Drugs in Psychiatric Disorders — MCQs

Drugs in Psychiatric Disorders Indian Medical PG Practice Questions and MCQs

Question 51: Which of the following is a NaSSa?

A. Mianserin (Correct Answer)
B. Clozapine
C. Nefazodone
D. Sertraline

Explanation: **Explanation:** **NaSSAs (Noradrenergic and Specific Serotonergic Antidepressants)** are a unique class of antidepressants that act by blocking **presynaptic $\alpha_2$-autoreceptors** and **heteroreceptors**. This blockade increases the release of both Norepinephrine and Serotonin (5-HT). 1. **Why Mianserin is correct:** **Mianserin** (along with Mirtazapine) is the classic example of a NaSSa. By antagonizing $\alpha_2$ receptors, it enhances adrenergic and serotonergic neurotransmission. Crucially, it also blocks **5-HT$_2$ and 5-HT$_3$ receptors**, which prevents the common side effects associated with non-specific SSRIs (like anxiety, insomnia, and sexual dysfunction), making it "Specific." 2. **Analysis of Incorrect Options:** * **Clozapine:** This is an **Atypical Antipsychotic** (SDA - Serotonin Dopamine Antagonist). While it has complex receptor activity, its primary clinical use is for treatment-resistant schizophrenia, not as a NaSSa. * **Nefazodone:** This belongs to the **SARI** (Serotonin Antagonist and Reuptake Inhibitor) class. It primarily blocks 5-HT$_2$ receptors and inhibits serotonin reuptake. * **Sertraline:** This is a prototype **SSRI** (Selective Serotonin Reuptake Inhibitor), the most commonly prescribed class for depression and anxiety disorders. **High-Yield Clinical Pearls for NEET-PG:** * **Mirtazapine vs. Mianserin:** Mirtazapine is more commonly used today; Mianserin is associated with a rare risk of **agranulocytosis**, requiring hematological monitoring. * **Side Effects:** NaSSAs are highly sedative (due to H1 blockade) and often cause **weight gain**. They are excellent choices for depressed patients suffering from significant insomnia or underweight elderly patients. * **Mechanism Tip:** Remember that NaSSAs do *not* inhibit the reuptake of amines; they work solely via receptor antagonism.

Question 52: Moclobemide is:

A. Selective serotonin reuptake inhibitor (SSRI)
B. Antipsychotic drug
C. Monoamine oxidase (MAO) inhibitor (Correct Answer)
D. Tricyclic antidepressant

Explanation: **Explanation:** **Moclobemide** is a **Reversible Inhibitor of MAO-A (RIMA)**. Monoamine oxidase (MAO) is an enzyme responsible for the oxidative deamination of neurotransmitters. MAO-A primarily metabolizes serotonin, norepinephrine, and dopamine. By inhibiting this enzyme, Moclobemide increases the synaptic concentration of these monoamines, thereby exerting its antidepressant effect. **Why the other options are incorrect:** * **Option A (SSRI):** Drugs like Fluoxetine, Sertraline, and Escitalopram belong to this class. They specifically inhibit the serotonin transporter (SERT) rather than the MAO enzyme. * **Option B (Antipsychotic):** These drugs (e.g., Haloperidol, Risperidone) primarily act by blocking Dopamine (D2) receptors or Serotonin (5-HT2A) receptors, not by inhibiting MAO. * **Option C (Tricyclic Antidepressant):** TCAs like Amitriptyline and Imipramine work by inhibiting the reuptake of both Norepinephrine and Serotonin (NET and SERT) and possess significant anticholinergic properties. **High-Yield Clinical Pearls for NEET-PG:** 1. **Cheese Reaction:** Unlike older, irreversible non-selective MAO inhibitors (e.g., Phenelzine), Moclobemide has a **lower risk of the "Cheese Reaction"** (hypertensive crisis caused by tyramine). This is because it is reversible; high levels of tyramine can displace Moclobemide from the enzyme, allowing tyramine metabolism to continue. 2. **Selectivity:** MAO-**A** inhibitors (Moclobemide) are used for **Depression**, while MAO-**B** inhibitors (Selegiline, Rasagiline) are used for **Parkinson’s Disease**. 3. **Serotonin Syndrome:** Even though it is a RIMA, Moclobemide should not be combined with SSRIs or TCAs due to the fatal risk of Serotonin Syndrome.

