Adverse Drug Reactions and Toxicity — MCQs
The risk of carbamazepine-induced Stevens-Johnson syndrome is increased in the presence of which of the following genes?
The therapeutic index of a drug is defined as the ratio between the toxic dose and the effective dose.
According to American society of Anesthesiologists the physical status of a patient with severe incapacitating systemic disease that is a constant threat to life may be classified as:
Acute allergic reaction to the penicillin group of drugs is classified as:
A patient on lithium therapy developed hypertension and was started on a thiazide diuretic. After a few days, he developed coarse tremors and other symptoms suggestive of lithium toxicity. What is the probable mechanism of interaction between thiazide diuretics and lithium?
Which of the following is/are hepatotoxic anesthetic agent(s)?
A drug is more likely to cause toxicity in elderly patients due to all of the following reasons except which of the following?
A patient given one of the following drug develops low grade fever, muscle and joint ache, chest pain and skin rashes. Lab investigations showed presence of antihistone antibodies. Symptoms however subsided after discontinuation of the drug. Which is the drug that caused the reaction?
Which of the following cytochromes is involved in monooxygenase mediated detoxification of drugs?
Which of the following statements about the PRIMARY mechanism of action of acetazolamide is correct?
Adverse Drug Reactions and Toxicity 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: The therapeutic index of a drug is defined as the ratio between the toxic dose and the effective dose.
- A. Margin of safety
- B. Ratio of toxic dose to effective dose (Correct Answer)
- C. Efficacy of the drug
- D. Drug potency
Explanation: ***Ratio of toxic dose to effective dose***- The **therapeutic index (TI)** is quantitatively defined as the ratio of the toxic dose (TD50 or LD50) to the effective dose (ED50) [1, 2].- This ratio provides a measure of **drug safety**, indicating the range between the therapeutic and toxic concentrations [1, 3].*Margin of safety*- While related to safety, the **margin of safety** is a different concept, often calculated as (TD1 - ED99) / ED99, focusing on the overlap between very few people experiencing toxicity and almost everyone receiving benefit [2].- The therapeutic index is a broader, simpler ratio that doesn't explicitly guarantee overlap safety but indicates overall drug risk.*Efficacy of the drug*- **Efficacy** refers to the maximal effect a drug can produce regardless of the dose, and it is independent of the therapeutic index [2].- A drug can have high efficacy but a narrow therapeutic index, meaning it is very effective but also very toxic at doses slightly above the therapeutic range.*Drug potency*- **Potency** is the amount of drug needed to produce a given effect (e.g., ED50), reflecting its affinity for receptors and efficiency of action [2].- It is distinct from the therapeutic index, which assesses the separation between desired and undesired effects, not the concentration required to achieve a therapeutic effect.
Question 3: According to American society of Anesthesiologists the physical status of a patient with severe incapacitating systemic disease that is a constant threat to life may be classified as:
- A. ASA 1
- B. ASA 3
- C. ASA 2
- D. ASA 4 (Correct Answer)
Explanation: ***ASA 4*** - **ASA (American Society of Anesthesiologists) Physical Status Class 4** describes a patient with severe incapacitating systemic disease that is a constant threat to life. - This category indicates a **high risk of mortality**, even without surgery, due to the severity of their underlying health conditions. *ASA 1* - **ASA 1** describes a **normal, healthy patient** with no systemic disease or other underlying health conditions. - These patients have **minimal risk** associated with anesthesia. *ASA 3* - **ASA 3** describes a patient with **severe systemic disease** that is not incapacitating and not a constant threat to life. - Examples include **well-controlled diabetes or hypertension** with some associated complications. *ASA 2* - **ASA 2** describes a patient with **mild systemic disease** that has no functional limitations. - This category includes patients with **well-controlled chronic conditions** such as mild hypertension, well-controlled asthma, or type 2 diabetes without systemic complications.
Question 4: Acute allergic reaction to the penicillin group of drugs is classified as:
- A. Type 1 reaction (Correct Answer)
- B. Type 2 reaction
- C. Type 3 reaction
- D. Type 4 reaction
Explanation: ***Type 1 reaction*** - Penicillin allergy is a classic example of a **Type I hypersensitivity reaction**, mediated by **IgE antibodies**. - Symptoms like **anaphylaxis**, **urticaria**, and **angioedema** develop rapidly upon re-exposure to the drug. *Type 2 reaction* - **Type II hypersensitivity reactions** involve **IgG** or **IgM antibodies** binding to antigens on cell surfaces, leading to cell destruction. - Examples include **hemolytic anemia** due to drug-induced antibodies, which is not the primary mechanism of typical penicillin allergy. *Type 3 reaction* - **Type III hypersensitivity reactions** involve the formation of **immune complexes** (antigen-antibody complexes) that deposit in tissues. - This can lead to conditions like **serum sickness** or **vasculitis**, which are less common manifestations of penicillin allergy. *Type 4 reaction* - **Type IV hypersensitivity reactions** are **delayed-type hypersensitivity (DTH)** reactions, mediated by **T cells** rather than antibodies. - These reactions typically manifest 24-72 hours after exposure, as seen in **contact dermatitis**; while some penicillin reactions can be T-cell mediated, the acute, life-threatening allergic response is Type I.
