Clinical Pharmacology and Drug Toxicity — MCQs

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

Question 761: Increased osmolar gap is not seen in poisoning of:

A. Methanol
B. Paracetamol (Correct Answer)
C. Acetone
D. Ethylene glycol

Explanation: ***Paracetamol*** - **Paracetamol (acetaminophen)** poisoning does NOT cause an **increased osmolar gap** because it is not an osmotically active alcohol or small molecule that accumulates significantly in the blood. - Paracetamol toxicity primarily causes **hepatotoxicity** through the formation of the toxic metabolite **NAPQI** (N-acetyl-p-benzoquinone imine), which depletes glutathione stores. - It may cause a **high anion gap metabolic acidosis** in severe cases due to lactic acidosis from hepatic failure, but this does not increase the osmolar gap. *Methanol* - **Methanol** poisoning leads to an **increased osmolar gap** because methanol itself is a small, osmotically active alcohol that accumulates in the blood before it is metabolized. - Its toxic metabolites, **formic acid** and **formaldehyde**, contribute to the characteristic **high anion gap metabolic acidosis** with visual disturbances. *Acetone* - **Acetone** (from isopropanol ingestion) causes an **increased osmolar gap** due to the presence of acetone itself as an osmotically active substance. - Unlike methanol or ethylene glycol, acetone metabolism does not produce highly acidic byproducts, so it typically causes an **increased osmolar gap without a significant anion gap metabolic acidosis** ("osmolar gap without anion gap"). *Ethylene glycol* - **Ethylene glycol** poisoning causes an **increased osmolar gap** due to the parent compound accumulating in the blood. - Its toxic metabolites, particularly **glycolic acid** and **oxalic acid**, lead to a significant **high anion gap metabolic acidosis** with calcium oxalate crystal formation and acute kidney injury.

Question 762: A 35 years old female presented with acne. She was treated for her acne but after the treatment, she developed pigmentation. Which drug is responsible for hyperpigmentation?

A. Minocycline (Correct Answer)
B. Doxycycline
C. Tetracycline
D. Erythromycin

Explanation: ***Minocycline*** - **Minocycline** is known to cause different types of hyperpigmentation, including blue-grey discoloration of the skin, scars, mucosa, eyes, and teeth, especially with long-term use. - This pigmentation can be due to the accumulation of **iron oxide** and **minocycline degradation products** in tissues. *Doxycycline (a tetracycline antibiotic)* - While doxycycline is a tetracycline, it is **less commonly associated with significant hyperpigmentation** compared to minocycline. - It can cause photosensitivity, which might lead to hyperpigmentation in sun-exposed areas, but direct drug-induced blue-grey discoloration is rare. *Tetracycline (a tetracycline antibiotic)* - **Tetracycline** can cause tooth discoloration, especially in children, and photosensitivity, but direct drug-induced skin hyperpigmentation as described is **less common** than with minocycline. - Other side effects like gastrointestinal upset are more prominent. *Erythromycin (a macrolide antibiotic)* - **Erythromycin** is a macrolide antibiotic and is **not typically associated with significant skin hyperpigmentation** as a side effect. - Common side effects include gastrointestinal disturbances like nausea, vomiting, and diarrhea.

Question 763: Carbonic anhydrase inhibitor should not be given in:

A. Epilepsy
B. High altitude sickness
C. Sulfonamide hypersensitivity (Correct Answer)
D. Glaucoma

Explanation: ***Sulfonamide hypersensitivity*** - Carbonic anhydrase inhibitors (CAIs) are **sulfonamide derivatives**, so they are absolutely contraindicated in patients with a history of **sulfonamide allergy**. - Administration to such patients can lead to severe **hypersensitivity reactions**, including rash, fever, and even anaphylaxis. *Epilepsy* - **Acetazolamide**, a carbonic anhydrase inhibitor, can be used as an **adjunct therapy for certain types of epilepsy**, such as absence seizures. - It works by reducing neuronal excitability through its effects on pH, thus it is not contraindicated but rather sometimes indicated. *High altitude sickness* - Carbonic anhydrase inhibitors like **acetazolamide** are commonly used to **prevent and treat high altitude cerebral and pulmonary edema** by inducing metabolic acidosis and stimulating respiration. - This is a recognized therapeutic indication, not a contraindication. *Glaucoma* - CAIs are a **primary treatment for glaucoma** (both open-angle and angle-closure) because they reduce the production of aqueous humor, thereby lowering intraocular pressure. - They are used both systemically and topically for this purpose, making it an indication, not a contraindication.

