Anti-inflammatory agents – Phenacetin MCQs With Answer

Anti-inflammatory agents – Phenacetin MCQs With Answer

Phenacetin was a widely used analgesic-antipyretic historically important for understanding drug metabolism, toxicity and regulatory withdrawal. This keyword-rich introduction covers phenacetin’s pharmacology, metabolism to paracetamol, mechanism of action (central prostaglandin inhibition), major adverse effects such as analgesic nephropathy, methemoglobinemia and carcinogenicity, analytical assay methods, and its clinical and toxicological relevance for B. Pharm students. These points help students master pharmacokinetics, biotransformation pathways, safety monitoring and regulatory aspects of anti-inflammatory agents. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Phenacetin belongs to which chemical class?

• Anilide (acetanilide derivative)
• Propionic acid derivative
• Salicylate
• Oxicam

Correct Answer: Anilide (acetanilide derivative)

Q2. The primary therapeutic uses of phenacetin were:

• Anti-inflammatory and antiplatelet
• Analgesic and antipyretic
• Local anesthetic and vasoconstrictor
• Antidepressant and anxiolytic

Correct Answer: Analgesic and antipyretic

Q3. The major active metabolite of phenacetin responsible for analgesic activity is:

• Salicylic acid
• Paracetamol (acetaminophen)
• Ibuprofen
• Phenylbutazone

Correct Answer: Paracetamol (acetaminophen)

Q4. The main mechanism by which phenacetin exerts analgesic and antipyretic effects is:

• Peripheral inhibition of cyclooxygenase in inflamed tissue
• Central inhibition of prostaglandin synthesis
• Activation of peripheral opioid receptors
• Blocking voltage-gated sodium channels

Correct Answer: Central inhibition of prostaglandin synthesis

Q5. A classic long-term adverse effect associated with phenacetin is:

• Hepatic cirrhosis only
• Analgesic nephropathy and renal papillary necrosis
• Severe bronchospasm
• Ototoxicity

Correct Answer: Analgesic nephropathy and renal papillary necrosis

Q6. Phenacetin toxicity can lead to methemoglobinemia primarily due to formation of:

• Organophosphate metabolites
• Aniline-type metabolites that oxidize hemoglobin
• Excess prostaglandins
• Free iron release

Correct Answer: Aniline-type metabolites that oxidize hemoglobin

Q7. Phenacetin was withdrawn or banned in many countries mainly because of:

• High cost of production
• Carcinogenicity and chronic renal toxicity
• Ineffectiveness as an analgesic
• Severe sedation in therapeutic doses

Correct Answer: Carcinogenicity and chronic renal toxicity

Q8. Which analytical techniques are commonly used for the assay and detection of phenacetin in formulations and biological samples?

• Only immunoassay
• HPLC and UV spectrophotometry
• Polarography exclusively
• Nuclear magnetic resonance in routine QC

Correct Answer: HPLC and UV spectrophotometry

Q9. The structural change that converts phenacetin to its major active metabolite involves:

• O-deethylation to form a hydroxyl group (paracetamol)
• Hydrogenation of the aromatic ring
• Conversion of amide to carboxylic acid
• Introduction of a nitro group

Correct Answer: O-deethylation to form a hydroxyl group (paracetamol)

Q10. Phenacetin is best described pharmacologically as a:

• Nonsteroidal anti-inflammatory drug (NSAID) with strong peripheral anti-inflammatory action
• Central analgesic and antipyretic with minimal peripheral anti-inflammatory effect
• Selective COX-2 inhibitor
• Topical anesthetic agent

Correct Answer: Central analgesic and antipyretic with minimal peripheral anti-inflammatory effect

Q11. Chronic combined use of phenacetin with other analgesics increases the risk of:

• Analgesic nephropathy
• Improved renal function
• Reduced risk of gastrointestinal bleeding
• Enhanced anti-inflammatory potency without toxicity

Correct Answer: Analgesic nephropathy

Q12. Which laboratory finding is most likely in severe phenacetin-induced methemoglobinemia?