Question 5: A patient on lithium therapy developed hypertension and was started on a thiazide diuretic. After a few days, he developed coarse tremors and other symptoms suggestive of lithium toxicity. What is the probable mechanism of interaction between thiazide diuretics and lithium?
- A. Thiazide increases the tubular reabsorption of lithium (Correct Answer)
- B. Thiazide inhibits the metabolism of lithium
- C. Thiazides act as an add-on drug to lithium
- D. None of the above
Explanation: ***Thiazide increases the tubular reabsorption of lithium*** - Thiazide diuretics cause a decrease in sodium reabsorption in the distal convoluted tubule, leading to increased sodium excretion in urine. - The kidneys, in an attempt to conserve sodium, increase reabsorption in the proximal tubule. Because **lithium** is reabsorbed similarly to sodium in the proximal tubule, this increased reabsorption also affects lithium, leading to a rise in its plasma concentration and toxicity. *Thiazide inhibits the metabolism of lithium* - Lithium is primarily excreted by the kidneys and is not significantly metabolized in the body. - Thiazide diuretics do not affect enzyme systems responsible for drug metabolism. *Thiazides act as an add on the drug to lithium* - This statement is vague and does not explain a mechanism of interaction leading to toxicity. - While both drugs might be prescribed concurrently for different conditions, "add on" does not describe a pharmacological interaction causing altered drug levels. *None of the above* - This option is incorrect because a clear and well-understood mechanism for the interaction between thiazide diuretics and lithium exists.
Question 6: Which of the following is/are hepatotoxic anesthetic agent(s)?
- A. Halothane
- B. Both Chloroform and Halothane (Correct Answer)
- C. None of the above
- D. Chloroform
Explanation: ***Both Chloroform and Halothane*** - Both agents are well-established hepatotoxins used historically in anesthesia - **Chloroform** causes direct hepatotoxicity through centrilobular necrosis due to reactive metabolites (CYP2E1-mediated) - **Halothane** causes halothane hepatitis, a rare but potentially fatal immune-mediated hepatotoxicity (occurs in 1:10,000-35,000 exposures) - This is the **most complete answer** as it includes all hepatotoxic agents listed *Halothane* - This is medically correct - halothane is indeed hepatotoxic - However, this is **incomplete** as it omits chloroform, another hepatotoxic anesthetic agent in the options - When multiple correct agents are listed, the most comprehensive answer is preferred *Chloroform* - This is medically correct - chloroform is indeed hepatotoxic - However, this is **incomplete** as it omits halothane, another hepatotoxic anesthetic agent in the options - Chloroform was historically used but abandoned due to hepatotoxicity and cardiac arrhythmias *None of the above* - This is incorrect as both chloroform and halothane have well-documented hepatotoxic effects - Both agents can cause liver damage ranging from transient enzyme elevation to fulminant hepatic failure
Question 7: A drug is more likely to cause toxicity in elderly patients due to all of the following reasons except which of the following?
- A. decreased renal excretion of drugs
- B. decreased hepatic metabolism
- C. decreased volume of distribution (Correct Answer)
- D. increased receptor sensitivity
Explanation: ***decreased volume of distribution*** - A **decreased volume of distribution** would generally lead to a higher peak plasma concentration for a given dose, potentially increasing drug effect and thus toxicity, particularly for **hydrophilic drugs**. - However, for drugs that primarily distribute into **fat** or have a large volume of distribution, age-related changes in body composition (e.g., increased body fat, decreased total body water) can actually lead to an **increased volume of distribution** for some lipophilic drugs. *decreased renal excretion of drugs* - **Aging** is associated with a decline in **glomerular filtration rate (GFR)** and **renal tubular function**, leading to reduced drug clearance. - This results in a longer **half-life** and accumulation of renally excreted drugs, increasing the risk of **toxicity**. *decreased hepatic metabolism* - Liver size, blood flow, and the activity of some **cytochrome P450 enzymes** may decrease with age. - This leads to reduced **first-pass metabolism** and slower systemic clearance of many hepatically metabolized drugs, increasing their **bioavailability** and plasma concentrations. *increased receptor sensitivity* - Elderly patients often exhibit altered **pharmacodynamic responses**, including **increased sensitivity** to certain drugs. - This means a lower concentration of the drug at the receptor site can produce a greater therapeutic or toxic effect, making them more susceptible to **adverse drug reactions**.
