Clinical Pharmacology and Drug Toxicity Practice Questions

Q: A child with acute lymphoblastic leukemia was given Vincristine in V.A.L.P regimen. However there was an extravasation of the drug. All should be done for management of the same except?

Keep limb dependant. ***Keep limb dependant*** - Keeping the limb dependent will **increase blood flow** and venous congestion at the extravasation site, potentially worsening tissue damage. - The affected limb should be **elevated** to minimize swelling and promote lymphatic drainage. - This is the **INCORRECT** management step. *Aspiration of drug from the extravasated site* - This is an appropriate **immediate step** for managing extravasation. - Use a small syringe to attempt to **withdraw residual drug** from the subcutaneous tissue to minimize further tissue damage. *Apply warm compresses* - **Warmth is recommended** for vinca alkaloid extravasation (vincristine, vinblastine). - Warm compresses promote **vasodilation and drug dispersion**, enhancing absorption and reducing local tissue injury. - Apply for **15-20 minutes several times daily**. *Hyaluronidase injections* - **Hyaluronidase is the specific antidote** for vinca alkaloid extravasation. - It breaks down **hyaluronic acid** in connective tissue, increasing tissue permeability. - This facilitates **dispersion and absorption** of the extravasated drug, thereby reducing tissue necrosis. - Typical dose: **150-900 units subcutaneously** around the extravasation site.

Q: Detection of magnesium toxicity in a patient receiving magnesium sulphate is noticed by which of the following? I. Loss of tendon reflexes II. Increased respiratory rate III. Heart block, prolonged PR interval IV. Cardiac arrest Select the correct answer using the code given below :

I, III and IV. ***I, III and IV*** - **Loss of tendon reflexes** is an early sign of magnesium toxicity, typically occurring at serum magnesium levels between **4-6 mEq/L**. - **Heart block** and a **prolonged PR interval** are cardiac manifestations of magnesium toxicity, indicating impaired electrical conduction in the heart. **Cardiac arrest** represents the most severe cardiac complication, usually occurring with very high magnesium levels (**>15 mEq/L**). *III and IV only* - This option correctly identifies **heart block** (prolonged PR interval) and **cardiac arrest** as signs of magnesium toxicity. - However, it **omits the loss of tendon reflexes**, which is a crucial and often earlier indicator of toxicity. *I and III only* - This option correctly includes **loss of tendon reflexes** and **heart block** (prolonged PR interval) as signs of magnesium toxicity. - It **fails to include cardiac arrest**, which is a severe and critical consequence of profound magnesium toxicity. *II and IV only* - **Increased respiratory rate** is generally **not a sign of magnesium toxicity**; rather, magnesium toxicity can lead to **respiratory depression** or arrest. - While **cardiac arrest** is a correct sign, the inclusion of increased respiratory rate makes this option inaccurate.

Q: Consider the following regarding salicylate poisoning : I. Arterial pH of 7.25 , anion gap of 18 mmol / L II. Arterial pH of 7.25 , anion gap of 10 mmol / L III. pCO2 of 20 mm Hg IV. pCO2 of 48 mm Hg Which disturbance is likely to be encountered?

I and III. ***I and III*** - Salicylate poisoning typically presents with a **mixed acid-base disorder** consisting of primary **respiratory alkalosis** and primary **metabolic acidosis with an increased anion gap** [1]. - A pH of 7.25 with an anion gap of 18 mmol/L (normal range 8-12 mmol/L) indicates **metabolic acidosis with an increased anion gap**, while a pCO2 of 20 mmHg (normal range 35-45 mmHg) indicates **respiratory alkalosis** [2]. *II and III* - An anion gap of 10 mmol/L is within the normal range, which is inconsistent with the **metabolic acidosis with increased anion gap** expected in salicylate poisoning [1]. - While pCO2 of 20 mmHg indicates respiratory alkalosis, the normal anion gap makes this combination less likely for salicylate poisoning. *II and IV* - An anion gap of 10 mmol/L is within the normal range, which does not reflect the typical **anion gap metabolic acidosis** seen in salicylate poisoning. - A pCO2 of 48 mmHg indicates respiratory acidosis, which is generally not the primary respiratory disturbance in salicylate poisoning; rather, **respiratory alkalosis** due to direct stimulation of the respiratory center is more characteristic [1]. *I and IV* - While an anion gap of 18 mmol/L is consistent with **anion gap metabolic acidosis**, a pCO2 of 48 mmHg indicates respiratory acidosis. - The classic picture of salicylate poisoning includes **respiratory alkalosis** due to direct stimulation of the respiratory center, not respiratory acidosis [1].

