Pharmacogenomics in Psychiatry — MCQs
Pharmacodynamics deals with:-
The risk of carbamazepine-induced Stevens-Johnson syndrome is increased in the presence of which of the following genes?
Maximum increase in prolactin level is caused by:-
Which of the following produces neuropsychiatric symptoms?
A patient on SSRI sertraline was also prescribed amitriptyline and subsequently developed serotonin toxicity. What is the likely treatment for serotonin toxicity?
Which of the following drugs is metabolized by CYP2D6?
Clozapine is used in:
Which antipsychotic has anti-suicidal properties?
What is the drug of choice for a schizophrenic patient with poor oral absorption?
Use of lithium in pregnancy can result in which of the following abnormalities in the baby?
Pharmacogenomics in Psychiatry Indian Medical PG Practice Questions and MCQs
Question 1: Pharmacodynamics deals with:-
- A. Latency of onset
- B. Mechanism of action of a drug (Correct Answer)
- C. Transport of drug across the biological membranes
- D. Mode of excretion of a drug
Explanation: Detailed study of the **Mechanism of action of a drug** [1][2] - **Pharmacodynamics** describes what the **drug does to the body**, including its **molecular targets** and biochemical effects [3]. - This involves the study of the drug's mechanisms to produce its therapeutic or toxic effects [2]. *Latency of onset* - **Latency of onset** refers to the time it takes for a drug to start producing its effects, which is a pharmacokinetic rather than a pharmacodynamic parameter. - It deals with the drug's absorption and distribution rather than its interaction with the body once it reaches its site of action. *Transport of drug across the biological membranes* - The **transport of drugs across biological membranes** is a key aspect of **pharmacokinetics**, specifically absorption and distribution [1]. - This process determines how much drug reaches its target site, not how it interacts with the target. *Mode of excretion of a drug* - The **mode of excretion** of a drug (e.g., renal, hepatic) falls under **pharmacokinetics**, addressing how the body gets rid of the drug. - This process influences the drug's duration of action and elimination half-life, not its mechanism of action.
Question 2: The risk of carbamazepine-induced Stevens-Johnson syndrome is increased in the presence of which of the following genes?
- A. HLA-B* 5801
- B. HLA-B* 1502 (Correct Answer)
- C. HLA-B* 5701
- D. HLA-B*27
Explanation: ***HLA-B\* 1502*** - The **HLA-B\*1502** allele is strongly associated with an increased risk of **carbamazepine-induced Stevens-Johnson syndrome (SJS)** and **toxic epidermal necrolysis (TEN)**, particularly in individuals of Asian ancestry. - Screening for this allele is often recommended before initiating **carbamazepine** in at-risk populations. *HLA-B\* 5801* - The **HLA-B\*5801** allele is associated with an increased risk of **allopurinol-induced severe cutaneous adverse reactions (SCARs)**, including SJS and TEN. - It is not directly linked to carbamazepine-induced SJS. *HLA-B\* 5701* - The **HLA-B\*5701** allele is strongly associated with a higher risk of **abacavir hypersensitivity reaction** [1]. - It is recommended to screen for this allele before starting abacavir therapy. *HLA-B 27* - **HLA-B27** is primarily associated with **seronegative spondyloarthropathies**, such as **ankylosing spondylitis** and **reactive arthritis**. - It does not have a known association with carbamazepine-induced SJS.
Question 3: Maximum increase in prolactin level is caused by:-
- A. Olanzapine (Primarily blocks 5HT2 receptors)
- B. Aripiprazole (D2 partial agonist)
- C. Risperidone (Potent D2 receptor antagonist) (Correct Answer)
- D. Clozapine (Primarily blocks 5HT2 receptors)
Explanation: ***Risperidone (Potent D2 receptor antagonist)*** - Risperidone is a **potent D2 receptor antagonist**, meaning it blocks dopamine's action at these receptors. Since dopamine inhibits prolactin release, blocking D2 receptors leads to a significant increase in **prolactin levels**. - Its high affinity for D2 receptors in the **tuberoinfundibular pathway** is a primary reason for its pronounced effect on prolactin. *Olanzapine (Primarily blocks 5HT2 receptors)* - While olanzapine can cause some prolactin elevation, its primary mechanism involves **5HT2 receptor blockade**, with less potent D2 antagonism compared to risperidone. - The degree of **hyperprolactinemia** associated with olanzapine is generally milder than that seen with risperidone. *Aripiprazole (D2 partial agonist)* - Aripiprazole is a **D2 partial agonist**, meaning it acts as an antagonist when dopamine levels are high and an agonist when dopamine levels are low, effectively stabilizing dopamine activity. - Due to its partial agonism, aripiprazole typically has a **low risk of hyperprolactinemia** and can even normalize elevated prolactin levels caused by other antipsychotics. *Clozapine (Primarily blocks 5HT2 receptors)* - Clozapine primarily blocks **5HT2 receptors** and has relatively weak D2 receptor antagonism, especially transient D2 blockade. - It generally causes **minimal to no prolactin elevation** and is considered a prolactin-sparing antipsychotic.
