Psychopharmacology — MCQs

Psychopharmacology Indian Medical PG Practice Questions and MCQs

Question 21: What is the most common receptor for typical antipsychotics?

A. Dopamine receptor 1 (D1)
B. Dopamine receptor 2 (D2) (Correct Answer)
C. Dopamine receptor 3 (D3)
D. Dopamine receptor 4 (D4)

Explanation: ### Explanation **Correct Option: B. Dopamine receptor 2 (D2)** The therapeutic efficacy of **typical (first-generation) antipsychotics** (e.g., Haloperidol, Chlorpromazine) is primarily attributed to their potent antagonism of **D2 receptors** in the **mesolimbic pathway**. According to the Dopamine Hypothesis of Schizophrenia, positive symptoms (hallucinations and delusions) result from overactivity in this pathway. Clinical studies show that for an antipsychotic to be effective, it must typically block approximately **60–80% of D2 receptors** in the brain. **Why other options are incorrect:** * **D1 Receptors:** While some antipsychotics (like Phenothiazines) have a mild affinity for D1, it is not the primary target for clinical efficacy in treating psychosis. * **D3 Receptors:** These are primarily located in the limbic system. While some newer atypical agents (like Cariprazine) target D3, typical antipsychotics do not primarily act here. * **D4 Receptors:** This receptor gained fame due to **Clozapine’s** high affinity for it. However, typical antipsychotics have a much higher affinity for D2 than D4. **High-Yield NEET-PG Clinical Pearls:** 1. **The "D2 Paradox":** While D2 blockade in the *mesolimbic* pathway treats psychosis, blockade in the *nigrostriatal* pathway leads to **Extrapyramidal Side Effects (EPS)**, and blockade in the *tuberoinfundibular* pathway causes **Hyperprolactinemia**. 2. **Potency:** The clinical potency of a typical antipsychotic is directly proportional to its D2 receptor binding affinity (e.g., Haloperidol is high-potency; Chlorpromazine is low-potency). 3. **Atypical Antipsychotics:** Unlike typicals, atypical antipsychotics (SGAs) are defined by a high **5-HT2A to D2 receptor blockade ratio**, which reduces the risk of EPS.

Question 22: Which drug possesses both antidepressant and antipsychotic properties?

A. Buspirone
B. Amoxapine (Correct Answer)
C. Trazodone
D. Minaserine

Explanation: **Explanation:** **Amoxapine** is a tetracyclic antidepressant (TeCA) and is a metabolite of the antipsychotic drug loxapine. It is unique because it possesses a dual mechanism of action: 1. **Antidepressant property:** It inhibits the reuptake of norepinephrine (and to a lesser extent, serotonin), similar to tricyclic antidepressants. 2. **Antipsychotic property:** Unlike other antidepressants, it significantly blocks **Dopamine D2 receptors**. Due to this dual action, Amoxapine is the drug of choice for **Psychotic Depression** (Major Depressive Disorder with psychotic features). **Analysis of Incorrect Options:** * **Buspirone (A):** An anxiolytic that acts as a partial agonist at 5-HT1A receptors. It lacks D2 blocking (antipsychotic) properties. * **Trazodone (C):** A Serotonin Antagonist and Reuptake Inhibitor (SARI). It is primarily used as an antidepressant and for its sedative properties in insomnia; it does not have antipsychotic efficacy. * **Mianserin (D):** A tetracyclic antidepressant that blocks alpha-2 adrenergic receptors. While it shares a chemical class with Amoxapine, it does not possess significant D2 receptor antagonism. **High-Yield Clinical Pearls for NEET-PG:** * **Side Effects:** Because of its D2 blocking activity, Amoxapine can cause **Extrapyramidal Side Effects (EPS)**, such as parkinsonism or akathisia, and hyperprolactinemia—side effects not typically seen with other antidepressants. * **Metabolism:** Remember that Amoxapine is the N-demethylated metabolite of **Loxapine**. * **Clinical Use:** Always consider Amoxapine or a combination of an SSRI + Antipsychotic for patients presenting with "delusional depression."

Question 23: Which of the following drug classes is most useful for acute depression and has a good side effect profile?

