Direct acting parasympathomimetics – Methacholine MCQs With Answer

Direct acting parasympathomimetics – Methacholine MCQs With Answer

Direct acting parasympathomimetics, especially methacholine, are essential topics for B.Pharm students studying muscarinic agonists, mechanism of action, pharmacodynamics and clinical applications. This focused set covers methacholine’s pharmacology, receptor selectivity, diagnostic use in bronchial hyperresponsiveness, dose-response relationships, adverse effects, contraindications and interactions. Emphasis is placed on structure-activity relationships, muscarinic receptor subtypes, clinical testing protocols, and management of complications. These MCQs are designed to deepen understanding, reinforce mechanistic concepts, and prepare you for exams and clinical reasoning in therapeutics. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which receptor subtype is primarily responsible for bronchoconstriction produced by methacholine?

• M1 muscarinic receptor
• M2 muscarinic receptor
• M3 muscarinic receptor
• M4 muscarinic receptor

Correct Answer: M3 muscarinic receptor

Q2. Methacholine is most commonly used clinically as:

• A bronchodilator for asthma treatment
• An intravenous vasopressor
• A diagnostic agent for bronchial hyperresponsiveness
• An anti-muscarinic antagonist

Correct Answer: A diagnostic agent for bronchial hyperresponsiveness

Q3. Compared with acetylcholine, methacholine differs mainly by having:

• A longer alkyl chain on the nitrogen
• A beta-methyl group on the acetate side chain increasing muscarinic selectivity
• A tertiary amine instead of quaternary ammonium
• Complete resistance to cholinesterase hydrolysis

Correct Answer: A beta-methyl group on the acetate side chain increasing muscarinic selectivity

Q4. Methacholine’s quaternary ammonium structure results in which pharmacokinetic property?

• High oral bioavailability
• Poor penetration of the blood–brain barrier
• Significant hepatic metabolism producing active metabolites
• Long half-life due to tissue accumulation

Correct Answer: Poor penetration of the blood–brain barrier

Q5. The methacholine challenge test assesses airway responsiveness by measuring:

• Change in arterial blood gases after inhalation
• Increase in sputum eosinophils post exposure
• Reduction in FEV1 (forced expiratory volume in 1 second)
• Change in heart rate during provocation

Correct Answer: Reduction in FEV1 (forced expiratory volume in 1 second)

Q6. A 20% fall in FEV1 during a methacholine challenge indicates:

• Normal airway responsiveness
• Significant bronchial hyperresponsiveness consistent with asthma
• Cardiac origin of dyspnea
• Immediate need for systemic steroids

Correct Answer: Significant bronchial hyperresponsiveness consistent with asthma

Q7. Which property of methacholine makes it more selective for muscarinic receptors than acetylcholine?

• Presence of a carbamate ester
• Beta-methyl substitution at the alpha carbon of the acetyl group
• Tertiary amine instead of quaternary ammonium
• Increased lipophilicity allowing muscarinic receptor binding

Correct Answer: Beta-methyl substitution at the alpha carbon of the acetyl group

Q8. Which of the following adverse effects is most likely after inhaled methacholine during testing?

• Widespread urticaria
• Bronchospasm causing cough and wheeze
• Severe hypotension leading to syncope
• Acute myocardial infarction

Correct Answer: Bronchospasm causing cough and wheeze

Q9. Which medication is recommended to reverse methacholine-induced bronchospasm immediately?

• Intravenous atropine
• Inhaled short-acting beta2 agonist (e.g., salbutamol)
• Oral theophylline
• Inhaled corticosteroid

Correct Answer: Inhaled short-acting beta2 agonist (e.g., salbutamol)

Q10. Methacholine is resistant to rapid hydrolysis by acetylcholinesterase because:

• It is a quaternary ammonium that blocks the enzyme active site
• The beta-methyl group sterically hinders enzymatic hydrolysis
• It lacks an ester bond susceptible to cholinesterase
• It is bound tightly to plasma proteins preventing access

Correct Answer: The beta-methyl group sterically hinders enzymatic hydrolysis

Q11. Which statement about methacholine pharmacodynamics is correct?

• It primarily activates nicotinic receptors at the neuromuscular junction
• It is a non-selective beta-adrenergic agonist
• It is a direct muscarinic receptor agonist causing smooth muscle contraction
• It acts by increasing sympathetic norepinephrine release

Correct Answer: It is a direct muscarinic receptor agonist causing smooth muscle contraction

Q12. In the methacholine challenge, which patient characteristic is a contraindication to performing the test?