Question 4: Which of the following produces neuropsychiatric symptoms?
- A. Cephalosporin
- B. Ethambutol
- C. Cyclosporine
- D. Cycloserine (Correct Answer)
Explanation: ***Cycloserine*** - **Cycloserine** is an antimicrobial agent that can cause a wide array of neuropsychiatric symptoms, including **headache**, **anxiety**, **depression**, **psychosis**, **seizures**, and **peripheral neuropathy**. - Its mechanism of action involves interfering with cell wall synthesis, but it also crosses the **blood-brain barrier**, leading to central nervous system effects. *Cephalosporin* - While some **cephalosporins** (especially at high doses or in patients with renal impairment) can cause CNS effects like **seizures**, they are not typically associated with a broad range of neuropsychiatric symptoms to the same extent as cycloserine. - The primary side effects of cephalosporins are usually **gastrointestinal disturbances** and **allergic reactions**. *Ethambutol* - **Ethambutol** is known for its ocular toxicity, specifically **optic neuritis**, which can lead to reduced visual acuity and **color blindness**. - It does not typically cause the generalized neuropsychiatric symptoms seen with cycloserine. *Cyclosporine* - **Cyclosporine**, an immunosuppressant, can cause neurological side effects such as **tremor**, **headache**, and **seizures**, and rarely **posterior reversible encephalopathy syndrome (PRES)**. - However, it is not primarily associated with the broad spectrum of psychiatric symptoms like depression or psychosis, unlike cycloserine.
Question 5: A patient on SSRI sertraline was also prescribed amitriptyline and subsequently developed serotonin toxicity. What is the likely treatment for serotonin toxicity?
- A. Flumazenil
- B. Cyproheptadine (Correct Answer)
- C. L-Carnitine
- D. Leucovorin
- E. Naloxone
Explanation: ***Cyproheptadine*** - **Cyproheptadine** is a serotonin antagonist that can help reverse the effects of excessive serotonin in the central nervous system. - It works by blocking **serotonin 5-HT2A receptors**, which are implicated in the pathophysiology of serotonin toxicity. *Flumazenil* - **Flumazenil** is a benzodiazepine receptor antagonist used to reverse the effects of benzodiazepine overdose. - It has no role in the treatment of **serotonin toxicity**, as it does not affect serotonin pathways. *L-Carnitine* - **L-Carnitine** is a mitochondrial co-factor used in fatty acid metabolism, sometimes supplemented for certain metabolic disorders or muscle pain. - It does not have any direct action on **serotonin receptors** or the serotonin system, making it ineffective for serotonin toxicity. *Leucovorin* - **Leucovorin** (folinic acid) is used to counteract the effects of methotrexate toxicity or to enhance the effects of fluorouracil in chemotherapy. - It is not involved in modulating **neurotransmitter levels** or reversing the symptoms of serotonin toxicity. *Naloxone* - **Naloxone** is an opioid receptor antagonist used to reverse opioid overdose. - It has no effect on **serotonin receptors** or serotonergic pathways, making it ineffective for treating serotonin toxicity.
Question 6: Which of the following drugs is metabolized by CYP2D6?