A. Reversible Inhibitors of Monoamine Oxidase A (RIMA)
B. Selective Serotonin Reuptake Inhibitors (SSRIs) (Correct Answer)
C. Tricyclic Antidepressants
D. Non-selective Monoamine Oxidase Inhibitors (MAO-inhibitors)

Explanation: **Explanation:** **Selective Serotonin Reuptake Inhibitors (SSRIs)** are considered the first-line treatment for acute depression. Their primary mechanism involves inhibiting the presynaptic reuptake of serotonin (5-HT), thereby increasing its availability in the synaptic cleft. They are preferred because they possess a **high therapeutic index**, lack significant anticholinergic or cardiotoxic effects, and are safe in overdose, making them the gold standard for both efficacy and tolerability. **Analysis of Incorrect Options:** * **Tricyclic Antidepressants (TCAs):** While highly effective, they have a narrow therapeutic index. They cause significant side effects (sedation, weight gain, dry mouth) and are **lethal in overdose** due to cardiotoxicity (arrhythmias via sodium channel blockade). * **Non-selective MAO-Is:** These are rarely used first-line due to the risk of **Hypertensive Crisis** ("Cheese Reaction") when taken with tyramine-rich foods and the risk of Serotonin Syndrome. * **RIMA (e.g., Moclobemide):** Although safer than non-selective MAO-Is, they are generally considered second-line or adjunctive and do not have the extensive clinical evidence base or "all-rounder" profile of SSRIs for acute depression. **High-Yield Clinical Pearls for NEET-PG:** * **Most common side effect of SSRIs:** Gastrointestinal upset (nausea/diarrhea) and sexual dysfunction. * **Drug of choice (DOC)** for Depression in patients with recent Myocardial Infarction: **Sertraline**. * **Fluoxetine** has the longest half-life, reducing the risk of discontinuation syndrome. * **Fluvoxamine** is specifically preferred for Obsessive-Compulsive Disorder (OCD).

Question 24: All of the following are typical antipsychotics, EXCEPT?

A. Risperidone (Correct Answer)
B. Haloperidol
C. Chlorpromazine
D. Pimozide

Explanation: **Explanation:** The classification of antipsychotics is based on their mechanism of action and side-effect profiles. Antipsychotics are divided into **Typical (First Generation)** and **Atypical (Second Generation)**. **1. Why Risperidone is the correct answer:** Risperidone is an **Atypical Antipsychotic**. Unlike typical agents that primarily block Dopamine (D2) receptors, atypical antipsychotics like Risperidone act as **Serotonin-Dopamine Antagonists (SDAs)**. They block both 5-HT2A and D2 receptors. This dual action helps reduce negative symptoms of schizophrenia and significantly lowers the risk of Extrapyramidal Side Effects (EPS) compared to typical agents. **2. Analysis of Incorrect Options (Typical Antipsychotics):** * **Haloperidol:** A high-potency typical antipsychotic and a potent D2 blocker. It is frequently used in acute psychosis but has a high incidence of EPS. * **Chlorpromazine:** A low-potency typical antipsychotic (the first ever discovered). It is known for causing significant sedation and orthostatic hypotension due to alpha-1 blockade. * **Pimozide:** A high-potency typical antipsychotic often used specifically for Tourette’s disorder and delusional parasitosis. **Clinical Pearls for NEET-PG:** * **Mechanism:** Typical = D2 blockade; Atypical = 5-HT2A + D2 blockade. * **Side Effects:** Typical drugs are associated with **EPS** and Hyperprolactinemia; Atypical drugs (except Ziprasidone/Aripiprazole) are associated with **Metabolic Syndrome** (weight gain, dyslipidemia). * **Risperidone Specific:** Among atypicals, Risperidone has the highest risk of causing **Hyperprolactinemia** and dose-dependent EPS. * **Clozapine:** The "Gold Standard" for treatment-resistant schizophrenia; watch for **agranulocytosis** (requires mandatory WBC monitoring).

Question 25: A 30-year-old patient with schizophrenia on antipsychotics presents with amenorrhea and galactorrhea. Which of the following antipsychotics should she be shifted to?

