Drug Metabolism and Excretion — MCQs

10 questions

Pharmacodynamics deals with:-

All of the following drugs require dose reduction in renal failure except?

Volume of distribution of a drug is 500 ml and target concentration of drug in blood is 5 g/L. 20% of administered drug is reached to systemic circulation. What will be the loading dose of that drug -

All are true for cytochrome P450 enzymes EXCEPT:

Drug X has an affinity for albumin, while drug Y has 150 times greater affinity. Which of the following statements is MOST accurate?

Which of the following drugs is known to have low first pass metabolism?

Which sedative is most appropriate in a patient with hepatic impairment?

Which of the following combinations can result in severe toxicity due to inhibition of cytochrome P450 enzymes?

A drug is more likely to cause toxicity in elderly patients due to all of the following reasons except which of the following?

Q10

Which drug is metabolized by glutathionation?

Drug Metabolism and Excretion Indian Medical PG Practice Questions and MCQs

Question 1: Pharmacodynamics deals with:-

A. Latency of onset
B. Mechanism of action of a drug (Correct Answer)
C. Transport of drug across the biological membranes
D. Mode of excretion of a drug

Explanation: Detailed study of the **Mechanism of action of a drug** [1][2] - **Pharmacodynamics** describes what the **drug does to the body**, including its **molecular targets** and biochemical effects [3]. - This involves the study of the drug's mechanisms to produce its therapeutic or toxic effects [2]. *Latency of onset* - **Latency of onset** refers to the time it takes for a drug to start producing its effects, which is a pharmacokinetic rather than a pharmacodynamic parameter. - It deals with the drug's absorption and distribution rather than its interaction with the body once it reaches its site of action. *Transport of drug across the biological membranes* - The **transport of drugs across biological membranes** is a key aspect of **pharmacokinetics**, specifically absorption and distribution [1]. - This process determines how much drug reaches its target site, not how it interacts with the target. *Mode of excretion of a drug* - The **mode of excretion** of a drug (e.g., renal, hepatic) falls under **pharmacokinetics**, addressing how the body gets rid of the drug. - This process influences the drug's duration of action and elimination half-life, not its mechanism of action.

Question 2: All of the following drugs require dose reduction in renal failure except?

A. Doxycycline (Correct Answer)
B. Vancomycin
C. Gentamicin
D. Acyclovir

Explanation: ***Doxycycline*** - **Doxycycline** is primarily eliminated via the gastrointestinal tract (fecal excretion) and does NOT require dose adjustment in patients with **renal impairment**. [1] - Its unique elimination pathway makes it a safe choice for treating infections in patients with **renal failure**. - This is a key distinguishing feature among tetracyclines. *Vancomycin* - **Vancomycin** is predominantly eliminated by the kidneys (80-90% unchanged in urine). - Accumulation in renal failure can lead to **ototoxicity** and **nephrotoxicity**. - Dosage must be carefully adjusted based on **creatinine clearance** and therapeutic drug monitoring is essential. *Gentamicin* - **Gentamicin**, an aminoglycoside, is almost entirely excreted unchanged by the kidneys. - Highly **nephrotoxic** and **ototoxic** with narrow therapeutic index. - Dose reduction and extended dosing intervals are critical in **renal failure** to prevent drug accumulation and serious adverse effects. [3] *Acyclovir* - **Acyclovir** is primarily eliminated renally (60-90% excreted unchanged in urine). - Requires significant **dose reduction in renal impairment** to prevent crystalluria and neurotoxicity. [2] - Dosing adjustment based on creatinine clearance is mandatory to avoid adverse effects.

Question 3: Volume of distribution of a drug is 500 ml and target concentration of drug in blood is 5 g/L. 20% of administered drug is reached to systemic circulation. What will be the loading dose of that drug -

A. 1 gm
B. 5 gm
C. 25 gm
D. 12.5 gm (Correct Answer)

Explanation: ***12.5 gm*** - The formula for loading dose (LD) is: LD = (Target Concentration × Volume of Distribution) / Bioavailability. - Given: Target Concentration = 5 g/L, Volume of Distribution = 500 mL = 0.5 L, Bioavailability = 20% = 0.2. - So, LD = (5 g/L × 0.5 L) / 0.2 = 2.5 g / 0.2 = **12.5 g**. *1 gm* - This value would be obtained if the target concentration was 2 g/L with 100% bioavailability, or if the calculation incorrectly handled the volume or bioavailability factor. - It does not account for the specified **bioavailability of 20%** or the given target concentration and volume of distribution. *5 gm* - This result would be obtained if the bioavailability was assumed to be 50% (LD = 2.5 g / 0.5 = 5 g), or if the volume of distribution was incorrectly used in the calculation. - This option does not correctly factor in the **20% bioavailability** of the administered drug. *25 gm* - This value would result from mistakes such as dividing by bioavailability of 10% instead of 20% (LD = 2.5 g / 0.1 = 25 g), or by multiplying bioavailability instead of dividing by it. - This answer significantly **overestimates** the required dose, which could lead to drug toxicity.

