Methadone hydrochloride MCQs With Answer

Methadone hydrochloride MCQs With Answer — This targeted introduction equips B. Pharm students with focused, exam-oriented practice on methadone hydrochloride. Covering pharmacology, mechanism of action, pharmacokinetics, dosing, adverse effects, drug interactions, formulation, analytical assays and clinical uses such as methadone maintenance therapy and opioid dependence management, these questions deepen conceptual understanding and application. Emphasis is placed on important keywords like methadone hydrochloride, methadone MCQs, QT prolongation, CYP interactions, therapeutic drug monitoring and opioid substitution therapy to improve SEO relevance and study outcomes. Clear explanations and clinically relevant scenarios prepare students for exams and pharmacy practice. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which receptor is primarily responsible for methadone’s opioid agonist effects?

• Delta (δ) opioid receptor
• Kappa (κ) opioid receptor
• Mu (μ) opioid receptor
• Nicotinic acetylcholine receptor

Correct Answer: Mu (μ) opioid receptor

Q2. Methadone hydrochloride is commonly used in opioid dependence because it:

• Has a very short half-life and is dosed hourly
• Is a partial agonist with no risk of respiratory depression
• Provides a long duration of action and reduces cravings
• Is an antagonist that blocks opioid receptors

Correct Answer: Provides a long duration of action and reduces cravings

Q3. The chemical form “methadone hydrochloride” compared to “methadone base” primarily affects which property?

• Intrinsic opioid receptor affinity
• Water solubility and salt stability
• Pharmacological half-life
• Metabolic pathway via CYP3A4

Correct Answer: Water solubility and salt stability

Q4. Which stereochemical characteristic of methadone influences its opioid potency?

• Methadone is an achiral compound with no stereoisomers
• The R-enantiomer has greater μ-opioid activity than the S-enantiomer
• The S-enantiomer is mainly responsible for μ-opioid effects
• Both enantiomers are inactive at opioid receptors

Correct Answer: The R-enantiomer has greater μ-opioid activity than the S-enantiomer

Q5. The major mechanism underlying methadone-induced QT prolongation is:

• Blockade of cardiac hERG (IKr) potassium channels
• Enhanced sodium channel conduction
• Increased calcium influx through L-type channels
• Activation of beta-adrenergic receptors

Correct Answer: Blockade of cardiac hERG (IKr) potassium channels

Q6. Methadone is primarily metabolized in the liver by which enzyme family?

• UDP-glucuronosyltransferases (UGTs)
• CYP450 enzymes (e.g., CYP3A4, CYP2B6)
• Monoamine oxidase (MAO)
• Alcohol dehydrogenase

Correct Answer: CYP450 enzymes (e.g., CYP3A4, CYP2B6)

Q7. Which pharmacokinetic property of methadone contributes most to risk of accumulation on repeated dosing?

• Low oral bioavailability
• Short volume of distribution
• Long and variable elimination half-life
• Rapid renal clearance unchanged

Correct Answer: Long and variable elimination half-life

Q8. Oral bioavailability of methadone hydrochloride is approximately:

• Less than 10%
• Approximately 50–90%
• 100% (complete absorption)
• Negligible due to first-pass inactivation

Correct Answer: Approximately 50–90%

Q9. Which clinical monitoring is recommended when initiating or increasing methadone dose due to QT risk?

• Basal metabolic panel only
• Routine echocardiography weekly
• Electrocardiogram (ECG) to measure QTc
• Pulmonary function testing

Correct Answer: Electrocardiogram (ECG) to measure QTc

Q10. A clinician converting a patient from morphine to methadone should be most cautious because:

• Methadone has predictable equianalgesic ratios across doses
• Methadone equianalgesic dose decreases with higher prior opioid doses
• There is no risk of overdose when converting to methadone
• Methadone is not effective for neuropathic pain

Correct Answer: Methadone equianalgesic dose decreases with higher prior opioid doses

Q11. Which adverse effect is most specific and clinically important for methadone compared to other opioids?

• Constipation
• Miosis
• QT prolongation and torsades de pointes
• Itching (pruritus)

Correct Answer: QT prolongation and torsades de pointes

Q12. Methadone’s analgesic activity involves NMDA receptor interactions. Which statement is true?

