Psychopharmacology — MCQs

Psychopharmacology Indian Medical PG Practice Questions and MCQs

Question 211: Which of the following substances is considered an anxiolytic?

A. Caffeine
B. Cholecystokinin
C. Neuropeptide Y (Correct Answer)
D. Carbon dioxide

Explanation: **Explanation:** **Neuropeptide Y (NPY)** is the correct answer because it is a potent endogenous **anxiolytic** peptide found in high concentrations in the amygdala and hippocampus. It acts as a natural "buffer" against stress by counteracting the effects of Corticotropin-Releasing Factor (CRF). High levels of NPY are associated with resilience to stress, while low levels are linked to anxiety disorders and PTSD. **Analysis of Incorrect Options:** * **Caffeine (Option A):** A methylxanthine that acts as an adenosine receptor antagonist. It is a well-known **anxiogenic** (anxiety-inducing) substance that can trigger panic attacks in susceptible individuals by increasing sympathetic outflow. * **Cholecystokinin (CCK) (Option B):** A peptide hormone that, when administered (specifically CCK-4), acts as a potent **panicogen**. It induces acute panic symptoms and is often used in research to study panic disorder. * **Carbon Dioxide (CO2) (Option C):** Inhalation of 5% or 35% CO2 is a classic **anxiogenic** stimulus. It triggers the "suffocation alarm" in the brainstem, leading to hyperventilation and acute anxiety/panic. **High-Yield Clinical Pearls for NEET-PG:** * **Panicogens (Anxiogenics):** Caffeine, CCK, CO2, Sodium Lactate, and Yohimbine (alpha-2 antagonist). * **Anxiolytics:** Benzodiazepines (GABA-A facilitators), Buspirone (5-HT1A partial agonist), and NPY. * **NPY & PTSD:** Research indicates that individuals with higher NPY levels show better recovery from trauma, making it a target for future pharmacological treatments.

Question 212: A patient was on treatment with trifluoperazine for some time. He presents with a complaint of hyperthermia, lethargy, and sweating. Which investigations are needed?

A. CT Scan brain & hemogram
B. Hemogram, Electrolyte level and creatinine
C. ECG, Chest X-ray and hemogram
D. Hemogram, CPK and renal function test (Correct Answer)

Explanation: ### Explanation The clinical presentation of **hyperthermia, lethargy, and sweating** in a patient taking **Trifluoperazine** (a high-potency typical antipsychotic) strongly suggests **Neuroleptic Malignant Syndrome (NMS)**. NMS is a life-threatening idiosyncratic reaction to dopamine antagonists. **Why Option D is Correct:** To confirm the diagnosis and assess the severity of NMS, specific laboratory investigations are critical: * **Hemogram:** Typically shows **leukocytosis** (elevated WBC count), which is a diagnostic marker for NMS. * **Creatine Phosphokinase (CPK):** Severe muscle rigidity (lead-pipe rigidity) leads to muscle necrosis, causing a significant **elevation in serum CPK levels**. * **Renal Function Test (RFT):** Massive muscle breakdown leads to **myoglobinuria**, which can cause **Acute Renal Failure**. Monitoring BUN and Creatinine is vital for management. **Why Other Options are Incorrect:** * **Option A:** CT Scan is used to rule out structural brain lesions or strokes, which do not typically present with this triad of symptoms. * **Option B:** While electrolytes are important in any systemic illness, they are not specific diagnostic markers for NMS compared to CPK. * **Option C:** ECG and Chest X-ray are supportive but do not aid in the primary diagnosis of NMS or the assessment of its most common complication (rhabdomyolysis). **Clinical Pearls for NEET-PG:** * **Mnemonic for NMS (FEVER):** **F**ever, **E**ncephalopathy (lethargy), **V**itals unstable, **E**levated enzymes (CPK), **R**igidity. * **Drug of Choice:** **Dantrolene** (muscle relaxant) or **Bromocriptine** (dopamine agonist). * **Key Difference:** Unlike Serotonin Syndrome, NMS is characterized by **"Lead-pipe" rigidity** and **bradyreflexia**, whereas Serotonin Syndrome presents with hyperreflexia and myoclonus.

