Pharmacogenomics Practice Questions

Q: Which HLA gene is associated with abacavir hypersensitivity?

B57. **Explanation:** **Correct Option: D (HLA-B*57:01)** Abacavir is a Nucleoside Reverse Transcriptase Inhibitor (NRTI) used in HIV treatment. Approximately 5–8% of patients develop a potentially fatal **Abacavir Hypersensitivity Syndrome (AHS)**, characterized by fever, rash, and gastrointestinal symptoms. This reaction is strongly associated with the **HLA-B*57:01** allele. The drug binds to the antigen-binding cleft of this specific HLA molecule, altering the repertoire of self-peptides presented to T-cells, which triggers an autoimmune-like systemic inflammatory response. Screening for this allele is mandatory before initiating abacavir to prevent AHS. **Incorrect Options:** * **A (B5):** This is a broad serotype that includes B51 and B52 but is not specifically linked to abacavir. * **B (B51):** This allele is the classic genetic marker associated with **Behçet’s Disease** (characterized by oral/genital ulcers and uveitis). * **C (DQ2):** This is an HLA Class II allele strongly associated with **Celiac Disease** (along with HLA-DQ8). **High-Yield Clinical Pearls for NEET-PG:** 1. **Mandatory Screening:** If a patient tests positive for HLA-B*57:01, Abacavir is strictly **contraindicated** and should be listed as an allergy in their records. 2. **Re-challenge Warning:** Never re-challenge a patient with abacavir if AHS is suspected; it can lead to rapid, fatal hypotension and multi-organ failure. 3. **Other HLA-Drug Associations:** * **HLA-B*15:02:** Carbamazepine-induced Stevens-Johnson Syndrome (SJS) (especially in Asians). * **HLA-B*58:01:** Allopurinol-induced severe cutaneous adverse reactions (SCAR).

Q: Which of the following does not cause hemolysis in G6PD deficiency?

Estrogen. ### Explanation **Concept Overview:** Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is an X-linked recessive disorder where RBCs lack the enzyme necessary to maintain levels of reduced glutathione. Reduced glutathione is essential for neutralizing reactive oxygen species (ROS). When patients are exposed to oxidative stress (drugs, infections, or fava beans), hemoglobin denatures into **Heinz bodies**, leading to hemolysis. **Why Estrogen is the Correct Answer:** * **Estrogen (Option A):** Estrogen and other hormonal preparations (like oral contraceptives) do not possess oxidative properties and do not interfere with the pentose phosphate pathway. Therefore, they do not trigger hemolytic episodes in G6PD-deficient individuals. **Why the Other Options are Incorrect:** * **Primaquine (Option C):** This is the classic "prototype" drug that causes hemolysis. It is an antimalarial that generates significant oxidative stress. Testing for G6PD deficiency is mandatory before prescribing Primaquine. * **Nitrofurantoin (Option D):** A common urinary antiseptic that undergoes redox cycling, producing superoxide radicals that overwhelm the limited antioxidant capacity of G6PD-deficient cells. * **Salicylates (Option B):** High doses of aspirin or salicylates can induce oxidative damage to RBC membranes, though they are considered "low-risk" compared to Primaquine, they are still documented triggers. **NEET-PG High-Yield Pearls:** * **Mnemonic for G6PD Triggers:** "**S**ell **P**ie **N**ow" (**S**ulfonamides/Salicylates, **P**rimaquine, **N**itrofurantoin). * **Peripheral Smear Findings:** Look for **Heinz Bodies** (denatured Hb) and **Bite Cells** (deformed RBCs after splenic macrophages remove Heinz bodies). * **Other Triggers:** Dapsone, Chloroquine, Rasburicase, and Fava beans (Favism). * **Inheritance:** X-linked recessive; more common in males of Mediterranean or African descent.

Q: All of the following drugs cause hemolysis in G-6PD deficiency except?

