Irreversible inhibitors – Isofluorphate MCQs With Answer

Irreversible inhibitors – Isofluorphate MCQs With Answer

Irreversible inhibitors such as isoflurophate are organophosphate acetylcholinesterase (AChE) inhibitors widely studied in pharmacology for their potent, long-lasting effects. This concise introduction for B.Pharm students covers mechanism of action (phosphorylation of the serine hydroxyl at AChE active site), clinical use in glaucoma, toxicology (cholinergic excess), concepts of “aging,” and antidotal therapy including atropine and oximes (pralidoxime). Understanding isoflurophate’s pharmacodynamics, pharmacokinetics, safety precautions, and laboratory assays is essential for therapeutics and toxicology. SEO keywords: irreversible inhibitors, isoflurophate, AChE inhibitors, organophosphate, pralidoxime, atropine, glaucoma, B.Pharm, toxicity, aging. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which molecular action best describes how isoflurophate irreversibly inhibits acetylcholinesterase?

• Noncovalent competitive binding at the active site
• Covalent phosphorylation of the serine hydroxyl in the active site
• Allosteric modulation of enzyme conformation
• Oxidative cleavage of the catalytic histidine residue

Correct Answer: Covalent phosphorylation of the serine hydroxyl in the active site

Q2. Isoflurophate is classified pharmacologically as which type of compound?

• Carbamate reversible AChE inhibitor
• Organophosphate irreversible AChE inhibitor
• Competitive muscarinic antagonist
• Nicotinic receptor blocker

Correct Answer: Organophosphate irreversible AChE inhibitor

Q3. What clinical indication was isoflurophate historically used for?

• Treatment of myasthenia gravis systemically
• Long-acting topical miotic for glaucoma
• Systemic analgesia in neuropathic pain
• Prophylaxis against organophosphate poisoning

Correct Answer: Long-acting topical miotic for glaucoma

Q4. Which of the following best describes the concept of “aging” in organophosphate-inhibited AChE?

• Reversible dissociation of inhibitor from enzyme over time
• Spontaneous loss of an alkyl group from the phosphorylated enzyme, preventing reactivation
• Metabolic breakdown of the organophosphate into inactive metabolites
• Upregulation of new AChE synthesis within minutes

Correct Answer: Spontaneous loss of an alkyl group from the phosphorylated enzyme, preventing reactivation

Q5. Which antidote is most appropriate to reverse muscarinic symptoms in acute isoflurophate poisoning?

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

Correct Answer: Atropine

Q6. Which agent can reactivate un-aged phosphorylated AChE by nucleophilic attack on the phosphorus atom?

• Atropine
• Pralidoxime (2-PAM)
• Propranolol
• Donepezil

Correct Answer: Pralidoxime (2-PAM)

Q7. Which symptom set primarily reflects nicotinic receptor overstimulation after organophosphate exposure?

• Bradycardia, miosis, bronchospasm
• Muscle fasciculations, weakness, paralysis
• Diaphoresis, salivation, lacrimation
• Hypotension and coma

Correct Answer: Muscle fasciculations, weakness, paralysis

Q8. Why are organophosphate inhibitors like isoflurophate long-acting compared with reversible inhibitors?

• They bind noncovalently but with high affinity
• They form covalent bonds with AChE that require enzyme resynthesis to reverse
• They are rapidly metabolized to active metabolites
• They are competitive antagonists at acetylcholine receptors

Correct Answer: They form covalent bonds with AChE that require enzyme resynthesis to reverse

Q9. Which laboratory assay is commonly used to measure acetylcholinesterase activity in clinical and research settings?

• ELISA for acetylcholine
• Ellman’s colorimetric assay
• Western blot for AChE protein
• Mass spectrometry of organophosphate metabolites

Correct Answer: Ellman’s colorimetric assay

Q10. Which precaution is most important when handling isoflurophate in a laboratory or pharmacy setting?