Question 4: All are true for cytochrome P450 enzymes EXCEPT:

A. Synthesize amino acids (Correct Answer)
B. Involved in drug metabolism
C. Present mainly in the liver
D. Part of Phase I metabolism

Explanation: ***Synthesize amino acids*** - Cytochrome P450 enzymes are primarily involved in the **metabolism of xenobiotics** and endogenous compounds, not in the synthesis of amino acids. - **Amino acid synthesis** occurs through different metabolic pathways involving various enzymes distinct from the cytochrome P450 system. *Involved in drug metabolism* - Cytochrome P450 enzymes are a major group of enzymes crucial for the **biotransformation of numerous drugs** and other foreign compounds. - They typically catalyze **oxidation reactions**, preparing drugs for excretion. *Present mainly in the liver* - While present in many tissues, the **highest concentration and diversity** of cytochrome P450 enzymes are found in the **liver**, which is the primary site of drug metabolism. - They are also found in the gastrointestinal tract, kidney, lung, and brain, but to a lesser extent. *Part of Phase I metabolism* - Cytochrome P450 enzymes are the **principal enzymes responsible for Phase I reactions** in drug metabolism. - **Phase I metabolism** generally involves reduction, oxidation, or hydrolysis reactions to introduce polar groups to the drug molecule.

Question 5: Drug X has an affinity for albumin, while drug Y has 150 times greater affinity. Which of the following statements is MOST accurate?

A. Drug X will be more available in tissues
B. Drug Y will be less available in tissues
C. Toxicity of drug Y may be influenced by multiple factors, not just its binding.
D. The free concentration of drug X in blood is higher, facilitating tissue distribution. (Correct Answer)

Explanation: ***Correct: The free concentration of drug X in blood is higher, facilitating tissue distribution.*** - This is the **MOST accurate and complete** answer because it directly addresses the pharmacokinetic mechanism - Drug X has **lower affinity for albumin** → larger proportion remains **unbound (free)** in plasma - Only **free (unbound) drug** can cross capillary membranes to distribute into tissues - This statement precisely explains both the **cause** (higher free concentration) and **effect** (facilitating tissue distribution) *Drug X will be more available in tissues* - This statement is **factually true** and follows logically from drug X's lower protein binding - However, it's **less precise** than the correct answer because it doesn't explicitly explain the **mechanism** (higher free concentration) - The term "available" is less specific than "free concentration," which is the key pharmacokinetic parameter *Drug Y will be less available in tissues* - This statement is also **factually true** - drug Y's **150× higher albumin affinity** means more drug is bound - Higher protein binding → **smaller free fraction** → less tissue distribution - However, like option 1, this doesn't explicitly state the **mechanistic principle** involving free drug concentration - The question asks for the MOST accurate statement, and this focuses on drug Y rather than explaining the core concept *Toxicity of drug Y may be influenced by multiple factors, not just its binding* - While this is a **true general principle**, it's **not directly relevant** to the specific question - This statement doesn't address the **pharmacokinetic implications** of differential albumin binding - It's too vague and doesn't demonstrate understanding of the relationship between protein binding and tissue distribution - The question specifically asks about the affinity differences and their consequences

Question 6: Which of the following drugs is known to have low first pass metabolism?

A. Lidocaine
B. Propranolol
C. Theophylline (Correct Answer)
D. Morphine

Explanation: ***Theophylline*** - **Theophylline** exhibits **low first-pass metabolism**, meaning a significant portion of the orally administered drug reaches systemic circulation unchanged. - This characteristic contributes to its relatively **high bioavailability** when given orally. *Lidocaine* - **Lidocaine** undergoes extensive **first-pass metabolism** in the liver, leading to very low oral bioavailability. - Due to this, it is typically administered **parenterally** (e.g., intravenously or topically) to achieve therapeutic concentrations. *Propranolol* - **Propranolol** is known for its significant **first-pass metabolism**, which results in a much lower bioavailability after oral administration compared to intravenous. - This extensive metabolism necessitates higher oral doses to achieve the same therapeutic effect as parenteral administration. *Morphine* - **Morphine** also undergoes substantial **first-pass metabolism** in the liver, where it is primarily glucuronidated. - This leads to a lower oral bioavailability compared to other routes of administration and contributes to a higher oral dose requirement.

Question 7: Which sedative is most appropriate in a patient with hepatic impairment?

