Clinical Pharmacology and Drug Toxicity — MCQs

Clinical Pharmacology and Drug Toxicity Indian Medical PG Practice Questions and MCQs

Question 951: Which of the following drugs is known to cause cholestasis?

A. All of the above (Correct Answer)
B. Phenothiazines
C. Oral contraceptives
D. Erythromycin

Explanation: ***All of the above***- **Cholestasis [1]** can be induced by various medications, and all three listed drug classes—**erythromycin**, **phenothiazines**, and **oral contraceptives**—are well-documented causes of drug-induced cholestasis. **Erythromycin:**- Associated with **idiosyncratic cholestatic hepatitis**, especially with the estolate form- Mechanism involves bile duct inflammation or obstruction [1]- Typically presents with jaundice [1], pruritus, and elevated alkaline phosphatase **Phenothiazines:**- Can cause **cholestatic jaundice** through hypersensitivity reactions- Effect is often delayed (2-4 weeks after initiation)- Reversible upon discontinuation of the drug **Oral contraceptives:**- Cause cholestasis particularly in susceptible individuals- More common in those with history of **cholestasis of pregnancy**- Estrogen component is primarily responsible for the cholestatic effect

Question 952: All the following drugs are teratogenic except?

A. Alcohol
B. Phenytoin
C. Warfarin
D. Metoclopramide (Correct Answer)

Explanation: ***Metoclopramide*** - **Metoclopramide** is an antiemetic and prokinetic agent generally considered **safe during pregnancy**. - It does **not** have established teratogenic effects and is often used to treat **nausea and vomiting** in pregnant women. *Alcohol* - **Alcohol** is a well-known teratogen, leading to **fetal alcohol syndrome** characterized by facial dysmorphia, growth restriction, and CNS abnormalities. - Even moderate consumption can have detrimental effects on fetal development, particularly brain development. *Phenytoin* - **Phenytoin** is an antiepileptic drug associated with **fetal hydantoin syndrome**, which includes craniofacial anomalies, mental deficits, and distal phalangeal hypoplasia. - It interferes with **folate metabolism** and can increase the risk of neural tube defects. *Warfarin* - **Warfarin** is an anticoagulant that can cause **fetal warfarin syndrome** when used during the first trimester, leading to chondrodysplasia punctata, nasal hypoplasia, and skeletal abnormalities. - Its mechanism involves interfering with **vitamin K-dependent coagulation factors**, affecting fetal bone and cartilage development.

Question 953: Which of the following is not an early adverse effect of methotrexate?

A. Myelosuppression
B. Nausea
C. Hepatic fibrosis (Correct Answer)
D. Stomatitis

Explanation: ***Hepatic fibrosis*** - **Hepatic fibrosis** is a *late-onset* adverse effect of **methotrexate** therapy, developing after prolonged use (months to years), rather than in the early stages. [2] - This complication is associated with cumulative doses and pre-existing liver conditions, requiring long-term monitoring rather than immediate concern after starting treatment. [1] *Myelosuppression* - **Myelosuppression** (bone marrow suppression) can occur relatively *early* in methotrexate treatment due to its impact on rapidly dividing cells, including hematopoietic stem cells. [1] - This can lead to **leukopenia**, **anemia**, or **thrombocytopenia**, necessitating close monitoring of blood counts. [2] *Nausea* - **Nausea** is a common *acute* gastrointestinal side effect that frequently occurs within hours or days of methotrexate administration. [3] - It results from the drug's effect on the gastrointestinal tract and can often be mitigated with antiemetics or dose adjustments. *Stomatitis* - **Stomatitis** (inflammation of the mouth lining) is another frequent and *early* adverse effect, often appearing within a few days of methotrexate exposure. [1], [2] - It is caused by the *antimetabolite* action of methotrexate on rapidly dividing oral mucosal cells, leading to painful ulcers.

Question 954: Prolonged use of which drug has been implicated in the causation of subacute myelo-optic neuropathy (SMON)?