• Ensure refrigeration at all times
• Use appropriate personal protective equipment and avoid skin contact
• Store under high-humidity conditions to prevent hydrolysis
• Combine with strong bases to neutralize

Correct Answer: Use appropriate personal protective equipment and avoid skin contact

Q11. Which statement about atropine and pralidoxime use in organophosphate poisoning is correct?

• Pralidoxime treats muscarinic symptoms while atropine regenerates AChE
• Atropine treats muscarinic symptoms while pralidoxime can reactivate AChE if given before aging
• Both drugs are interchangeable and have identical mechanisms
• Neither drug is useful for nicotinic effects at neuromuscular junctions

Correct Answer: Atropine treats muscarinic symptoms while pralidoxime can reactivate AChE if given before aging

Q12. Which structural feature of many organophosphates determines the lability of the enzyme–inhibitor complex and the rate of aging?

• Presence of a bulky aromatic ring only
• Nature of alkyl substituents on the phosphorus atom
• Chirality at adjacent carbon atoms
• Degree of glycosylation of the molecule

Correct Answer: Nature of alkyl substituents on the phosphorus atom

Q13. Which clinical test helps monitor recovery of cholinesterase activity after organophosphate exposure?

• Serum pseudocholinesterase (butyrylcholinesterase) assay
• Complete blood count only
• Serum creatinine measurement
• Fasting blood glucose

Correct Answer: Serum pseudocholinesterase (butyrylcholinesterase) assay

Q14. Which of the following best differentiates organophosphate poisoning from anticholinergic toxicity clinically?

• Organophosphates cause dry skin and mydriasis
• Organophosphates cause bradycardia, miosis, bronchorrhea and salivation
• Anticholinergic toxicity causes increased secretions and diarrhea
• Both produce hyperthermia and dry mucous membranes

Correct Answer: Organophosphates cause bradycardia, miosis, bronchorrhea and salivation

Q15. Which of the following is a primary reason oximes may fail to reverse AChE inhibition by isoflurophate if given late?

• Atropine interaction reduces oxime efficacy
• The phosphorylated enzyme undergoes aging, becoming resistant to nucleophilic attack
• Oximes cannot reach peripheral tissues
• Oximes convert AChE to an inactive form themselves

Correct Answer: The phosphorylated enzyme undergoes aging, becoming resistant to nucleophilic attack

Q16. Which organ system is most critically affected by accumulation of acetylcholine at synapses after isoflurophate exposure?

• Endocrine system
• Cardiovascular and respiratory systems via autonomic and neuromuscular junctions
• Skeletal system bone remodeling
• Renal tubular secretion only

Correct Answer: Cardiovascular and respiratory systems via autonomic and neuromuscular junctions

Q17. Which sign is an early muscarinic effect of isoflurophate exposure?

• Muscle weakness
• Miosis and excessive lacrimation
• Hyperreflexia
• Dry mouth

Correct Answer: Miosis and excessive lacrimation

Q18. Which treatment modality is essential along with pharmacologic antidotes in severe organophosphate poisoning?

• Gastric lavage and activated charcoal for dermal exposure
• Supportive airway management, oxygenation, and mechanical ventilation if needed
• High-dose insulin therapy
• Immediate administration of beta-blockers

Correct Answer: Supportive airway management, oxygenation, and mechanical ventilation if needed

Q19. Which pharmacokinetic trait contributes to prolonged local effect of topical isoflurophate in the eye?

• Rapid renal excretion
• Irreversible AChE binding in ocular tissues and slow enzyme turnover
• High first-pass hepatic metabolism after topical use
• Active efflux from ocular tissues into systemic circulation

Correct Answer: Irreversible AChE binding in ocular tissues and slow enzyme turnover

Q20. Which laboratory parameter is decreased in plasma after significant organophosphate exposure?