A. Haloperidol
B. Olanzapine
C. Risperidone
D. Aripiprazole (Correct Answer)

Explanation: ### Explanation The patient is experiencing **hyperprolactinemia** (manifesting as amenorrhea and galactorrhea), a common side effect of antipsychotics that block dopamine ($D_2$) receptors in the **tuberoinfundibular pathway**. Dopamine normally acts as a prolactin-inhibiting factor; blocking it leads to increased prolactin levels. **Why Aripiprazole is the correct answer:** Aripiprazole is a **partial $D_2$ receptor agonist**. Unlike pure antagonists, it provides enough dopaminergic tone to inhibit the excessive release of prolactin from the anterior pituitary. It is considered "prolactin-neutral" and is the drug of choice when switching a patient who has developed symptomatic hyperprolactinemia on other antipsychotics. **Analysis of Incorrect Options:** * **Haloperidol (Option A):** A high-potency typical antipsychotic and a strong $D_2$ antagonist. It is one of the most common causes of significant hyperprolactinemia. * **Risperidone (Option C):** Among atypical antipsychotics, Risperidone is the **most notorious** for causing hyperprolactinemia (often comparable to typical antipsychotics) because it crosses the blood-brain barrier poorly but binds strongly to $D_2$ receptors in the pituitary gland. * **Olanzapine (Option B):** While it has a lower risk than Risperidone or Haloperidol, it can still cause mild to moderate elevations in prolactin. It is not the preferred "switch" drug compared to Aripiprazole. **High-Yield Clinical Pearls for NEET-PG:** * **Tuberoinfundibular Pathway:** Responsible for prolactin control (Antipsychotics $\rightarrow$ Blockade $\rightarrow$ Hyperprolactinemia). * **Nigrostriatal Pathway:** Responsible for Extrapyramidal Symptoms (EPS). * **Mesolimbic Pathway:** Target for treating positive symptoms of schizophrenia. * **Drug of Choice for Hyperprolactinemia:** Aripiprazole (or Quetiapine as an alternative). * **Most Prolactin-Sparing:** Aripiprazole. * **Most Prolactin-Elevating (Atypical):** Risperidone and Paliperidone.

Question 26: Which of the following psychotropic drugs requires monitoring for hematotoxic effects?

A. Buspirone
B. Clozapine (Correct Answer)
C. Haloperidol
D. Lithium carbonate

Explanation: **Explanation:** **Clozapine** is the correct answer because it is associated with a significant risk of **agranulocytosis** (a severe decrease in white blood cell count), which occurs in approximately 1% of patients. It is an atypical antipsychotic reserved for treatment-resistant schizophrenia. Due to its hematotoxic potential, mandatory monitoring of the **Absolute Neutrophil Count (ANC)** is required (weekly for the first 6 months, then biweekly, then monthly) to prevent life-threatening infections. **Analysis of Incorrect Options:** * **Buspirone:** An anxiolytic (5-HT1A partial agonist) primarily known for lacking sedative or addictive properties; it does not cause bone marrow suppression. * **Haloperidol:** A typical antipsychotic (D2 blocker) known for Extrapyramidal Side Effects (EPS) and Hyperprolactinemia, but it is not associated with hematotoxicity. * **Lithium Carbonate:** Used in Bipolar Disorder. While it requires monitoring, it is for **renal, thyroid, and serum drug levels**. Interestingly, Lithium causes *leukocytosis* (increased WBC count), the opposite of hematotoxicity, and is sometimes used to treat clozapine-induced neutropenia. **High-Yield Clinical Pearls for NEET-PG:** * **Clozapine Monitoring:** Treatment must be interrupted if ANC falls below **1500/mm³**. * **Side Effect Profile:** Clozapine is the only antipsychotic that **reduces suicide risk** but carries a "5-Black Box Warning" for: Agranulocytosis, Seizures, Myocarditis, Orthostatic Hypotension, and Increased mortality in elderly patients with dementia. * **Sialorrhea:** Hypersalivation is a unique and common side effect of Clozapine.

Question 27: A 28-year-old patient presents with a 3-month history of suspiciousness, auditory hallucinations, aggression, and poor sleep and appetite. An ECG revealed a QTc of 480 ms. Which of the following medications should be avoided in this patient?

