Irreversible inhibitors – Parathione MCQs With Answer

Irreversible inhibitors – Parathione MCQs With Answer

As B.Pharm students, understanding irreversible inhibitors—especially organophosphate agents like parathione—is essential for pharmacology and toxicology. Parathione is bioactivated to a potent oxon metabolite that covalently phosphorylates the active-site serine of acetylcholinesterase (AChE), producing irreversible inhibition, cholinergic crisis, and features such as miosis, bronchospasm, salivation, and muscle fasciculations. Key concepts include mechanism of covalent binding, aging, antidotes like pralidoxime and atropine, diagnostic assays (RBC cholinesterase), metabolism by CYPs, and occupational prevention. These MCQs cover mechanism, metabolism, clinical presentation, laboratory diagnosis, treatment protocols, and prevention strategies relevant to pharmacy practice. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which molecular event primarily defines irreversible inhibition of acetylcholinesterase by parathione?

• Covalent phosphorylation of the active site serine
• Non-covalent competitive binding at the anionic site
• Allosteric modulation of enzyme conformation
• Temporary hydrogen-bonding to the catalytic histidine

Correct Answer: Covalent phosphorylation of the active site serine

Q2. Parathione itself is a prodrug that requires metabolic activation to which species to inhibit AChE?

• Paraoxon (oxon metabolite)
• Paraquat radical
• Phosphorothioate anion
• Thiophosphate ester

Correct Answer: Paraoxon (oxon metabolite)

Q3. Which enzyme system predominantly bioactivates parathione to its oxon form?

• CYP450 (hepatic microsomal cytochromes)
• Monoamine oxidase
• Glutathione S-transferase
• Alcohol dehydrogenase

Correct Answer: CYP450 (hepatic microsomal cytochromes)

Q4. The clinical signs of organophosphate poisoning are primarily due to accumulation of which neurotransmitter?

• Acetylcholine
• Norepinephrine
• Dopamine
• Gamma-aminobutyric acid (GABA)

Correct Answer: Acetylcholine

Q5. Which of the following is NOT a typical muscarinic sign of parathione poisoning?

• Bradycardia
• Bronchorrhea
• Hyperglycemia
• Miosis

Correct Answer: Hyperglycemia

Q6. The term “aging” of the phosphorylated AChE refers to:

• Dealkylation of the phosphorylated enzyme making reactivation difficult
• Spontaneous dephosphorylation and enzyme recovery
• Conformational refolding restoring activity
• Proteolytic degradation of the inhibited enzyme

Correct Answer: Dealkylation of the phosphorylated enzyme making reactivation difficult

Q7. Which antidote regenerates phosphorylated AChE if given before aging occurs?

• Pralidoxime (2-PAM)
• Atropine
• Diazepam
• Physostigmine

Correct Answer: Pralidoxime (2-PAM)

Q8. Which drug is used to antagonize muscarinic symptoms in organophosphate poisoning?

• Atropine
• Neostigmine
• Edrophonium
• Pyridostigmine

Correct Answer: Atropine

Q9. Measurement of which enzyme activity is most useful to confirm organophosphate exposure clinically?

• RBC acetylcholinesterase (true AChE)
• Plasma pseudocholinesterase
• Serum alkaline phosphatase
• Liver transaminases

Correct Answer: RBC acetylcholinesterase (true AChE)

Q10. Which mechanism explains nicotinic effects (muscle weakness, fasciculations) seen in severe parathione poisoning?

• Excessive stimulation of nicotinic receptors at neuromuscular junctions by accumulated ACh
• Blockade of voltage-gated sodium channels
• Direct myotoxicity of parathione on muscle fibers
• Inhibition of GABAergic interneurons in the spinal cord

Correct Answer: Excessive stimulation of nicotinic receptors at neuromuscular junctions by accumulated ACh

Q11. Organophosphate-induced delayed neuropathy (OPIDN) is primarily associated with inhibition of which enzyme?

