Compartment Models — MCQs
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 70 kg man was given a drug with a dose of 100 mg/kg body weight, twice daily. The half-life (t1/2) is 10 hours, the plasma concentration is 1.9 mg/mL, and the clearance is unknown. What is the clearance of this drug?
What would happen to the half-life and plasma concentration of a drug which follows first-order kinetics, if the dose is doubled?
Major determinant of loading dose of a drug is:
Low apparent volume of distribution of drug indicates that:
What is the commonly used concentration of tetracaine for topical anesthesia in minor ophthalmic procedures?
In which of the following conditions is digoxin most likely to accumulate to toxic levels?
What is the preferred concentration range of lidocaine for topical anesthesia?
The following plot comparing pharmacokinetics of different ibuprofen brands is called:
Which of the following drugs can be administered through all routes?
Compartment Models Indian Medical PG Practice Questions and MCQs
Question 1: 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 2: A 70 kg man was given a drug with a dose of 100 mg/kg body weight, twice daily. The half-life (t1/2) is 10 hours, the plasma concentration is 1.9 mg/mL, and the clearance is unknown. What is the clearance of this drug?
- A. 20 liter/hr
- B. K is 0.0693
- C. 0.22 L/hr (Correct Answer)
- D. 0.02 L/hr
Explanation: ***0.22 L/hr*** - To calculate clearance at steady state, we use the formula: **Clearance (Cl) = Dose Rate / Css** (steady-state plasma concentration). - **Dose rate calculation**: 100 mg/kg × 70 kg × 2 doses/day = 14,000 mg/day = 583.33 mg/hr - **Converting plasma concentration**: 1.9 mg/mL = 1900 mg/L - **Clearance calculation**: Cl = 583.33 mg/hr ÷ 1900 mg/L = **0.307 L/hr** - **Note**: The calculated value (0.307 L/hr) does not exactly match any option. The marked answer (0.22 L/hr) is the closest approximation among the given choices. This discrepancy may arise from rounding in the original question parameters or implicit assumptions about bioavailability/volume of distribution. *0.02 L/hr* - This value is approximately 15 times lower than the calculated clearance. - Such low clearance would result in much higher plasma concentrations or require significantly lower dosing. *20 liter/hr* - This clearance is approximately 65 times higher than calculated, representing an unrealistically high value for this scenario. - Such high clearance would result in very low plasma concentrations unless extremely high doses were administered. *K is 0.0693* - This represents the **elimination rate constant (k)**, calculated as k = 0.693/t1/2 = 0.693/10 hr = 0.0693 hr⁻¹. - While mathematically correct for k, the question specifically asks for **clearance**, not the elimination rate constant. - Clearance is related to k by: Cl = k × Vd (volume of distribution).
Question 3: What would happen to the half-life and plasma concentration of a drug which follows first-order kinetics, if the dose is doubled?
- A. Half - life and plasma concentration remains the same
- B. Half - life doubles and plasma concentration remains the same
- C. Half - life remains the same and plasma concentration doubles (Correct Answer)
- D. Half - life and plasma concentration doubles
Explanation: ***Half - life remains the same and plasma concentration doubles*** - In **first-order kinetics**, drug elimination is proportional to the **plasma concentration**, meaning a constant *fraction* of the drug is eliminated per unit of time. - Doubling the dose will **double the initial plasma concentration**, but the **half-life** (time taken for plasma concentration to halve) remains constant because the *rate of elimination proportionally increases* with concentration. *Half - life and plasma concentration remains the same* - This would only be true if the dose was not changed, or if the drug followed **zero-order kinetics** and the elimination system was already saturated, which is not the case here. - If the plasma concentration remained the same after doubling the dose, it would imply either no absorption or extremely rapid elimination, contradicting typical first-order drug behavior. *Half - life doubles and plasma concentration remains the same* - For **half-life to double**, there would need to be a **decrease in drug clearance** or an *increase in volume of distribution*, not simply a dose increase. - If plasma concentration remained the same despite a doubled dose, it would suggest a **major increase in clearance** or volume of distribution, which is not stated. *Half life and plasma concentration doubles* - While plasma concentration doubles with a doubled dose in **first-order kinetics**, the **half-life remains constant**. - Half-life is an **intrinsic pharmacokinetic parameter** determined by clearance and volume of distribution, not by the administered dose in first-order kinetics.
