Pharmacokinetics and Pharmacodynamics Practice Questions

Q: Alkaline diuresis is done for which of the following drugs?

Phenobarbitone. ***Phenobarbitone*** - **Phenobarbitone** is a weak acid, and its elimination can be enhanced by **alkaline diuresis**. - By increasing the pH of urine, **ionization** of the drug increases, reducing its reabsorption in the renal tubules and promoting excretion. *Morphine* - **Morphine** is an opioid analgesic that is largely metabolized in the liver and primarily excreted as **glucuronide conjugates** in the urine; alkaline diuresis is not a primary method for its elimination. - Although morphine is a **weak base**, its excretion is not significantly affected by alteration of urine pH because it is primarily eliminated through hepatic metabolism and conjugation rather than pH-dependent renal excretion. *Amphetamine* - **Amphetamine** is a weak base, and its elimination is enhanced by **acidic diuresis**, which increases its ionization in the urine. - **Alkaline diuresis** would *decrease* its excretion by promoting its reabsorption in the renal tubules. *Atropine* - **Atropine** is an anticholinergic drug with both renal and hepatic elimination, but its excretion is not significantly altered by **alkaline diuresis**. - Its elimination is influenced by its metabolism and renal excretion of unchanged drug, but not substantially by urinary pH manipulation for therapeutic purposes.

Q: An acidic drug with a pKa value of 4.5 has what percentage of ionized drug at a pH of 3.5?

10%. ***Correct: 10%*** - For an acidic drug, use the **Henderson-Hasselbalch equation**: **pH = pKa + log([ionized]/[unionized])** - Rearranging: **pH - pKa = log([ionized]/[unionized])** - Given **pH = 3.5** and **pKa = 4.5**: 3.5 - 4.5 = **-1** - Therefore: **log([ionized]/[unionized]) = -1** - This means: **[ionized]/[unionized] = 10^-1 = 0.1 = 1/10** - Percentage ionized = **1/(1+10) × 100% = 1/11 × 100% = 9.09%**, which rounds to **~10%** - **Key principle**: When pH < pKa for an acidic drug, the drug is predominantly **unionized** (protonated, HA form) *Incorrect: 1%* - This percentage would occur if **pH - pKa = -2** (e.g., pH 2.5 and pKa 4.5) - At this difference, [ionized]/[unionized] = 10^-2 = **1/100**, giving **~1% ionized** - Does not match the given values where the difference is only **-1** *Incorrect: 90%* - This represents the percentage of **unionized drug** in this scenario, not ionized - For an acidic drug to be **90% ionized**, the pH must be **significantly higher than pKa** (pH - pKa ≈ +1) - Since pH > pKa** (specifically when **pH - pKa ≥ +2**) - For example, at pH 6.5 and pKa 4.5, the drug would be **~99% ionized** - The given **pH of 3.5 is below the pKa**, so the drug is predominantly **unionized** (~91%), not ionized

Q: 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?

0.22 L/hr. ***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).

Q: MDR gene acts by what mechanism?

Causes efflux of drug. ***Causes efflux of drug*** - The **MDR gene** (multidrug resistance gene) encodes for **P-glycoprotein**, an ATP-dependent efflux pump. - This pump actively **transports drugs out of the cell**, reducing their intracellular concentration and effectiveness. *Inhibit drug activation* - This mechanism is associated with enzymes like **CYP450 isoenzymes** or **esterases** that metabolize prodrugs into their active forms. - The MDR gene and its product, P-glycoprotein, are efflux pumps and do not directly inhibit drug activation. *Inhibit intracellular DNA synthesis* - This is the mechanism of action for certain classes of drugs, such as **antimetabolites** (e.g., methotrexate) or **nucleoside analogs**. - The MDR gene's role is in drug transport, not in interfering with DNA synthesis itself. *Inhibit DNA repair* - Some chemotherapeutic agents, like **PARP inhibitors**, work by preventing cells from repairing DNA damage, leading to apoptosis. - While related to drug action, this is not the primary mechanism by which the MDR gene confers resistance; instead, it reduces drug exposure to DNA targets.

Q: Which of the following is an example of a prodrug?

