Implementation of Pharmacogenomics in Clinical Practice — MCQs

10 questions

The risk of carbamazepine-induced Stevens-Johnson syndrome is increased in the presence of which of the following genes?

Which of the following is not considered a pharmacogenetic condition?

Which of the following is used to detect abnormal gene sequences EXCEPT?

A patient with history of ischemic stroke was started on clopidogrel. However, she had another attack of stroke after 6 months. Which of the following is likely to be responsible for the failure of clopidogrel in this patient?

A 75-year-old male on warfarin is prescribed an antibiotic for pneumonia. Which antibiotic requires INR monitoring due to increased bleeding risk?

Which of the following statements about phase IV clinical trials is correct?

Provision of the Mental Health Act 2017, based on WHO guidelines, includes all, except:

Which of the following conditions is least likely to present with polyarticular involvement in clinical practice?

Q10

Which of the following statements are correct regarding audit in Obstetrics and Gynaecology? I. It can replace the out of date clinical practices with better ones. II. It is an efficient educational tool. III. It should be based on scientific evidences with facts and figures. IV. It is not labour-intensive. Select the answer using the code given below :

Implementation of Pharmacogenomics in Clinical Practice Indian Medical PG Practice Questions and MCQs

Question 1: 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 2: Which of the following is not considered a pharmacogenetic condition?

A. Adenosine deaminase deficiency (Correct Answer)
B. Coumarin insensitivity
C. G6PD deficiency
D. Malignant hyperthermia

Explanation: ***Adenosine deaminase deficiency*** - **Adenosine deaminase deficiency** (ADA deficiency) is an **autosomal recessive** metabolic disorder causing severe immunodeficiency, primarily affecting gene function rather than drug response. - While it can be treated with enzyme replacement therapies or gene therapy, it is not primarily characterized by an altered response to standard therapeutic drugs. *Coumarin insensitivity* - **Coumarin insensitivity** refers to an individual's reduced response to **warfarin (a coumarin derivative)**, requiring higher doses to achieve effective anticoagulation. - This is a well-documented **pharmacogenetic condition**, often linked to variations in genes like *CYP2C9* and *VKORC1*. *G6PD deficiency* - **Glucose-6-phosphate dehydrogenase (G6PD) deficiency** is an X-linked genetic disorder that can lead to **hemolytic anemia** upon exposure to certain drugs (e.g., antimalarials, sulfonamides, aspirin) and fava beans [1]. - It is a classic example of a **pharmacogenetic condition** where genetic variations dictate drug-induced adverse reactions [1]. *Malignant hyperthermia* - **Malignant hyperthermia** is a life-threatening, inherited disorder triggered by certain **inhalation anesthetics** (e.g., halothane, isoflurane) and the **depolarizing muscle relaxant succinylcholine**. - This condition is caused by mutations in genes involved in calcium regulation in muscle cells (e.g., *RYR1*) and is a critical **pharmacogenetic response**.

Question 3: Which of the following is used to detect abnormal gene sequences EXCEPT?

A. RFLP analysis
B. Pyrosequencing
C. Flow cytometry (Correct Answer)
D. FISH

Explanation: ***Flow cytometry*** - **Flow cytometry** is primarily used to analyze **cell populations** based on their physical and biochemical characteristics (e.g., size, granularity, and protein expression) by passing them single file through a laser beam, not for direct gene sequencing. - It detects and quantifies cells labeled with **fluorescent antibodies**, making it useful for immunophenotyping, cell sorting, and DNA content analysis, but not for identifying specific gene sequences or mutations. *RFLP analysis* - **Restriction fragment length polymorphism (RFLP) analysis** detects variations in **DNA sequences** by using **restriction enzymes** to cut DNA at specific sites. - Differences in fragment lengths indicate **polymorphisms** or **mutations** within the recognition sites, thereby identifying abnormal gene sequences. *Pyrosequencing* - **Pyrosequencing** is a method of **DNA sequencing** that determines the sequence of nucleotides by detecting the release of pyrophosphate during DNA synthesis. - It is used to identify **single nucleotide polymorphisms (SNPs)** and **short genetic variations**, making it suitable for detecting abnormal gene sequences. *FISH* - **Fluorescence in situ hybridization (FISH)** uses **fluorescently labeled DNA probes** that bind to specific complementary **DNA sequences** on chromosomes. - It is a powerful cytogenetic technique for detecting **chromosomal abnormalities**, such as deletions, translocations, and amplifications, thereby identifying abnormal gene sequences.