• Elevated methemoglobin level and chocolate-colored blood
• Markedly prolonged prothrombin time only
• Severe leukocytosis with left shift
• Isolated hyperkalemia

Correct Answer: Elevated methemoglobin level and chocolate-colored blood

Q13. Phenacetin acts as a prodrug because:

• It is converted to an active metabolite (paracetamol) in the body
• It directly binds opioid receptors in intact form
• It is only active when applied topically
• It requires acidic pH in stomach to be active

Correct Answer: It is converted to an active metabolite (paracetamol) in the body

Q14. Which patient counseling point is most important for a patient who had chronic phenacetin exposure historically?

• No follow-up needed after discontinuation
• Report symptoms like hematuria, flank pain or reduced urine output promptly
• Continue using phenacetin intermittently for benefit
• Avoid all analgesics forever

Correct Answer: Report symptoms like hematuria, flank pain or reduced urine output promptly

Q15. Which organ system is primarily affected in analgesic nephropathy caused by phenacetin?

• Central nervous system
• Renal medulla and papillae
• Cardiovascular system exclusively
• Skeletal muscle

Correct Answer: Renal medulla and papillae

Q16. The biochemical pathway implicated in phenacetin carcinogenicity involves:

• Formation of DNA-reactive metabolites leading to mutagenesis
• Immediate immunosuppression causing infection-related cancer
• Direct incorporation into cell membranes
• Inhibition of vitamin D activation

Correct Answer: Formation of DNA-reactive metabolites leading to mutagenesis

Q17. Which of the following is the most appropriate modern substitute for phenacetin for analgesia and antipyresis?

• Paracetamol (acetaminophen)
• Phenylbutazone
• Phenacetin in reduced dose
• Mercaptopurine

Correct Answer: Paracetamol (acetaminophen)

Q18. In the context of drug metabolism, phenacetin undergoes hepatic biotransformation mainly in which phase?

• Only Phase III transport
• Phase I oxidation (O-deethylation) followed by Phase II conjugation
• Direct renal excretion without metabolism
• Phase IV photodegradation

Correct Answer: Phase I oxidation (O-deethylation) followed by Phase II conjugation

Q19. Which adverse hematologic effect has been reported with phenacetin use?

• Aplastic anemia exclusively
• Hemolytic anemia and methemoglobinemia
• Polycythemia vera
• Essential thrombocythemia

Correct Answer: Hemolytic anemia and methemoglobinemia

Q20. Routine monitoring of a patient with a history of chronic phenacetin use should include:

• Renal function tests and urinalysis
• Only chest X-ray annually
• No monitoring is necessary
• Only lipid profile measurement

Correct Answer: Renal function tests and urinalysis

Q21. Which statement about phenacetin’s anti-inflammatory activity is correct?

• It has potent peripheral anti-inflammatory action comparable to NSAIDs
• It shows minimal peripheral anti-inflammatory activity
• It increases prostaglandin synthesis
• It is a specific COX-2 inhibitor

Correct Answer: It shows minimal peripheral anti-inflammatory activity

Q22. Which of the following best describes the pharmacokinetic property of phenacetin?

• Extensively metabolized in the liver to active and toxic metabolites
• Excreted unchanged in urine without metabolism
• Not absorbed orally
• Used only as an intravenous formulation due to poor oral bioavailability

Correct Answer: Extensively metabolized in the liver to active and toxic metabolites

Q23. Which cellular event contributes to phenacetin-induced renal papillary necrosis?

• Ischemia and direct toxic injury to papillary cells
• Autoimmune glomerulonephritis only
• Primary lipid accumulation in renal cortex
• Excessive calcium deposition in tubules

Correct Answer: Ischemia and direct toxic injury to papillary cells

Q24. Which regulatory action was commonly taken for phenacetin in the late 20th century?

• Reclassification as an antibiotic
• Market withdrawal or prohibition of over-the-counter sales
• Mandated high-dose therapy for chronic pain
• Approval for pediatric use only

Correct Answer: Market withdrawal or prohibition of over-the-counter sales

Q25. Which metabolite-mediated toxicity is most relevant to phenacetin’s carcinogenic risk?

• Formation of reactive nitroso species that directly alkylate DNA
• Production of benign glucuronide conjugates only
• Generation of large amounts of carbon dioxide
• Production of stable, nonreactive metabolites

Correct Answer: Formation of reactive nitroso species that directly alkylate DNA

Q26. In pharmaceutical analysis, the sample preparation for phenacetin quantification in plasma commonly requires:

• Protein precipitation or solid-phase extraction prior to HPLC
• No preparation — direct injection of whole blood
• Lyophilization only without extraction
• Only dilution with saline

Correct Answer: Protein precipitation or solid-phase extraction prior to HPLC

Q27. Which age group was most concerning for long-term harms from phenacetin-containing analgesics?