Question 213: Which drug is most useful in treating an episode of antipsychotic-induced acute dystonia?

A. Lorazepam
B. Haloperidol
C. Promethazine (Correct Answer)
D. Phenobarbitone

Explanation: **Explanation:** **Acute Dystonia** is an Extrapyramidal Side Effect (EPS) characterized by sudden, involuntary muscle spasms (e.g., torticollis, oculogyric crisis). It occurs due to a functional excess of **acetylcholine** resulting from the blockade of dopamine (D2) receptors in the nigrostriatal pathway by antipsychotics. **Why Promethazine is Correct:** The mainstay of treatment for acute dystonia is **anticholinergic medications**. Promethazine is a first-generation antihistamine with potent **central anticholinergic properties**. It effectively restores the dopamine-acetylcholine balance in the basal ganglia, leading to rapid resolution of muscle spasms. It is often preferred in emergency settings due to its availability in injectable forms. **Analysis of Incorrect Options:** * **A. Lorazepam:** While benzodiazepines can provide muscle relaxation and sedation, they are not the primary treatment for dystonia as they do not address the underlying cholinergic imbalance. * **B. Haloperidol:** This is a high-potency typical antipsychotic and is a common *cause* of acute dystonia. Administering it would worsen the condition. * **C. Phenobarbitone:** This is a barbiturate used for seizures and sedation; it has no role in treating EPS. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC):** Centrally acting anticholinergics like **Benztropine** (IV/IM) or **Procyclidine**. * **Alternative:** Promethazine or Diphenhydramine (due to anticholinergic effects). * **Risk Factors:** Young males, high-potency antipsychotics (e.g., Haloperidol), and recent initiation of therapy (usually occurs within hours to 5 days). * **Prophylaxis:** If a patient must continue a high-potency antipsychotic, oral anticholinergics (Trihexyphenidyl) are often co-prescribed.

Question 214: Which of the following statements regarding clozapine is incorrect?

A. It was withdrawn from the market during phase 4 clinical trials.
B. It is used in treatment-resistant schizophrenia.
C. It has a narrow therapeutic window. (Correct Answer)
D. It can cause seizures at doses exceeding 300mg/day.

Explanation: ### Explanation **1. Why Option C is the Correct Answer (The Incorrect Statement):** Clozapine does **not** have a narrow therapeutic window. A "narrow therapeutic window" implies that the dose required for efficacy is very close to the dose that causes toxicity (e.g., Lithium, Digoxin, Phenytoin). While Clozapine requires strict monitoring due to its side effect profile (agranulocytosis), its therapeutic range is relatively broad. Serum levels are typically maintained between **350–600 ng/mL**, but toxicity usually manifests at much higher levels (often >1000 ng/mL). **2. Analysis of Incorrect Options (Correct Statements):** * **Option A:** Clozapine was indeed withdrawn in 1975 during Phase 4 (post-marketing surveillance) after several deaths in Finland due to **agranulocytosis**. It was later reintroduced in 1989 with mandatory hematological monitoring. * **Option B:** It is the **gold standard** and the only FDA-approved drug for **treatment-resistant schizophrenia** (defined as failure of at least two different antipsychotic trials of adequate dose and duration). * **Option D:** Clozapine causes **dose-dependent seizures**. The risk increases significantly at doses above **300–450 mg/day**, reaching approximately 5% at doses above 600 mg/day. **3. High-Yield Clinical Pearls for NEET-PG:** * **Agranulocytosis:** Occurs in ~1% of patients. Monitor Absolute Neutrophil Count (ANC) weekly for the first 6 months. * **Metabolic Side Effects:** Highest risk among antipsychotics for weight gain, dyslipidemia, and Type 2 Diabetes. * **Sialorrhea:** Paradoxical excessive salivation (often nocturnal) is a common side effect. * **Myocarditis:** A rare but fatal side effect; usually occurs within the first month of treatment. * **No Extrapyramidal Symptoms (EPS):** It has the lowest risk of EPS and Tardive Dyskinesia because it is a weak D2 blocker and a potent 5HT2A antagonist.