A. Ziprasidone (Correct Answer)
B. Aripiprazole
C. Clozapine
D. Risperidone

Explanation: **Explanation:** The patient presents with symptoms of psychosis (suspiciousness, hallucinations, aggression) and an **ECG showing a QTc interval of 480 ms**. In clinical practice, a QTc interval >450 ms in men or >470 ms in women is considered prolonged. Starting medications that further prolong the QT interval increases the risk of **Torsades de Pointes (TdP)**, a life-threatening ventricular arrhythmia. **Why Ziprasidone is the correct answer:** Among the atypical antipsychotics, **Ziprasidone** is most strongly associated with dose-dependent QTc prolongation. It is contraindicated in patients with a known history of QT prolongation, recent myocardial infarction, or uncompensated heart failure. Given this patient’s baseline QTc of 480 ms, Ziprasidone must be avoided. **Analysis of Incorrect Options:** * **Aripiprazole:** This is considered one of the "QT-neutral" antipsychotics. It has a very low risk of cardiac conduction issues and is often a preferred choice in patients with cardiac concerns. * **Clozapine:** While Clozapine can cause myocarditis or tachycardia, its effect on the QTc interval is significantly less than that of Ziprasidone. * **Risperidone:** Risperidone can cause mild QTc prolongation, but the effect is generally negligible at standard doses compared to Ziprasidone. **High-Yield Clinical Pearls for NEET-PG:** * **Highest QTc Risk (IV):** IV Haloperidol (highest risk among all). * **Highest QTc Risk (Oral):** Thioridazine (Typical) and Ziprasidone (Atypical). * **Safest/QT-Neutral:** Aripiprazole, Lurasidone, and Olanzapine. * **Monitoring:** Always check electrolytes (Hypokalemia and Hypomagnesemia) as they exacerbate drug-induced QT prolongation.

Question 28: Which of the following are atypical (second generation or newer) antipsychotics?

A. Aripiprazole
B. Risperidone
C. Olanzapine
D. All of the above (Correct Answer)

Explanation: **Explanation:** The correct answer is **D (All of the above)**. Antipsychotics are broadly classified into First Generation (Typical) and Second Generation (Atypical) based on their mechanism of action and side-effect profiles. **1. Why the options are correct:** * **Aripiprazole:** A unique atypical antipsychotic known as a **D2 partial agonist**. It also acts as a 5-HT1A agonist and 5-HT2A antagonist. It is often called a "dopamine stabilizer." * **Risperidone:** A potent **D2 and 5-HT2A antagonist**. It is one of the most commonly used atypicals but has a higher risk of prolactin elevation compared to others in its class. * **Olanzapine:** A MARTA (Multi-Acting Receptor Targeted Antagonist) that acts on D2, 5-HT2A, H1, and Muscarinic receptors. It is highly effective but associated with significant **metabolic side effects** (weight gain, dyslipidemia). **2. Underlying Medical Concept:** Unlike Typical antipsychotics (e.g., Haloperidol), which primarily block D2 receptors in the mesolimbic and nigrostriatal pathways, **Atypical antipsychotics** are characterized by **Serotonin-Dopamine Antagonism (SDA)**. By blocking 5-HT2A receptors, they increase dopamine release in the nigrostriatal and mesocortical pathways, which reduces Extrapyramidal Side Effects (EPS) and helps improve the negative symptoms of schizophrenia. **High-Yield NEET-PG Clinical Pearls:** * **Clozapine:** The "Gold Standard" for treatment-resistant schizophrenia; requires monitoring for **agranulocytosis** (absolute neutrophil count). * **Quetiapine:** Preferred in Parkinson’s disease patients with psychosis due to low EPS risk. * **Ziprasidone:** Notable for causing **QTc prolongation**; should be taken with food. * **Weight Gain Risk:** Olanzapine/Clozapine (Highest) > Quetiapine > Risperidone > Aripiprazole/Ziprasidone (Lowest).

Question 29: Which of the following drugs is used as a general anesthetic in Electroconvulsive Therapy (ECT)?