Q: A 45 year old farmer came with accidental consumption of a pesticide. He complained of frequent urination and excessive salivation. Which one of the following toxidromes is most likely to be associated with this poisoning?

Cholinergic. ***Cholinergic*** The patient's symptoms of frequent urination and excessive salivation, along with accidental pesticide consumption, are classic signs of **organophosphate poisoning**, which falls under the **cholinergic toxidrome** [1, 2]. This toxidrome is characterized by excessive stimulation of the **cholinergic system**, leading to symptoms memorized by the acronyms **SLUDGE** (Salivation, Lacrimation, Urination, Defecation, Gastrointestinal upset, Emesis) and **DUMBBELS** (Diarrhea, Urination, Miosis, Bradycardia, Bronchorrhea, Emesis, Lacrimation, Salivation) [1]. *Adrenergic* The adrenergic toxidrome is associated with sympathetic overactivity, leading to symptoms like **tachycardia**, **hypertension**, **mydriasis**, agitation, and hyperthermia. These symptoms are opposite to the parasympathetic overactivity observed in this patient. *Hypnotic* The hypnotic toxidrome typically presents with **CNS depression**, including **sedation**, **respiratory depression**, **bradycardia**, and **hypotension**. This toxidrome does not match the patient's symptoms of excessive salivation and frequent urination. *Serotonergic* The serotonergic toxidrome (serotonin syndrome) is characterized by a triad of mental status changes, autonomic hyperactivity (e.g., **tachycardia**, **hypertension**, hyperthermia), and neuromuscular abnormalities (e.g., **hyperreflexia**, clonus). The patient's presentation does not align with these hallmark features.

Q: What is the antidote for belladonna poisoning?

Physostigmine. ***Physostigmine*** - **Physostigmine** is a **reversible acetylcholinesterase inhibitor** that increases acetylcholine levels at the muscarinic and nicotinic receptors. - This effectively counteracts the **anticholinergic effects** of belladonna, which contains atropine and scopolamine, by overcoming the competitive blockade. *Atropine* - **Atropine** is the primary toxic component in belladonna, acting as a **muscarinic acetylcholine receptor antagonist**. - Administering atropine would worsen the existing anticholinergic toxidrome, making it a contraindicated treatment. *Amitriptyline* - **Amitriptyline** is a **tricyclic antidepressant** and has significant **anticholinergic properties** itself. - Using amitriptyline would exacerbate rather than treat the symptoms of belladonna poisoning due to its similar mechanism of action. *Flumazenil* - **Flumazenil** is an **antagonist of benzodiazepine receptors** and is used to reverse benzodiazepine overdose. - It has no effect on the muscarinic receptor blockade caused by belladonna alkaloids and would not be effective in this poisoning.

Q: Fomepizole is an antidote used to treat poisoning from which of the following substances? I. Methanol II. Digoxin III. Cocaine IV. Ethylene glycol Select the correct answer using the code given below :

I and IV. ***I and IV*** - **Fomepizole** is a competitive inhibitor of **alcohol dehydrogenase**, the enzyme that metabolizes both methanol and ethylene glycol into toxic metabolites [1]. - For **methanol** poisoning: Prevents conversion to **formic acid**, which causes metabolic acidosis and optic nerve damage [2]. - For **ethylene glycol** poisoning: Prevents conversion to **glycolic acid and oxalic acid**, which cause metabolic acidosis, renal failure, and calcium oxalate crystal deposition [1]. - Fomepizole is the preferred antidote over ethanol due to its safer profile and ease of administration. *III and IV* - While ethylene glycol (IV) is correctly identified, **cocaine** (III) poisoning is not treated with fomepizole. - Cocaine toxicity management involves supportive care, benzodiazepines for agitation and seizures, and management of cardiovascular complications (hypertension, arrhythmias). - Fomepizole has no role in cocaine overdose as the toxic mechanism does not involve alcohol dehydrogenase. *I and II* - While methanol (I) is correctly identified, **digoxin** (II) poisoning is not treated with fomepizole. - Digoxin toxicity is managed with **digoxin-specific antibody fragments (Digoxin Fab)**, which bind and neutralize digoxin. - Fomepizole's mechanism of alcohol dehydrogenase inhibition is irrelevant to digoxin toxicity. *II and III* - Neither **digoxin** (II) nor **cocaine** (III) poisoning is treated with fomepizole. - Both substances have different toxic mechanisms unrelated to alcohol dehydrogenase. - Digoxin requires Fab fragments; cocaine requires supportive care and symptomatic management.