A. Quiniodochlor (Correct Answer)
B. Diloxanide furoate
C. Furazolidone
D. Emetine

Explanation: ***Quiniodochlor*** - **Quiniodochlor** (also known as clioquinol) is an antimicrobial agent whose prolonged use was historically linked to **subacute myelo-optic neuropathy (SMON)**, particularly in Japan. - SMON is characterized by ascending sensory disturbances, motor weakness, and visual impairment due to damage to the spinal cord and optic nerves. *Diloxanide furoate* - **Diloxanide furoate** is an effective luminal amebicide used for asymptomatic carriers of **Entamoeba histolytica**. - Its primary side effects are mild gastrointestinal disturbances, and it is not associated with neurotoxicity like SMON. *Furazolidone* - **Furazolidone** is a nitrofuran antimicrobial used to treat bacterial and protozoal infections, particularly in the gastrointestinal tract. - While it can cause gastrointestinal upset, peripheral neuropathy, and hemolysis in G6PD-deficient individuals, it is not implicated in SMON. *Emetine* - **Emetine** is an alkaloid used as an anti-amebic agent, typically for severe amebiasis. - Its main toxicities include **cardiac toxicity** (e.g., arrhythmias, heart failure), neuromuscular weakness, and gastrointestinal issues, but not SMON.

Question 955: At what percentage of carboxyhemoglobin is the risk of death significantly increased?

A. 75%
B. 80%
C. 82%
D. 70% (Correct Answer)

Explanation: ***70%*** - A carboxyhemoglobin (COHb) level of **70% or higher** is the widely recognized clinical threshold at which the risk of death becomes **significantly increased** and mortality is highly probable. - This represents the standard cutoff in toxicology literature where **severe tissue hypoxia**, cardiovascular collapse, and central nervous system depression become life-threatening. - At this level, immediate aggressive treatment including hyperbaric oxygen therapy is critical to prevent fatal outcomes. *75%* - While a COHb level of 75% is undoubtedly lethal, this exceeds the **established threshold** of 70% where mortality risk is already considered significantly elevated. - This is not the standard clinical reference point used in toxicology for defining high mortality risk. - The question asks for the threshold percentage, not just any lethal level. *80%* - An 80% COHb level represents a concentration well above the recognized threshold for significantly increased mortality. - This value is far beyond the 70% cutoff where death risk becomes critically high. - While certainly fatal, this is not the standard clinical threshold cited in medical literature. *82%* - At 82%, this represents an extremely high COHb level that is almost universally fatal, but it exceeds the **recognized clinical threshold** of 70%. - This percentage is not the standard reference point used to define significantly increased mortality risk. - Medical consensus identifies 70% as the key threshold, making this option incorrect despite its lethality.

Question 956: A patient with pulmonary tuberculosis, who is receiving anti-tuberculosis therapy consisting of rifampicin, isoniazid, ethambutol, and pyrazinamide, should be advised to take which of the following supplements?

A. Niacin
B. Riboflavin
C. Pyridoxine (Correct Answer)
D. Thiamine

Explanation: ***Pyridoxine*** - **Isoniazid** in the anti-tuberculosis regimen can cause **peripheral neuropathy** by interfering with **pyridoxine (vitamin B6)** metabolism. - Supplementation with **pyridoxine** is advised to prevent this neurotoxic side effect, especially in patients at higher risk such as those with diabetes, malnutrition, or alcoholism. *Niacin* - **Niacin (vitamin B3)** deficiency can lead to **pellagra**, characterized by dermatitis, diarrhea, and dementia. - While important for general health, niacin supplementation is not specifically required to counteract side effects of standard anti-tuberculosis drugs. *Riboflavin* - **Riboflavin (vitamin B2)** is essential for various metabolic processes and cellular energy production. - There is no direct significant depletion or interference with riboflavin metabolism caused by the common anti-tuberculosis drugs. *Thiamine* - **Thiamine (vitamin B1)** deficiency can lead to **beriberi** and neurological symptoms, particularly in those with chronic alcoholism. - While thiamine is crucial for neurological function, antitubercular drugs do not specifically deplete or interfere with its metabolism to the extent of requiring routine supplementation.

