Biological clock – significance and relation to chronotherapy MCQs With Answer

The biological clock governs circadian rhythms that coordinate physiology, behavior and molecular processes across a ~24-hour cycle. Understanding clock genes, the suprachiasmatic nucleus, peripheral clocks, and Zeitgebers is essential for B.Pharm students learning chronopharmacology and chronotherapy. Drug absorption, distribution, metabolism and excretion show time-of-day variation, affecting pharmacokinetics and pharmacodynamics. Chronotherapy and chrono-drug delivery aim to optimize drug timing to improve efficacy and reduce toxicity in conditions like hypertension, asthma and cancer. This topic links molecular chronobiology with practical dosing strategies and formulation design, preparing pharmacists to apply time-based therapeutics. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the biological clock?

  • An endogenous timing system that generates circadian rhythms
  • An external environmental cue like light
  • A hormone secreted only at night
  • A therapeutic device to regulate sleep

Correct Answer: An endogenous timing system that generates circadian rhythms

Q2. Which structure is the master pacemaker of mammalian circadian rhythms?

  • Hypothalamic arcuate nucleus
  • Pineal gland
  • Suprachiasmatic nucleus
  • Ventral tegmental area

Correct Answer: Suprachiasmatic nucleus

Q3. Which pair of genes act as positive transcriptional activators in the core mammalian clock feedback loop?

  • PER and CRY
  • CLOCK and BMAL1
  • REV-ERB and ROR
  • p53 and RB

Correct Answer: CLOCK and BMAL1

Q4. What is a Zeitgeber?

  • A clock gene mutation
  • An environmental cue that entrains circadian rhythms
  • A type of chronotherapeutic drug
  • A peripheral clock oscillator

Correct Answer: An environmental cue that entrains circadian rhythms

Q5. The intrinsic period of the human circadian rhythm is closest to:

  • 12 hours
  • 24 hours
  • 48 hours
  • 7 days

Correct Answer: 24 hours

Q6. Peripheral clocks are found in which tissues?

  • Only the brain
  • Only the pineal gland
  • Most peripheral tissues such as liver and heart
  • Only in reproductive organs

Correct Answer: Most peripheral tissues such as liver and heart

Q7. Which gland secretes melatonin in a circadian manner?

  • Adrenal gland
  • Pineal gland
  • Thyroid gland
  • Pancreas

Correct Answer: Pineal gland

Q8. Chronopharmacology is the study of:

  • Drug-drug interactions only
  • Time-dependent variations in drug effects and pharmacokinetics
  • The genetic basis of disease
  • Nanoparticle drug delivery

Correct Answer: Time-dependent variations in drug effects and pharmacokinetics

Q9. Chronotherapy for hypertension often recommends dosing certain antihypertensives at what time to reduce morning blood pressure surge?

  • Before breakfast
  • At midday
  • At bedtime
  • Immediately upon waking

Correct Answer: At bedtime

Q10. Cytochrome P450 enzyme activity over 24 hours typically:

  • Remains constant throughout the day
  • Shows circadian variation affecting drug metabolism
  • Is only active during sleep
  • Is independent of clock gene regulation

Correct Answer: Shows circadian variation affecting drug metabolism

Q11. Which pharmacokinetic parameter is directly influenced by daily variations in gastric emptying and intestinal motility?

  • Drug receptor affinity
  • Absorption rate
  • Renal clearance only
  • Protein tertiary structure

Correct Answer: Absorption rate

Q12. Hepatic blood flow and liver enzyme expression varying with time of day most directly affect:

  • Drug absorption in the stomach
  • First-pass metabolism and systemic clearance
  • Drug taste and odor
  • Transdermal penetration only

Correct Answer: First-pass metabolism and systemic clearance

Q13. Chronomodulated chemotherapy aims to:

  • Increase dosing frequency without altering outcome
  • Deliver cytotoxic agents at times that maximize tumor kill and minimize host toxicity
  • Use lower drug doses with no timing consideration
  • Administer drugs only in the morning

Correct Answer: Deliver cytotoxic agents at times that maximize tumor kill and minimize host toxicity

Q14. For many patients with nocturnal asthma, optimal control may improve with dosing inhaled corticosteroids at:

  • Morning only
  • Evening
  • Once weekly
  • At random times

Correct Answer: Evening

Q15. A person’s chronotype refers to:

  • The frequency of medication dosing
  • Genetic polymorphisms in CYP enzymes only
  • The behavioral preference for timing of sleep and activity (morningness/eveningness)
  • ECG waveform patterns

Correct Answer: The behavioral preference for timing of sleep and activity (morningness/eveningness)