A. Midazolam
B. Lorazepam (Correct Answer)
C. Zolpidem
D. Diazepam

Explanation: ***Lorazepam*** - **Lorazepam** is primarily metabolized by **glucuronidation**, a phase II metabolic pathway that is relatively preserved in most forms of hepatic impairment - This makes it a safer choice in patients with **liver disease** compared to other benzodiazepines that rely heavily on oxidative metabolism - Preferred sedative in cirrhosis and acute liver failure *Midazolam* - **Midazolam** is primarily metabolized by the **cytochrome P450 3A4 (CYP3A4)** enzyme system in the liver - Hepatic impairment can significantly reduce **CYP3A4 activity**, leading to prolonged half-life, increased sedative effects, and accumulation of the drug - Should be avoided or dose-reduced in hepatic impairment *Zolpidem* - **Zolpidem** is extensively metabolized by **hepatic cytochrome P450 enzymes**, particularly CYP3A4 and CYP2C9 - In patients with **hepatic impairment**, its clearance is significantly reduced, necessitating dose reduction to avoid excessive sedation and adverse effects - Maximum dose should be limited to 5 mg in hepatic dysfunction *Diazepam* - **Diazepam** undergoes extensive **hepatic oxidative metabolism** via CYP2C19 and CYP3A4 to active metabolites such as **desmethyldiazepam**, which also have long half-lives - In patients with **liver disease**, this metabolism is impaired, leading to prolonged drug action, increased sedation, and accumulation of the parent drug and active metabolites - Active metabolites can accumulate for days to weeks in hepatic impairment

Question 8: Which of the following combinations can result in severe toxicity due to inhibition of cytochrome P450 enzymes?

A. Amiodarone + Atorvastatin
B. Carbamazepine + Atorvastatin
C. Atorvastatin + Itraconazole (Correct Answer)
D. Phenytoin + Atorvastatin

Explanation: ***Atorvastatin + Itraconazole*** - **Itraconazole** is a potent inhibitor of **CYP3A4**, the primary enzyme responsible for atorvastatin's metabolism. - Co-administration leads to significantly increased **atorvastatin plasma concentrations**, raising the risk of severe side effects like **rhabdomyolysis** and **hepatotoxicity**. *Amiodarone + Atorvastatin* - **Amiodarone** is a moderate **CYP3A4 inhibitor** and can increase atorvastatin levels, but the inhibition is **less potent** than itraconazole. - While this combination does carry a risk and requires dose adjustment, the interaction is **less severe** compared to the potent inhibition seen with itraconazole. - The direct CYP inhibition leading to severe atorvastatin toxicity is less pronounced than with itraconazole. *Carbamazepine + Atorvastatin* - **Carbamazepine** is a potent **CYP3A4 inducer**, meaning it would increase the metabolism of atorvastatin, potentially *decreasing* its efficacy rather than causing toxicity through inhibition. - This interaction would typically lead to subtherapeutic atorvastatin levels, rather than severe toxicity. *Phenytoin + Atorvastatin* - **Phenytoin** is also a potent **CYP3A4 inducer**, similar to carbamazepine. - Concurrent use would likely lead to enhanced metabolism and **reduced efficacy of atorvastatin**, not increased toxicity due to enzyme inhibition.

Question 9: 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 10: Which drug is metabolized by glutathionation?

A. Nicotinic acid
B. Fosfomycin
C. Benzodiazepines
D. Dapsone (Correct Answer)

Explanation: ***Dapsone***- **Dapsone** undergoes hepatic metabolism via **N-hydroxylation** by CYP450 enzymes (particularly CYP2E1 and CYP3A4), forming reactive **hydroxylamine metabolites**.- These reactive metabolites are toxic and can cause **methemoglobinemia** and **hemolysis**.- **Glutathione conjugation (glutathionation)** serves as an important **detoxification pathway** for these reactive dapsone metabolites [1].- Individuals with **glutathione deficiency** (such as G6PD deficiency) are at increased risk of dapsone-induced hemolytic anemia [2].*Fosfomycin*- **Fosfomycin** is primarily eliminated by the kidneys as an **unchanged drug** (up to 90% excreted unchanged in urine).- It undergoes **minimal hepatic metabolism** and does NOT undergo significant glutathionation.- Its primary route of elimination is **renal excretion** via glomerular filtration.*Benzodiazepines*- **Benzodiazepines** are primarily metabolized in the liver via **CYP450 enzymes** (Phase I oxidation) followed by **glucuronidation** (Phase II conjugation).- They do NOT undergo glutathionation as a significant metabolic pathway.*Nicotinic acid*- **Nicotinic acid** (niacin) undergoes conjugation with **glycine** to form nicotinuric acid and **methylation** to form N-methylnicotinamide.- It does NOT undergo glutathione conjugation.

Want unlimited practice?

Get full access to all questions, explanations, and performance tracking.

Start For Free