Chronopharmacology: biological and circadian rhythms MCQs With Answer

Chronopharmacology: biological and circadian rhythms MCQs With Answer

This quiz set is designed for M.Pharm students taking Advanced Pharmacology-II and focuses on chronopharmacology — the study of how biological timing systems influence drug action, metabolism and toxicity. The questions cover fundamental concepts (central and peripheral clocks, zeitgebers), measurement and analysis of rhythms (acrophase, mesor, cosinor), molecular mechanisms (clock genes, entrainment pathways), and clinical applications (chronotherapy, chronotoxicity, formulation strategies). Designed to deepen understanding beyond definitions, these MCQs emphasize practical implications for dosing time, drug development and trial design, helping students apply circadian principles to optimize therapy and reduce adverse effects.

Q1. What is the primary focus of chronopharmacology?

• The effect of genetic polymorphisms on drug targets
• The influence of environmental toxins on drug stability
• The timing-dependent variation in drug pharmacokinetics and pharmacodynamics
• Formulation techniques for extended-release tablets

Correct Answer: The timing-dependent variation in drug pharmacokinetics and pharmacodynamics

Q2. Which structure is considered the master circadian pacemaker in mammals?

• The pineal gland
• The suprachiasmatic nucleus (SCN) of the hypothalamus
• The ventrolateral preoptic nucleus
• The locus coeruleus

Correct Answer: The suprachiasmatic nucleus (SCN) of the hypothalamus

Q3. In chronobiology, what is a zeitgeber?

• A genetic mutation that alters clock genes
• An external cue that synchronizes biological rhythms to the environment
• An endogenous hormone produced in a circadian manner
• An analytical tool for rhythm analysis

Correct Answer: An external cue that synchronizes biological rhythms to the environment

Q4. A circadian rhythm is defined by which approximate period?

• About 12 hours
• About 24 hours
• About 7 days
• About 1 hour

Correct Answer: About 24 hours

Q5. What does the term “acrophase” refer to in rhythm analysis?

• The overall mean level of the rhythm
• The time of the peak of a rhythmic variable
• The duration of one complete cycle
• The lowest point (nadir) in the cycle

Correct Answer: The time of the peak of a rhythmic variable

Q6. Which statistical method is commonly used to quantify circadian rhythm parameters such as mesor, amplitude and acrophase?

• Kruskal–Wallis test
• Cosinor analysis
• Kaplan–Meier survival analysis
• Principal component analysis

Correct Answer: Cosinor analysis

Q7. Which pair of core molecular clock components form a transcriptional activator heterodimer driving circadian gene expression?

• PER and CRY
• CLOCK and BMAL1
• REV-ERBα and RORα
• CK1ε and CK1δ

Correct Answer: CLOCK and BMAL1

Q8. Light entrains the central circadian clock primarily via which neural pathway?

• The spinothalamic tract
• The retinohypothalamic tract
• The nigrostriatal pathway
• The corticospinal tract

Correct Answer: The retinohypothalamic tract

Q9. Circadian variation in which hepatic enzyme family is most often cited as affecting time-of-day differences in drug metabolism?

• Methyltransferases
• CYP450 (e.g., CYP3A4) enzymes
• Glutathione peroxidases
• Carboxylesterases

Correct Answer: CYP450 (e.g., CYP3A4) enzymes

Q10. Why are many HMG-CoA reductase inhibitors (statins) recommended for evening dosing?

• Gastric acid secretion is highest at night improving absorption
• Liver HMG-CoA reductase activity and cholesterol synthesis peak during night fasting
• Statins cause daytime drowsiness that is avoided by night dosing
• Renal clearance of statins is maximal at night

Correct Answer: Liver HMG-CoA reductase activity and cholesterol synthesis peak during night fasting

Q11. Chronotherapy for hypertension sometimes favors bedtime dosing of ACE inhibitors because:

• ACE inhibitors have no circadian variation in efficacy
• Nocturnal blood pressure surge makes morning dosing superior
• Bedtime dosing improves control of nocturnal blood pressure and restores dipping pattern
• They cause insomnia when taken in the morning

Correct Answer: Bedtime dosing improves control of nocturnal blood pressure and restores dipping pattern

Q12. Chronotoxicity refers to which concept?

• The constant toxicity level of a drug regardless of dose
• The variation in adverse effects of a drug depending on the time of administration
• The ability of a drug to alter circadian rhythms permanently
• The misuse of chronotherapy leading to overdose

Correct Answer: The variation in adverse effects of a drug depending on the time of administration

Q13. Peak endogenous melatonin secretion in humans typically occurs at which time relative to the light–dark cycle?

• Midday (around noon)
• Early morning (around 6 AM)
• Night (during the dark period)
• Immediately at sunset only

Correct Answer: Night (during the dark period)

Q14. Which statement about peripheral clocks is correct?

• Peripheral clocks are only found in the brain
• Peripheral clocks in organs (e.g., liver, heart) can be phase-shifted independently of the SCN by feeding and drugs
• Peripheral clocks do not express core clock genes
• Peripheral clocks are identical in phase to the SCN under all conditions

Correct Answer: Peripheral clocks in organs (e.g., liver, heart) can be phase-shifted independently of the SCN by feeding and drugs

Q15. The phase response curve (PRC) describes:

• The daily amplitude of hormone secretion
• How a stimulus (e.g., light) at different circadian times produces phase advances or delays
• The half-life change of drugs over 24 hours
• The genetic variability of clock genes among populations

Correct Answer: How a stimulus (e.g., light) at different circadian times produces phase advances or delays

Q16. Chronopharmaceutics primarily concerns:

• Designing drug delivery systems that release drugs at predetermined times to match biological rhythms
• Stability testing of drugs under accelerated conditions
• The study of drug interactions at the molecular level
• The development of generic formulations

Correct Answer: Designing drug delivery systems that release drugs at predetermined times to match biological rhythms

Q17. Long-term circadian misalignment such as chronic shift work has been epidemiologically associated with increased risk of:

• Improved glucose tolerance
• Reduced cardiovascular risk
• Metabolic syndrome, type 2 diabetes and cardiovascular disease
• Enhanced nocturnal immunity

Correct Answer: Metabolic syndrome, type 2 diabetes and cardiovascular disease

Q18. In chronobiology, “mesor” refers to:

• The timing of the peak value of a rhythm
• The rhythm-adjusted mean around which oscillation occurs
• The total area under the rhythmic curve
• The frequency of oscillation per hour

Correct Answer: The rhythm-adjusted mean around which oscillation occurs

Q19. Which pharmacokinetic factor is commonly affected by circadian changes in gastrointestinal physiology, altering oral drug absorption?

• Renal glomerular filtration rate only
• The rate of gastric emptying and intestinal motility
• The stability of intravenous formulations
• The encapsulation efficiency of nanoparticles

Correct Answer: The rate of gastric emptying and intestinal motility

Q20. When designing a clinical trial to test a chronotherapy hypothesis, which design consideration is most important?

• Ignoring time of dosing because biological variability averages out
• Including time-of-day as a controlled variable and possibly using crossover designs to compare dosing times
• Using only a single morning dose group to simplify analysis
• Excluding measurements of circadian markers to reduce cost

Correct Answer: Including time-of-day as a controlled variable and possibly using crossover designs to compare dosing times

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