• Neuropathy target esterase (NTE)
• Monoamine oxidase
• Butyrylcholinesterase
• Tyrosine hydroxylase

Correct Answer: Neuropathy target esterase (NTE)

Q12. Which property of parathione increases its ability to penetrate skin and cause dermal toxicity?

• High lipid solubility
• High molecular weight
• Strong ionic charge
• High water solubility

Correct Answer: High lipid solubility

Q13. Which laboratory change is expected in acute severe organophosphate poisoning?

• Marked reduction in RBC AChE activity
• Marked increase in plasma glucose
• Marked elevation of serum creatinine kinase
• Marked elevation of thyroid hormones

Correct Answer: Marked reduction in RBC AChE activity

Q14. The structural feature of organophosphates that allows covalent binding to AChE is the presence of:

• Phosphoryl group capable of forming a covalent bond with serine OH
• Sulfhydryl groups that bind cysteine residues
• Quaternary ammonium moiety targeting anionic site
• Carboxyl group that forms ester bonds

Correct Answer: Phosphoryl group capable of forming a covalent bond with serine OH

Q15. Which statement best differentiates reversible from irreversible AChE inhibitors?

• Irreversible inhibitors form covalent bonds and require new enzyme synthesis for recovery
• Reversible inhibitors permanently inactivate the enzyme
• Irreversible inhibitors are always competitive antagonists
• Reversible inhibitors are always prodrugs

Correct Answer: Irreversible inhibitors form covalent bonds and require new enzyme synthesis for recovery

Q16. Which factor accelerates “aging” of phosphorylated AChE making pralidoxime ineffective?

• Electron-withdrawing alkyl groups on the phosphoryl moiety
• Presence of bulky aromatic rings in the inhibitor
• High pH favoring dephosphorylation
• Concurrent administration of atropine

Correct Answer: Electron-withdrawing alkyl groups on the phosphoryl moiety

Q17. For prophylaxis against nerve agents, which reversible AChE inhibitor is sometimes used in military settings?

• Pyridostigmine bromide
• Atropine sulfate
• Pralidoxime
• Physostigmine

Correct Answer: Pyridostigmine bromide

Q18. Which clinical triad best characterizes severe cholinergic crisis from organophosphates?

• Miosis, bronchospasm/bronchorrhea, bradycardia
• Hypertension, mydriasis, hyperreflexia
• Dry skin, urinary retention, tachycardia
• Hyperthermia, seizures, mydriasis

Correct Answer: Miosis, bronchospasm/bronchorrhea, bradycardia

Q19. Which of the following is the immediate life-threatening effect of organophosphate poisoning?

• Respiratory failure due to bronchorrhea and respiratory muscle weakness
• Acute renal failure
• Hepatic encephalopathy
• Cardiac arrhythmias due to hyperkalemia

Correct Answer: Respiratory failure due to bronchorrhea and respiratory muscle weakness

Q20. Which monitoring parameter helps guide atropine therapy in organophosphate poisoning?

• Resolution of bronchorrhea and normalization of heart rate
• Serum parathione concentration
• Plasma glucose levels
• Arterial pH

Correct Answer: Resolution of bronchorrhea and normalization of heart rate

Q21. Which enzyme measured in plasma reflects hepatic exposure but is less specific for neuromuscular toxicity?

• Butyrylcholinesterase (pseudocholinesterase)
• Red cell acetylcholinesterase
• Creatine kinase
• Monoamine oxidase

Correct Answer: Butyrylcholinesterase (pseudocholinesterase)

Q22. Which of the following best describes pralidoxime’s mechanism of action?

• Nucleophilic oxime that cleaves the phosphoryl-enzyme bond to regenerate AChE
• Competitive antagonist at muscarinic receptors
• Central GABA receptor agonist to control seizures
• Enzyme inducer increasing AChE synthesis

Correct Answer: Nucleophilic oxime that cleaves the phosphoryl-enzyme bond to regenerate AChE

Q23. Which of these agents would be contraindicated as monotherapy in severe organophosphate poisoning?

• Pralidoxime alone without atropine
• Atropine with supportive care
• Atropine combined with pralidoxime
• Benzodiazepines for seizures

Correct Answer: Pralidoxime alone without atropine

Q24. A patient with organophosphate poisoning shows muscle weakness and respiratory depression despite atropine. Which additional therapy is indicated?