A. Methohexital (Correct Answer)
B. Labetalol
C. Amiodarone
D. Propranolol

Explanation: **Explanation:** **1. Why Methohexital is Correct:** Methohexital (a ultra-short-acting barbiturate) is considered the **gold standard** anesthetic agent for Electroconvulsive Therapy (ECT). The primary goal of anesthesia in ECT is to provide rapid induction and quick recovery without significantly interfering with seizure activity. Methohexital is preferred because it has a **minimal effect on the seizure threshold** compared to other induction agents (like propofol, which significantly shortens seizure duration). It ensures a rapid onset of action and a predictable, short duration of anesthesia, allowing for efficient post-ictal recovery. **2. Why the Other Options are Incorrect:** * **Labetalol & Propranolol:** These are beta-blockers. While they are sometimes used *adjunctively* during ECT to control the transient hypertensive surge and tachycardia that occurs during the tonic-clonic phase, they are not anesthetic agents and cannot induce unconsciousness. * **Amiodarone:** This is a Class III antiarrhythmic drug. It has no role in anesthesia induction and is not used in the standard ECT protocol. **3. High-Yield Clinical Pearls for NEET-PG:** * **Muscle Relaxant of Choice:** **Succinylcholine** is the preferred muscle relaxant in ECT to prevent musculoskeletal injuries (fractures/dislocations) during the seizure. * **Propofol vs. Methohexital:** While Propofol is commonly used, it is known to **shorten seizure duration** more than methohexital, which may potentially reduce the therapeutic efficacy of the treatment. * **Pre-medication:** Atropine or Glycopyrrolate (anticholinergics) may be given to prevent vagally-mediated bradycardia and reduce secretions. * **Absolute Contraindication:** The only absolute contraindication to ECT is **Increased Intracranial Pressure (ICP)**.

Question 30: A 50-year-old male developed cerebrovascular accident and subsequently presented with hemiplegia and pathological emotions. What is the management plan for the pathological emotions?

A. Amitriptyline
B. Sertraline
C. Escitalopram (Correct Answer)
D. Clomipramine

Explanation: ### **Explanation** The clinical presentation of hemiplegia following a cerebrovascular accident (CVA) accompanied by "pathological emotions" describes **Post-Stroke Emotional Incontinence (PSEI)**, also known as **Pseudobulbar Affect (PBA)**. This condition is characterized by sudden, involuntary, and inappropriate episodes of laughing or crying that are disproportionate to the actual emotional state. **1. Why Escitalopram is Correct:** Selective Serotonin Reuptake Inhibitors (SSRIs) are the first-line pharmacological treatment for pathological emotions post-stroke. **Escitalopram** is preferred in elderly post-stroke patients due to its high efficacy, superior safety profile, and minimal drug-drug interactions (it has the lowest effect on the Cytochrome P450 system). It effectively modulates the serotonergic pathways that are often disrupted in subcortical or frontal lobe strokes. **2. Why Other Options are Incorrect:** * **Amitriptyline & Clomipramine (Options A & D):** These are Tricyclic Antidepressants (TCAs). While TCAs can treat PBA, they are generally avoided in post-stroke patients due to their **anticholinergic side effects** (confusion, urinary retention) and **cardiotoxicity** (arrhythmias, orthostatic hypotension), which pose a high risk to patients with existing cardiovascular or cerebrovascular disease. * **Sertraline (Option B):** While Sertraline is an SSRI and can be used, Escitalopram is often favored in recent clinical guidelines and exams for its cleaner side-effect profile and faster onset of action in emotional regulation specifically for post-stroke sequelae. **3. NEET-PG High-Yield Pearls:** * **Pseudobulbar Affect (PBA):** Seen in CVA, Multiple Sclerosis, ALS, and Traumatic Brain Injury. * **First-line treatment:** SSRIs (Escitalopram, Fluoxetine, Citalopram). * **Alternative (FDA-approved):** Nuedexta (Dextromethorphan + Quinidine). * **Post-Stroke Depression (PSD):** Also treated primarily with SSRIs; Escitalopram is often the drug of choice due to its safety in cardiac patients.

Practice by Chapter

Principles of Psychopharmacology

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Antipsychotic Medications

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Antidepressant Medications

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Mood Stabilizers

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Anxiolytics and Hypnotics

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Stimulants and Cognitive Enhancers

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Pharmacokinetics and Pharmacodynamics

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Drug Interactions

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Adverse Effects and Management

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Pharmacogenomics in Psychiatry

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Special Populations Considerations

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Treatment Algorithms and Guidelines

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