Question 957: Ergometrine is contraindicated in:

A. Induction of labour
B. Post partum hemorrhage
C. Eclampsia (Correct Answer)
D. Abortion

Explanation: ***Eclampsia*** - Ergometrine is an **ergot alkaloid** that causes generalized **vasoconstriction**, which can lead to a dangerous increase in blood pressure. - In a patient with **eclampsia** (characterized by hypertension, proteinuria, and seizures), this vasoconstriction can worsen **hypertension** and increase the risk of **stroke, seizures, or cardiac events**, making it an absolute contraindication. - **Pre-eclampsia and severe hypertension** are also contraindications for the same reason. *Induction of labour* - Ergometrine is **absolutely contraindicated during active labor** because it causes **tetanic (sustained, continuous) uterine contractions** rather than the coordinated contractions needed for delivery. - These sustained contractions can cause **fetal hypoxia** (due to impaired placental blood flow), **uterine rupture**, and **fetal distress**. - It is used only **after delivery of the baby** (third stage of labor) to contract the uterus and prevent postpartum hemorrhage. *Abortion* - Ergometrine can be used in cases of **incomplete abortion** to help contract the uterus and expel retained products of conception, thereby reducing blood loss. - It is not contraindicated in abortion management when used appropriately under medical supervision. *Post partum hemorrhage* - Ergometrine is a **first-line agent for the prevention and treatment of postpartum hemorrhage** because it effectively contracts the uterus, reducing blood loss. - Its ability to induce strong, sustained uterine contractions makes it highly effective in this setting, unless there are specific contraindications like **severe hypertension or eclampsia**.

Question 958: Which of the following drugs is NOT associated with hypertrichosis?

A. Cyclosporine
B. Phenytoin
C. Minoxidil
D. Barbiturates (Correct Answer)

Explanation: ***Barbiturates*** - **Barbiturates** are medications primarily used as sedatives, hypnotics, or anticonvulsants. - They are **not typically associated** with hypertrichosis (excessive hair growth) as a side effect. *Minoxidil* - **Minoxidil** is a well-known drug that causes **hypertrichosis** as a systemic side effect, especially when used orally for hypertension. - Its topical formulation is specifically used to **promote hair growth** in androgenetic alopecia. *Cyclosporine* - **Cyclosporine**, an immunosuppressant often used in organ transplant recipients and for autoimmune diseases, frequently causes **hypertrichosis**. - This side effect can be **significant** enough to affect patient adherence to treatment. *Phenytoin* - **Phenytoin**, an anticonvulsant, is commonly associated with several side effects, including **gingival hyperplasia** and **hypertrichosis**. - The excessive hair growth can be **generalized** and affects many individuals on long-term therapy.

Question 959: Which of the following drugs is not part of the standard immunosuppressive therapy for post-renal transplant patients?

A. Cyclosporine
B. Azathioprine
C. Rituximab (Correct Answer)
D. Prednisolone

Explanation: ***Rituximab*** - **Rituximab** is a monoclonal antibody targeting **CD20 on B-lymphocytes**, primarily used in lymphomas, leukemias, and some autoimmune diseases. - While it can be used in highly selected cases for antibody-mediated rejection, it is **not considered standard immunosuppressive therapy** for maintenance of post-renal transplant patients. *Cyclosporine* - **Cyclosporine** is a **calcineurin inhibitor** that plays a central role in most maintenance immunosuppression regimens after renal transplant. - It works by inhibiting the activation of T-lymphocytes, thereby **preventing organ rejection**. *Azathioprine* - **Azathioprine** is an **antimetabolite** that inhibits lymphocyte proliferation and is a common component of standard immunosuppressive regimens. - It works by interfering with purine synthesis, thus **suppressing the immune response**. *Prednisolone* - **Prednisolone** (a corticosteroid) is a fundamental component of most immunosuppressive protocols for **renal transplant recipients**. - It provides broad-spectrum immunosuppression by reducing inflammation and suppressing various immune cells.

Question 960: 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.

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