Pharmacogenomics

Pharmacogenomics Indian Medical PG Question 1: Match List-I with List-II and select the correct answer using the code given below the Lists:

• A. A→4 B→3 C→1 D→2
• B. A→4 B→2 C→3 D→1
• C. A→3 B→4 C→1 D→2
• D. A→4 B→1 C→3 D→2 (Correct Answer)

Pharmacogenomics Explanation: **A→4 B→1 C→3 D→2** - This option correctly matches each endocrine gland with its primary hormone: the **pineal gland** produces **melatonin**, the **testis** produces **testosterone**, the **adrenal gland** produces **cortisol**, and the **ovary** produces **estrogen**. - These pairings are fundamental to understanding the basic functions of the endocrine system. *A→4 B→3 C→1 D→2* - This option incorrectly matches the **testis** with **cortisol** (should be testosterone) and the **adrenal gland** with **melatonin** (should be cortisol). - Cortisol is a steroid hormone produced by the adrenal cortex, while melatonin from the pineal gland regulates sleep-wake cycles. *A→4 B→2 C→3 D→1* - This option incorrectly matches the **testis** with **estrogen** (should be testosterone) and the **ovary** with **melatonin** (should be estrogen). - Estrogen is the primary female sex hormone, while testosterone is the primary male sex hormone. *A→3 B→4 C→1 D→2* - This option incorrectly matches the **pineal gland** with **cortisol** (should be melatonin) and the **testis** with **estrogen** (should be testosterone). - The pineal gland is known for its role in circadian rhythms through melatonin production, not stress response hormones like cortisol.

Pharmacogenomics Indian Medical PG Question 2: An SSRI antidepressant, such as fluoxetine, will be prescribed for an adult patient. You should advise him or her that two of the most likely side effects or adverse responses that may eventually occur at therapeutic blood levels are which of the following?

• A. Sexual dysfunction and sleep disturbances (Correct Answer)
• B. Sexual dysfunction and nausea
• C. Headache and diarrhea
• D. Tremor and weight gain

Pharmacogenomics Explanation: ***Sexual dysfunction and sleep disturbances*** - **Sexual dysfunction** is one of the most common and persistent adverse effects of SSRIs, affecting 40-65% of patients and continuing throughout treatment at therapeutic levels [2], [3]. - **Sleep disturbances** (insomnia or altered sleep architecture) can persist during long-term SSRI therapy and are among the eventual side effects patients experience [1], [2], [3]. - Both effects are characteristic of chronic SSRI use and significantly impact patient compliance and quality of life. *Sexual dysfunction and nausea* - While **sexual dysfunction** is indeed very common and persistent, **nausea** is typically a transient side effect that occurs during the first 1-2 weeks of treatment and usually resolves with continued use [2]. - The question specifically asks about *eventual* occurrence at therapeutic levels over time, making nausea less appropriate as it is not a chronic issue. *Tremor and weight gain* - **Tremor** is not among the most common side effects of SSRIs and occurs less frequently than sexual dysfunction or sleep disturbances. - **Weight gain** can occur with some SSRIs (particularly paroxetine), but fluoxetine is actually considered weight-neutral or may even cause weight loss in some patients, making this combination less likely for fluoxetine specifically [1]. *Headache and diarrhea* - Both **headache** and **diarrhea** are common initial side effects when starting SSRIs but typically improve or resolve within the first few weeks of treatment [1]. - These are transient effects rather than eventual persistent side effects that characterize long-term therapeutic use.

Pharmacogenomics Indian Medical PG Question 3: Which of the following attributes are essential for an ideal screening test?

• A. Safe
• B. Reliable
• C. Valid
• D. All of the options (Correct Answer)

Pharmacogenomics Explanation: ***All of the options*** - An ideal screening test must possess **all three essential attributes**: safety, reliability, and validity. - **Safe**: Minimizes harm to participants and ensures ethical implementation - **Reliable**: Produces consistent, reproducible results with minimal random error - **Valid**: Accurately measures what it intends to measure (high sensitivity and specificity) - These three attributes work together as fundamental requirements for any effective screening program, ensuring that early detection benefits outweigh potential risks. *Safe (alone)* - While safety is absolutely essential, it is **not sufficient by itself** to make an ideal screening test. - A test that is safe but unreliable or invalid would produce inconsistent or inaccurate results, rendering it ineffective for screening purposes. *Reliable (alone)* - Reliability ensures consistent results, which is crucial, but **reliability alone is insufficient**. - A test can be highly reliable (consistently giving the same result) yet completely invalid if it measures the wrong thing or is unsafe. *Valid (alone)* - Validity is critical for accurate measurement, but **validity alone does not make a test ideal**. - Even a valid test must be safe to protect participants and reliable to ensure consistency across different settings and times.

Pharmacogenomics Indian Medical PG Question 4: 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

Pharmacogenomics 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.

Pharmacogenomics Indian Medical PG Question 5: Choose the correct options regarding the route of administration and bioavailability. A- Intravenous =1 B- 0.75< Oral <1 C-0.75 <IM ≤ 1 D- 0.75<SC ≤ 1 IM - Intramuscular SC- Subcutaneous

• A. A and D
• B. A and C
• C. A, C, D (Correct Answer)
• D. A, B, D

Pharmacogenomics Explanation: ***A, C, D*** - Intravenous (IV) administration has **100% bioavailability** because the drug enters the systemic circulation directly, bypassing any absorption barriers. - Intramuscular (IM) and subcutaneous (SC) routes generally have **high bioavailability**, often between 75% and 100%, as drugs are absorbed directly into the bloodstream without first-pass metabolism. *A and D* - While options A and D are correct, this choice is incomplete as option C is also a correct statement regarding bioavailability. - IM administration typically results in high systemic bioavailability, similar to SC, making its exclusion here incorrect. *A and C* - While options A and C are correct, this choice is incomplete as option D is also a correct statement regarding bioavailability. - Subcutaneous administration also generally results in high bioavailability, as absorption tends to be complete. *A, B, D* - While options A and D are correct, option B is typically incorrect for oral bioavailability. - Oral bioavailability of many drugs is often less than 0.75 (75%) due to factors like **first-pass metabolism** and incomplete absorption in the gastrointestinal tract.

Pharmacogenomics Flashcard 1 of 5

Question: _____ is a urinary antiseptic that can trigger hemolysis in G6PD deficiency patients.

Answer: Nitrofurantoin

Pharmacogenomics Flashcard 2 of 5

Question: Drug induced lupus may be caused by _____ acetylation of Isoniazid by NAT-2

Answer: impaired

Pharmacogenomics Flashcard 3 of 5

Question: _____ is the MC gene responsible for isoniazid resistance

Answer: Kat G

Extra Information: 

Pharmacogenomics Flashcard 4 of 5

Question: Metabolism of warfarin is affected by polymorphisms in the genes for _____ and CYP2C9 (p450 enzyme which metabolizes warfarin)

Answer: vitamin K epoxide reductase complex (VKORC1)

Pharmacogenomics Flashcard 5 of 5

Question: Which antimalarials (4) can cause hemolysis in G6PD?_____, Artesunate, Dapsone, Quinidine

Answer: Primaquine