Q16. Jet lag results primarily from:

  • Permanent damage to clock genes
  • Desynchronization between internal circadian clocks and the new local time
  • An acute allergic response to altitude
  • Dehydration only

Correct Answer: Desynchronization between internal circadian clocks and the new local time

Q17. Lesioning the suprachiasmatic nucleus in animal models typically causes:

  • Enhanced circadian rhythmicity
  • Abolition of behavioral and physiological circadian rhythms
  • Immediate death
  • Increased melatonin secretion during day only

Correct Answer: Abolition of behavioral and physiological circadian rhythms

Q18. A mutation in the PERIOD (PER) gene most likely alters:

  • The absorption of oral drugs
  • The length of the circadian period (e.g., shorter or longer cycle)
  • Renal filtration rate directly
  • Vaccine efficacy only

Correct Answer: The length of the circadian period (e.g., shorter or longer cycle)

Q19. Chronotherapeutic drug delivery systems are designed to:

  • Release medication at a constant rate regardless of time
  • Target drug release to specific times of day when therapeutic need or efficacy is optimal
  • Eliminate all dosing requirements
  • Only release drug during sleep

Correct Answer: Target drug release to specific times of day when therapeutic need or efficacy is optimal

Q20. The term “acrophase” in chronobiology refers to:

  • The trough or lowest point of a rhythm
  • The peak time of a biological rhythm
  • The duration of drug action
  • The half-life of a hormone

Correct Answer: The peak time of a biological rhythm

Q21. Many HMG-CoA reductase inhibitors (statins) are most effective when administered at:

  • Night, due to nocturnal cholesterol synthesis
  • Midday only
  • Once per week
  • Immediately after heavy exercise

Correct Answer: Night, due to nocturnal cholesterol synthesis

Q22. Which anticancer drug has been reported to show time-dependent toxicity and efficacy, informing chronotherapy schedules?

  • Paracetamol
  • 5-fluorouracil
  • Amoxicillin
  • Ibuprofen

Correct Answer: 5-fluorouracil

Q23. Clock-controlled genes are responsible for regulating which processes relevant to pharmacology?

  • Metabolism, cell cycle and drug transporter expression
  • Only structural protein folding
  • Visual acuity exclusively
  • None of the physiological processes

Correct Answer: Metabolism, cell cycle and drug transporter expression

Q24. Entrainment of circadian rhythms refers to:

  • The loss of rhythmicity
  • The synchronization of internal clocks to external cues like light
  • Random fluctuations in gene expression
  • Permanent phase shifts without external input

Correct Answer: The synchronization of internal clocks to external cues like light

Q25. Chronic shift work has been epidemiologically linked to increased risk of:

  • Metabolic syndrome and cardiovascular disease
  • Improved long-term memory only
  • Decreased cancer risk universally
  • Immediate onset of diabetes within 24 hours

Correct Answer: Metabolic syndrome and cardiovascular disease

Q26. A chronobiotic is best described as:

  • An agent that shifts or entrains the circadian clock, for example melatonin
  • A drug that only increases blood pressure
  • A device measuring core body temperature
  • A chronically toxic compound

Correct Answer: An agent that shifts or entrains the circadian clock, for example melatonin

Q27. The sleep–wake cycle is regulated primarily by which two interacting processes?

  • Renal filtration and hepatic clearance
  • Circadian timing system and homeostatic sleep drive
  • Only environmental temperature
  • Immune response and digestive enzymes

Correct Answer: Circadian timing system and homeostatic sleep drive

Q28. Which statement best describes why time-of-day can affect both pharmacokinetics and pharmacodynamics?

  • Clock genes degrade all drugs at night
  • Physiological processes (enzyme activity, blood flow, receptor expression) vary across the day, altering drug ADME and response
  • Time-of-day has no measurable effect on drugs
  • Only drug taste is altered by time-of-day

Correct Answer: Physiological processes (enzyme activity, blood flow, receptor expression) vary across the day, altering drug ADME and response

Q29. Which biomarker is commonly used to determine circadian phase in humans?

  • Plasma insulin peak only
  • Dim light melatonin onset (DLMO)
  • Random daytime cortisol measurement
  • Skin pigmentation changes

Correct Answer: Dim light melatonin onset (DLMO)

Q30. When designing clinical trials for chronotherapy, which factor is most important to include as a variable?

  • Time-of-day or dosing time as an explicit factor in the protocol
  • Only age and gender, time is irrelevant
  • Exclude all circadian measurements to reduce complexity
  • Use a single time point for all subjects without rationale

Correct Answer: Time-of-day or dosing time as an explicit factor in the protocol

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