• Well-controlled seasonal allergic rhinitis
• Baseline FEV1 less than 50% predicted
• History of childhood asthma with normal adult lung function
• Mild stable COPD

Correct Answer: Baseline FEV1 less than 50% predicted

Q13. The diagnostic sensitivity of the methacholine test is highest for:

• Ruling in COPD
• Detecting bronchial hyperresponsiveness in asthma
• Diagnosing pulmonary embolism
• Identifying cardiac asthma

Correct Answer: Detecting bronchial hyperresponsiveness in asthma

Q14. Which structural feature of methacholine reduces its nicotinic activity compared to acetylcholine?

• Beta-methyl substituent near the ester oxygen
• Lack of an ester linkage
• Presence of an aromatic ring
• Secondary amine instead of quaternary

Correct Answer: Beta-methyl substituent near the ester oxygen

Q15. Which of the following best explains why methacholine is administered by inhalation for bronchial challenge?

• Inhalation increases systemic toxicity but provides better results
• Inhalation delivers drug directly to airway smooth muscle with minimal systemic effects
• Methacholine is inactive unless inhaled
• Inhalation prolongs methacholine half-life systemically

Correct Answer: Inhalation delivers drug directly to airway smooth muscle with minimal systemic effects

Q16. Which of these is an expected cardiovascular effect of systemic muscarinic stimulation by methacholine?

• Tachycardia due to beta1 stimulation
• Bradycardia due to activation of vagal M2 receptors in the heart
• Prolonged QT interval via potassium channel blockade
• Increased cardiac contractility via direct M3 receptors on myocardium

Correct Answer: Bradycardia due to activation of vagal M2 receptors in the heart

Q17. Which pharmacological property of methacholine makes it suitable for diagnostic testing rather than therapeutic use?

• Strong nicotinic receptor activation producing systemic effects
• High oral bioavailability and long duration of action
• Potent local muscarinic effects on bronchial smooth muscle with limited systemic penetration
• Marked stimulation of CNS muscarinic receptors causing sedation

Correct Answer: Potent local muscarinic effects on bronchial smooth muscle with limited systemic penetration

Q18. Which lab or measurement is most critical to monitor during a methacholine challenge?

• Serum cholinesterase levels
• Pulmonary function tests (spirometry)
• Serum methacholine concentration
• 12-lead ECG continuously

Correct Answer: Pulmonary function tests (spirometry)

Q19. A patient with suspected asthma demonstrates no bronchoconstriction to methacholine. Which interpretation is most appropriate?

• Asthma is definitively excluded
• Bronchial hyperresponsiveness is absent at testing time but asthma cannot be completely ruled out
• The test is invalid and must be repeated immediately with a higher dose
• The patient definitely has COPD instead

Correct Answer: Bronchial hyperresponsiveness is absent at testing time but asthma cannot be completely ruled out

Q20. Which of the following medications must be withheld before a methacholine challenge to avoid false negatives?

• Short-acting beta2 agonists for 8 hours
• Antihistamines for 24 hours
• Oral antibiotics for 48 hours
• Proton pump inhibitors for 24 hours

Correct Answer: Short-acting beta2 agonists for 8 hours

Q21. The primary downstream signaling event after M3 receptor activation in airway smooth muscle is:

• Increased cAMP via Gs protein
• Activation of adenylate cyclase via Gi protein
• Activation of phospholipase C leading to IP3 and Ca2+ release
• Opening of voltage-gated sodium channels directly

Correct Answer: Activation of phospholipase C leading to IP3 and Ca2+ release

Q22. Which structural classification applies to methacholine?

• Alkaloid derived tertiary amine
• Quaternary ammonium ester analog of acetylcholine
• Non-ester lipophilic amine
• Synthetic steroidal muscarinic agonist

Correct Answer: Quaternary ammonium ester analog of acetylcholine

Q23. Methacholine challenge is more likely to produce a positive result in which patient?

• A patient with well-controlled allergic asthma
• A patient with no respiratory symptoms
• A patient currently on high-dose inhaled corticosteroids
• A patient who smoked heavily for decades with emphysema

Correct Answer: A patient with well-controlled allergic asthma

Q24. Which of these is a common precaution before performing methacholine testing?

• Ensure patient has eaten a heavy meal within 30 minutes
• Withhold bronchodilators as per protocol
• Administer beta-blockers to accentuate response
• Start prophylactic antibiotics

Correct Answer: Withhold bronchodilators as per protocol

Q25. Which clinical scenario would make methacholine challenge inappropriate?

• Mild intermittent wheeze with normal baseline spirometry
• Known severe coronary artery disease with unstable angina
• Young adult with exercise-induced symptoms only
• Patient off bronchodilators for required washout period

Correct Answer: Known severe coronary artery disease with unstable angina

Q26. Which of the following effects is least likely to be produced by systemic muscarinic agonists like methacholine?