Question 215: A 25-year-old man with a psychotic illness was treated with haloperidol 30mg/day. On the third day, he developed pacing and an inability to sit still. Which medication is likely to be helpful?

A. Phenytoin
B. Propranolol (Correct Answer)
C. Methylphenidate
D. Trihexyphenidyl

Explanation: ### Explanation **Diagnosis: Akathisia** The patient is experiencing **Akathisia**, a common Extrapyramidal Side Effect (EPS) occurring within days of starting high-potency antipsychotics like Haloperidol. It is clinically characterized by subjective feelings of inner restlessness and objective signs of pacing or an inability to sit still. **Why Propranolol is Correct:** **Propranolol**, a lipophilic beta-blocker, is the **first-line treatment** for akathisia. It crosses the blood-brain barrier and acts on central beta-receptors to alleviate the symptoms of restlessness. Benzodiazepines (like Lorazepam) are considered second-line. **Why Other Options are Incorrect:** * **A. Phenytoin:** This is an antiepileptic medication used for generalized tonic-clonic seizures; it has no role in managing movement disorders caused by antipsychotics. * **C. Methylphenidate:** This is a CNS stimulant used for ADHD. It can actually worsen psychosis and agitation. * **D. Trihexyphenidyl:** This is an anticholinergic used to treat **Acute Dystonia** (muscle spasms) and **Drug-Induced Parkinsonism** (tremors/rigidity). While frequently tested, it is generally **less effective** than propranolol for akathisia. **High-Yield Clinical Pearls for NEET-PG:** * **Timeline of EPS:** 1. **Acute Dystonia:** Hours to days (Treatment: Promethazine/Trihexyphenidyl). 2. **Akathisia:** Days to weeks (Treatment: Propranolol). 3. **Drug-Induced Parkinsonism:** Weeks to months (Treatment: Trihexyphenidyl). 4. **Tardive Dyskinesia:** Months to years (Treatment: Switch to Clozapine/VMAT2 inhibitors). * **Key Differentiator:** Akathisia is often mistaken for worsening psychotic agitation. Increasing the antipsychotic dose will worsen akathisia, whereas it might improve agitation. Always look for the "pacing" keyword.

Question 216: Coarse tremors, polyuria, and hypothyroidism are adverse effects of which of the following medications?

A. Lithium (Correct Answer)
B. Haloperidol
C. Imipramine
D. Valproate

Explanation: **Explanation:** **Lithium** is the correct answer. It is a monovalent cation used as a first-line mood stabilizer for Bipolar Affective Disorder (BPAD). Its narrow therapeutic index (0.6–1.2 mEq/L) leads to a distinct side-effect profile: * **Coarse Tremors:** While fine tremors are common at therapeutic levels, **coarse tremors** are a hallmark sign of **Lithium Toxicity**. * **Polyuria:** Lithium inhibits the action of ADH on the distal tubules, leading to **Nephrogenic Diabetes Insipidus**. * **Hypothyroidism:** Lithium interferes with iodine organification and thyroid hormone release, often presenting with goiter or elevated TSH. **Analysis of Incorrect Options:** * **Haloperidol:** A typical antipsychotic primarily associated with **Extrapyramidal Side Effects (EPS)** like dystonia, akathisia, and tardive dyskinesia, rather than metabolic or renal issues. * **Imipramine:** A Tricyclic Antidepressant (TCA) known for **anticholinergic effects** (dry mouth, blurred vision, constipation) and cardiotoxicity (prolonged QTc). * **Valproate:** An anticonvulsant mood stabilizer. Common side effects include **weight gain, alopecia, hepatotoxicity, and PCOS**, but not polyuria or hypothyroidism. **High-Yield Clinical Pearls for NEET-PG:** * **L-I-T-H:** **L**eukocytosis, **I**nsipidus (Diabetes), **T**remors/Teratogenicity (Ebstein’s Anomaly), **H**ypothyroidism. * **Monitoring:** Thyroid Function Tests (TFT) and Renal Function Tests (RFT) must be done before and during treatment. * **Toxicity Precipitants:** Dehydration, low-sodium diet, and drugs like **NSAIDs, Thiazides, and ACE inhibitors** can increase Lithium levels.