• Methadone is a selective NMDA agonist enhancing pain
• Methadone has NMDA antagonism that may reduce neuropathic pain
• NMDA effects are absent and irrelevant for clinical action
• Methadone enhances glutamate release via NMDA activation

Correct Answer: Methadone has NMDA antagonism that may reduce neuropathic pain

Q13. Which factor significantly increases methadone plasma concentration when co-administered?

• Co-administration with strong CYP3A4 inducers like rifampin
• Co-administration with strong CYP3A4 inhibitors like ketoconazole
• Administration with charcoal-containing antacid
• Administration with cholestyramine

Correct Answer: Co-administration with strong CYP3A4 inhibitors like ketoconazole

Q14. Methadone is highly protein bound. Which statement reflects its distribution?

• Low protein binding leads to small volume of distribution
• High lipophilicity leads to large volume of distribution and tissue accumulation
• It remains only in plasma and does not cross blood-brain barrier
• Protein binding prevents any CNS effects

Correct Answer: High lipophilicity leads to large volume of distribution and tissue accumulation

Q15. The elimination half-life of methadone typically ranges from:

• 1–3 hours
• 8–59 hours, often variable and prolonged
• 3–5 minutes
• More than 30 days consistently

Correct Answer: 8–59 hours, often variable and prolonged

Q16. In pregnant women maintained on methadone, which statement is correct?

• Methadone must always be discontinued in pregnancy
• Maintenance therapy reduces illicit opioid use and is recommended with monitoring
• Methadone causes no neonatal withdrawal syndrome
• Methadone is contraindicated during labor only

Correct Answer: Maintenance therapy reduces illicit opioid use and is recommended with monitoring

Q17. Which laboratory test is useful for therapeutic drug monitoring of methadone in complex cases?

• Serum methadone concentration measurement by GC-MS or LC-MS/MS
• Complete blood count only
• Urine glucose level
• Serum troponin

Correct Answer: Serum methadone concentration measurement by GC-MS or LC-MS/MS

Q18. What is the primary route of methadone excretion?

• Exhalation unchanged in breath
• Predominantly renal excretion of metabolites
• Fecal excretion of unchanged drug only
• Complete biliary excretion of the parent drug

Correct Answer: Predominantly renal excretion of metabolites

Q19. Which clinical situation increases the risk of methadone toxicity due to reduced metabolism?

• Concurrent use of strong CYP450 inducers like St. John’s wort
• Concurrent use of strong CYP450 inhibitors like fluconazole
• Concurrent use of non-interacting vitamins
• Administration with a high-fat meal only

Correct Answer: Concurrent use of strong CYP450 inhibitors like fluconazole

Q20. Methadone maintenance programs aim to achieve which primary public health outcome?

• Complete abstinence from all medication including methadone
• Reduction in illicit opioid use and related harms (overdose, infection)
• Increase in street availability of methadone
• Universal cure of addiction without psychosocial support

Correct Answer: Reduction in illicit opioid use and related harms (overdose, infection)

Q21. The usual initial supervised oral dose range for methadone maintenance in opioid-dependent adults is approximately:

• 0.5–2 mg once daily
• 20–30 mg once daily under supervision, titrated carefully
• 200–400 mg once daily
• 1000 mg weekly

Correct Answer: 20–30 mg once daily under supervision, titrated carefully

Q22. Which contraindication is most relevant when prescribing methadone?

• Known severe hypersensitivity to methadone
• Controlled hypertension
• Mild seasonal allergies
• Well-controlled type 2 diabetes

Correct Answer: Known severe hypersensitivity to methadone

Q23. When switching from methadone to buprenorphine for dependence, the clinician should:

• Start buprenorphine immediately after last methadone dose regardless of withdrawal
• Always increase methadone dose before switching
• Wait for moderate opioid withdrawal before initiating buprenorphine to avoid precipitated withdrawal
• Use naloxone to facilitate the switch

Correct Answer: Wait for moderate opioid withdrawal before initiating buprenorphine to avoid precipitated withdrawal

Q24. Which of the following is a serious central nervous system adverse effect of methadone overdose?

• Hypersalivation only
• Respiratory depression leading to hypoxia
• Peripheral neuropathy without respiratory involvement
• Hyperreflexia without sedation

Correct Answer: Respiratory depression leading to hypoxia

Q25. Which drug class when combined with methadone significantly increases risk of fatal respiratory depression?