Question 8: A patient given one of the following drug develops low grade fever, muscle and joint ache, chest pain and skin rashes. Lab investigations showed presence of antihistone antibodies. Symptoms however subsided after discontinuation of the drug. Which is the drug that caused the reaction?
- A. Paracetamol
- B. Furosemide
- C. Rifampicin
- D. Hydralazine (Correct Answer)
Explanation: ***Hydralazine*** - This drug is a well-known cause of **drug-induced lupus erythematosus (DILE)**, which presents with symptoms like fever, myalgia, arthralgia, pleuritic chest pain, and skin rashes. - The presence of **antihistone antibodies** is a hallmark laboratory finding in DILE, and symptoms typically resolve upon discontinuation of the causative drug. *Paracetamol* - Paracetamol (acetaminophen) is an **analgesic** and **antipyretic** and is generally well-tolerated. - It does not typically cause a lupus-like syndrome or induce the formation of antihistone antibodies. *Furosemide* - Furosemide is a **loop diuretic** primarily used for treating edema and hypertension. - While it can cause side effects like electrolyte imbalances, it is not associated with drug-induced lupus or antihistone antibodies. *Rifampicin* - Rifampicin is an **antibiotic** used to treat tuberculosis and other bacterial infections. - Its side effects can include hepatotoxicity, gastrointestinal disturbances, and reddish discoloration of body fluids, but not typically a lupus-like syndrome with antihistone antibodies.
Question 9: Which of the following cytochromes is involved in monooxygenase mediated detoxification of drugs?
- A. Cytochrome b5
- B. Cytochrome P450 (Correct Answer)
- C. Cytochrome c
- D. NADPH-cytochrome P450 reductase
Explanation: ***Cyt P 450*** - **Cytochrome P450** enzymes are a superfamily of **monooxygenases** that play a critical role in the metabolism and detoxification of a wide variety of endogenous and exogenous substances, including drugs. - They facilitate phase I reactions (e.g., **oxidation**, reduction, hydrolysis), which typically introduce or expose functional groups to make compounds more polar and easier to excrete. *Cytochrome b5* - **Cytochrome b5** is involved in various metabolic reactions, including **fatty acid desaturation** and cholesterol biosynthesis, and can sometimes interact with P450 systems but is not the primary monooxygenase for drug detoxification. - It also participates in the reduction of methemoglobin and can act as an electron donor, but its role in drug detoxification is secondary and accessory to P450. *Cytochrome c* - **Cytochrome c** is a key component of the **electron transport chain** in mitochondria, primarily involved in cellular respiration and ATP production. - It has a crucial role in **apoptosis** when released into the cytosol, but it is not directly involved in drug monooxygenase detoxification. *NADPH-cytochrome P450 reductase* - **NADPH-cytochrome P450 reductase** is an enzyme that transfers electrons from NADPH to **cytochrome P450 enzymes**, enabling their monooxygenase activity. - While essential for P450 function, it is the **reductase** (electron donor) and not the monooxygenase enzyme itself, which is Cytochrome P450.
Question 10: Which of the following statements about the PRIMARY mechanism of action of acetazolamide is correct?
- A. It causes metabolic alkalosis
- B. It decreases potassium excretion
- C. Has structural resemblance to penicillins
- D. Reversible inhibitor of carbonic anhydrase (Correct Answer)
Explanation: ***Reversible inhibitor of carbonic anhydrase*** - Acetazolamide is a **carbonic anhydrase inhibitor** that primarily acts by reducing the reabsorption of bicarbonate in the proximal tubule of the kidney. - This inhibition leads to increased urinary excretion of **bicarbonate, sodium, and water**, ultimately reducing intraocular pressure, intracranial pressure, and systemic fluid retention. *It decreases potassium excretion* - Acetazolamide actually **increases potassium excretion** indirectly by increasing the delivery of sodium and bicarbonate to the collecting duct, which enhances potassium secretion. - This can lead to **hypokalemia** with prolonged use. *It causes metabolic alkalosis* - Acetazolamide causes **metabolic acidosis**, not alkalosis, because it inhibits the reabsorption of bicarbonate in the renal tubules, leading to increased bicarbonate excretion and a decrease in serum bicarbonate levels. - This effect makes it useful in treating metabolic alkalosis, but it does not cause it. *Has structural resemblance to penicillins* - Acetazolamide is a **sulfonamide derivative** and does not have a structural resemblance to penicillins. - Its mechanism of action is completely distinct from that of antibiotics in the penicillin class.
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