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: 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: 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: Forced diuresis with acidification or alkalinization of urine is a common method for elimination of certain poisons/drugs from the body. The elimination of which of the following drugs is commonly enhanced by alkaline diuresis?

Phenobarbitone. ***Phenobarbitone*** - **Alkaline diuresis** enhances the elimination of weak acids like **phenobarbitone** by keeping them in their ionized form within the renal tubules, preventing reabsorption. - Ionized drugs are more water-soluble and are thus efficiently excreted in the urine. *Amphetamines* - **Amphetamines** are **weak bases**, and their elimination is enhanced by **acidification of urine**, which ionizes them and reduces their reabsorption. - Alkaline diuresis would not be effective, and might even hinder, the elimination of amphetamines. *Theophylline* - Theophylline is primarily metabolized in the liver, and its renal excretion is less influenced by urinary pH manipulation. - While it behaves as a weak acid, forced diuresis is not a primary method for its elimination in overdose situations. *Phencyclidine* - **Phencyclidine (PCP)** is a **weak base**, and its elimination is increased by **acidification of urine**, similar to amphetamines. - Alkaline diuresis would decrease the excretion of phencyclidine.

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

Which of the following drugs is metabolized by CYP2D6?

Accepted Answer

Propranolol

Answer

Warfarin

Answer

Statins

Answer

Amiodarone

Question 9

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 10

Forced diuresis with acidification or alkalinization of urine is a common method for elimination of certain poisons/drugs from the body. The elimination of which of the following drugs is commonly enhanced by alkaline diuresis?

Accepted Answer

Phenobarbitone

Answer

Amphetamines

Answer

Theophylline

Answer

Phencyclidine

Pharmacokinetics and Pharmacodynamics — MCQs

Pharmacokinetics and Pharmacodynamics — MCQs

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