• Plasma acetylcholinesterase activity
• Serum potassium concentration permanently
• Blood urea nitrogen only
• Hemoglobin concentration

Correct Answer: Plasma acetylcholinesterase activity

Q21. In the context of isoflurophate toxicity, what does “cholinergic crisis” primarily refer to?

• Severe deficiency of acetylcholine at synapses
• Excessive stimulation of cholinergic receptors due to inhibited AChE
• Autoimmune destruction of cholinergic neurons
• Ischemic injury to peripheral nerves

Correct Answer: Excessive stimulation of cholinergic receptors due to inhibited AChE

Q22. Which organophosphate-related concept is most relevant for B.Pharm students studying drug safety and storage?

• They are stable indefinitely at room temperature
• They can hydrolyze in moisture and require careful storage and labeling to prevent accidental exposure
• They are immune to photodegradation
• They become non-toxic when diluted below active concentrations

Correct Answer: They can hydrolyze in moisture and require careful storage and labeling to prevent accidental exposure

Q23. Which clinical intervention reduces mortality in severe organophosphate poisoning by preventing respiratory failure?

• Early atropine titration and ventilatory support
• Administration of benzodiazepines only
• Oral activated charcoal alone
• High-dose corticosteroids

Correct Answer: Early atropine titration and ventilatory support

Q24. Which structural class best distinguishes carbamate inhibitors from organophosphate inhibitors in terms of reversibility?

• Carbamates form reversible carbamylated enzyme intermediates; organophosphates form phosphorylated, often irreversible intermediates
• Carbamates are larger molecules and always irreversible
• Organophosphates are always noncovalent inhibitors
• Carbamates act only on muscarinic receptors, not AChE

Correct Answer: Carbamates form reversible carbamylated enzyme intermediates; organophosphates form phosphorylated, often irreversible intermediates

Q25. Which monitoring sign indicates adequate atropinization in a patient treated for organophosphate poisoning?

• Resolution of bronchorrhea and wet secretions
• Bradycardia with persistent bronchospasm
• Onset of muscle fasciculations
• Profuse sweating and miosis

Correct Answer: Resolution of bronchorrhea and wet secretions

Q26. Which statement about pralidoxime (2-PAM) is correct regarding blood–brain barrier (BBB) penetration?

• Pralidoxime freely crosses the BBB and reverses central AChE inhibition effectively
• Pralidoxime poorly penetrates the BBB, limiting central nervous system reactivation
• Pralidoxime permanently inactivates central AChE
• Pralidoxime is a lipophilic molecule that accumulates in brain tissue

Correct Answer: Pralidoxime poorly penetrates the BBB, limiting central nervous system reactivation

Q27. Which of the following is NOT a typical muscarinic sign of organophosphate poisoning?

• Bronchospasm
• Excessive salivation
• Urinary retention
• Diarrhea

Correct Answer: Urinary retention

Q28. Which feature distinguishes diisopropyl fluorophosphate (DFP) from isoflurophate in teaching examples?

• DFP is a model organophosphate used in research; isoflurophate is a clinically used ophthalmic organophosphate
• DFP is a reversible inhibitor while isoflurophate is irreversible
• Isoflurophate is not an organophosphate
• DFP does not inhibit AChE

Correct Answer: DFP is a model organophosphate used in research; isoflurophate is a clinically used ophthalmic organophosphate

Q29. Which educational point is most important when teaching safe disposal of isoflurophate?

• Flush small amounts down the sink with water
• Follow hazardous waste protocols and neutralize per institutional guidelines to prevent environmental contamination
• Store indefinitely in unlabeled containers
• Mix with household bleach before disposal

Correct Answer: Follow hazardous waste protocols and neutralize per institutional guidelines to prevent environmental contamination

Q30. Which term best describes isoflurophate’s effect duration on AChE in treated tissues?

• Short-acting and reversible
• Intermediate-acting and competitive
• Long-acting due to covalent irreversible inhibition
• Transient receptor blockade

Correct Answer: Long-acting due to covalent irreversible inhibition

Q31. Which is a key differential point between organophosphate poisoning and myasthenia gravis exacerbation at presentation?