Question 53: Elderly persons taking antipsychotics are especially susceptible to all of the following side effects except?

A. Tardive dyskinesia
B. Paresthesias (Correct Answer)
C. Dry mouth
D. Akathisia

Explanation: **Explanation:** Antipsychotic medications, particularly first-generation (typical) agents, are associated with a wide range of side effects due to their blockade of dopaminergic, cholinergic, alpha-adrenergic, and histaminergic receptors [3]. The elderly population is physiologically more vulnerable to these effects due to age-related changes in pharmacokinetics and pharmacodynamics. **Why Paresthesias is the Correct Answer:** Paresthesias (tingling or "pins and needles" sensations) are **not** a characteristic side effect of antipsychotic therapy. Paresthesias are more commonly associated with metabolic disturbances, vitamin B12 deficiency, or specific drugs like Topiramate and Acetazolamide. While antipsychotics cause numerous neurological side effects, they do not typically involve peripheral sensory nerve disturbances. **Analysis of Incorrect Options:** * **Tardive Dyskinesia (TD):** Elderly patients, especially women, are at a significantly higher risk of developing TD [1]. It involves involuntary choreoathetoid movements resulting from dopamine receptor supersensitivity after prolonged blockade [3]. * **Dry Mouth:** This is a classic **anticholinergic** side effect (M1 blockade) [3]. Elderly patients have decreased physiological reserves and are highly susceptible to "atropine-like" effects, including dry mouth, urinary retention, and constipation [3]. * **Akathisia:** This is a common Extrapyramidal Side Effect (EPS) characterized by subjective motor restlessness [2]. The elderly are more prone to EPS due to the natural decline in nigrostriatal dopamine levels associated with aging. **NEET-PG High-Yield Pearls:** * **Drug of Choice for Psychosis in Parkinson’s:** Pimavanserin (a 5-HT2A inverse agonist) or Quetiapine/Clozapine (due to low D2 affinity). * **Black Box Warning:** The FDA warns that antipsychotic use in elderly patients with dementia-related psychosis is associated with an increased risk of **death** (primarily due to cardiovascular events or pneumonia). * **Most Potent Anticholinergic Antipsychotic:** Thioridazine and Clozapine.

Question 54: Which of the following is a tricyclic antidepressant?

A. Sertraline
B. Clomipramine (Correct Answer)
C. Bupropion
D. Fluvoxamine

Explanation: **Explanation:****Clomipramine** is a **Tricyclic Antidepressant (TCA)** belonging to the dibenzazepine class [1]. TCAs primarily work by inhibiting the reuptake of norepinephrine (NE) and serotonin (5-HT) into the presynaptic neuron [1]. Clomipramine is unique among TCAs because it is highly selective for serotonin reuptake inhibition, making it the "gold standard" pharmacological treatment for **Obsessive-Compulsive Disorder (OCD)** [1].**Analysis of Incorrect Options:** * **Sertraline (Option A):** A Selective Serotonin Reuptake Inhibitor (SSRI) [1]. It is a first-line treatment for depression and anxiety disorders due to its favorable side-effect profile compared to TCAs.* **Bupropion (Option B):** An Atypical Antidepressant that acts as a Norepinephrine-Dopamine Reuptake Inhibitor (NDRI) [1]. It is notable for having no sexual side effects and is used for smoking cessation [1].* **Fluvoxamine (Option D):** Another member of the SSRI class, frequently used in the management of OCD and social anxiety disorder [1].**High-Yield Clinical Pearls for NEET-PG:** * **Classification Tip:** TCAs are divided into Tertiary amines (e.g., Amitriptyline, Clomipramine, Imipramine) and Secondary amines (e.g., Nortriptyline, Desipramine) [1].* **Side Effects:** TCAs are notorious for "3 Cs": **C**oma, **C**onvulsions, and **C**ardiotoxicity (arrhythmias due to sodium channel blockade). They also cause significant anticholinergic effects (dry mouth, blurred vision, constipation) [1].* **Antidote:** Sodium bicarbonate is used to manage TCA-induced cardiotoxicity (QRS widening).* **Drug of Choice:** While SSRIs are first-line for OCD, Clomipramine remains the most efficacious drug for resistant cases.

Question 55: Pimvanserin is used in the treatment of which of the following conditions?