Question 764: All of the following are causes of drug-induced lupus, except:

A. Penicillamine
B. Hydralazine
C. Clofibrate (Correct Answer)
D. Chlorpromazine

Explanation: ***Clofibrate*** - Clofibrate is a **fibric acid derivative** (fibrate) used to treat hyperlipidemia and is not known to cause drug-induced lupus. - Its primary mechanism of action involves activating **PPAR-alpha**, leading to decreased triglyceride levels and increased HDL production. *Penicillamine* - Penicillamine is a known cause of **drug-induced lupus**, often leading to symptoms mimicking systemic lupus erythematosus. - It is a chelating agent used to treat conditions like **Wilson's disease** and severe rheumatoid arthritis. *Hydralazine* - Hydralazine is a classic and frequent cause of **drug-induced lupus**, particularly at higher doses. - It is an **antihypertensive medication** that acts as a direct vasodilator. *Chlorpromazine* - Chlorpromazine, an antipsychotic medication, can induce a **lupus-like syndrome** in some susceptible individuals. - It is a **phenothiazine derivative** primarily used to treat schizophrenia and other psychotic disorders.

Question 765: Which of the following is the FIRST-LINE antiemetic drug most commonly used for post-operative nausea and vomiting (PONV) prophylaxis?

A. Lorazepam
B. Metoclopramide
C. Promethazine
D. Ondansetron (Correct Answer)

Explanation: ***Ondansetron*** - **Ondansetron** is a **5-HT3 receptor antagonist** and is considered a first-line agent due to its high efficacy and favorable side effect profile in preventing PONV. - It works by blocking serotonin receptors in the **chemoreceptor trigger zone** and the **gastrointestinal tract**, reducing the sensation of nausea and vomiting. *Lorazepam* - **Lorazepam** is a **benzodiazepine** primarily used for its **anxiolytic** and **sedative effects**, and sometimes as an adjunct for refractory nausea, but not as a first-line antiemetic for PONV prophylaxis. - While it can help indirectly by reducing anxiety, it does not directly target the key pathways involved in PONV as effectively as 5-HT3 antagonists. *Phenytoin* - **Phenytoin** is an **anticonvulsant** medication used to prevent seizures and has no role in the direct treatment or prophylaxis of PONV. - It primarily acts on voltage-gated sodium channels in neurons and does not possess antiemetic properties. *Metoclopramide* - **Metoclopramide** is a **dopamine D2 receptor antagonist** and a **prokinetic agent** that can be used for PONV, particularly when gastric stasis is a concern. - However, it is generally considered a second-line agent due to the risk of **extrapyramidal side effects**, especially with higher doses or prolonged use. *Promethazine* - **Promethazine** is a **first-generation antihistamine** with **antidopaminergic** and **anticholinergic properties** that can be effective for nausea and vomiting. - It is often used as a rescue antiemetic or in combination therapy, but its sedative effects and potential for extrapyramidal symptoms make it less preferable as a first-line prophylactic agent compared to ondansetron.

Question 766: Anti-leprosy drug causing ichthyosis is?

A. Dapsone
B. Clarithromycin
C. Rifampicin
D. Clofazimine (Correct Answer)

Explanation: ***Clofazimine*** - **Clofazimine** is a common anti-leprosy drug known to cause side effects such as skin discoloration (reddish-brown), **ichthyosis** (dry, scaly skin), and gastrointestinal symptoms. - Its mechanism of action involves DNA binding and generation of reactive oxygen species, but the exact cause of ichthyosis is thought to be related to its accumulation in the skin. *Dapsone* - **Dapsone** is a primary drug for leprosy treatment but is more commonly associated with side effects like methemoglobinemia, hemolysis (especially in G6PD deficiency), and peripheral neuropathy. - It does not typically cause **ichthyosis**; its dermatological side effects often include hypersensitivity reactions. *Clarithromycin* - **Clarithromycin** is an antibiotic from the macrolide class, primarily used for bacterial infections, and is not a first-line drug for leprosy. - While it can cause gastrointestinal upset and QT prolongation, **ichthyosis** is not a recognized side effect of clarithromycin. *Rifampicin* - **Rifampicin** is a crucial drug in multi-drug therapy for leprosy and is known for its ability to cause orange-red discoloration of body fluids, hepatotoxicity, and flu-like symptoms. - **Ichthyosis** is not a known side effect of rifampicin.

Question 767: 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 768: A 6-year-old boy is admitted to the ward with drowsiness, dull deep tendon reflexes and seizures. On examination the child has a line on gums and there is a history of constipation. Which will be most appropriate drug that should be used for this child?

