The therapeutic index is a core concept for B. Pharm students linking pharmacokinetics and pharmacodynamics to patient safety. This introduction explains how the therapeutic index, therapeutic window, and narrow therapeutic index drugs determine dosing decisions, adverse effect risk, and the need for therapeutic drug monitoring. You will review calculations (LD50/ED50 or TD50/ED50), factors that alter safety margins (age, renal function, protein binding, pharmacogenetics), and clinical implications for dose adjustments, loading doses, and steady‑state monitoring. Solid grasp of these keywords—therapeutic index, therapeutic window, TDM, narrow therapeutic index drugs, pharmacokinetics, pharmacodynamics—improves rational prescribing and patient care. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the standard definition of the therapeutic index (TI) in toxicology and pharmacology?
- The ratio of toxic dose in humans to effective dose in animals
- The ratio of LD50 to ED50 determined experimentally
- The difference between maximum tolerated dose and minimum effective dose
- The plasma concentration range between MEC and MTC
Correct Answer: The ratio of LD50 to ED50 determined experimentally
Q2. A high therapeutic index generally indicates which of the following?
- A narrow safety margin and frequent monitoring required
- Greater likelihood of serious adverse effects at therapeutic doses
- A wider safety margin and lower risk of toxicity at usual doses
- A drug that requires complex dose titration in all patients
Correct Answer: A wider safety margin and lower risk of toxicity at usual doses
Q3. Which phrase best describes the therapeutic window?
- The dose range from LD1 to LD99
- The plasma concentration range between minimum effective concentration (MEC) and minimum toxic concentration (MTC)
- The interval between two successive doses
- The absolute difference between ED50 and LD50 values
Correct Answer: The plasma concentration range between minimum effective concentration (MEC) and minimum toxic concentration (MTC)
Q4. Which group of drugs is typically classified as narrow therapeutic index (NTI) drugs?
- Paracetamol, ibuprofen, amoxicillin
- Warfarin, digoxin, lithium, phenytoin
- Metformin, atenolol, omeprazole
- Atorvastatin, amlodipine, losartan
Correct Answer: Warfarin, digoxin, lithium, phenytoin
Q5. If LD50 = 200 mg and ED50 = 20 mg, what is the therapeutic index?
- 0.10
- 2
- 10
- 20
Correct Answer: 10
Q6. Which metric is commonly used to express the margin of safety rather than the classical TI?
- TD50/ED50
- LD50/ED50
- LD1/ED99
- ED50/LD50
Correct Answer: LD1/ED99
Q7. Therapeutic drug monitoring (TDM) is most indicated under which circumstance?
- The drug has a wide therapeutic window and predictable effects
- No measurable relationship exists between plasma concentration and effect
- The drug has a narrow therapeutic index, high variability, and clear concentration–effect relationship
- The drug is only used as a single acute dose
Correct Answer: The drug has a narrow therapeutic index, high variability, and clear concentration–effect relationship
Q8. Approximately how long does it take to reach steady state for a drug given at regular intervals?
- One half-life
- Two half-lives
- Four to five half-lives
- Ten to twelve half-lives
Correct Answer: Four to five half-lives
Q9. When is a loading dose most useful for drugs with a narrow therapeutic index?
- When rapid attainment of therapeutic concentration is required and volume of distribution is known
- Only for topical medications
- When the drug has negligible protein binding
- When there is no oral formulation available
Correct Answer: When rapid attainment of therapeutic concentration is required and volume of distribution is known
Q10. Which factor can significantly reduce the therapeutic index of a highly protein‑bound drug?
- Increased renal clearance with preserved protein levels
- Hypoalbuminemia leading to increased free drug fraction
- Enhanced first‑pass metabolism that decreases bioavailability
- Co‑administration of an inert placebo
Correct Answer: Hypoalbuminemia leading to increased free drug fraction
Q11. How does the therapeutic index differ from the therapeutic window?
- TI is a ratio of doses; therapeutic window is a range of plasma concentrations
- TI measures plasma concentrations; therapeutic window measures doses
- Both are identical concepts with different names
- TI is only used for antibiotics whereas therapeutic window is for cardiovascular drugs
Correct Answer: TI is a ratio of doses; therapeutic window is a range of plasma concentrations
Q12. ED50 is most closely related to which pharmacological concept?
- Potency—the dose producing half the maximal population response
- Safety—the dose that causes death in 50% of subjects
- Bioavailability—the fraction of dose reaching systemic circulation
- Clearance—the volume of plasma cleared per unit time
Correct Answer: Potency—the dose producing half the maximal population response
Q13. What does LD50 represent?
- The dose that produces a therapeutic effect in 50% of animals
- The dose lethal to 50% of a test animal population
- The plasma concentration at which 50% of patients experience side effects
- The time required for 50% of the drug to be eliminated
Correct Answer: The dose lethal to 50% of a test animal population
Q14. Which of these patient factors most commonly increases variability and narrows the effective therapeutic index?