• SSRIs when used alone
• Benzodiazepines and other central nervous system depressants
• Proton pump inhibitors
• Topical antibiotics

Correct Answer: Benzodiazepines and other central nervous system depressants

Q26. Methadone-induced adrenal insufficiency is best characterized by:

• Acute hypertensive crisis
• Chronic suppression of the hypothalamic-pituitary-adrenal axis with nonspecific symptoms
• Immediate hypoglycemia after single dose
• Excess cortisol production

Correct Answer: Chronic suppression of the hypothalamic-pituitary-adrenal axis with nonspecific symptoms

Q27. Which monitoring parameter is most important for patients on chronic methadone therapy for safety?

• Periodic ECG, assessment of QTc interval
• Weekly complete blood count only
• Daily liver biopsy
• No monitoring required after initiation

Correct Answer: Periodic ECG, assessment of QTc interval

Q28. Which pharmacologic antagonist is used to reverse methadone-induced respiratory depression in emergency settings?

• Naloxone
• Flumazenil
• Atropine
• Propranolol

Correct Answer: Naloxone

Q29. In the context of pharmaceutical formulation, methadone hydrochloride is most often presented as:

• Insoluble crystalline base for inhalation
• Water-soluble hydrochloride salt for oral solution and tablets
• Topical cream only
• Powder for compounding into aerosols

Correct Answer: Water-soluble hydrochloride salt for oral solution and tablets

Q30. Which excipient property is critical when formulating an oral methadone solution?

• Non-aqueous solvent selection only
• pH control and preservative system for stability and palatability
• High sugar content to neutralize methadone effects
• Use of reactive metals to improve potency

Correct Answer: pH control and preservative system for stability and palatability

Q31. For methadone tablets, which quality attribute is essential per pharmacopeial standards?

• Friability, disintegration and assay for labeled content
• Inability to dissolve in gastric fluid
• Mandatory immediate release of 100% within 1 minute
• No requirement for content uniformity

Correct Answer: Friability, disintegration and assay for labeled content

Q32. Which interaction increases methadone clearance and can lead to withdrawal symptoms?

• Coadministration with strong CYP inhibitors like ritonavir
• Coadministration with strong CYP inducers like carbamazepine
• Co-use with antacids only
• Co-use with topical steroids

Correct Answer: Coadministration with strong CYP inducers like carbamazepine

Q33. Which opioid receptor-related tolerance phenomenon is seen with long-term methadone use?

• No tolerance develops to any methadone effects
• Tolerance to analgesic effects may develop, requiring dose reassessment
• Tolerance to renal clearance increases metabolism
• Tolerance causes immediate withdrawal symptoms upon dose increase

Correct Answer: Tolerance to analgesic effects may develop, requiring dose reassessment

Q34. Which statement about methadone and breastfeeding is correct?

• Methadone is absolutely contraindicated during breastfeeding
• Low levels in breast milk make breastfeeding often acceptable with monitoring
• Methadone prevents neonatal withdrawal if given postpartum
• Breastfeeding eliminates need for neonatal monitoring

Correct Answer: Low levels in breast milk make breastfeeding often acceptable with monitoring

Q35. Which laboratory finding might indicate chronic methadone hepatotoxicity is developing?

• Elevated liver enzymes (ALT/AST)
• Low hemoglobin only
• Hyperkalemia only
• Decreased creatinine clearance only

Correct Answer: Elevated liver enzymes (ALT/AST)

Q36. Methadone used in pain management vs maintenance therapy often differs how?

• Maintenance doses are always lower than pain doses
• Indications, dosing strategies, monitoring and goals differ between analgesia and opioid dependence management
• Methadone is never used for pain management
• Route of administration is inhalational for pain but oral for maintenance

Correct Answer: Indications, dosing strategies, monitoring and goals differ between analgesia and opioid dependence management

Q37. Which analytical technique is most specific and commonly used for methadone quantification in biological samples?

• Thin layer chromatography without confirmation
• Gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS)
• pH meter titration
• Naked eye color comparison

Correct Answer: Gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS)

Q38. Which stability concern is particularly relevant for methadone hydrochloride oral solutions?

• Photodegradation and microbial growth if preservative and packaging are inadequate
• Spontaneous polymerization into inactive chains
• Instant crystallization at room temperature without cause
• Explosive decomposition on contact with air

Correct Answer: Photodegradation and microbial growth if preservative and packaging are inadequate

Q39. Methadone’s pKa influences its absorption. Which statement is correct?

