Clinical Pharmacology and Drug Toxicity — MCQs

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

Question 911: Which of the following drugs has not been withdrawn from the Indian market for safety reasons?

A. Gatifloxacin
B. Cotrimoxazole (Correct Answer)
C. Phenformin
D. Rofecoxib

Explanation: ### Cotrimoxazole - Cotrimoxazole, a combination of **trimethoprim and sulfamethoxazole**, remains a widely used and available antibiotic in India [1], [2]. - It treats various bacterial infections, including **urinary tract infections** and respiratory infections, and has not been withdrawn for safety reasons [1]. ### Gatifloxacin - **Gatifloxacin** was withdrawn from the Indian market due to concerns about **severe glycemic disturbances**, including both hypo- and hyperglycemia. - These side effects posed significant risks, especially in patients with diabetes or those predisposed to blood sugar fluctuations. ### Rofecoxib - **Rofecoxib**, an NSAID, was withdrawn globally, including from India, due to an increased risk of **cardiovascular events** such as heart attack and stroke. - Its selective inhibition of COX-2 was found to disturb the balance of prostaglandins, leading to adverse cardiovascular outcomes. ### Phenformin - **Phenformin**, an oral antidiabetic drug, was withdrawn from the Indian market due to its association with a high incidence of **lactic acidosis**, a severe and often fatal metabolic complication. - This serious side effect made its risk-benefit profile unacceptable for continued use.

Question 912: What is the most serious side effect associated with Raltegravir?

A. Hyperglycemia
B. Hypertension
C. Headache
D. Rhabdomyolysis (Correct Answer)

Explanation: ***Rhabdomyolysis*** - Raltegravir, an **integrase strand transfer inhibitor (INSTI)**, can cause muscle-related side effects, including **rhabdomyolysis** and **myopathy**. [2] - Patients may present with muscle pain, weakness, and elevated **creatine kinase (CK)** levels. *Headache* - While headache can be a general side effect of many medications, it is not a **distinguishing or severe adverse effect commonly associated with Raltegravir** that would require specific monitoring. - Other more prominent side effects are typically prioritized in counseling and monitoring for this drug. *Hyperglycemia* - **Hyperglycemia** is not a commonly reported or significant side effect of Raltegravir. - While some antiretrovirals, particularly certain **protease inhibitors (PIs)** and **nucleoside reverse transcriptase inhibitors (NRTIs)**, are associated with altered glucose metabolism, INSTIs like Raltegravir generally have a more favorable metabolic profile. [1] *Hypertension* - Hypertension is generally **not a recognized or common side effect** of Raltegravir. - Cardiovascular events and hypertension are more frequently associated with other classes of antiretroviral drugs or as comorbidities in HIV-positive patients, rather than directly with INSTIs.

Question 913: Visual field monitoring is important before starting which of the following drugs for epilepsy treatment?

A. Vigabatrin (Correct Answer)
B. Topiramate
C. Valproic acid
D. Carbamazepine

Explanation: ***Vigabatrin*** - **Vigabatrin** is known to cause **irreversible concentric visual field constriction** (peripheral vision loss) due to retinal toxicity. - Regular **ophthalmological monitoring**, including **visual field testing**, is crucial before and during treatment to detect and manage this adverse effect early. *Topiramate* - Topiramate can cause **acute angle-closure glaucoma** and **myopia**, which affect vision, but regular visual field monitoring is not a primary requirement for this specific side effect. - Its main concerns often relate to cognitive side effects and kidney stones, rather than progressive visual field loss requiring baseline and ongoing field testing. *Valproic acid* - Valproic acid is not typically associated with specific visual field defects requiring routine monitoring. - Its major side effects often involve **hepatotoxicity**, **pancreatitis**, and **teratogenicity**. *Carbamazepine* - Carbamazepine's notable side effects include **aplastic anemia**, **hyponatremia**, and **Stevens-Johnson syndrome**. - While it can cause some ocular side effects like **diplopia** or **nystagmus**, it does not typically lead to the progressive and irreversible visual field constriction seen with vigabatrin, which necessitates strict monitoring.

Question 914: Tetracycline injection causes palsy of which nerve?

A. Radial (Correct Answer)
B. Median
C. Ulnar
D. Superficial peroneal

Explanation: ***Radial*** - Tetracycline injections, especially when given in the deltoid region, can inadvertently injure the **radial nerve** due to its superficial course. - Damage to the radial nerve typically results in **wrist drop** and sensory deficits over the dorsum of the hand. *Ulnar* - The **ulnar nerve** is commonly injured at the elbow (cubital tunnel syndrome) or wrist (Guyon's canal). - Injury typically results in weakness of intrinsic hand muscles and sensory loss in the little finger and ulnar half of the ring finger, which is not characteristic of an injection injury in the deltoid region. *Median* - The **median nerve** is more frequently injured at the wrist (carpal tunnel syndrome) or elbow. - Injury causes difficulty with thumb opposition and sensation in the first three and a half digits on the palmar side. *Superficial peroneal* - The **superficial peroneal nerve** is found in the lower leg and foot, innervating the lateral compartment muscles and providing sensation to the dorsum of the foot. - It would not be affected by an injection in the upper arm or shoulder region.

