Irreversible inhibitors – Echothiophate iodide MCQs With Answer

Understanding irreversible inhibitors such as echothiophate iodide is essential for B.Pharm students studying pharmacology and therapeutic agents. Echothiophate iodide is an organophosphate acetylcholinesterase inhibitor that phosphorylates the active-site serine, producing long-lasting cholinergic effects used primarily in glaucoma management. This topic covers mechanism of action, pharmacokinetics, ocular application, systemic toxicity, aging and reactivation principles, clinical uses, adverse effects, interactions (e.g., with succinylcholine), monitoring and emergency treatment of organophosphate poisoning. Mastery of these concepts helps with drug selection, safe dispensing and patient counseling. Keywords: irreversible inhibitors, echothiophate iodide, acetylcholinesterase, organophosphate, glaucoma, aging, pralidoxime. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which functional group in echothiophate iodide is primarily responsible for its irreversible inhibition of acetylcholinesterase?

• Quaternary ammonium moiety
• Phosphate (phosphoryl) group
• Iodide counterion
• Ether linkage

Correct Answer: Phosphate (phosphoryl) group

Q2. Echothiophate iodide irreversibly inhibits acetylcholinesterase by forming a covalent bond with which amino acid residue in the enzyme’s active site?

• Lysine
• Serine
• Cysteine
• Histidine

Correct Answer: Serine

Q3. The term “aging” in organophosphate inhibition refers to:

• Progressive hydrolysis of organophosphate in the environment
• Irreversible loss of alkyl groups from the phosphorylated enzyme making it resistant to reactivation
• Gradual increase in drug potency over time
• Metabolic activation of echothiophate to a more toxic metabolite

Correct Answer: Irreversible loss of alkyl groups from the phosphorylated enzyme making it resistant to reactivation

Q4. Which antidote is most effective for reactivating acetylcholinesterase inhibited by echothiophate if administered before aging occurs?

• Atropine
• Pralidoxime (2-PAM)
• Diazepam
• N-acetylcysteine

Correct Answer: Pralidoxime (2-PAM)

Q5. What is the primary therapeutic indication for echothiophate iodide in clinical use?

• Myasthenia gravis systemic therapy
• Treatment of organophosphate poisoning
• Topical therapy for glaucoma
• Analgesia for neuropathic pain

Correct Answer: Topical therapy for glaucoma

Q6. Which property of echothiophate iodide limits its central nervous system penetration?

• High lipophilicity
• Quaternary ammonium positive charge
• Extensive plasma protein binding
• Rapid hepatic metabolism

Correct Answer: Quaternary ammonium positive charge

Q7. Which ocular effect results directly from echothiophate’s acetylcholinesterase inhibition?

• Mydriasis (pupil dilation)
• Miosis (pupil constriction)
• Loss of corneal sensitivity
• Retinal detachment

Correct Answer: Miosis (pupil constriction)

Q8. Echothiophate increases aqueous humor outflow mainly by causing:

• Relaxation of ciliary muscle
• Contraction of ciliary muscle and opening of trabecular meshwork
• Decreased aqueous humor production by ciliary epithelium
• Elevation of episcleral venous pressure

Correct Answer: Contraction of ciliary muscle and opening of trabecular meshwork

Q9. Systemic adverse effects of echothiophate are related to excess stimulation of which receptor types?

• Only adrenergic receptors
• Only GABA receptors
• Muscarinic and nicotinic cholinergic receptors
• Histaminic receptors

Correct Answer: Muscarinic and nicotinic cholinergic receptors

Q10. Which of the following is a typical sign of excessive cholinergic effect from echothiophate?

• Tachycardia and dry mouth
• Bradycardia and bronchospasm
• Mydriasis and urinary retention
• Hyperthermia and constipation

Correct Answer: Bradycardia and bronchospasm

Q11. Which laboratory measurement is most specific for monitoring acetylcholinesterase inhibition by organophosphates?

• Plasma cholinesterase (butyrylcholinesterase) activity
• Red blood cell acetylcholinesterase activity
• Serum creatinine
• Urinary acetylcholine level

Correct Answer: Red blood cell acetylcholinesterase activity

Q12. Why does echothiophate have a prolonged duration of action compared with reversible cholinesterase inhibitors like neostigmine?

• It is more rapidly metabolized
• It binds non-covalently to the enzyme
• It phosphorylates and irreversibly inactivates acetylcholinesterase
• It is a prodrug activated by esterases

Correct Answer: It phosphorylates and irreversibly inactivates acetylcholinesterase

Q13. Interaction concern: Prior use of echothiophate may prolong the action of which neuromuscular blocker used in anesthesia?