• Organophosphate poisoning produces increased secretions and miosis; myasthenia gravis causes dry mouth and normal pupillary size
• Myasthenia gravis always causes diarrhea
• Organophosphate poisoning never affects muscle strength
• Myasthenia gravis presents with hyperreflexia only

Correct Answer: Organophosphate poisoning produces increased secretions and miosis; myasthenia gravis causes dry mouth and normal pupillary size

Q32. Which pharmacological agent is contraindicated as an antidote in organophosphate poisoning?

• High-dose atropine
• Pralidoxime
• Physostigmine
• Benzodiazepines for seizures

Correct Answer: Physostigmine

Q33. Why is skin decontamination critical after dermal exposure to isoflurophate?

• Dermal exposure is harmless and self-limited
• Persistent dermal absorption can continue to inhibit AChE and cause systemic toxicity
• Isoflurophate is only active when ingested
• Skin decontamination increases ageing of AChE

Correct Answer: Persistent dermal absorption can continue to inhibit AChE and cause systemic toxicity

Q34. Which is an expected ECG change in severe organophosphate poisoning?

• Tachyarrhythmias only without bradycardia
• Bradycardia and possible conduction abnormalities due to vagal stimulation
• Hyperkalemia-specific peaked T waves only
• Fixed ST-elevation myocardial infarction pattern

Correct Answer: Bradycardia and possible conduction abnormalities due to vagal stimulation

Q35. Which statement about enzyme turnover after irreversible AChE inhibition is correct?

• AChE activity is immediately restored within minutes after exposure ends
• Recovery depends on de novo synthesis of AChE, which can take days to weeks
• AChE is permanently lost and never regenerates
• Only pseudocholinesterase regenerates, not AChE

Correct Answer: Recovery depends on de novo synthesis of AChE, which can take days to weeks

Q36. Which clinical feature indicates severe central nervous system involvement in organophosphate poisoning?

• Excessive lacrimation without CNS signs
• Seizures and coma
• Isolated miosis only
• Local skin irritation only

Correct Answer: Seizures and coma

Q37. Which preventive pharmacologic measure has been used to protect troops from irreversible nerve agents but is less relevant to isoflurophate therapy?

• Prophylactic administration of a reversible carbamate (pyridostigmine) to protect AChE
• Continuous atropine infusion as prophylaxis
• Daily pralidoxime injections
• High-dose corticosteroid prophylaxis

Correct Answer: Prophylactic administration of a reversible carbamate (pyridostigmine) to protect AChE

Q38. Which laboratory value is useful to assess exposure severity and correlate with clinical status?

• Butyrylcholinesterase (pseudocholinesterase) activity
• Serum sodium level only
• Serum albumin concentration
• Platelet count only

Correct Answer: Butyrylcholinesterase (pseudocholinesterase) activity

Q39. Which management step is NOT recommended in acute organophosphate exposure?

• Immediate removal of contaminated clothing and skin washing
• Early administration of atropine and oxime if indicated
• Giving succinylcholine for airway management without caution
• Providing respiratory support and monitoring

Correct Answer: Giving succinylcholine for airway management without caution

Q40. Which statement best explains why pediatric patients may be at greater risk from organophosphate exposure?

• Pediatrics have lower surface area to body weight ratio
• Pediatrics have higher skin permeability and smaller body mass, leading to higher systemic exposure per dose
• Children have fully matured detoxification enzymes
• Isoflurophate is less toxic in children

Correct Answer: Pediatrics have higher skin permeability and smaller body mass, leading to higher systemic exposure per dose

Q41. Which concept is crucial when teaching B.Pharm students about the difference between acetylcholinesterase and butyrylcholinesterase?

