Chronopharmacology – definition and concepts MCQs With Answer

Chronopharmacology studies how biological timing and circadian rhythms influence drug action, pharmacokinetics and pharmacodynamics. For B. Pharm students, understanding chronopharmacology, chronotherapy, circadian clock genes (CLOCK, BMAL1, PER, CRY) and the role of the suprachiasmatic nucleus (SCN) is essential for optimizing dosing times, reducing toxicity and improving therapeutic outcomes. Time-dependent variation in absorption, distribution, hepatic metabolism (CYP enzymes), and renal excretion affects drug exposure and efficacy. Practical concepts include chronotype, zeitgebers, phase shifts, internal desynchrony, and chronotherapeutic drug delivery systems. This foundation helps design time-based regimens for antihypertensives, statins, cancer chemotherapy and asthma drugs. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary focus of chronopharmacology?

  • Studying drug interactions at the molecular level
  • Studying the effects of biological timing on drug action and disposition
  • Developing novel drug molecules
  • Evaluating placebo effects in clinical trials

Correct Answer: Studying the effects of biological timing on drug action and disposition

Q2. Which brain structure is the central pacemaker that coordinates circadian rhythms?

  • Hippocampus
  • Suprachiasmatic nucleus (SCN)
  • Basal ganglia
  • Thalamus

Correct Answer: Suprachiasmatic nucleus (SCN)

Q3. Which set of clock genes forms the core transcriptional feedback loop in mammals?

  • NF-κB, AP-1, CREB
  • CLOCK, BMAL1, PER, CRY
  • TP53, RB1, MYC
  • AKT, mTOR, PI3K

Correct Answer: CLOCK, BMAL1, PER, CRY

Q4. Chronokinetics refers to time-dependent variation in which of the following?

  • Drug discovery rates
  • Pharmacokinetic processes such as absorption and metabolism
  • Patient adherence patterns
  • Drug formulation stability

Correct Answer: Pharmacokinetic processes such as absorption and metabolism

Q5. Which term describes environmental cues that entrain biological rhythms?

  • Chronotype
  • Drug chronotherapy
  • Zeitgebers
  • Homeostasis

Correct Answer: Zeitgebers

Q6. Peak hepatic metabolism of many drugs often occurs at which circadian phase in humans?

  • Midnight to early morning
  • Late morning to afternoon
  • Evening to midnight
  • Randomly without pattern

Correct Answer: Late morning to afternoon

Q7. Which cytochrome P450 family shows pronounced circadian variation affecting drug metabolism?

  • CYP7A1
  • CYP3A4
  • CYP19A1
  • CYP26A1

Correct Answer: CYP3A4

Q8. Chronotherapy aims to:

  • Increase pill size for better absorption
  • Align drug dosing with biological rhythms to maximize efficacy and minimize toxicity
  • Replace drugs with herbal medicines
  • Reduce the number of drugs in a regimen

Correct Answer: Align drug dosing with biological rhythms to maximize efficacy and minimize toxicity

Q9. Which clinical condition is a classic example where evening dosing improves outcomes (e.g., HMG-CoA reductase inhibitors)?

  • Asthma
  • Hyperlipidemia
  • Parkinson’s disease
  • Bacterial infections

Correct Answer: Hyperlipidemia

Q10. What does “chronotype” refer to?

  • Time of drug expiration
  • Individual preference for timing of activity and sleep (morningness–eveningness)
  • Type of drug delivery device
  • Rate of drug absorption

Correct Answer: Individual preference for timing of activity and sleep (morningness–eveningness)

Q11. Which parameter is least likely to show circadian variation?

  • Plasma cortisol levels
  • Core body temperature
  • Renal glomerular filtration rate
  • Atomic weight of elements

Correct Answer: Atomic weight of elements

Q12. For antihypertensive therapy, which dosing time is commonly recommended to better control nocturnal blood pressure?

  • Early morning only
  • Evening or bedtime dosing for some agents
  • Midday dosing only
  • Randomized dosing times each day

Correct Answer: Evening or bedtime dosing for some agents

Q13. Which hormone is widely used as a chronobiotic to shift circadian rhythms?

  • Insulin
  • Melatonin
  • Prolactin
  • Thyroxine

Correct Answer: Melatonin

Q14. “Internal desynchrony” describes which situation?

  • Perfect alignment of all peripheral clocks
  • Mismatch between central and peripheral clocks
  • Mutation in CLOCK gene causing arrhythmia
  • Drug overdose causing toxicity

Correct Answer: Mismatch between central and peripheral clocks

Q15. Which analytical method is commonly used to assess rhythmicity in pharmacological time-series data?