Question 4: A patient with history of ischemic stroke was started on clopidogrel. However, she had another attack of stroke after 6 months. Which of the following is likely to be responsible for the failure of clopidogrel in this patient?

A. Upregulation of CYP1A1
B. Downregulation of CYP2E1
C. Downregulation of CYP2C19 (Correct Answer)
D. Downregulation of CYP2D6

Explanation: ***Reduced function/Loss of function of CYP2C19*** - **Clopidogrel** is a **prodrug** that requires activation by **hepatic cytochrome P450 (CYP) enzymes**, primarily **CYP2C19**, to its active metabolite. - **Genetic polymorphisms** causing **reduced function or loss of function of CYP2C19** (e.g., CYP2C19*2, *3 alleles) result in insufficient conversion of clopidogrel to its active form, leading to **clopidogrel resistance** and increased risk of thrombotic events like recurrent stroke. - These **poor metabolizers** have significantly reduced antiplatelet response to standard clopidogrel doses. *Upregulation of CYP1A1* - **CYP1A1** is involved in the metabolism of various xenobiotics but plays a **minimal role** in clopidogrel activation. - Upregulation of CYP1A1 would not be a primary factor in clopidogrel failure as it is not the main enzyme responsible for its bioactivation. *Downregulation of CYP2E1* - **CYP2E1** is primarily involved in the metabolism of small organic molecules, some drugs, and toxins, and has **no significant role** in the bioactivation of clopidogrel. - Therefore, changes in its expression would not impact clopidogrel's efficacy. *Downregulation of CYP2D6* - **CYP2D6** is a major enzyme involved in the metabolism of many psychoactive drugs, beta-blockers, and opioids, but plays only a **minor role** in clopidogrel activation compared to CYP2C19. - Downregulation of CYP2D6 would not be the primary cause of clopidogrel failure.

Question 5: A 75-year-old male on warfarin is prescribed an antibiotic for pneumonia. Which antibiotic requires INR monitoring due to increased bleeding risk?

A. Ciprofloxacin (Correct Answer)
B. Amoxicillin
C. Clindamycin
D. Azithromycin

Explanation: ***Ciprofloxacin*** - **Ciprofloxacin** and other fluoroquinolones can interact with **warfarin**, though the mechanism is **not well-established** and likely multifactorial (may involve gut flora disruption, protein binding displacement, or metabolic effects). - This interaction can lead to **increased INR** and bleeding risk, requiring close monitoring. - Among fluoroquinolones, the interaction is **less predictable** compared to some other antibiotics. *Amoxicillin* - **Amoxicillin** and other beta-lactam antibiotics can interact with warfarin through **gut flora disruption**, reducing vitamin K synthesis. - This can lead to increased INR, though the effect is generally **mild to moderate**. - Routine INR monitoring is typically sufficient without intensive monitoring. *Clindamycin* - **Clindamycin** has **minimal documented interaction** with warfarin. - It does not significantly affect warfarin metabolism or vitamin K synthesis. - Generally considered a **safer option** for patients on warfarin therapy. *Azithromycin* - **Azithromycin** is well-documented to **significantly increase INR** and bleeding risk in patients on warfarin. - The mechanism may involve **CYP3A4 effects** and other pharmacokinetic interactions. - **FDA warnings exist** regarding this interaction, and close INR monitoring is essential. - Note: While this option is also clinically significant, the question focuses on identifying ONE antibiotic requiring monitoring, with ciprofloxacin being the presented answer in this educational context.