Question 217: Which is a feature of haloperidol toxicity?

A. Weight loss
B. Long QT (Correct Answer)
C. Diarrhea
D. Tendinitis

Explanation: **Explanation:** Haloperidol is a high-potency, typical (first-generation) antipsychotic that acts primarily as a potent **D2 receptor antagonist**. **Why Option B is Correct:** Haloperidol toxicity is strongly associated with cardiovascular side effects, most notably **QT interval prolongation**. This occurs because haloperidol blocks the delayed rectifier potassium channels ($I_{Kr}$) in the cardiac myocytes. Prolongation of the QT interval increases the risk of life-threatening ventricular arrhythmias, specifically **Torsades de Pointes**. This risk is significantly higher with intravenous administration or high doses. **Why Other Options are Incorrect:** * **A. Weight loss:** Antipsychotics, including haloperidol, are more commonly associated with **weight gain** (though less so than atypical antipsychotics like Olanzapine) due to metabolic changes and H1 receptor blockade. * **C. Diarrhea:** Haloperidol possesses mild anticholinergic properties, which are more likely to cause **constipation** rather than diarrhea. * **D. Tendinitis:** This is a classic side effect associated with **Fluoroquinolones** (e.g., Ciprofloxacin), not antipsychotics. **High-Yield Clinical Pearls for NEET-PG:** * **Extrapyramidal Symptoms (EPS):** Due to high D2 potency, Haloperidol has the highest risk of acute dystonia, akathisia, and parkinsonism. * **Neuroleptic Malignant Syndrome (NMS):** A life-threatening reaction characterized by "lead-pipe" rigidity, hyperthermia, and autonomic instability. * **Hyperprolactinemia:** Haloperidol frequently causes galactorrhea and gynecomastia by blocking dopamine in the tuberoinfundibular pathway. * **Monitoring:** Always perform a baseline ECG before starting high-dose or IV haloperidol to monitor the QTc interval.

Question 218: Which of the following is the drug of choice for Obsessive-Compulsive Disorder (OCD)?

A. Haloperidol
B. Clozapine
C. Doxepin
D. Clomipramine (Correct Answer)

Explanation: **Explanation:** **Correct Answer: D. Clomipramine** The pharmacological management of Obsessive-Compulsive Disorder (OCD) primarily involves enhancing serotonergic neurotransmission. **Clomipramine**, a Tricyclic Antidepressant (TCA), is considered the "gold standard" and the most effective drug for OCD due to its potent and selective inhibition of serotonin reuptake. While Selective Serotonin Reuptake Inhibitors (SSRIs) like Fluoxetine or Fluvoxamine are often used as first-line agents due to a better side-effect profile, Clomipramine remains the drug of choice in terms of absolute efficacy, especially in refractory cases. **Analysis of Incorrect Options:** * **A. Haloperidol:** This is a typical antipsychotic (D2 blocker). It is not a primary treatment for OCD but may be used as an *augmentation* strategy in patients with comorbid tics or those resistant to SSRIs. * **B. Clozapine:** An atypical antipsychotic used for treatment-resistant schizophrenia. Interestingly, Clozapine can actually *induce* or worsen obsessive-compulsive symptoms as a side effect. * **C. Doxepin:** A TCA primarily used for insomnia and depression. Unlike Clomipramine, it lacks the specific, potent serotonergic activity required to treat OCD effectively. **Clinical Pearls for NEET-PG:** * **Dosage:** OCD requires higher doses of SSRIs/Clomipramine compared to depression. * **Latency:** Clinical response in OCD takes longer (8–12 weeks) than in depression (2–4 weeks). * **First-line:** While Clomipramine is the most effective, **SSRIs** are the first-line treatment due to safety. * **Mechanism:** Clomipramine’s metabolite, desmethylclomipramine, also inhibits norepinephrine reuptake, but its anti-obsessional effect is strictly linked to its parent compound's serotonergic action.