• Infants on single doses
• Adults with chronic prolonged use over years
• Young athletes using topical forms
• Postoperative patients on short-term therapy

Correct Answer: Adults with chronic prolonged use over years

Q28. The conversion of phenacetin to paracetamol occurs predominantly in which organ?

• Liver (hepatic metabolism)
• Skin via topical enzymes
• Large intestine by bacteria only
• Bone marrow

Correct Answer: Liver (hepatic metabolism)

Q29. Which of the following clinical features would suggest analgesic nephropathy from chronic phenacetin exposure?

• Chronic flank pain, anemia and impaired concentrating ability of kidneys
• Isolated persistent cough without urinary symptoms
• Episodes of acute hypertension only
• Progressive peripheral neuropathy without renal signs

Correct Answer: Chronic flank pain, anemia and impaired concentrating ability of kidneys

Q30. Which adjunct therapy is used to treat paracetamol toxicity, the main metabolite of phenacetin?

• Deferoxamine
• N-acetylcysteine (NAC)
• Atropine
• Calcium gluconate

Correct Answer: N-acetylcysteine (NAC)

Q31. Which of the following is true about phenacetin’s absorption and formulation?

• Well absorbed after oral administration and commonly formulated as tablets historically
• Only effective when administered intra-arterially
• Not formulated as tablets due to instability
• Administered exclusively by inhalation

Correct Answer: Well absorbed after oral administration and commonly formulated as tablets historically

Q32. Which laboratory parameter is most critical to monitor in suspected chronic phenacetin toxicity?

• Serum creatinine and estimated GFR
• Serum triglycerides
• Serum vitamin B12
• Fasting blood glucose only

Correct Answer: Serum creatinine and estimated GFR

Q33. Which statement about phenacetin and paracetamol relationship is correct?

• Phenacetin is an active metabolite formed from paracetamol
• Phenacetin is a prodrug that is metabolized to paracetamol
• They are unrelated structurally and pharmacologically
• Paracetamol is a prodrug of phenacetin

Correct Answer: Phenacetin is a prodrug that is metabolized to paracetamol

Q34. A pharmacology exam question: which enzyme class primarily mediates O-deethylation of phenacetin during hepatic metabolism?

• Microsomal mixed-function oxidases (cytochrome P450 enzymes)
• Proteases in lysosomes
• DNA polymerases
• Peptidyl transferase

Correct Answer: Microsomal mixed-function oxidases (cytochrome P450 enzymes)

Q35. Which safety measure reduced risks when phenacetin was still in use?

• Using the lowest effective dose for the shortest duration
• Doubling the dose to reduce frequency of dosing
• Combining with nephrotoxic drugs intentionally
• Prophylactic long-term use without monitoring

Correct Answer: Using the lowest effective dose for the shortest duration

Q36. Which histopathological renal change is typical in analgesic nephropathy from phenacetin?

• Renal papillary necrosis with interstitial fibrosis
• Diffuse mesangial hypercellularity only
• Fatty change in glomeruli
• Isolated tubular hypertrophy without necrosis

Correct Answer: Renal papillary necrosis with interstitial fibrosis

Q37. In toxicology, chronic phenacetin abuse is epidemiologically associated with increased risk of:

• Upper urinary tract urothelial cancers
• Benign prostatic hyperplasia exclusively
• Decreased risk of renal malignancy
• Only skin cancers

Correct Answer: Upper urinary tract urothelial cancers

Q38. Which statement best describes phenacetin’s analgesic potency compared to paracetamol?

• Phenacetin is approximately equipotent because it is a prodrug of paracetamol
• Phenacetin is vastly more potent and longer acting than paracetamol
• Phenacetin has no analgesic potency
• Phenacetin acts as an opioid agonist making it stronger

Correct Answer: Phenacetin is approximately equipotent because it is a prodrug of paracetamol

Q39. During formulation development, a stability concern specific to phenacetin is:

• Formation of oxidative or hydrolytic degradation products that may be toxic
• Complete chemical inertness making it unformulatable
• Spontaneous polymerization into harmless polymers
• Stable at all temperatures indefinitely

Correct Answer: Formation of oxidative or hydrolytic degradation products that may be toxic

Q40. Which clinical test can help detect early renal concentrating defect from chronic analgesic use?