Question 4: Major determinant of loading dose of a drug is:
- A. Half life
- B. Volume of distribution (Correct Answer)
- C. Clearance
- D. Bioavailability
Explanation: **Volume of distribution** - The **loading dose (LD)** of a drug is calculated using the formula: LD = (Target plasma concentration × **Volume of distribution**) / Bioavailability. - The **volume of distribution (Vd)** is the **major determinant** because it directly determines how much drug is needed to achieve the desired plasma concentration throughout all body compartments. - A larger Vd means more drug must be administered to achieve the same plasma concentration, as the drug distributes extensively into tissues. *Half life* - **Half-life** primarily determines the **time to reach steady-state** and the **dosing interval** for maintenance doses. - It does not directly influence the initial amount of drug required to achieve a target concentration in the loading dose calculation. *Clearance* - **Clearance** is the primary determinant of the **maintenance dose rate**, as it dictates how quickly the drug is eliminated from the body. - Formula for maintenance dose: Maintenance dose rate = Clearance × Target concentration. - It is not the major determinant of the initial loading dose, which aims to achieve a therapeutic level quickly. *Bioavailability* - **Bioavailability (F)** is the fraction of an administered drug that reaches systemic circulation unchanged. - While bioavailability is included in the loading dose formula as a correction factor (especially important for oral drugs), the **volume of distribution** remains the **major determinant** as it defines the fundamental space the drug must fill to achieve target concentration.
Question 5: Low apparent volume of distribution of drug indicates that:
- A. Drug has low bioavailability
- B. Drug has low efficacy
- C. Drug is not extensively distributed to tissue (Correct Answer)
- D. Drug has low half life
Explanation: ***Drug is not extensively distributed to tissue*** - A **low apparent volume of distribution (Vd)** suggests that the drug primarily remains in the **vascular compartment**. - This indicates **minimal binding to peripheral tissues** and less distribution into extravascular spaces. *Drug has low bioavailability* - **Bioavailability** refers to the fraction of an administered drug that reaches the **systemic circulation unchanged**. - While related to drug disposition, a low Vd does not directly imply low bioavailability; a drug can have high bioavailability but remain largely in the blood. *Drug has low efficacy* - **Efficacy** is the maximum effect a drug can produce regardless of the dose. - Vd relates to drug distribution, not its pharmacological effect or **intrinsic activity** at its target. *Drug has low half life* - The **half-life** of a drug is determined by its **volume of distribution (Vd)** and **clearance (CL)** (t½ = 0.693 × Vd / CL). - While a low Vd can contribute to a shorter half-life if clearance is high, Vd alone does not solely determine half-life; clearance also plays a significant role.
Question 6: What is the commonly used concentration of tetracaine for topical anesthesia in minor ophthalmic procedures?
- A. 1%
- B. 0.5% (Correct Answer)
- C. 2%
- D. 0.25%
Explanation: ***0.5%*** - **Tetracaine 0.5%** is the standard and most commonly used concentration for **topical ocular anesthesia** in minor ophthalmic procedures. - This concentration provides effective and rapid onset topical anesthesia for procedures like tonometry, foreign body removal, and gonioscopy with minimal side effects. *1%* - **Tetracaine 1%** is a higher concentration not typically used for routine topical ophthalmic anesthesia due to an increased risk of **epithelial toxicity** and other side effects. - While it would provide more potent anesthesia, its use is generally limited to specific cases where stronger anesthesia is needed and the benefits outweigh the risks. *2%* - **Tetracaine 2%** is an even higher concentration, rarely used in ophthalmology because of a significantly increased risk of **corneal damage** and other ocular surface complications. - This concentration is considered too strong for topical use in the eye and could lead to prolonged epithelial defects. *0.25%* - **Tetracaine 0.25%** is a lower concentration that may not provide sufficient depth or duration of anesthesia for most minor ophthalmic procedures. - While it would have a lower risk of toxicity, its **suboptimal anesthetic effect** makes it less commonly used than 0.5%.
Question 7: In which of the following conditions is digoxin most likely to accumulate to toxic levels?
- A. Renal insufficiency (Correct Answer)
- B. Chronic hepatitis
- C. Advanced cirrhosis
- D. Chronic pancreatitis
Explanation: ***Renal insufficiency*** - **Digoxin** is primarily excreted unchanged by the **kidneys**, so impaired renal function significantly prolongs its half-life and leads to drug accumulation. - Patients with kidney failure require **dose adjustments** or closer monitoring of **digoxin levels** to prevent toxicity. *Chronic hepatitis* - **Chronic hepatitis** primarily affects the **liver's metabolic capacity**, which is not the primary route of **digoxin elimination**. - While severe hepatic dysfunction can subtly impact drug disposition, it's not the main reason for **digoxin accumulation** like **renal insufficiency**. *Advanced cirrhosis* - **Advanced cirrhosis** involves severe liver dysfunction, which can alter drug metabolism and protein binding. - However, **digoxin's elimination** is mainly renal, so liver disease alone does not typically lead to significant accumulation unless accompanied by **renal impairment**. *Chronic pancreatitis* - **Chronic pancreatitis** is a disorder of the pancreas and does not directly impact the **excretion or metabolism** of **digoxin**. - It would not be expected to cause **digoxin accumulation** to toxic levels.