A. Schizophrenia
B. Down's syndrome
C. Parkinsonism (Correct Answer)
D. Huntington's chorea

Explanation: **Explanation:** **Pimvanserin** is a novel atypical antipsychotic specifically FDA-approved for the treatment of **hallucinations and delusions associated with Parkinson’s disease psychosis (PDP).** **Mechanism of Action:** Unlike traditional antipsychotics that block Dopamine D2 receptors, Pimvanserin acts as a **selective inverse agonist and antagonist at Serotonin 5-HT2A receptors**, with little to no affinity for D2, histaminergic, or muscarinic receptors. This is the "medical gold" for Parkinson’s patients: because it lacks D2 antagonism, it treats psychosis **without worsening motor symptoms** (tremor, rigidity, or bradykinesia). **Analysis of Incorrect Options:** * **A. Schizophrenia:** While it is an antipsychotic, Pimvanserin is not a first-line or standard treatment for primary schizophrenia; D2 blockade is usually required for managing positive symptoms in schizophrenia. * **B. Down’s Syndrome:** There is no established clinical role for Pimvanserin in Down’s syndrome. Psychosis in these patients is managed with standard atypical antipsychotics if necessary. * **D. Huntington’s Chorea:** The drug of choice for chorea is **Tetrabenazine** or **Deutetrabenazine** (VMAT-2 inhibitors). While antipsychotics can be used for behavioral issues in Huntington’s, Pimvanserin is not the indicated drug. **High-Yield Clinical Pearls for NEET-PG:** 1. **Drug of Choice:** Pimvanserin is the preferred agent for Parkinson’s Psychosis. **Quetiapine** and **Clozapine** are other alternatives due to their low D2 affinity. 2. **Avoid:** Traditional antipsychotics (e.g., Haloperidol) are strictly contraindicated in Parkinson’s as they exacerbate the movement disorder. 3. **Side Effect:** Pimvanserin can cause **QT interval prolongation**; baseline and periodic ECG monitoring may be required.

Question 56: Risperidone increases the risk of which of the following?

A. Cerebrovascular accidents
B. Extrapyramidal symptoms (Correct Answer)
C. Agranulocytosis
D. Diabetes insipidus

Explanation: **Explanation:** **Risperidone** is a second-generation (atypical) antipsychotic. While atypical antipsychotics generally have a lower risk of **Extrapyramidal Symptoms (EPS)** compared to first-generation drugs (like Haloperidol), Risperidone is unique because it exhibits **dose-dependent EPS**. At higher therapeutic doses (>6 mg/day), its potent D2 receptor antagonism outweighs its 5-HT2A antagonism, leading to a significantly increased risk of parkinsonian symptoms, akathisia, and dystonia. **Analysis of Incorrect Options:** * **A. Cerebrovascular accidents:** While atypical antipsychotics carry a "Black Box Warning" for increased mortality and stroke risk in *elderly patients with dementia-related psychosis*, EPS is a more direct and characteristic pharmacological side effect of Risperidone across the general population. * **C. Agranulocytosis:** This is the classic, life-threatening adverse effect associated with **Clozapine**, requiring mandatory WBC monitoring. Risperidone does not typically cause bone marrow suppression. * **D. Diabetes insipidus:** This is a classic side effect of **Lithium** (Nephrogenic DI), not antipsychotics. Risperidone is more commonly associated with metabolic syndrome (weight gain, dyslipidemia) and hyperprolactinemia. **NEET-PG High-Yield Pearls:** * **Hyperprolactinemia:** Among atypical antipsychotics, Risperidone has the highest propensity to increase prolactin levels (leading to gynecomastia/amenorrhea) because it lacks significant blood-brain barrier selectivity in the pituitary gland. * **Metabolic Profile:** Risperidone has a moderate risk for weight gain and diabetes, higher than Ziprasidone/Aripiprazole but lower than Clozapine/Olanzapine. * **Active Metabolite:** **Paliperidone** is the major active metabolite of Risperidone.

Question 57: Activation of which of the following receptors would be expected to decrease anxiety?