A. EDTA
B. DMSA (Correct Answer)
C. BAL
D. Penicillamine

Explanation: ***DMSA*** - The child's symptoms of **drowsiness**, **dull deep tendon reflexes**, **seizures**, a **gingival line**, and **constipation** are classic signs of **lead poisoning**. - **DMSA (dimercaptosuccinic acid)** is a chelating agent that is generally considered the **first-line treatment** for pediatric lead poisoning due to its oral administration, good safety profile, and efficacy in reducing lead levels. *Penicillamine* - While penicillamine is a chelating agent, it is **less commonly used** for lead poisoning in children due to a higher incidence of **side effects** compared to DMSA. - Its use is often reserved for patients who cannot tolerate other chelating agents or in specific situations. *EDTA* - **EDTA (ethylenediaminetetraacetic acid)** is a powerful chelator often used for severe lead poisoning, but it is typically administered **intravenously** or **intramuscularly**. - It is often combined with BAL to prevent redistribution of lead to the brain and is not usually the first choice for chronic, less severe lead poisoning in an ambulatory setting. *BAL* - **BAL (British Anti-Lewisite)**, or **dimercaprol**, is an oil-based intramuscular injection and is usually reserved for **severe lead encephalopathy**. - It has a high incidence of **adverse effects** and should not be used as monotherapy for lead poisoning due to the risk of redistributing lead to the brain; it is typically administered with EDTA for very high lead levels.

Question 769: In case of cyanide poisoning, antidote of amyl nitrite is given. This is an example of:

A. Receptor antagonism
B. Chemical antagonism (Correct Answer)
C. Physical antagonism
D. Physiological antagonism

Explanation: ***Chemical antagonism*** - Amyl nitrite functions by inducing the formation of **methemoglobin**, which has a higher affinity for **cyanide ions** than cytochrome c oxidase. - This effectively sequesters cyanide, rendering it unable to bind to and inhibit the **cytochrome oxidase enzyme**, thus preventing its toxic effects [3]. *Receptor antagonism* - This involves a drug binding to a **receptor** and blocking the action of an **agonist**, without activating the receptor itself [1], [2]. - Amyl nitrite does not exert its effect by binding to a specific receptor and blocking cyanide's action; instead, it directly interacts with cyanide itself. *Physical antagonism* - This type of antagonism involves a drug preventing another drug's action through a **physical property**, such as adsorption or chelation. - While there is an interaction, the formation of methemoglobin and its subsequent binding to cyanide is more precisely described as a chemical reaction rather than a simple physical interaction or adsorption. *Physiological antagonism* - This occurs when two drugs act on **different receptors** or pathways to produce **opposite physiological effects**. - Amyl nitrite does not produce an opposite physiological effect by acting on a different pathway; rather, it directly counteracts the chemical nature of cyanide.

Question 770: Antidote for acetaminophen poisoning is?

A. Penicillamine
B. N-Acetyl cysteine (Correct Answer)
C. Glycolamine
D. Fomepizole

Explanation: ***N-Acetyl cysteine*** - **N-acetyl cysteine (NAC)** is the specific antidote for acetaminophen (paracetamol) poisoning, acting by replenishing hepatic **glutathione stores**. - **Glutathione** is crucial for detoxifying the toxic metabolite **N-acetyl-p-benzoquinone imine (NAPQI)**, preventing liver damage. *Penicillamine* - **Penicillamine** is a chelating agent used primarily in conditions like **Wilson's disease** (copper toxicity) and **rheumatoid arthritis**. - It has no role in the treatment or detoxification of **acetaminophen poisoning**. *Glycolamine* - **Glycolamine** is not a recognized pharmaceutical antidote for any specific poisoning. - This compound is not therapeutically relevant in toxicology scenarios, particularly for **acetaminophen overdose**. *Fomipezole* - **Fomepizole** is an antidote used for poisoning by **methanol** and **ethylene glycol**, not acetaminophen. - It works by inhibiting **alcohol dehydrogenase**, preventing the formation of toxic metabolites from these alcohols.

Practice by Chapter

Principles of Clinical Pharmacology

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Therapeutic Drug Monitoring

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Drug Toxicity and Overdose

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Antidotes and Their Applications

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Management of Drug Poisoning

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Drug-Induced Liver Injury

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Drug-Induced Kidney Injury

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Drug-Induced Blood Dyscrasias

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Drug-Induced QT Prolongation

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Pharmacovigilance

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