Levodopa. ***Levodopa is a prodrug that converts to dopamine.*** - A **prodrug** is an inactive precursor of a drug that is converted into its active form within the body. - **Levodopa** is converted to the active neurotransmitter **dopamine** in the brain, making it effective for Parkinson's disease. *Primidone is an anticonvulsant with active metabolites.* - While Primidone has **active metabolites** (phenobarbital and phenylethylmalonamide), the parent drug itself also possesses significant **anticonvulsant activity**, meaning it is not an inactive precursor. - A true prodrug is therapeutically inactive until metabolized. *Digitoxin is a cardiac glycoside that acts directly.* - **Digitoxin** is a cardiac glycoside that directly inhibits the **Na+/K+-ATPase pump**, exerting its therapeutic effect without requiring conversion to an active metabolite. - It does not undergo enzymatic conversion to an active form to produce its primary action. *Amitriptyline is an antidepressant that acts directly.* - **Amitriptyline** is a **tricyclic antidepressant** that directly inhibits the reuptake of norepinephrine and serotonin. - While it is metabolized to an active metabolite (nortriptyline), Amitriptyline itself is **pharmacologically active** as the parent drug.

Q: Which of the following drugs does not concentrate in bile?

Alpha methyl dopa. ***Alpha methyl dopa*** - **Alpha methyl dopa** is primarily excreted by the kidneys and does not undergo significant biliary excretion or concentration in bile. - Its concentration in bile is negligible compared to other drugs known for biliary excretion. *Erythromycin* - **Erythromycin** is well-known for its significant biliary excretion and concentration in bile. - This characteristic can lead to drug interactions and cholestasis in some patients due to its processing in the liver. *Tetracycline* - **Tetracycline** antibiotics, including tetracycline itself, are excreted extensively in bile. - **Enterohepatic recirculation** is a common phenomenon with tetracyclines, contributing to their prolonged half-life. *Oral contraceptives* - Many components of **oral contraceptives**, particularly estrogen metabolites, undergo extensive hepatic metabolism and enterohepatic recirculation, leading to their concentration in bile. - The biliary excretion of these compounds is a key factor in their pharmacokinetic profile and drug interactions.

Q: Which drug exhibits zero-order kinetics at high doses?

Phenytoin. ***Phenytoin*** - At **high doses**, the metabolic enzymes for phenytoin become saturated, leading to **zero-order kinetics** where a constant amount of drug is eliminated per unit time, regardless of concentration. - This saturation can result in a disproportionate increase in plasma concentration with small dose increases, making **phenytoin toxicity** a significant concern. *Propranolol* - Generally follows **first-order kinetics** within its therapeutic dose range, meaning a constant *fraction* of the drug is eliminated per unit time. - Its elimination rate is **concentration-dependent** at typical doses. *Amiloride* - This diuretic is primarily eliminated unchanged by the kidneys and follows **first-order kinetics**. - Its elimination is proportional to its plasma concentration. *Lithium* - Primarily eliminated renally and exhibits **first-order kinetics**, with its elimination rate proportional to its concentration. - It has a **narrow therapeutic index** but its elimination profile does not switch to zero-order at high doses.

Q: Assuming the half-life of gentamicin is 3 hours in this patient, what percentage of the initial dose is most likely to remain in the body 6 hours later?

25%. ***25%*** - After **one half-life** (3 hours), 50% of the initial dose remains. - After **two half-lives** (6 hours), 25% of the initial dose remains (50% of the remaining 50%). *12.5%* - This percentage would remain after **three half-lives** (9 hours), not 6 hours. - Each half-life reduces the remaining drug by 50%, so 50% -> 25% -> 12.5%. *33%* - This value does not correspond to a direct calculation based on the given half-life. - The drug concentration would decrease by a factor of 4 (100% to 25%) over two half-lives. *50%* - This percentage would remain after **one half-life** (3 hours), not 6 hours. - The question asks for the amount remaining after two half-lives have passed.

Q: Which of the following drugs is metabolized by CYP2D6?