A. Nicotinic cholinergic receptors
B. Glutamate receptors
C. GABA receptors (Correct Answer)
D. Glucocorticoid receptors

Explanation: **Explanation:** The correct answer is **C. GABA receptors.** **Mechanism of Action:** GABA (Gamma-Aminobutyric Acid) is the primary inhibitory neurotransmitter in the Central Nervous System (CNS) [2]. The **GABA-A receptor** is a ligand-gated chloride channel [3]. When GABA binds to this receptor, it increases chloride conductance, leading to hyperpolarization of the postsynaptic neuron. This reduces neuronal excitability and produces a **sedative, hypnotic, and anxiolytic effect.** [3] Most clinical anxiolytics, such as Benzodiazepines (BZDs) and Barbiturates, work by positively modulating the GABA-A receptor [1]. **Analysis of Incorrect Options:** * **A. Nicotinic cholinergic receptors:** Activation generally leads to CNS stimulation and arousal. While nicotine has complex effects on mood, its acute activation is not a primary mechanism for clinical anxiolysis; withdrawal actually increases anxiety. * **B. Glutamate receptors:** Glutamate is the major **excitatory** neurotransmitter. Activation of NMDA or AMPA receptors increases neuronal firing, which is associated with agitation and anxiety. Glutamate antagonists (like Ketamine) are being studied for mood disorders, but agonists would worsen anxiety. * **D. Glucocorticoid receptors:** Chronic activation by cortisol (the stress hormone) is associated with the stress response and can lead to neuronal atrophy in the hippocampus, potentially worsening anxiety and depression. **NEET-PG High-Yield Pearls:** * **Benzodiazepines:** Increase the **frequency** of GABA-A channel opening [3]. * **Barbiturates:** Increase the **duration** of GABA-A channel opening (higher risk of toxicity). * **Drug of Choice (DOC):** While BZDs provide rapid relief for acute anxiety, **SSRIs** (Selective Serotonin Reuptake Inhibitors) are the first-line long-term treatment for Generalized Anxiety Disorder (GAD) and Panic Disorder. * **Buspirone:** A 5-HT1A partial agonist used for GAD that does *not* act on GABA receptors and lacks sedative/addictive properties.

Question 58: All of the following statements are true, except?

A. Dipyridamole shows coronary steal phenomena.
B. Omeprazole inhibits CYP 2C19.
C. SNRIs are the drug of choice for severe depression.
D. Agranulocytosis is the most common side effect of clozapine. (Correct Answer)

Explanation: The correct answer is **D** because while agranulocytosis is the most **serious** and characteristic side effect of Clozapine, it is not the most **common**. ### 1. Why Option D is the "Except" (The Correct Answer) Clozapine is an atypical antipsychotic reserved for treatment-resistant schizophrenia. * **Agranulocytosis** occurs in only about **0.8–1%** of patients. Because it is life-threatening, mandatory WBC monitoring is required. * The **most common** side effects of Clozapine are actually **Sialorrhea (excessive salivation)**, sedation, and weight gain. Other significant risks include seizures (dose-dependent) and myocarditis. ### 2. Analysis of Incorrect Options * **A. Dipyridamole shows coronary steal phenomena:** This is **true**. Dipyridamole is a vasodilator that expands healthy vessels, "stealing" blood flow away from ischemic areas where vessels are already maximally dilated, potentially worsening ischemia. * **B. Omeprazole inhibits CYP 2C19:** This is **true**. This is clinically significant because it reduces the conversion of Clopidogrel (a prodrug) to its active form, decreasing its antiplatelet efficacy. * **C. SNRIs are the drug of choice for severe depression:** This is **true**. While SSRIs are first-line for mild-to-moderate depression, SNRIs (like Venlafaxine or Duloxetine) are often preferred for severe or melancholic depression due to their dual action on serotonin and norepinephrine. ### 3. NEET-PG High-Yield Pearls: Clozapine * **Drug of Choice:** Treatment-resistant schizophrenia and schizophrenia with suicidal behavior. * **Monitoring:** Absolute Neutrophil Count (ANC) must be checked weekly for the first 6 months. * **Side Effect Profile:** It is the only antipsychotic that **does not** cause significant Extrapyramidal Symptoms (EPS) and does not increase Prolactin levels. * **Metabolic Risk:** High risk of dyslipidemia and Type 2 Diabetes Mellitus.

Question 59: Weight gain caused by antipsychotics is due to antagonism of which receptor subtype?