• Increased gastrointestinal motility
• Bronchoconstriction
• Mydriasis (pupil dilation)
• Increased salivary secretion

Correct Answer: Mydriasis (pupil dilation)

Q27. In pharmacology, methacholine is classified as a:

• Indirect parasympathomimetic (cholinesterase inhibitor)
• Direct parasympathomimetic (muscarinic agonist)
• Mixed muscarinic-nicotinic antagonist
• Beta-adrenergic agonist

Correct Answer: Direct parasympathomimetic (muscarinic agonist)

Q28. The ED50 concept in methacholine challenge refers to:

• The dose producing 50% maximum heart rate increase
• The concentration producing a 20% fall in FEV1 in 50% of subjects
• The concentration that produces a 50% reduction in sputum eosinophils
• The dose at which 50% of methacholine is metabolized by plasma cholinesterase

Correct Answer: The concentration producing a 20% fall in FEV1 in 50% of subjects

Q29. Which is the main reason methacholine has limited systemic toxicity when inhaled in diagnostic doses?

• It is rapidly absorbed and metabolized in the liver
• It cannot bind muscarinic receptors in the lung
• Low inhaled doses and poor systemic absorption due to quaternary structure
• It is a prodrug activated only in airway tissues

Correct Answer: Low inhaled doses and poor systemic absorption due to quaternary structure

Q30. Which pharmacologic agent would most directly antagonize the bronchoconstrictive effects of methacholine?

• Muscarinic receptor antagonist such as ipratropium
• Beta-blocker such as propranolol
• ACE inhibitor such as enalapril
• Leukotriene receptor antagonist such as montelukast

Correct Answer: Muscarinic receptor antagonist such as ipratropium

Q31. Methacholine challenge sensitivity and specificity are influenced by:

• Choice of inhalation device, dosing increments and spirometry technique
• Patient’s hair color and height only
• Ambient room temperature alone
• Time of day without other clinical factors

Correct Answer: Choice of inhalation device, dosing increments and spirometry technique

Q32. Which organ system effect is commonly monitored as a side effect during methacholine challenge?

• Renal function tests
• Gastrointestinal bleeding
• Airway function and respiratory symptoms
• Skin photosensitivity reactions

Correct Answer: Airway function and respiratory symptoms

Q33. In experimental pharmacology, methacholine is used to study which cellular event in airway smooth muscle?

• cAMP-dependent protein kinase activation
• IP3-mediated intracellular calcium release and contraction
• Activation of nicotinic receptor-mediated sodium influx
• Downregulation of beta2-adrenergic receptors only

Correct Answer: IP3-mediated intracellular calcium release and contraction

Q34. Which patient instruction is important before methacholine testing?

• Take short-acting bronchodilator 30 minutes prior to test
• Avoid caffeine and vigorous exercise for several hours before testing
• Start antibiotics the night before
• Increase physical activity immediately before the test

Correct Answer: Avoid caffeine and vigorous exercise for several hours before testing

Q35. Which pharmacologic interaction could blunt the response to methacholine?

• Recent use of inhaled beta2-agonists
• Concurrent anticholinesterase therapy enhancing methacholine effect
• Administration of muscarinic agonists prior to the test
• Use of inhaled muscarinic antagonists stopped weeks earlier

Correct Answer: Recent use of inhaled beta2-agonists

Q36. The mechanism by which ipratropium reduces methacholine-induced bronchoconstriction is:

• Competitive antagonism at muscarinic receptors
• Irreversible blockade of beta2 receptors
• Inhibition of acetylcholinesterase to reduce acetylcholine breakdown
• Stimulation of histamine receptors to oppose contraction

Correct Answer: Competitive antagonism at muscarinic receptors

Q37. For B.Pharm students, which receptor property explains methacholine’s action being more potent in airways with inflammation?

• Downregulation of muscarinic receptors in inflamed tissue
• Increased muscarinic receptor expression and enhanced airway reactivity
• Complete blockade of M3 receptors in inflamed airways
• Decreased IP3 production in inflamed airway smooth muscle

Correct Answer: Increased muscarinic receptor expression and enhanced airway reactivity

Q38. Which is true about methacholine dosing in challenge protocols?

• A single high dose is given to provoke immediate response
• Doses are given in incremental doubling concentrations until threshold is reached
• Doses are given orally for convenience
• Intramuscular injection is preferred for airway provocation

Correct Answer: Doses are given in incremental doubling concentrations until threshold is reached

Q39. Methacholine-induced bronchoconstriction primarily involves which cellular change in airway smooth muscle?