  • Cosinor analysis
  • Western blotting
  • Northern blotting
  • Liquid chromatography-mass spectrometry (LC-MS) only

Correct Answer: Cosinor analysis

Q16. Which factor can mask circadian rhythms and complicate chronopharmacology studies?

  • Controlled lighting
  • Shift work or irregular sleep
  • Standardized meal times
  • Use of actigraphy

Correct Answer: Shift work or irregular sleep

Q17. In chronopharmacokinetics, which process is most directly affected by gastric emptying rhythms?

  • Hepatic metabolism
  • Drug absorption from the gut
  • Renal secretion
  • Transdermal delivery

Correct Answer: Drug absorption from the gut

Q18. Which concept explains entrainment of the biological clock to the external 24-hour day?

  • Homeostatic sleep drive
  • Phase response curve to zeitgebers
  • Random noise theory
  • First-pass metabolism

Correct Answer: Phase response curve to zeitgebers

Q19. Which drug class has shown time-dependent efficacy in asthma when dosed in the evening?

  • Inhaled corticosteroids
  • Beta-blockers
  • Statins
  • Anticoagulants

Correct Answer: Inhaled corticosteroids

Q20. Which experimental model is commonly used to study circadian drug effects at the molecular level?

  • Cell-free enzyme assays only
  • Clock gene knockout mice
  • Human randomized controlled trials only
  • In silico QSAR models only

Correct Answer: Clock gene knockout mice

Q21. Which term describes advancing or delaying the phase of the circadian clock?

  • Entrainment
  • Phase shift
  • Homeostasis
  • Biotransformation

Correct Answer: Phase shift

Q22. Chronotherapeutic drug delivery systems are designed primarily to:

  • Release drug uniformly regardless of time
  • Deliver drug at predetermined biological times to match disease rhythms
  • Increase pill taste
  • Reduce manufacturing costs

Correct Answer: Deliver drug at predetermined biological times to match disease rhythms

Q23. Which biomarker is commonly measured to assess central circadian phase in humans?

  • Plasma glucose only
  • Dim light melatonin onset (DLMO)
  • Serum creatinine
  • Urinary sodium

Correct Answer: Dim light melatonin onset (DLMO)

Q24. Which of the following is a likely consequence of dosing a short half-life drug at the wrong circadian phase?

  • No change in therapeutic outcome
  • Marked change in efficacy or increased toxicity
  • Permanent cure of disease
  • Instant tolerance development

Correct Answer: Marked change in efficacy or increased toxicity

Q25. In chronopharmacology, “masking” refers to:

  • Pharmacokinetic assays using masks
  • External factors hiding the true endogenous rhythm
  • Drug-induced sedation only
  • Genetic deletions of clock genes

Correct Answer: External factors hiding the true endogenous rhythm

Q26. Which physiological variable commonly shows a nadir (lowest point) during night sleep affecting drug response?

  • Blood pressure in nondippers
  • Plasma cortisol
  • Alkaline phosphatase
  • Bone density

Correct Answer: Plasma cortisol

Q27. For anticancer chronotherapy, timing can influence which of the following?

  • Tumor cell sensitivity and host toxicity
  • The chemical structure of the drug
  • Patentability of the drug
  • Color of the formulation

Correct Answer: Tumor cell sensitivity and host toxicity

Q28. Which practice helps reduce chronopharmacology variability in clinical studies?

  • Ignoring subject sleep habits
  • Standardizing meal, light and sampling times
  • Allowing unrestricted shift work during study
  • Randomly changing dosing times during the trial

Correct Answer: Standardizing meal, light and sampling times

Q29. Jet lag primarily results from:

  • Permanent damage to clock genes
  • Transient misalignment between internal clock and external time after rapid travel across time zones
  • Excessive caffeine intake only
  • Lack of exercise

Correct Answer: Transient misalignment between internal clock and external time after rapid travel across time zones

Q30. Which statement best summarizes the clinical value of chronopharmacology for pharmacists?

  • It only matters for veterinary medicine
  • Timing of drug administration can be optimized to improve efficacy, reduce adverse effects and personalize therapy
  • It replaces the need for pharmacokinetic studies
  • It suggests all drugs should be administered at midnight

Correct Answer: Timing of drug administration can be optimized to improve efficacy, reduce adverse effects and personalize therapy

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