- Stable hepatic and renal function
- Consistent adherence to dosing schedule
- Marked pharmacogenetic differences in metabolism
- Fixed body weight across population
Correct Answer: Marked pharmacogenetic differences in metabolism
Q15. Which of the following drugs typically requires routine TDM because of a narrow therapeutic index?
- Amoxicillin
- Digoxin
- Paracetamol (therapeutic dosing)
- Omeprazole
Correct Answer: Digoxin
Q16. When therapeutic and toxic effects are described using ED50 and TD50, how is an index similar to TI calculated?
- ED50/TD50
- TD50/ED50
- ED50 × TD50
- TD50 − ED50
Correct Answer: TD50/ED50
Q17. The minimum effective concentration (MEC) and minimum toxic concentration (MTC) define which clinical concept?
- Therapeutic window
- Bioavailability
- First‑order elimination kinetics
- Volume of distribution
Correct Answer: Therapeutic window
Q18. For a renally eliminated drug with a narrow therapeutic index, which dosing strategy is generally safest in renal impairment?
- Increase dose size and shorten dosing interval
- Maintain usual dose and interval regardless of renal function
- Reduce dose size or extend dosing interval and monitor plasma levels
- Switch to oral placebo until renal function recovers
Correct Answer: Reduce dose size or extend dosing interval and monitor plasma levels
Q19. Which source of interindividual variability is most important to consider when interpreting therapeutic index in practice?
- Uniform drug manufacturing standards
- Patient pharmacogenetics affecting metabolism
- Identical diets among patients
- Fixed route of administration for all drugs
Correct Answer: Patient pharmacogenetics affecting metabolism
Q20. Which drug below is least likely to be considered a narrow therapeutic index drug?
- Phenytoin
- Warfarin
- Digoxin
- Amoxicillin
Correct Answer: Amoxicillin
Q21. A small therapeutic index means what in clinical terms?
- Large margin of safety between effective and toxic doses
- Easy interchangeability between brands without monitoring
- High risk of adverse effects at doses close to therapeutic ones
- No need for dose adjustments in special populations
Correct Answer: High risk of adverse effects at doses close to therapeutic ones
Q22. LD50 is usually estimated during which stage of drug development?
- Phase III randomized clinical trials in humans
- Phase IV post‑marketing surveillance
- Preclinical animal toxicity studies
- Manufacturing quality control only
Correct Answer: Preclinical animal toxicity studies
Q23. If a drug has a therapeutic index of 2, what does this indicate?
- The drug is extremely safe with no monitoring needed
- The toxic dose is only twice the effective dose, indicating a narrow safety margin
- The effective dose exceeds the toxic dose
- The drug shows zero-order kinetics always
Correct Answer: The toxic dose is only twice the effective dose, indicating a narrow safety margin
Q24. For aminoglycosides, which TDM practice is most important to minimize toxicity?
- Measuring peak levels only after multiple doses
- Measuring trough concentrations before the next dose at steady state
- Performing daily liver enzyme assays
- Assessing urinary glucose levels
Correct Answer: Measuring trough concentrations before the next dose at steady state
Q25. Which pharmacokinetic parameter, when prolonged, most commonly predisposes to drug accumulation and narrowed effective TI?
- Shortened half‑life
- Increased clearance
- Prolonged half‑life
- Decreased bioavailability due to first‑pass effect
Correct Answer: Prolonged half‑life
Q26. If a patient’s plasma drug concentration exceeds the therapeutic window, the immediate clinical step should usually be:
- Increase the dose to overcome tolerance
- Discontinue or reduce the dose and reassess clinically and by plasma concentration
- Ignore and continue dosing as planned
- Switch to an unrelated medication without evaluation
Correct Answer: Discontinue or reduce the dose and reassess clinically and by plasma concentration
Q27. During clinical development, where is the therapeutic index most directly assessed for human relevance?
- During Phase I and dose‑escalation studies in humans
- Only during animal lethality testing
- In manufacturing stability studies
- After marketing when adverse reports accumulate
Correct Answer: During Phase I and dose‑escalation studies in humans
Q28. The loading dose formula uses which of the following parameters to calculate the initial dose?
- Volume of distribution, desired plasma concentration, and bioavailability
- Clearance, half‑life, and renal function only
- Route of excretion and pKa exclusively
- Therapeutic index and LD50 only
Correct Answer: Volume of distribution, desired plasma concentration, and bioavailability
Q29. When is the best time to collect a plasma sample for TDM to assess trough concentration?
- One hour after an oral dose
- Immediately before the next scheduled dose at steady state
- Randomly any time during therapy
- Exactly at the time of drug administration
Correct Answer: Immediately before the next scheduled dose at steady state
Q30. Which clinical condition increases the unbound fraction of highly protein‑bound drugs and may lower the effective therapeutic index?
- Hyperalbuminemia
- Hypoalbuminemia
- High hematocrit
- Normal plasma protein levels
Correct Answer: Hypoalbuminemia
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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