Question 915: Which vaccine is associated with a risk of encephalopathy?

A. OPV
B. Rubella
C. Measles (Correct Answer)
D. BCG

Explanation: ***Measles*** - Among the options provided, **measles vaccine** has been reported to have a very rare association with **post-vaccination encephalitis/encephalopathy** (approximately 1 per million doses). - **Important note:** The **pertussis vaccine (particularly whole-cell DTP)** is the vaccine most classically associated with encephalopathy risk, but it is not among the options here. - The risk of encephalopathy from the measles vaccine is significantly lower than the risk from natural measles infection itself. - Modern measles vaccines are highly purified and safer than earlier formulations. *OPV* - **Oral Polio Vaccine (OPV)** is associated with **vaccine-associated paralytic poliomyelitis (VAPP)**, not encephalopathy. - VAPP occurs at a rate of approximately 1 case per 2.4 million doses due to reversion of the attenuated virus to a neurovirulent form. - Manifests as flaccid paralysis, not encephalopathy. *Rubella* - **Rubella vaccine** (component of MMR) is very safe with no significant association with encephalopathy. - Rare adverse effects include transient arthralgia (especially in adult women), mild rash, or lymphadenopathy. - Severe neurological complications are extremely rare. *BCG* - **Bacillus Calmette-Guérin (BCG) vaccine** protects against tuberculosis and is not associated with encephalopathy. - Common adverse effects are local reactions: induration, ulceration, scarring, and rarely lymphadenitis. - Disseminated BCG infection can occur in immunocompromised individuals but is distinct from encephalopathy.

Question 916: Which of the following is not commonly recognized as a hepatotoxic drug?

A. Chlorpropamide
B. Allopurinol
C. Streptomycin (Correct Answer)
D. Halothane

Explanation: ***Streptomycin*** - Streptomycin is primarily associated with **ototoxicity** (vestibular and cochlear damage) and **nephrotoxicity** (kidney damage), not significant hepatotoxicity. - While most drugs can theoretically cause liver injury, streptomycin is not frequently cited as a major hepatotoxin in clinical practice. *Chlorpropamide* - This **sulfonylurea oral hypoglycemic agent** can cause a range of liver injuries, from asymptomatic enzyme elevations to severe **cholestatic hepatitis** or hepatocellular damage. - Its hepatotoxic potential is well-documented, leading to its decreased use compared to newer antidiabetic agents. *Allopurinol* - Allopurinol, used to treat **gout** and hyperuricemia, is known to cause a variety of adverse effects, including **hypersensitivity reactions** that can involve the liver. - It can lead to **hepatocellular injury**, cholestasis, or mixed liver damage, sometimes as part of a severe drug reaction with eosinophilia and systemic symptoms (**DRESS syndrome**). *Halothane* - Halothane is a potent **halogenated inhalational anesthetic** historically associated with a rare but severe form of idiosyncratic liver injury known as **halothane hepatitis**. - This condition involves **massive hepatic necrosis** and has a high mortality rate, leading to its eventual replacement by newer anesthetics.

Question 917: Most clinically significant side effect of topiramate requiring immediate medical attention?

A. Weight loss
B. Visual impairment (Correct Answer)
C. Insomnia
D. Hemolysis

Explanation: ***Visual impairment*** - Topiramate can cause **acute angle-closure glaucoma**, a medical emergency that typically occurs within the **first month of therapy**. - Mechanism: Topiramate causes **ciliary body swelling** and **uveal effusion**, leading to anterior rotation of the iris-lens diaphragm and angle closure. - Clinical presentation: Rapid-onset **blurred vision**, **eye pain**, **headache**, **redness**, and may progress to permanent vision loss if untreated. - Management: **Immediate discontinuation** of topiramate and urgent **ophthalmology referral** for intraocular pressure management. *Weight loss* - Weight loss is a common and often desired side effect of topiramate, related to its effect on **appetite suppression** and enhanced satiety. - While it can be significant, it does not typically require immediate medical attention unless it becomes excessive or leads to nutritional deficiencies. - This side effect is sometimes therapeutically exploited in migraine prophylaxis. *Insomnia* - Insomnia is a known side effect of topiramate and can impact quality of life but is generally not life-threatening or an immediate medical emergency. - Management often involves adjusting the dosage, timing of administration (dosing earlier in the day), or prescribing sleep aids. *Hemolysis* - Hemolysis is **not a recognized side effect** of topiramate. - Topiramate is not known to directly cause the destruction of red blood cells. - Other serious side effects of topiramate include metabolic acidosis, kidney stones, and cognitive impairment, but not hemolysis.