Question 6: Which of the following statements about phase IV clinical trials is correct?

A. It is primarily focused on the efficacy of the drug.
B. It involves monitoring the long-term effects and safety of drugs. (Correct Answer)
C. It is conducted before a drug is submitted for approval.
D. It focuses primarily on determining the optimal dosage for patients.

Explanation: ***It involves monitoring the long-term effects and safety of drugs.*** - **Phase IV clinical trials** are conducted **after a drug has been approved and marketed** to monitor its performance in the general population. - The primary goals include assessing the **long-term safety profile**, identifying rare adverse effects, and evaluating effectiveness under real-world conditions. *It is primarily focused on the efficacy of the drug.* - The primary focus on **drug efficacy** is typically addressed in **Phase II and Phase III clinical trials**, where controlled studies evaluate if the drug works as intended. - While efficacy is re-evaluated in real-world settings during Phase IV, it's not the primary or exclusive focus, which broadens to safety and comparative effectiveness. *It is conducted before a drug is submitted for approval.* - Trials conducted **before drug submission for approval** are typically **Phase I, Phase II, and Phase III clinical trials**, which are designed to establish safety, dosage, and initial efficacy. - **Phase IV trials** specifically begin **after a drug has received regulatory approval** and is available to the public. *It focuses primarily on determining the optimal dosage for patients.* - **Optimal dosage determination** is largely the domain of **Phase I and Phase II clinical trials**, where escalating doses are tested in small groups to identify a safe and effective range. - Phase IV studies might explore different dosing regimens in specific patient populations, but they do not primarily determine initial optimal dosing.

Question 7: Match the following drugs in Column A with their contraindications in Column B. | Column A | Column B | | :-- | :-- | | 1. Morphine | 1. QT prolongation | | 2. Amiodarone | 2. Thromboembolism | | 3. Vigabatrin | 3. Pregnancy | | 4. Estrogen preparations | 4. Head injury |

A. A-1, B-3, C-2, D-4
B. A-4, B-1, C-3, D-2 (Correct Answer)
C. A-3, B-2, C-4, D-1
D. A-2, B-4, C-1, D-3

Explanation: ***A-4, B-1, C-3, D-2*** - **Morphine** is contraindicated in **head injury** as it can increase intracranial pressure and mask neurological symptoms. - **Amiodarone** is contraindicated in patients with **QT prolongation** due to its risk of inducing more severe arrhythmias like Torsades de Pointes. - **Vigabatrin** is contraindicated during **pregnancy** due to its potential for teratogenicity and adverse effects on fetal development. - **Estrogen preparations** are contraindicated in patients with a history of **thromboembolism** due to their increased risk of blood clot formation. *A-1, B-3, C-2, D-4* - This option incorrectly matches **Morphine** with QT prolongation and **Estrogen preparations** with head injury, which are not their primary contraindications. - It also incorrectly links **Vigabatrin** with thromboembolism and **Amiodarone** with pregnancy. *A-3, B-2, C-4, D-1* - This choice incorrectly associates **Morphine** with pregnancy and **Vigabatrin** with head injury, which are not the most critical or direct contraindications. - It also misaligns **Amiodarone** with thromboembolism and **Estrogen preparations** with QT prolongation. *A-2, B-4, C-1, D-3* - This option incorrectly matches **Morphine** with thromboembolism and **Amiodarone** with head injury, which are not their most significant contraindications. - It also incorrectly links **Vigabatrin** with QT prolongation and **Estrogen preparations** with pregnancy.