Propranolol. ***Correct Answer: Propranolol*** - **Propranolol** is a non-selective beta-blocker that undergoes extensive **first-pass metabolism**, primarily via the **CYP2D6** and CYP1A2 enzymes. - Genetic variations in **CYP2D6** can significantly affect propranolol's metabolism, leading to altered drug levels and therapeutic responses. *Incorrect: Warfarin* - **Warfarin** is predominantly metabolized by **CYP2C9**, with minor contributions from other CYP enzymes. - Genetic polymorphisms in **CYP2C9** are a major factor in determining individual warfarin dose requirements. *Incorrect: Statins* - Most **statins** (e.g., simvastatin, lovastatin, atorvastatin) are primarily metabolized by **CYP3A4**. - **Fluvastatin** is an exception, being mainly metabolized by CYP2C9, while **rosuvastatin** is largely unmetabolized. *Incorrect: Amiodarone* - **Amiodarone** is primarily metabolized by **CYP3A4** and to a lesser extent by CYP2C8. - Due to its **long half-life** and extensive metabolism, amiodarone has numerous drug interactions, often involving CYP3A4 inhibition.

Q: What does the time for peak plasma concentration (Tmax) indicate?

The rate of absorption. ***The rate of absorption*** - **Tmax** is the time at which the **maximum drug concentration** in the plasma is reached [1]. - A shorter **Tmax** indicates a faster rate at which the drug is absorbed from its administration site into the systemic circulation [1]. *The rate of elimination* - The rate of elimination is primarily reflected by the **elimination half-life (t½)** of the drug, which is the time it takes for the plasma concentration to decrease by half. - While Tmax is influenced by both absorption and elimination, it does not directly indicate the elimination rate [1]. *The duration of effect* - The **duration of effect** is related to how long the drug concentration remains above the minimum effective concentration (MEC), which is influenced by both absorption and elimination, but not directly indicated by Tmax alone. - A drug's duration of action is better described by its **elimination half-life** and the **therapeutic window**. *The intensity of effect* - The **intensity of effect** is largely related to the **maximum plasma concentration (Cmax)** and the drug's affinity for its target, and not directly by the time it takes to reach that concentration. - **Cmax** indicates how much drug is in the bloodstream, which often correlates with the intensity of the pharmacological response.

Question 1

Alkaline diuresis is done for which of the following drugs?

Accepted Answer

Phenobarbitone

Answer

Morphine

Answer

Amphetamine

Answer

Atropine

Question 2

An acidic drug with a pKa value of 4.5 has what percentage of ionized drug at a pH of 3.5?

Accepted Answer

10%

Answer

1%

Answer

90%

Answer

99%

Question 3

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?

Accepted Answer

0.22 L/hr

Answer

20 liter/hr

Answer

K is 0.0693

Answer

0.02 L/hr

Question 4

MDR gene acts by what mechanism?

Accepted Answer

Causes efflux of drug

Answer

Inhibit drug activation

Answer

Inhibit intracellular DNA synthesis

Answer

Inhibit DNA repair

Question 5

Which of the following is an example of a prodrug?

Accepted Answer

Levodopa

Answer

Primidone

Answer

Digitoxin

Answer

Amitriptyline

Question 6

Which of the following drugs does not concentrate in bile?

Accepted Answer

Alpha methyl dopa

Answer

Erythromycin

Answer

Tetracycline

Answer

Oral contraceptives

Question 7

Which drug exhibits zero-order kinetics at high doses?

Accepted Answer

Phenytoin

Answer

Propranolol

Answer

Amiloride

Answer

Lithium

Question 8

Assuming the half-life of gentamicin is 3 hours in this patient, what percentage of the initial dose is most likely to remain in the body 6 hours later?

Accepted Answer

25%

Answer

12.5%

Answer

33%

Answer

50%

Question 9

Which of the following drugs is metabolized by CYP2D6?

Accepted Answer

Propranolol

Answer

Warfarin

Answer

Statins

Answer

Amiodarone

Question 10

What does the time for peak plasma concentration (Tmax) indicate?

Accepted Answer

The rate of absorption

Answer

The rate of elimination

Answer

The duration of effect

Answer

The intensity of effect

Pharmacokinetics and Pharmacodynamics — MCQs

Pharmacokinetics and Pharmacodynamics — MCQs

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