Q: Which one of the following is used to reverse the anticoagulant effects of Dabigatran?

Idarucizumab. ***Idarucizumab*** - **Idarucizumab** is a **monoclonal antibody fragment** specifically designed to bind to dabigatran and its active metabolites. - This binding neutralizes the anticoagulant effect of dabigatran, providing **rapid reversal** in emergency situations. *Desferrioxamine* - **Desferrioxamine** is a **chelating agent** used to treat **iron poisoning**. - It works by binding to iron in the bloodstream, facilitating its excretion from the body, and has no effect on anticoagulant drugs. *Protamine* - **Protamine** is used to reverse the anticoagulant effects of **heparin** by forming a stable salt with it. - It is **not effective** for reversing the effects of direct oral anticoagulants like dabigatran. *Glucarpidase* - **Glucarpidase** is an enzyme used to reduce toxic plasma methotrexate concentrations in patients with impaired renal function. - It catalyzes the hydrolysis of methotrexate into inactive metabolites and has **no role** in anticoagulant reversal.

Q: Which one of the following is an antidote for Rivaroxaban and Apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding?

Andexanet Alfa. ***Andexanet Alfa*** - **Andexanet Alfa** is a **modified recombinant factor Xa molecule** that acts as a decoy to bind and sequester direct factor Xa inhibitors like rivaroxaban and apixaban. - It is specifically indicated for the reversal of anticoagulation in patients treated with **rivaroxaban** or **apixaban** experiencing life-threatening or uncontrolled bleeding [1]. *Hydroxocobalamin* - **Hydroxocobalamin** is an antidote for **cyanide poisoning**, not for anticoagulant reversal. - It works by binding to cyanide to form cyanocobalamin, which can be excreted, thereby detoxifying the patient. *Glucarpidase* - **Glucarpidase** is used to rapidly lower **methotrexate concentrations** in patients with delayed methotrexate elimination and associated toxicity. - It is an enzyme that hydrolyzes methotrexate into inactive metabolites, facilitating its clearance. *Idarucizumab* - **Idarucizumab** is a specific reversal agent for **dabigatran**, a direct thrombin inhibitor. - It is a monoclonal antibody fragment that binds to dabigatran with high affinity, neutralizing its anticoagulant effect.

Q: Which of the following drugs can cause secondary weight gain? I. Insulin II. Propranolol III. Orlistat IV. Thyroxine Select the correct answer using the code given below :

I and II only. ***I and II only*** - **Insulin** promotes glucose uptake and storage as glycogen or fat, and its therapeutic use can lead to **weight gain** due to increased fat deposition. - **Propranolol**, a non-selective beta-blocker, can decrease metabolic rate and physical activity tolerance due to slowed heart rate, contributing to **weight gain**. *I and III* - While **Insulin** causes weight gain, **Orlistat** specifically acts as a **lipase inhibitor** to *reduce* fat absorption, thereby *promoting weight loss*, not gain. *II, III and IV* - **Propranolol** can cause weight gain, but **Orlistat** facilitates weight loss. **Thyroxine**, used to treat hypothyroidism, generally *promotes weight loss* by increasing metabolism, not weight gain. *I, II and IV* - **Insulin** and **Propranolol** can cause weight gain. However, **Thyroxine** (levothyroxine) is used to correct hypothyroidism and typically leads to **weight loss** by normalizing metabolic rate, rather than causing weight gain.