Question 8: Provision of the Mental Health Act 2017, based on WHO guidelines, includes all, except:

A. Social support
B. Screening family members (Correct Answer)
C. Human rights
D. Communication regarding care and treatment

Explanation: ***Screening family members*** - The Mental Health Act 2017 focuses on the **rights, treatment, and support of individuals with mental illness**, not routine screening of their family members. - The Act does not contain provisions mandating **screening of asymptomatic family members**, though family history may be relevant for clinical assessment. - This is **not a provision** outlined in the Act based on WHO guidelines. *Human rights* - The Act is explicitly grounded in the **protection and promotion of human rights** for persons with mental illness (Chapter I). - Ensures care with **dignity, respect, and freedom from discrimination** as core principles. - Aligns with WHO's mental health action plan and human rights framework. *Communication regarding care and treatment* - **Section 4** emphasizes the right to information and **informed consent** for all treatment decisions. - Patients must receive clear communication about their **diagnosis, treatment options, and care plans**. - Includes provisions for **advance directives** and involvement in treatment decisions. *Social support* - **Chapter V** addresses rehabilitation and community-based services, emphasizing the role of **social support systems**. - Promotes **community integration** and access to social resources for recovery. - Recognizes family and community support as essential for long-term mental health management.

Question 9: Which of the following conditions is least likely to present with polyarticular involvement in clinical practice?

A. Psoriatic arthritis
B. SLE
C. Gout
D. Ankylosing spondylitis (Correct Answer)

Explanation: ***SLE*** - Systemic lupus erythematosus (SLE) is a **systemic autoimmune disease** and while it can present with polyarthritis, other systemic features also occur, making it less common in isolation [1]. - It encompasses a broad spectrum of **clinical manifestations**, often leading to multi-organ involvement beyond joint symptoms [1]. *Gout* - Usually triggers **acute inflammatory arthritis**, characterized by sudden and severe pain in a single joint, particularly the big toe [2]. - It is significantly common and frequently treated in clinical practice. *Ankylosing spondylitis* - Primarily affects the spine and sacroiliac joints, causing stiffness and is quite an **identifiable form of inflammatory arthritis** [3]. - It has a notable association with **HLA-B27** and can present with back pain, making it relatively common among spondyloarthropathies [3]. *Psoriatic arthritis* - Associated with **psoriasis**, this form of arthritis can occur and is known for **asymmetrical polyarthritis** and dactylitis [4]. - It is a recognized inflammatory condition that leads to joint destruction and is increasingly prevalent among patients with skin involvement [4].

Question 10: Which of the following statements are correct regarding audit in Obstetrics and Gynaecology? I. It can replace the out of date clinical practices with better ones. II. It is an efficient educational tool. III. It should be based on scientific evidences with facts and figures. IV. It is not labour-intensive. Select the answer using the code given below :

A. I, II and IV
B. I, II and III (Correct Answer)
C. I, III and IV
D. II, III and IV

Explanation: ***Correct: I, II and III*** - Statement I is correct: Clinical audit aims to improve **patient care** and **outcomes** by systematically reviewing care against explicit criteria, identifying areas for improvement, and implementing changes that **replace outdated practices** with evidence-based approaches. - Statement II is correct: Audit serves as a powerful **educational tool** by providing feedback to clinicians, highlighting best practices, and encouraging critical appraisal of current methods. - Statement III is correct: Effective audits must be based on **scientific evidence** with facts and figures to ensure validity, robustness, and clinical relevance. - Statement IV is **incorrect**: Clinical audit is **labour-intensive**, requiring significant time, resources, and coordination for data collection, analysis, meetings, implementation of changes, and follow-up assessments. *Incorrect: I, II and IV* - While statements I and II are correct, statement IV is incorrect because audit is generally **labour-intensive**, not the opposite. Effective audits involve substantial resource-demanding tasks. *Incorrect: I, III and IV* - While statements I and III are correct (audit replaces outdated practices with evidence-based approaches), statement IV is incorrect as thorough audits require **considerable effort and resources**. *Incorrect: II, III and IV* - While statements II and III are correct (audit as educational tool based on scientific evidence), statement IV is incorrect; audits often require **substantial time and effort** for all phases of the audit cycle.

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