• Increased intracellular calcium concentration leading to contraction
• Enhanced cGMP synthesis causing relaxation
• Activation of potassium channels causing hyperpolarization
• Decreased intracellular sodium concentration leading to relaxation

Correct Answer: Increased intracellular calcium concentration leading to contraction

Q40. Methacholine is less useful in diagnosing which respiratory condition?

• Allergic asthma
• Occupational asthma
• Fixed airflow obstruction due to advanced COPD
• Exercise-induced bronchoconstriction

Correct Answer: Fixed airflow obstruction due to advanced COPD

Q41. Which physiological reflex could exaggerate bronchoconstriction during a methacholine challenge?

• Bainbridge reflex increasing heart rate
• Hering–Breuer inflation reflex relaxing bronchi
• Vagal reflex arc increasing parasympathetic outflow to airways
• Splenic contraction reflex

Correct Answer: Vagal reflex arc increasing parasympathetic outflow to airways

Q42. Which statement about methacholine safety is accurate?

• The test carries no risk and requires no resuscitation equipment
• Emergency bronchodilator and monitoring must be available due to risk of severe bronchospasm
• Methacholine commonly causes seizures during testing
• The test is safe to perform in unstable cardiac patients

Correct Answer: Emergency bronchodilator and monitoring must be available due to risk of severe bronchospasm

Q43. Which parameter defines a PD20 (provocative dose) in methacholine testing?

• The dose causing a 20% increase in heart rate
• The cumulative dose causing a 20% decrease in FEV1
• The dose causing 20% rise in blood pressure
• The dose that increases sputum production by 20%

Correct Answer: The cumulative dose causing a 20% decrease in FEV1

Q44. How does aging affect methacholine responsiveness in general?

• All elderly patients show exaggerated response compared to young adults
• Airway responsiveness may change with age and comorbidities; interpretation requires clinical context
• Aging abolishes muscarinic receptors completely
• Older age leads to universal false-positive tests

Correct Answer: Airway responsiveness may change with age and comorbidities; interpretation requires clinical context

Q45. Methacholine’s action can be described as which pharmacologic phenomenon at muscarinic receptors?

• Full agonist at muscarinic receptors producing maximal receptor activation
• Inverse agonist reducing basal receptor activity
• Allosteric antagonist blocking receptor indirectly
• Partial agonist producing submaximal activation only

Correct Answer: Full agonist at muscarinic receptors producing maximal receptor activation

Q46. Which of the following is true regarding methacholine storage and handling in the lab?

• Methacholine is highly stable at room temperature indefinitely
• It should be prepared and stored according to manufacturer instructions and used within recommended times due to limited stability
• It can be left in nebulizers overnight without loss of potency
• Exposure to light permanently inactivates methacholine making it unsafe

Correct Answer: It should be prepared and stored according to manufacturer instructions and used within recommended times due to limited stability

Q47. In receptor theory terms, methacholine’s beta-methyl substitution primarily affects:

• Intrinsic activity at nicotinic receptors only
• Increased muscarinic potency and resistance to cholinesterase
• Conversion to an antagonist at muscarinic receptors
• Ability to cross the blood–brain barrier

Correct Answer: Increased muscarinic potency and resistance to cholinesterase

Q48. Which finding during methacholine testing indicates that bronchodilator therapy has reversed bronchoconstriction?

• Further fall in FEV1 after bronchodilator
• Rapid return of FEV1 to baseline or improvement by more than 12% and 200 mL
• New onset of hemoptysis
• Persistent wheeze despite bronchodilator

Correct Answer: Rapid return of FEV1 to baseline or improvement by more than 12% and 200 mL

Q49. For a B.Pharm student, which differential point helps distinguish methacholine from carbachol?

• Methacholine has prominent nicotinic activity unlike carbachol
• Carbachol is more resistant to cholinesterase and has more nicotinic activity than methacholine
• Carbachol is a beta-adrenergic agonist while methacholine is muscarinic
• Both are identical in receptor selectivity and clinical uses

Correct Answer: Carbachol is more resistant to cholinesterase and has more nicotinic activity than methacholine

Q50. Which educational point is important for B.Pharm students regarding methacholine challenge interpretation?

• A single positive test definitively diagnoses asthma in all clinical contexts
• Test results must be integrated with history, clinical exam and other investigations for accurate diagnosis
• Methacholine can replace allergy testing in all cases
• Results are universally applicable regardless of testing protocol variations

Correct Answer: Test results must be integrated with history, clinical exam and other investigations for accurate diagnosis

G S Sachin

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.

Mail- Sachin@pharmacyfreak.com