia**, **akathisia**, **parkinsonism**, and **neuroleptic malignant syndrome**, rather than the specific constellation of symptoms described. - **Neuroleptic malignant syndrome** shares some features like fever and autonomic instability, but it typically involves severe **muscle rigidity** (lead-pipe rigidity) and **bradykinesia**, in contrast to the tremors and hyperreflexia observed here. *Abnormal ryanodine receptor* - An abnormal ryanodine receptor is associated with **malignant hyperthermia**, a life-threatening condition triggered by certain **anesthetics** or **succinylcholine**. - While it causes **fever**, **tachycardia**, and **muscle rigidity**, it is unlikely given the patient's medication history and the absence of anesthetic exposure. *Suspected amphetamine intake* - Amphetamine intoxication can cause **tachycardia**, **hypertension**, **agitation**, and **hyperthermia**, which overlap with some of the patient's symptoms. - However, the rapid onset of symptoms immediately following a change in antidepressant medication, particularly the presence of **hyperreflexia** and **tremors**, makes **serotonin syndrome** a more direct and likely explanation in this clinical context.

Question 8: A 26-year-old man is brought to the hospital by his wife who complains that her husband has been behaving oddly for the past few hours. The patient’s wife says that she has known him for only 4 months. The wife is unable to give any past medical history. The patient’s speech is difficult to follow, and he seems very distracted. After 15 minutes, he becomes agitated and starts to bang his head on a nearby pillar. He is admitted to the psychiatric ward and is given an emergency medication, after which he calms down. In the next 2 days, he continues to become agitated at times and required 2 more doses of the same drug. On the 4th day of admission, he appears very weak, confused, and does not respond to questions appropriately. His vital signs include: temperature 40.0°C (104.0°F), blood pressure 160/95 mm Hg, and pulse 114/min. On physical examination, he is profusely diaphoretic. He is unable to stand upright or even get up from his bed. Which of the following is the mechanism of action of the drug which most likely caused this patient’s current condition?

A. Skeletal muscle relaxation
B. Agonistic effect on dopamine receptors
C. Serotonin reuptake inhibition
D. Histamine H2 receptor blocking
E. Dopamine receptor blocking (Correct Answer)

Explanation: ***Dopamine receptor blocking*** - The patient's presentation with **fever, altered mental status, muscle rigidity**, and **autonomic instability** (tachycardia, hypertension, diaphoresis) after receiving antipsychotic medication strongly suggests **neuroleptic malignant syndrome (NMS)**. - NMS is caused by a severe decrease in **dopaminergic activity**, primarily due to the blockade of **D2 dopamine receptors** in the basal ganglia and hypothalamus by antipsychotics. - The classic tetrad of NMS includes: **hyperthermia, muscle rigidity, altered mental status**, and **autonomic instability**. *Skeletal muscle relaxation* - While agitation might be treated with benzodiazepines, which cause muscle relaxation, this mechanism does not explain the **severe rigidity, hyperthermia**, and **autonomic dysfunction** seen in the patient. - **Muscle rigidity** (lead-pipe rigidity) is a hallmark of the patient's current condition, contradicting the idea of muscle relaxation. *Agonistic effect on dopamine receptors* - An agonistic effect on dopamine receptors would typically lead to symptoms similar to **psychosis** or **mania**, not the severe rigidity and hypodopaminergic state observed in NMS. - This mechanism would counteract the effects of antipsychotics and would not cause NMS. *Serotonin reuptake inhibition* - This is the mechanism of action for **SSRIs**, and an excess of serotonin can lead to **serotonin syndrome**, which shares some features with NMS but typically includes **hyperreflexia** and **myoclonus**, rather than lead-pipe rigidity. - The context of treating acute psychosis with an emergency medication points more towards an antipsychotic, not an antidepressant. *Histamine H2 receptor blocking* - **Histamine H2 receptor blockers** are used to treat conditions like **acid reflux** and **peptic ulcers**; they have no direct neurological effects that would cause NMS. - This mechanism is entirely irrelevant to the patient's psychiatric symptoms and subsequent severe adverse reaction.

Question 9: A 16-year-old college student presents to the emergency department with a 3-day history of fever, muscle rigidity, and confusion. He was started on a new medication for schizophrenia 2 months ago. There is no history of sore throat, burning micturition, or loose motions. At the hospital, his temperature is 38.6°C (101.5°F); the blood pressure is 108/62 mm Hg; the pulse is 120/min, and the respiratory rate is 16/min. His urine is cola-colored. On physical examination, he is sweating profusely. Treatment is started with antipyretics and intravenous hydration. Which of the following is most likely responsible for this patient's condition?