A. 5-HT3
B. 5-HT2A
C. 5-HT2B
D. 5-HT2C (Correct Answer)

Explanation: **Explanation:** The metabolic side effects of antipsychotics, particularly weight gain, are primarily attributed to the antagonism of **5-HT2C receptors** and **H1 (Histamine)** receptors in the hypothalamus. 1. **Why 5-HT2C is correct:** The 5-HT2C receptor subtype plays a crucial role in regulating satiety and energy homeostasis. Antagonism of these receptors leads to increased appetite (hyperphagia) and a decreased metabolic rate, resulting in significant weight gain. This is most notably seen with "Atypical" or Second-Generation Antipsychotics (SGAs) like **Clozapine** and **Olanzapine**, which have a high affinity for this receptor. 2. **Why other options are incorrect:** * **5-HT3:** These are ligand-gated ion channels primarily involved in the emetic reflex (vomiting). Antagonists (e.g., Ondansetron) are used as anti-emetics, not associated with weight gain. * **5-HT2A:** Antagonism here is the hallmark of SGAs and helps reduce Extrapyramidal Side Effects (EPS) and improve negative symptoms of schizophrenia, but it is not the primary driver of weight gain. * **5-HT2B:** These receptors are mainly located in the heart and GI tract. Agonism of 5-HT2B is linked to valvular heart disease (e.g., with Fenfluramine). **NEET-PG High-Yield Pearls:** * **Highest weight gain risk:** Clozapine > Olanzapine. * **Weight neutral/Lowest risk:** Ziprasidone, Aripiprazole, and Lurasidone. * **Dual Mechanism:** Weight gain is often a synergistic effect of **5-HT2C + H1 blockade**. * **Metabolic Syndrome:** Monitoring of BMI, fasting glucose, and lipid profile is mandatory for patients on SGAs.

Question 60: All of the following are predictable adverse effects of treatment with phenothiazines such as chlorpromazine, EXCEPT?

A. Orthostatic hypotension
B. Parkinson's syndrome
C. Excessive salivation (Correct Answer)
D. Hyperprolactinemia

Explanation: **Explanation:** Chlorpromazine is a low-potency typical antipsychotic (phenothiazine) that acts by blocking multiple receptors, including Dopamine ($D_2$), Alpha-1 ($\alpha_1$), Muscarinic ($M_1$), and Histamine ($H_1$). **Why "Excessive Salivation" is the correct answer:** Phenothiazines like chlorpromazine have significant **anticholinergic (antimuscarinic) properties**. Blockade of $M_1$ receptors leads to decreased secretions, resulting in **Dry Mouth (Xerostomia)**, not excessive salivation. *(Note: Clozapine is a unique exception among antipsychotics as it causes sialorrhea/excessive salivation).* **Analysis of Incorrect Options:** * **A. Orthostatic Hypotension:** This is a predictable effect caused by the blockade of **$\alpha_1$-adrenergic receptors** in the peripheral vasculature, leading to vasodilation. * **B. Parkinson’s Syndrome:** By blocking **$D_2$ receptors** in the **Nigrostriatal pathway**, phenothiazines cause Extrapyramidal Symptoms (EPS), including drug-induced Parkinsonism (tremors, rigidity, bradykinesia). * **D. Hyperprolactinemia:** $D_2$ blockade in the **Tuberoinfundibular pathway** removes the inhibitory effect of dopamine on prolactin release. This leads to elevated prolactin levels, potentially causing galactorrhea and gynecomastia. **NEET-PG High-Yield Pearls:** 1. **Low Potency (Chlorpromazine/Thioridazine):** High sedation, high anticholinergic effects, high alpha-blockade, but lower risk of EPS. 2. **High Potency (Haloperidol/Fluphenazine):** Low sedation, low anticholinergic effects, but very high risk of EPS. 3. **Thioridazine Warning:** Associated with Retinitis Pigmentosa and QTc prolongation. 4. **Clozapine:** The "rule breaker"—it is the only antipsychotic that commonly causes **excessive salivation** (likely due to $M_4$ receptor agonism or inhibition of the swallowing reflex).

Practice by Chapter

Antipsychotics: Typical and Atypical

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Antidepressants: SSRIs and SNRIs

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Tricyclic Antidepressants

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MAO Inhibitors

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Mood Stabilizers

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Anxiolytics

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Drugs for ADHD

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Drugs for Sleep Disorders

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Drugs for Dementia

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Drug-Induced Psychiatric Symptoms

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