• Pralidoxime to restore nicotinic function
• High-dose insulin infusion
• Beta-blockers to reduce secretions
• Naloxone to reverse opioid-like effects

Correct Answer: Pralidoxime to restore nicotinic function

Q25. Which of the following correctly lists common routes of parathione exposure?

• Dermal, inhalation, oral
• Intravenous only
• Ocular only
• Gastrointestinal via intact skin only

Correct Answer: Dermal, inhalation, oral

Q26. Which clinical feature distinguishes organophosphate poisoning from carbamate poisoning?

• Organophosphate inhibition is generally irreversible and ages; carbamate inhibition is reversible
• Carbamates cause permanent enzyme aging
• Organophosphates cause hyperglycemia while carbamates do not
• Carbamates do not affect muscarinic receptors

Correct Answer: Organophosphate inhibition is generally irreversible and ages; carbamate inhibition is reversible

Q27. In forensic toxicology, which sample is preferred to assess long-term organophosphate exposure?

• Red blood cells to measure AChE activity
• Urine for immediate oxon levels only
• Saliva for chronic exposure
• Hair for acute enzyme inhibition

Correct Answer: Red blood cells to measure AChE activity

Q28. Which factor increases susceptibility to parathione toxicity?

• Genetic pseudocholinesterase deficiency
• High body fat reducing distribution
• Prior vaccination status
• Use of H2 blockers

Correct Answer: Genetic pseudocholinesterase deficiency

Q29. Which preventive measure is most effective for workers handling parathione?

• Use of appropriate personal protective equipment (gloves, respirators)
• Regular ingestion of activated charcoal
• Wearing only cotton clothes without gloves
• Frequent hand washing with oil-based cleansers

Correct Answer: Use of appropriate personal protective equipment (gloves, respirators)

Q30. Which diagnostic test would best correlate with severity and prognosis in organophosphate poisoning?

• Degree of RBC AChE inhibition
• Serum sodium concentration
• Chest X-ray opacity score
• Serum bilirubin level

Correct Answer: Degree of RBC AChE inhibition

Q31. Which symptom is most characteristic of nicotinic receptor overstimulation?

• Muscle weakness and fasciculations
• Excessive salivation
• Diarrhea
• Bronchospasm

Correct Answer: Muscle weakness and fasciculations

Q32. Which organ is primarily responsible for metabolism and bioactivation of parathione?

• Liver
• Kidney
• Lung
• Heart

Correct Answer: Liver

Q33. During management, which supportive intervention is critical to prevent hypoxia in organophosphate poisoning?

• Airway protection and mechanical ventilation if needed
• Immediate hemodialysis
• Induced hypothermia
• High-dose vitamin C infusion

Correct Answer: Airway protection and mechanical ventilation if needed

Q34. Which statement about pralidoxime administration is true?

• It is most effective if given early before AChE aging
• It acts primarily as a muscarinic antagonist
• It should never be given with atropine
• It directly blocks nicotinic receptors

Correct Answer: It is most effective if given early before AChE aging

Q35. Which adverse effect can high doses of atropine produce during treatment?

• Hyperthermia, agitation, urinary retention
• Excessive salivation and lacrimation
• Profuse sweating and bradycardia
• Severe hypoglycemia

Correct Answer: Hyperthermia, agitation, urinary retention

Q36. Which of the following organophosphate properties influences environmental persistence?

• Chemical stability and soil adsorption
• Color of the compound
• Presence of a nitro group only
• Ability to fluoresce under UV

Correct Answer: Chemical stability and soil adsorption

Q37. In an acute parathione ingestion case, which immediate decontamination is recommended if dermal exposure occurred?

• Remove contaminated clothing and wash skin with soap and water
• Apply oil to the skin to dissolve parathione
• Delay washing to allow prn absorption
• Use isopropyl alcohol only

Correct Answer: Remove contaminated clothing and wash skin with soap and water

Q38. Which pharmacokinetic property affects the onset of organophosphate toxicity?