• Urine osmolality or specific gravity after water restriction
• Serum amylase only
• Pulmonary function test
• Electrocardiogram (ECG)

Correct Answer: Urine osmolality or specific gravity after water restriction

Q41. Which of the following best explains why phenacetin was more hazardous in combination cold remedies?

• Frequent dosing and combination with other analgesics increased cumulative renal and carcinogenic risk
• Combination eliminated its metabolism so it accumulated unchanged
• It became an effective antibiotic only in mixtures
• Combination prevented systemic absorption entirely

Correct Answer: Frequent dosing and combination with other analgesics increased cumulative renal and carcinogenic risk

Q42. Which pharmacovigilance signal most directly contributed to regulatory scrutiny of phenacetin?

• Reports linking chronic use with renal papillary necrosis and upper tract cancers
• Immediate anaphylaxis in all users
• Widespread beneficial effects without adverse events
• Consistent improvement in renal function

Correct Answer: Reports linking chronic use with renal papillary necrosis and upper tract cancers

Q43. Which protective counseling is appropriate if a patient took an overdose of a phenacetin-containing product long ago and presents asymptomatically now?

• Advise to seek evaluation for renal function and urinalysis due to potential delayed effects
• No action needed if asymptomatic
• Recommend immediate dialysis regardless of tests
• Prescribe another phenacetin dose to counteract toxicity

Correct Answer: Advise to seek evaluation for renal function and urinalysis due to potential delayed effects

Q44. Which chromatographic detector is commonly paired with HPLC for sensitive phenacetin detection in biological samples?

• UV or PDA (photodiode array) detector
• Geiger–Müller counter
• Flame ionization detector (FID) used for gas chromatography only
• None — detectors are unnecessary

Correct Answer: UV or PDA (photodiode array) detector

Q45. Which differential diagnosis should be considered when a patient presents with methemoglobinemia after exposure to an analgesic?

• Aniline or nitrite exposure and oxidative drug metabolites
• Chronic obstructive pulmonary disease without exposure
• Acute myocardial infarction only
• Hypothyroidism as sole cause

Correct Answer: Aniline or nitrite exposure and oxidative drug metabolites

Q46. For an exam question: which of the following statements is FALSE regarding phenacetin?

• Phenacetin is currently widely recommended as first-line analgesic
• Phenacetin was historically used as an analgesic and antipyretic
• Long-term use is associated with renal and urothelial toxicity
• Phenacetin is metabolized to paracetamol

Correct Answer: Phenacetin is currently widely recommended as first-line analgesic

Q47. Which precaution is important when interpreting historical epidemiologic data on phenacetin risk?

• Consider confounding by combined analgesic use and cumulative dose
• Assume data apply only to single-use low-dose exposure
• Ignore duration of exposure as irrelevant
• Only animal data are meaningful for humans

Correct Answer: Consider confounding by combined analgesic use and cumulative dose

Q48. Which of the following best represents a key learning point for B. Pharm students about phenacetin?

• Understand prodrug metabolism, toxicity mechanisms, analytical detection and regulatory outcomes
• Memorize its current recommended dose for pediatrics
• Focus solely on its analgesic potency without safety considerations
• Use it routinely in formulation labs without safety protocols

Correct Answer: Understand prodrug metabolism, toxicity mechanisms, analytical detection and regulatory outcomes

Q49. Which experimental model finding would support phenacetin’s nephrotoxicity mechanism?

• Histological evidence of papillary ischemia and interstitial fibrosis in chronically treated animals
• Complete renal regeneration after high-dose short-term exposure
• No histopathological changes despite lifetime exposure
• Exclusive liver-only damage with no renal findings

Correct Answer: Histological evidence of papillary ischemia and interstitial fibrosis in chronically treated animals

Q50. For quality control of an old phenacetin tablet formulation, which specification would be most relevant?

• Assay of phenacetin content and identification of toxic degradation products using HPLC
• Only organoleptic testing (color and taste)
• Measurement of tablet radioactivity
• Testing for opioid contamination only

Correct Answer: Assay of phenacetin content and identification of toxic degradation products using HPLC

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