• Methadone is a strong acid and ionized in the stomach
• As a weak base, methadone is more unionized in less acidic intestinal pH, aiding absorption
• Methadone pKa makes it impermeable to mucosal membranes
• pKa has no impact on oral absorption

Correct Answer: As a weak base, methadone is more unionized in less acidic intestinal pH, aiding absorption

Q40. What is a common formulation strategy to reduce methadone diversion from clinics?

• Providing large multi-month supplies without supervision
• Using supervised daily dosing and liquid formulations dispensed by clinics
• Switching to intravenous routes for home use
• Removing all labeling from products

Correct Answer: Using supervised daily dosing and liquid formulations dispensed by clinics

Q41. Which population requires special caution and often lower methadone doses due to slower metabolism?

• Young healthy adults with no comorbidities
• Elderly patients and those with hepatic impairment
• Patients with rapid CYP450 activity only
• Patients with hyperthyroidism exclusively

Correct Answer: Elderly patients and those with hepatic impairment

Q42. Which regulatory classification commonly applies to methadone in many countries?

• Over-the-counter non-controlled substance
• Schedule II (or equivalent) controlled opioid with strict prescribing rules
• Herbal supplement category
• Non-pharmacological therapy

Correct Answer: Schedule II (or equivalent) controlled opioid with strict prescribing rules

Q43. In forensic toxicology, prolonged detection of methadone in urine is due mainly to:

• Rapid renal clearance of unchanged drug only
• Extensive tissue distribution and slow release from tissues producing prolonged elimination
• Complete metabolism into volatile compounds
• Immediate exhalation through lungs

Correct Answer: Extensive tissue distribution and slow release from tissues producing prolonged elimination

Q44. Which counseling point is essential when dispensing methadone to outpatients?

• It is safe to drive and operate heavy machinery without caution
• Avoid alcohol and other CNS depressants due to additive respiratory depression risk
• Methadone has no interaction with any other medications
• Doubling the dose when pain is uncontrolled is safe without consulting prescriber

Correct Answer: Avoid alcohol and other CNS depressants due to additive respiratory depression risk

Q45. A patient on methadone presents with syncope. The most appropriate immediate investigation is:

• Serum glucose only
• Electrocardiogram (ECG) to assess for prolonged QTc
• Skin allergy testing
• Chest X-ray immediately only

Correct Answer: Electrocardiogram (ECG) to assess for prolonged QTc

Q46. When performing a stability study for methadone tablets, which condition should be evaluated?

• Only appearance under a microscope
• Assay of active substance, dissolution, moisture content and stability under ICH conditions
• Only taste and flavor stability
• Only color change at subzero temperatures

Correct Answer: Assay of active substance, dissolution, moisture content and stability under ICH conditions

Q47. Which adverse neonatal outcome is associated with maternal methadone use during pregnancy?

• Complete immunity to opioids in the neonate
• Neonatal abstinence syndrome requiring monitoring and sometimes treatment
• Permanent cardiac malformations in all cases
• No postnatal effects at any dose

Correct Answer: Neonatal abstinence syndrome requiring monitoring and sometimes treatment

Q48. Which enzyme polymorphism is most likely to affect methadone plasma levels between individuals?

• CYP2D6 polymorphism only
• CYP2B6 and CYP3A4 polymorphisms affecting clearance
• Polymorphism in acetylcholinesterase only
• Polymorphism in lactase persistence

Correct Answer: CYP2B6 and CYP3A4 polymorphisms affecting clearance

Q49. Which assay parameter is critical for validating an LC-MS/MS method for methadone quantification?

• Specificity/selectivity, accuracy, precision, linearity and lower limit of quantification
• Only colorimetric response at one wavelength
• Ability to measure pH only
• Non-specific turbidity measurements

Correct Answer: Specificity/selectivity, accuracy, precision, linearity and lower limit of quantification

Q50. For safe prescribing, which documentation is important when initiating methadone for opioid dependence?

• No documentation is required due to its safety
• Detailed treatment plan, consent, ECG baseline, and documentation of counseling and monitoring strategy
• Only a verbal agreement without written record
• Only pharmacy inventory records without patient details

Correct Answer: Detailed treatment plan, consent, ECG baseline, and documentation of counseling and monitoring strategy

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