- A. Propranolol (Correct Answer)
- B. Warfarin
- C. Statins
- D. Amiodarone
Explanation: ***Correct Answer: Propranolol*** - **Propranolol** is a non-selective beta-blocker that undergoes extensive **first-pass metabolism**, primarily via the **CYP2D6** and CYP1A2 enzymes. - Genetic variations in **CYP2D6** can significantly affect propranolol's metabolism, leading to altered drug levels and therapeutic responses. *Incorrect: Warfarin* - **Warfarin** is predominantly metabolized by **CYP2C9**, with minor contributions from other CYP enzymes. - Genetic polymorphisms in **CYP2C9** are a major factor in determining individual warfarin dose requirements. *Incorrect: Statins* - Most **statins** (e.g., simvastatin, lovastatin, atorvastatin) are primarily metabolized by **CYP3A4**. - **Fluvastatin** is an exception, being mainly metabolized by CYP2C9, while **rosuvastatin** is largely unmetabolized. *Incorrect: Amiodarone* - **Amiodarone** is primarily metabolized by **CYP3A4** and to a lesser extent by CYP2C8. - Due to its **long half-life** and extensive metabolism, amiodarone has numerous drug interactions, often involving CYP3A4 inhibition.
Question 7: Clozapine is used in:
- A. Depression
- B. Resistant schizophrenia (Correct Answer)
- C. Mania
- D. Delirium
Explanation: **Explanation:** **Clozapine** is an atypical (second-generation) antipsychotic and is considered the **gold standard** for the management of **Treatment-Resistant Schizophrenia (TRS)**. 1. **Why Option B is Correct:** Resistance in schizophrenia is defined as a lack of satisfactory clinical improvement despite the use of adequate doses of at least two different antipsychotics (including one atypical) for a duration of 6–8 weeks each. Clozapine is uniquely effective in these cases due to its complex receptor profile (low D2 affinity, high 5-HT2A, D4, and alpha-adrenergic blockade). It is the only antipsychotic proven to reduce suicidal behavior in schizophrenic patients. 2. **Why Other Options are Incorrect:** * **A. Depression:** First-line treatments are SSRIs/SNRIs. While some atypicals (like Quetiapine or Aripiprazole) are used as adjuncts in resistant depression, Clozapine is not used due to its side-effect profile. * **C. Mania:** Acute mania is treated with Lithium, Valproate, or standard antipsychotics (e.g., Olanzapine, Risperidone). Clozapine is reserved only for ultra-resistant cases, not as a standard indication. * **D. Delirium:** Low-dose Haloperidol is the drug of choice. Clozapine is contraindicated in delirium because its strong anticholinergic properties can worsen the confusional state. **High-Yield Clinical Pearls for NEET-PG:** * **Agranulocytosis:** The most dreaded side effect (occurs in ~1%). Mandatory **WBC monitoring** is required (weekly for the first 6 months). * **Seizures:** Clozapine carries a dose-dependent risk of seizures. * **Sialorrhea:** Paradoxical hypersalivation is a common, bothersome side effect. * **Myocarditis:** A rare but fatal side effect; monitor for tachycardia and chest pain. * **Metabolic Syndrome:** High risk of weight gain and diabetes (similar to Olanzapine).
Question 8: Which antipsychotic has anti-suicidal properties?
- A. clozapine (Correct Answer)
- B. chlorpromazine
- C. aripiprazole
- D. amisulpride
Explanation: **Explanation:** **Clozapine** is the correct answer because it is the only antipsychotic with a specifically FDA-approved indication for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. This anti-suicidal effect is independent of its primary antipsychotic action and is believed to be mediated by its unique modulation of serotonergic (5-HT2A) and noradrenergic systems, which helps reduce impulsivity and aggression. **Analysis of Incorrect Options:** * **B. Chlorpromazine:** A typical (first-generation) antipsychotic primarily used for acute psychosis. While it treats positive symptoms, it has no proven specific anti-suicidal properties and may even worsen depressive symptoms in some patients. * **C. Aripiprazole:** A partial dopamine agonist. While effective for mood stabilization and augmentation in depression, it does not carry a specific indication for suicide prevention. * **D. Amisulpride:** A substituted benzamide that is effective for both positive and negative symptoms of schizophrenia, but lacks evidence for a direct anti-suicidal effect. **High-Yield Clinical Pearls for NEET-PG:** * **The "Rule of Two":** There are two main drugs in psychiatry known for reducing suicide risk: **Clozapine** (in Schizophrenia) and **Lithium** (in Bipolar Disorder). * **Clozapine Monitoring:** Due to the risk of **agranulocytosis**, regular monitoring of Absolute Neutrophil Count (ANC) is mandatory. * **Other Side Effects:** Clozapine is associated with the highest risk of seizures (dose-dependent), sialorrhea (drooling), myocarditis, and metabolic syndrome among antipsychotics. * **Indication:** It remains the gold standard for **Treatment-Resistant Schizophrenia** (defined as failure of two adequate trials of other antipsychotics).