Erythromycin. ### Explanation **Concept Overview:** Glucose-6-Phosphate Dehydrogenase (G6PD) is a critical enzyme in the pentose phosphate pathway that maintains the supply of **reduced glutathione**. This molecule protects red blood cells (RBCs) from oxidative stress. In G6PD deficiency, exposure to oxidizing agents leads to the denaturation of hemoglobin (forming **Heinz bodies**) and subsequent hemolysis. **Why Erythromycin is the Correct Answer:** **Erythromycin** is a macrolide antibiotic that does not possess significant oxidizing properties. It is considered safe to use in patients with G6PD deficiency. It does not interfere with the redox state of the erythrocyte or trigger the destruction of RBCs. **Analysis of Incorrect Options:** * **Primaquine:** This is the classic "textbook" trigger. It is an antimalarial that generates reactive oxygen species (ROS), causing severe hemolysis in G6PD-deficient individuals. * **Nitrofurantoin:** A urinary antiseptic known to cause oxidative stress. It is strictly contraindicated in G6PD-deficient patients due to the high risk of hemolytic anemia. * **Sulfonamides (e.g., Sulfamethoxazole):** These drugs act as oxidizing agents. They are well-documented triggers for hemolytic crises in affected patients. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** G6PD deficiency is an **X-linked recessive** disorder (more common in males). * **Peripheral Smear Findings:** Look for **Heinz bodies** (denatured hemoglobin) and **Bite cells** (degmacytes) formed by splenic macrophages removing these bodies. * **Other Common Triggers:** Dapsone, Rasburicase, Methylene blue, and **Fava beans** (Favism). * **Safe Alternatives:** Penicillins, Cephalosporins, and Macrolides (like Erythromycin) are generally safe. * **Key Contraindication:** Never give **Primaquine** without first screening the patient for G6PD levels.

Q: Therapeutic drug monitoring is used in which of the following medications?

Digoxin. **Explanation:** **Therapeutic Drug Monitoring (TDM)** is the clinical practice of measuring drug concentrations in the blood to maintain a constant concentration within a specific **therapeutic window**. It is primarily indicated for drugs with a **narrow therapeutic index**, where the difference between the effective dose and the toxic dose is minimal. **Why Digoxin is the Correct Answer:** Digoxin has a very narrow therapeutic index (typically **0.5–2.0 ng/mL**). Small fluctuations in serum levels can lead to life-threatening toxicity (arrhythmias, xanthopsia, or gastrointestinal distress). Factors like renal impairment, hypokalemia, and drug interactions (e.g., with Amiodarone or Verapamil) significantly alter its pharmacokinetics, making TDM essential for safety and efficacy. **Why Other Options are Incorrect:** * **A. Diuretics:** Their effect is easily monitored clinically by measuring urine output, body weight, blood pressure, and serum electrolytes. * **B. Metformin:** Its efficacy is monitored by measuring clinical markers like blood glucose levels and HbA1c, rather than plasma drug concentrations. * **C. Levodopa:** The clinical response (improvement in Parkinsonian symptoms) and the appearance of side effects (dyskinesia) are used to titrate the dose. **High-Yield Clinical Pearls for NEET-PG:** * **Indications for TDM:** Remember the mnemonic **"THEAL"** – **T**ricyclic antidepressants, **H**eart meds (Digoxin, Quinidine), **E**pilepsy meds (Phenytoin, Carbamazepine), **A**minoglycosides (Gentamicin), and **L**ithium. * **Sampling Time:** For Digoxin, TDM should be performed at least **6–8 hours after the last dose** (post-distribution phase) to ensure accurate results. * **Exceptions:** TDM is **not** useful for drugs with "hit and run" pharmacokinetics (e.g., Omeprazole) or those with easily measurable physiological endpoints (e.g., Warfarin via PT/INR).

Question 1

Which HLA gene is associated with abacavir hypersensitivity?

Accepted Answer

B57

Answer

B5

Answer

B51

Answer

DQ2

Question 2

Which of the following does not cause hemolysis in G6PD deficiency?

Accepted Answer

Estrogen

Answer

Salicylates

Answer

Primaquine

Answer

Nitrofurantoin

Question 3

All of the following drugs cause hemolysis in G-6PD deficiency except?

Accepted Answer

Erythromycin

Answer

Primaquine

Answer

Nitrofurantoin

Answer

Sulfonamides

Question 4

Therapeutic drug monitoring is used in which of the following medications?

Accepted Answer

Digoxin

Answer

Diuretic

Answer

Metformin

Answer

Levodopa

Question 5

Which of the following drugs does not act on cytoplasmic receptors?

Accepted Answer

Thyroxine

Answer

Corticosteroids

Answer

Vitamin D

Answer

Aldosterone

Pharmacogenomics — MCQs

Pharmacogenomics — MCQs

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