A. Diazepam
B. Phenytoin
C. Levodopa
D. Amantadine
E. Chlorpromazine (Correct Answer)

Explanation: ***Chlorpromazine*** - The patient's symptoms of **fever**, **muscle rigidity**, and **confusion**, combined with a history of starting an antipsychotic medication (**Chlorpromazine**), are highly indicative of **neuroleptic malignant syndrome (NMS)**. - **Chlorpromazine** is a typical antipsychotic known to block dopamine receptors, which can lead to NMS. The **cola-colored urine** suggests **rhabdomyolysis**, a common complication of severe muscle rigidity in NMS. *Diazepam* - **Diazepam** is a benzodiazepine used to treat anxiety, seizures, and muscle spasms, and does not typically cause NMS. - Its mechanism of action involves enhancing GABAergic neurotransmission, which is distinct from the dopaminergic blockade associated with NMS. *Phenytoin* - **Phenytoin** is an anticonvulsant medication that can cause a variety of side effects, but NMS is not one of them. - Common side effects include **gingival hyperplasia**, **ataxia**, and **nystagmus**. *Levodopa* - **Levodopa** is primarily used to treat Parkinson's disease by increasing dopamine levels in the brain. - While abrupt withdrawal of **Levodopa** can sometimes precipitate NMS-like symptoms in Parkinson's patients due to inadequate dopamine, starting it does not cause NMS, and it is not typically used for schizophrenia. *Amantadine* - **Amantadine** is an antiviral drug also used to treat Parkinson's disease; it is not an antipsychotic. - It primarily acts as a dopamine agonist and NMDA receptor antagonist, and its use is not associated with causing NMS.

Question 10: A 36-year-old woman with schizophrenia comes to the office for a follow-up appointment. She has been hospitalized 4 times in the past year, and she has failed to respond to multiple trials of antipsychotic medications. Six weeks ago, she was brought to the emergency department by her husband because of a bizarre behavior, paranoid delusions, and hearing voices that others did not hear. She was started on a new medication, and her symptoms have improved. Laboratory studies show: Hemoglobin 13.8 g/dL Leukocyte count 1,200/mm3 Segmented neutrophils 6% Eosinophils 0% Lymphocytes 92% Monocytes 2% Platelet count 245,000/mm3 This patient was most likely started on which of the following medications?

A. Clozapine (Correct Answer)
B. Promethazine
C. Fluphenazine
D. Lithium
E. Quetiapine

Explanation: ***Clozapine*** - The patient's presentation of **treatment-resistant schizophrenia** (failure to respond to multiple antipsychotics and recurrent hospitalizations) strongly points to clozapine as the most likely effective treatment. - The abnormal lab results, particularly **leukopenia** (total WBC 1,200/mm³) and severe **neutropenia** (segmented neutrophils 6%, absolute neutrophil count ~72/mm³), are a known and serious side effect of clozapine, requiring careful monitoring. *Promethazine* - Promethazine is an **antihistamine** with antiemetic and sedative properties, not a primary antipsychotic for schizophrenia. - It would not be used for chronic management of severe, treatment-resistant schizophrenia and is not associated with the severe hematological side effects seen here. *Fluphenazine* - Fluphenazine is a **first-generation antipsychotic** that could be used for schizophrenia, but the patient's history indicates failure of multiple antipsychotic trials. - While it can cause some side effects, severe leukopenia and neutropenia to the degree seen here are not characteristic of fluphenazine. *Lithium* - Lithium is a **mood stabilizer** primarily used for bipolar disorder, not typical first-line or even second-line treatment for schizophrenia as a monotherapy. - Notably, lithium typically causes **leukocytosis** (increased WBC count), not leukopenia, making it inconsistent with the lab findings showing severe leukopenia and neutropenia. *Quetiapine* - Quetiapine is a **second-generation antipsychotic** that is used for schizophrenia, but it is less effective for treatment-resistant cases compared to clozapine. - While some antipsychotics can cause mild hematologic changes, quetiapine is not known for causing the profound leukopenia and severe neutropenia seen in this patient, which are distinctly associated with clozapine.

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