• Only acetylcholinesterase is inhibited by organophosphates
• Butyrylcholinesterase activity in plasma is a biomarker of exposure but has different tissue distribution and function
• Butyrylcholinesterase regenerates AChE
• They are identical enzymes with the same function and distribution

Correct Answer: Butyrylcholinesterase activity in plasma is a biomarker of exposure but has different tissue distribution and function

Q42. Which research method helps determine the binding kinetics of isoflurophate to AChE?

• Behavioral testing only
• Enzyme kinetics studies measuring rate constants for phosphorylation and aging
• Crystal ball prediction
• Simple pH measurement

Correct Answer: Enzyme kinetics studies measuring rate constants for phosphorylation and aging

Q43. Which sign suggests nicotinic blockade at the neuromuscular junction rather than nicotinic overstimulation?

• Muscle weakness and respiratory muscle paralysis
• Fasciculations and initial tremor
• Increased salivation
• Miosis and bronchospasm

Correct Answer: Muscle weakness and respiratory muscle paralysis

Q44. Which teaching point about isoflurophate’s routes of exposure is correct?

• Only ingestion is hazardous; skin contact is safe
• Dermal, inhalational, and ocular exposures can all produce systemic toxicity
• Inhalation exposure is impossible with organophosphates
• Ocular exposure causes no systemic effects

Correct Answer: Dermal, inhalational, and ocular exposures can all produce systemic toxicity

Q45. Which factor most influences the speed at which symptoms develop after isoflurophate exposure?

• Rate of AChE resynthesis only
• Dose, route of exposure and compound lipophilicity
• Time of day when exposed
• Patient’s eye color

Correct Answer: Dose, route of exposure and compound lipophilicity

Q46. Which pharmacodynamic interaction is most relevant when combining isoflurophate exposure with beta-blockers?

• Beta-blockers reverse organophosphate poisoning
• Beta-blockers may exacerbate bronchospasm caused by muscarinic stimulation
• Beta-blockers increase AChE activity
• No clinically relevant interactions exist

Correct Answer: Beta-blockers may exacerbate bronchospasm caused by muscarinic stimulation

Q47. Which educational outcome is important for B.Pharm students regarding reporting and regulatory aspects of isoflurophate?

• There are no regulations governing organophosphate use
• Appropriate reporting of accidental exposures and adherence to hazardous material regulations is mandatory
• Only verbal notifications are needed for spills
• Isoflurophate can be freely distributed without record

Correct Answer: Appropriate reporting of accidental exposures and adherence to hazardous material regulations is mandatory

Q48. Which clinical feature differentiates intermediate syndrome from acute cholinergic crisis after organophosphate poisoning?

• Intermediate syndrome is characterized by delayed onset respiratory muscle weakness occurring 24–96 hours after recovery from initial cholinergic symptoms
• Intermediate syndrome occurs immediately with excessive secretions
• Intermediate syndrome presents only with gastrointestinal symptoms
• Intermediate syndrome is a chronic allergenic reaction

Correct Answer: Intermediate syndrome is characterized by delayed onset respiratory muscle weakness occurring 24–96 hours after recovery from initial cholinergic symptoms

Q49. Which educational laboratory safety measure should students perform after handling organophosphates like isoflurophate?

• Leave contaminated gloves on bench
• Remove protective clothing, wash hands and exposed skin thoroughly, and follow institutional decontamination protocols
• Rinse hands briefly with water and return to work
• Store contaminated PPE in personal backpack

Correct Answer: Remove protective clothing, wash hands and exposed skin thoroughly, and follow institutional decontamination protocols

Q50. Which long-term teaching point should B.Pharm students remember about irreversible AChE inhibitors like isoflurophate?

• Their effects are trivial and do not require follow-up
• They present unique clinical challenges due to irreversible enzyme inhibition, potential delayed complications, and the need for specific antidotes and supportive care
• They can be safely used systemically without monitoring
• They primarily act as beta-adrenergic agonists

Correct Answer: They present unique clinical challenges due to irreversible enzyme inhibition, potential delayed complications, and the need for specific antidotes and supportive care

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