Question 219: Which of the following is the best treatment for extrapyramidal symptoms?

A. Procyclidine
B. Metoclopramide
C. Haloperidol
D. Trihexyphenidyl (Correct Answer)

Explanation: ### Explanation **Correct Answer: D. Trihexyphenidyl** **Mechanism and Rationale:** Extrapyramidal symptoms (EPS)—such as acute dystonia, parkinsonism, and akathisia—are primarily caused by a blockade of dopamine ($D_2$) receptors in the nigrostriatal pathway. This leads to a relative **excess of cholinergic activity**. Anticholinergic drugs restore the dopaminergic-cholinergic balance. **Trihexyphenidyl (Benzhexol)** is a potent centrally acting anticholinergic and is considered the first-line treatment for drug-induced parkinsonism and acute dystonia. **Analysis of Options:** * **A. Procyclidine:** While also an anticholinergic used for EPS, Trihexyphenidyl is more frequently cited in standard textbooks and clinical practice as the "best" or most common initial choice for long-term management of EPS in the Indian context. * **B. Metoclopramide:** This is a dopamine antagonist used as an antiemetic. It is a **cause** of EPS, not a treatment. * **C. Haloperidol:** This is a high-potency typical antipsychotic. It is one of the most common culprits for **inducing** EPS due to its strong $D_2$ receptor antagonism. **NEET-PG High-Yield Pearls:** * **Acute Dystonia:** The earliest EPS to appear (within hours/days). Treatment of choice: Intravenous/Intramuscular Promethazine or Benztropine. * **Akathisia:** The most common EPS. Treatment of choice: **Propranolol** (Beta-blocker). * **Tardive Dyskinesia:** Occurs after long-term use. Characterized by orofacial dyskinesia. Anticholinergics like Trihexyphenidyl can **worsen** this condition. Treatment: Switching to Clozapine or using VMAT2 inhibitors (Valbenazine). * **Drug of choice for Neuroleptic Malignant Syndrome (NMS):** Dantrolene or Bromocriptine.

Question 220: What is the drug of choice for bipolar disorder?

A. Lithium (Correct Answer)
B. Imipramine
C. Phenytoin
D. Clozapine

Explanation: **Explanation:** **Lithium (Option A)** is the gold-standard treatment and the **drug of choice for Bipolar Disorder (Bipolar Affective Disorder - BPAD)**. It is effective for treating acute manic episodes and serves as the primary maintenance therapy to prevent both manic and depressive relapses. Its unique clinical value lies in its proven **anti-suicidal properties**, a high-yield fact for NEET-PG. Lithium works by modulating second messenger systems (inhibiting inositol monophosphatase) and stabilizing neuronal membranes. **Why other options are incorrect:** * **Imipramine (Option B):** This is a Tricyclic Antidepressant (TCA). While it treats depression, using it in bipolar patients can trigger a "switch" into acute mania. * **Phenytoin (Option C):** Although an anticonvulsant, it has no role in mood stabilization. Other anticonvulsants like Valproate, Carbamazepine, and Lamotrigine are used in BPAD, but Lithium remains the first-line choice. * **Clozapine (Option D):** An atypical antipsychotic reserved for treatment-resistant schizophrenia. While some antipsychotics (like Olanzapine) are used in mania, Clozapine is not the first-line drug for BPAD. **High-Yield Clinical Pearls for NEET-PG:** * **Therapeutic Index:** Lithium has a narrow therapeutic index. Target serum levels: **0.8–1.2 mEq/L** (Acute Mania) and **0.6–0.8 mEq/L** (Maintenance). * **Teratogenicity:** Use in pregnancy is associated with **Ebstein’s Anomaly** (atrialization of the right ventricle). * **Side Effects:** Common ones include fine tremors, polyuria (nephrogenic diabetes insipidus), hypothyroidism, and weight gain. * **Drug of Choice for Rapid Cyclers:** Valproate (not Lithium).

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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