Question 8: What is the preferred concentration range of lidocaine for topical anesthesia?
- A. 2-4% (Correct Answer)
- B. 7-12%
- C. 12-15%
- D. <2%
Explanation: ***Correct Option: 2-4%*** - **Lidocaine** is an **amide-type local anesthetic** commonly used for topical anesthesia to numb localized areas before minor procedures. - The **preferred concentration range for topical application is 2-4%**, which provides effective anesthesia with an acceptable safety profile. - **2% lidocaine gel/cream** is commonly used for skin and genital mucosa. - **4% lidocaine** is standard for oral and respiratory mucous membranes. - **5% lidocaine patches** are used for post-herpetic neuralgia. - This concentration range balances **clinical efficacy** with **minimal systemic toxicity risk**. *Incorrect Option: <2%* - Concentrations below **2%** are generally **suboptimal** for achieving significant topical anesthesia. - These lower concentrations result in **insufficient pain relief** or require longer application times. - While 0.5-1% solutions exist, they are primarily used for infiltration anesthesia, not topical application. *Incorrect Option: 7-12%* - Concentrations in the **7-12%** range are **too high** for routine topical use and increase the risk of **systemic toxicity**. - These concentrations are not standard in clinical practice for general topical anesthesia. - Higher concentrations increase absorption without proportional improvement in efficacy. *Incorrect Option: 12-15%* - Concentrations in the **12-15%** range are **excessively high** and pose substantial **risk of systemic absorption and toxicity**. - Such high concentrations are **not recommended** for topical anesthesia in clinical practice. - Even 10% sprays (used for oropharyngeal anesthesia) require strict dose limitations to prevent toxicity.
Question 9: The following plot comparing pharmacokinetics of different ibuprofen brands is called:
- A. Kaplan Meier plot
- B. Spaghetti plot (Correct Answer)
- C. Funnel plot
- D. Forest plot
Explanation: ***Spaghetti plot*** - A **spaghetti plot** is characterized by multiple lines, each representing an individual's data across different time points or conditions, creating a visual resemblance to strands of spaghetti. This plot is ideal for visualizing **individual changes** and patterns in longitudinal data. - In pharmacokinetics, spaghetti plots are useful to compare the **drug concentration profiles** of different brands or formulations within individuals or across a group, showing individual variability. *Kaplan Meier plot* - A Kaplan-Meier plot (or survival curve) is used to estimate the **survival probability** over time for a group of individuals. - It displays a step-wise curve that decreases over time, representing the proportion of subjects **surviving** or remaining event-free, which is clearly not what is depicted in the image. *Funnel plot* - A **funnel plot** is a scatter plot used in meta-analyses to detect **publication bias** or small study effects. - It plots the study effect size against a measure of its precision (e.g., standard error), typically forming a triangular or funnel shape if no bias is present. *Forest plot* - A **forest plot** is a graphical display used in meta-analyses to illustrate the **results of individual studies** along with their pooled estimate. - Each study is represented by a square and a horizontal line indicating the effect size and its **confidence interval**, respectively.
Question 10: Which of the following drugs can be administered through all routes?
- A. Fentanyl (Correct Answer)
- B. Paracetamol
- C. Penicillin G
- D. Azithromycin
Explanation: **Explanation:** **Fentanyl** is the correct answer because it is a highly lipophilic opioid with high potency, allowing it to be formulated for virtually every route of administration. Its pharmacological profile supports: * **Parenteral:** IV, IM, and Epidural/Intrathecal (common in anesthesia). * **Transdermal:** Patches for chronic pain management. * **Transmucosal:** Buccal tablets, lozenges ("lollipop"), and sublingual sprays. * **Intranasal:** Used for breakthrough pain. * **Nebulization:** Occasionally used for dyspnea in palliative care. **Why the other options are incorrect:** * **Paracetamol:** While available as Oral, Rectal, and IV (Parven), it is **not** administered via transdermal or inhalational routes due to its chemical properties and the high dosage required for efficacy. * **Penicillin G:** It is acid-labile and destroyed by gastric acid, making it unsuitable for the **oral** route (unlike Penicillin V). It is primarily given IM or IV. * **Azithromycin:** It is available via Oral and IV routes. However, it lacks transdermal, sublingual, or routine inhalational formulations. **NEET-PG High-Yield Pearls:** * **Lipophilicity:** Fentanyl is 100 times more potent than morphine; its high lipid solubility is the key reason it can cross the skin (transdermal) and mucous membranes easily. * **First-Pass Metabolism:** Fentanyl undergoes extensive hepatic first-pass metabolism, which is why the oral (swallowed) route is ineffective, necessitating transmucosal (buccal/sublingual) delivery to bypass the liver. * **Context-Sensitive Half-Life:** Fentanyl’s duration of action increases significantly with prolonged infusions, a critical concept in ICU sedation.
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