Question 918: Gynaecomastia is caused by which drug?

A. Spironolactone (Correct Answer)
B. Rifampicin
C. Thiazide
D. Propranolol

Explanation: ***Spironolactone*** - Spironolactone is a **well-established cause of gynaecomastia**, occurring in 5-10% of patients in a dose-dependent manner. - It acts as an **anti-androgen** by blocking androgen receptors and inhibiting testosterone synthesis, thereby increasing the estrogen to androgen ratio. - It is a **potassium-sparing diuretic** and aldosterone antagonist, commonly used in heart failure, hypertension, and conditions requiring androgen blockade. *Rifampicin* - Rifampicin is an **antibiotic** primarily used to treat tuberculosis and acts as a **strong inducer of cytochrome P450 enzymes**. - While rare hormonal effects have been reported, it is **not a recognized common cause** of gynaecomastia. - Main side effects include hepatotoxicity, orange discoloration of bodily fluids, and drug interactions. *Thiazide* - Thiazide diuretics work by inhibiting the **sodium-chloride cotransporter** in the distal convoluted tubule. - They are **not commonly associated** with gynaecomastia; typical side effects include hypokalemia, hyponatremia, and hyperglycemia. *Propranolol* - Propranolol is a **non-selective beta-blocker** used for hypertension, angina, arrhythmias, and anxiety. - While beta-blockers have rarely been implicated, propranolol is **not a well-established cause** of gynaecomastia compared to spironolactone. - Common side effects include bradycardia, fatigue, and bronchospasm.

Question 919: Which one of the following agents has been associated with hemorrhagic stroke?

A. Phenylpropanolamine (Correct Answer)
B. Terfenadine
C. Quinidine
D. Fenfluramine

Explanation: ***Phenylpropanolamine*** - **Phenylpropanolamine (PPA)** is a sympathomimetic agent that was formerly used as a nasal decongestant and anorectic. - Its use has been linked to an increased risk of **hemorrhagic stroke**, particularly in young women, due to its **vasoconstrictive effects** and potential to cause a sudden, severe rise in blood pressure. *Terfenadine* - **Terfenadine** is a second-generation antihistamine that was voluntarily withdrawn from the market due to its association with severe **cardiac arrhythmias (QT prolongation and Torsades de Pointes)**, not hemorrhagic stroke. - It works by blocking H1 histamine receptors but also had effects on cardiac potassium channels. *Quinidine* - **Quinidine** is an antiarrhythmic drug (Class Ia) primarily used to treat supraventricular and ventricular arrhythmias. - Its main side effects include **gastrointestinal disturbances**, **cinchonism**, and the risk of **QT prolongation** leading to Torsades de Pointes; it is not typically associated with hemorrhagic stroke. *Fenfluramine* - **Fenfluramine** was an anorectic drug used in the treatment of obesity, often in combination with phentermine. - It was withdrawn from the market due to its association with **pulmonary hypertension** and **cardiac valvulopathy**, not hemorrhagic stroke.

Question 920: Which of the following antiretroviral drugs is not associated with peripheral neuropathy?

A. Stavudine
B. Zalcitabine
C. Didanosine
D. Indinavir (Correct Answer)

Explanation: ***Indinavir*** - **Indinavir** is a **protease inhibitor** that can cause side effects such as **nephrolithiasis** (kidney stones) and **hyperbilirubinemia**, but it is generally *not associated with peripheral neuropathy*. - It works by blocking the viral protease enzyme, preventing the cleavage of viral polyproteins into functional proteins, which disrupts viral replication. *Stavudine* - **Stavudine** is a **nucleoside reverse transcriptase inhibitor (NRTI)** notorious for causing dose-dependent **peripheral neuropathy**. - This toxicity is due to its interference with **mitochondrial DNA synthesis**, leading to nerve damage. *Zalcitabine* - **Zalcitabine** (ddC) is another **NRTI** strongly associated with a high incidence of **peripheral neuropathy**. - Its mechanism of action and side effect profile are similar to those of stavudine in causing **mitochondrial toxicity**. *Didanosine* - **Didanosine** (ddI) is an **NRTI** known to cause several adverse effects, including **peripheral neuropathy**, particularly at higher doses. - Like other dideoxynucleoside analogs, its toxicity is linked to **mitochondrial dysfunction**.

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