Q: Absolute contraindication to combined oral contraceptive is:

History of thrombo-embolism. ***History of thrombo-embolism*** - A history of **thromboembolism** (e.g., DVT, pulmonary embolism) is an **absolute contraindication** to combined oral contraceptives (COCs) due to the increased risk of further thrombotic events associated with estrogen. - COCs, particularly their estrogen component, can increase levels of clotting factors and decrease natural anticoagulants, significantly raising the risk of **venous thromboembolism (VTE)**. *History of gallbladder disease* - A history of **gallbladder disease** is generally considered a **relative contraindication** rather than an absolute one for COCs. - While COCs may exacerbate pre-existing gallbladder conditions or increase the risk of gallstone formation in some individuals, it doesn't preclude their use in all cases. *History of GDM* - A history of **gestational diabetes mellitus (GDM)** is a **relative contraindication** or caution for COC use, particularly in women with additional risk factors for diabetes. - While COCs can affect glucose tolerance, they are not absolutely contraindicated unless the woman has developed overt diabetes or has poorly controlled metabolic issues. *History of previous two caesarean section* - A history of previous **two cesarean sections** is **not a contraindication** to combined oral contraceptive use. - This obstetric history does not impact the metabolic or thrombotic risks associated with COCs, and thus, does not directly interact with their safety profile.

Question 1

A child with acute lymphoblastic leukemia was given Vincristine in V.A.L.P regimen. However there was an extravasation of the drug. All should be done for management of the same except?

Accepted Answer

Keep limb dependant

Answer

Aspiration of drug from the extravasated site

Answer

Hyaluronidase injections

Answer

Apply warm compresses

Question 2

Detection of magnesium toxicity in a patient receiving magnesium sulphate is noticed by which of the following?
I. Loss of tendon reflexes
II. Increased respiratory rate
III. Heart block, prolonged PR interval
IV. Cardiac arrest

Select the correct answer using the code given below :

Accepted Answer

I, III and IV

Answer

III and IV only

Answer

I and III only

Answer

II and IV only

Question 3

Consider the following regarding salicylate poisoning :
I. Arterial pH of 7.25 , anion gap of 18 mmol / L
II. Arterial pH of 7.25 , anion gap of 10 mmol / L
III. pCO2 of 20 mm Hg
IV. pCO2 of 48 mm Hg

Which disturbance is likely to be encountered?

Accepted Answer

I and III

Answer

II and III

Answer

II and IV

Answer

I and IV

Question 4

A 45 year old farmer came with accidental consumption of a pesticide. He complained of frequent urination and excessive salivation. Which one of the following toxidromes is most likely to be associated with this poisoning?

Accepted Answer

Cholinergic

Answer

Adrenergic

Answer

Hypnotic

Answer

Serotonergic

Question 5

What is the antidote for belladonna poisoning?

Accepted Answer

Physostigmine

Answer

Atropine

Answer

Amitriptyline

Answer

Flumazenil

Question 6

Fomepizole is an antidote used to treat poisoning from which of the following substances?
I. Methanol
II. Digoxin
III. Cocaine
IV. Ethylene glycol

Select the correct answer using the code given below :

Accepted Answer

I and IV

Answer

III and IV

Answer

I and II

Answer

II and III

Question 7

Which one of the following is used to reverse the anticoagulant effects of Dabigatran?

Accepted Answer

Idarucizumab

Answer

Desferrioxamine

Answer

Protamine

Answer

Glucarpidase

Question 8

Which one of the following is an antidote for Rivaroxaban and Apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding?

Accepted Answer

Andexanet Alfa

Answer

Hydroxocobalamin

Answer

Glucarpidase

Answer

Idarucizumab

Question 9

Which of the following drugs can cause secondary weight gain?
I. Insulin
II. Propranolol
III. Orlistat
IV. Thyroxine

Select the correct answer using the code given below :

Accepted Answer

I and II only

Answer

I and III

Answer

II, III and IV

Answer

I, II and IV

Question 10

Absolute contraindication to combined oral contraceptive is:

Accepted Answer

History of thrombo-embolism

Answer

History of gallbladder disease

Answer

History of GDM

Answer

History of previous two caesarean section

Clinical Pharmacology and Drug Toxicity — MCQs

Clinical Pharmacology and Drug Toxicity — MCQs

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