• Rate of absorption and bioactivation to oxon
• Renal tubular secretion rate only
• Binding to plasma albumin only
• Gastrointestinal pH alone

Correct Answer: Rate of absorption and bioactivation to oxon

Q39. Which clinical scale or sign is useful to monitor severity in organophosphate poisoning?

• Respiratory rate, oxygenation, and level of consciousness (clinical respiratory scoring)
• Morse fall scale
• Glasgow coma scale only without respiratory assessment
• APGAR score

Correct Answer: Respiratory rate, oxygenation, and level of consciousness (clinical respiratory scoring)

Q40. Which of the following drugs can exacerbate organophosphate toxicity by inhibiting AChE reactivation?

• Organophosphorus compounds with rapid aging kinetics
• Beta-2 agonists
• Calcium channel blockers
• ACE inhibitors

Correct Answer: Organophosphorus compounds with rapid aging kinetics

Q41. Which occupational monitoring practice reduces risk of chronic low-level exposure to parathione?

• Regular biomonitoring of cholinesterase activity
• Annual chest X-rays
• Daily vitamin supplements
• Weekly hair analysis only

Correct Answer: Regular biomonitoring of cholinesterase activity

Q42. In organophosphate poisoning, which anticonvulsant is preferred for seizure control?

• Benzodiazepines (e.g., diazepam)
• Phenytoin as first-line sole therapy
• Carbamazepine only
• Methotrexate

Correct Answer: Benzodiazepines (e.g., diazepam)

Q43. Which structural change in AChE after phosphorylation makes spontaneous reactivation unlikely?

• Loss of alkyl group from phosphoryl moiety during aging
• Transient hydrogen bonding that reverses quickly
• Formation of disulfide bonds
• Acetylation of active-site histidine

Correct Answer: Loss of alkyl group from phosphoryl moiety during aging

Q44. Which decontamination method is useful for ingested parathione within one hour?

• Activated charcoal administration
• Gastric lavage after 24 hours
• Administering fatty meals to sequester toxin
• Whole bowel irrigation immediately for all cases

Correct Answer: Activated charcoal administration

Q45. Which sign would suggest central nervous system involvement in organophosphate poisoning?

• Seizures and altered mental status
• Isolated miosis without confusion
• Hematuria only
• Localized muscle pain only

Correct Answer: Seizures and altered mental status

Q46. Which population is at higher risk for severe parathione toxicity due to reduced detoxification?

• Individuals with inhibited or polymorphic CYP450 enzymes
• People with very high daily exercise levels
• Persons with high dietary fiber intake
• Individuals taking multivitamins

Correct Answer: Individuals with inhibited or polymorphic CYP450 enzymes

Q47. Long-term neurological sequelae after organophosphate poisoning may include:

• Peripheral neuropathy and cognitive deficits
• Permanent hyperthyroidism
• Chronic pancreatitis only
• Persistent hepatic failure in all cases

Correct Answer: Peripheral neuropathy and cognitive deficits

Q48. Which of the following best describes the role of butyrylcholinesterase in organophosphate exposure?

• Acts as a bioscavenger binding organophosphates, reducing AChE inhibition
• Directly activates parathione to oxon
• Is the primary neuronal AChE isoform
• Increases organophosphate lipophilicity

Correct Answer: Acts as a bioscavenger binding organophosphates, reducing AChE inhibition

Q49. In treatment protocols, pralidoxime is contraindicated or less useful in which scenario?

• When significant aging of phosphorylated AChE has already occurred
• When muscarinic signs are prominent
• When seizures persist despite benzodiazepines
• When airway is compromised

Correct Answer: When significant aging of phosphorylated AChE has already occurred

Q50. In a community health context, which intervention most effectively reduces parathione poisoning incidence?

• Education on safe pesticide use, proper storage, and PPE
• Mass distribution of pralidoxime to households
• Banning all agricultural pesticides immediately
• Promoting ingestion of antidotes prophylactically

Correct Answer: Education on safe pesticide use, proper storage, and PPE

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