Question 9: What is the drug of choice for a schizophrenic patient with poor oral absorption?
- A. Haloperidol
- B. Fluphenazine
- C. Clozapine (Correct Answer)
- D. Olanzapine
Explanation: ### Explanation **Correct Option: C. Clozapine** The core concept here is the **pharmacokinetic profile** of antipsychotics. Clozapine is unique because it undergoes extensive first-pass metabolism, but more importantly, it is the only antipsychotic where **therapeutic drug monitoring (TDM)** is frequently used to overcome absorption issues or treatment resistance. In clinical scenarios involving "poor oral absorption" (often due to gastrointestinal issues or high first-pass effect), Clozapine remains the **Drug of Choice (DOC) for treatment-resistant schizophrenia**. While other drugs have parenteral formulations, Clozapine is the gold standard for patients who fail to respond to standard therapy, which often includes those with metabolic or absorption variations that render other oral medications ineffective. **Analysis of Incorrect Options:** * **A & B (Haloperidol & Fluphenazine):** These are typical antipsychotics. While they are available as long-acting decanoate injections (useful for poor *compliance*), they are not specifically indicated for poor *absorption* over Clozapine in a refractory context. * **D. Olanzapine:** An atypical antipsychotic similar to Clozapine but lacks the same level of efficacy in treatment-resistant cases. It is often a second-line choice but does not supersede Clozapine for complex absorption/resistance profiles. **High-Yield Clinical Pearls for NEET-PG:** * **Clozapine Indications:** Treatment-resistant schizophrenia (failed 2+ antipsychotics) and reducing suicidal behavior in schizophrenia. * **Adverse Effects:** Agranulocytosis (requires mandatory ANC monitoring), seizures (dose-dependent), myocarditis, and sialorrhea (hypersalivation). * **Lacks Extrapyramidal Symptoms (EPS):** Clozapine has the lowest risk of EPS and tardive dyskinesia among all antipsychotics. * **Metabolic Syndrome:** Both Clozapine and Olanzapine carry the highest risk of weight gain and diabetes.
Question 10: Use of lithium in pregnancy can result in which of the following abnormalities in the baby?
- A. Anencephaly
- B. Ebstein's anomaly (Correct Answer)
- C. Caudal dysgenesis syndrome
- D. Elfin facies
Explanation: **Explanation:** The correct answer is **Ebstein’s anomaly**. Lithium is a mood stabilizer used primarily for Bipolar Disorder. When taken during the first trimester of pregnancy, it acts as a teratogen, specifically affecting cardiac development. **1. Why Ebstein’s Anomaly is Correct:** Ebstein’s anomaly is a rare congenital heart defect characterized by the **downward displacement of the tricuspid valve** leaflets into the right ventricle ("atrialization" of the right ventricle). While the absolute risk remains low (approx. 1 in 1,000 to 2,000 exposures), it represents a significant increase compared to the general population. **2. Analysis of Incorrect Options:** * **Anencephaly:** This is a neural tube defect (NTD). NTDs are more commonly associated with **Valproate** or Carbamazepine use during pregnancy, not Lithium. * **Caudal dysgenesis syndrome:** This is a rare malformation (sacral agenesis) highly specific to **maternal diabetes mellitus**. * **Elfin facies:** This facial phenotype (along with hypercalcemia and supravalvular aortic stenosis) is characteristic of **Williams Syndrome**, a genetic deletion on chromosome 7. **Clinical Pearls for NEET-PG:** * **Monitoring:** If a pregnant woman must continue Lithium, fetal echocardiography is recommended at 18–22 weeks. * **Dosage:** Lithium clearance increases during pregnancy (due to increased GFR) and drops abruptly at delivery; close serum monitoring is vital to avoid toxicity. * **Breastfeeding:** Lithium is generally discouraged during breastfeeding as it is excreted in milk and can cause "Floppy Baby Syndrome" (hypotonia, cyanosis). * **Alternative:** Lamotrigine is often considered a safer mood stabilizer during pregnancy regarding structural malformations.
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