• Rocuronium (non-depolarizing)
• Succinylcholine (depolarizing)
• Propofol
• Ketamine

Correct Answer: Succinylcholine (depolarizing)

Q14. In the event of local ocular toxicity from echothiophate, immediate management should include:

• Topical beta-blocker application
• Instillation of pilocarpine
• Copious irrigation of the eye and cessation of the drug
• Oral naloxone

Correct Answer: Copious irrigation of the eye and cessation of the drug

Q15. Compared with nerve agents, therapeutic organophosphates like echothiophate differ mainly because they:

• Are more volatile and lethal at low doses
• Are formulated for limited local ophthalmic exposure and have reduced systemic absorption
• Do not phosphorylate acetylcholinesterase
• Act as competitive antagonists at muscarinic receptors

Correct Answer: Are formulated for limited local ophthalmic exposure and have reduced systemic absorption

Q16. Which patient condition is a relative contraindication for echothiophate therapy?

• Controlled hypertension
• Reactive airway disease (asthma)
• Hyperlipidemia
• Well-managed diabetes mellitus

Correct Answer: Reactive airway disease (asthma)

Q17. Which of the following best describes the role of atropine in organophosphate toxicity?

• Reactivates phosphorylated acetylcholinesterase
• Antagonizes muscarinic effects of excess acetylcholine
• Enhances cholinesterase synthesis
• Acts as an anticonvulsant by GABA modulation

Correct Answer: Antagonizes muscarinic effects of excess acetylcholine

Q18. Which statement about the iodide in echothiophate iodide is correct?

• Iodide is the active inhibitory moiety on acetylcholinesterase
• Iodide confers significant systemic toxicity when applied ophthalmically
• Iodide is a counterion that contributes to drug stability and formulation
• Iodide converts the drug into an active radical in the eye

Correct Answer: Iodide is a counterion that contributes to drug stability and formulation

Q19. Which of the following best explains why echothiophate is used topically in the eye rather than systemically?

• It is ineffective when given systemically
• Topical ophthalmic use limits systemic exposure while achieving local effect
• Systemic administration causes immediate CNS depression
• It is unstable in the gastrointestinal tract

Correct Answer: Topical ophthalmic use limits systemic exposure while achieving local effect

Q20. Which of the following symptoms is characteristic of nicotinic overstimulation due to organophosphate exposure?

• Bronchorrhea and miosis
• Muscle fasciculations and weakness
• Excessive lacrimation and salivation
• Bradycardia and hypotension only

Correct Answer: Muscle fasciculations and weakness

Q21. Which enzyme other than acetylcholinesterase is also inhibited by echothiophate and is useful as a biomarker of exposure?

• Monoamine oxidase
• Butyrylcholinesterase (plasma cholinesterase)
• Cytochrome P450 3A4
• Acid phosphatase

Correct Answer: Butyrylcholinesterase (plasma cholinesterase)

Q22. Which pharmacokinetic aspect contributes to echothiophate’s prolonged ocular effect?

• Rapid renal excretion
• Slow hydrolysis of the phosphorylated enzyme and irreversible inactivation
• Extensive metabolism by ocular cytochrome P450
• High first-pass hepatic metabolism

Correct Answer: Slow hydrolysis of the phosphorylated enzyme and irreversible inactivation

Q23. Which of the following is a major ocular adverse effect associated with long-term echothiophate use?

• Lens opacities (cataract formation)
• Retinal hemorrhage
• Macular edema
• Optic neuritis

Correct Answer: Lens opacities (cataract formation)

Q24. The chemical classification of echothiophate iodide is:

• Carbamate cholinesterase inhibitor
• Organophosphate cholinesterase inhibitor
• Benzodiazepine derivative
• Beta-blocker

Correct Answer: Organophosphate cholinesterase inhibitor

Q25. Which phrase best describes why pralidoxime must be given early in organophosphate poisoning?

• It is only active when administered intrathecally
• It cannot cross cell membranes once the enzyme has aged and lost alkyl groups
• It requires coadministration with procaine
• It is rapidly degraded by gastric acid

Correct Answer: It cannot cross cell membranes once the enzyme has aged and lost alkyl groups

Q26. Which monitoring parameter is most relevant during chronic echothiophate therapy for glaucoma?

• Serum liver enzymes weekly
• Intraocular pressure and signs of cholinergic toxicity
• 20-minute post-dose blood glucose
• Pulse oximetry continuously at home

Correct Answer: Intraocular pressure and signs of cholinergic toxicity

Q27. Which statement about echothiophate’s effect on pupil size and accommodation is correct?

• It causes mydriasis and loss of accommodation
• It causes miosis and increased accommodation (spasm)
• It has no effect on pupil size or accommodation
• It causes fluctuation in pupil size without accommodation change

Correct Answer: It causes miosis and increased accommodation (spasm)

Q28. A patient on echothiophate is scheduled for surgery. Which anesthetic consideration is most important?

• No special considerations are needed
• Anticipate prolonged effect of succinylcholine and altered response to neuromuscular blockers
• Reduce inhalational anesthetic concentrations by 50%
• Expect rapid clearance of all drugs due to enzyme induction

Correct Answer: Anticipate prolonged effect of succinylcholine and altered response to neuromuscular blockers

Q29. Which clinical test differentiates between reversible carbamate and irreversible organophosphate acetylcholinesterase inhibition?

• Observation of pupillary response only
• Time to spontaneous recovery of cholinesterase activity after stopping the drug
• Measure of blood glucose
• Chest X-ray

Correct Answer: Time to spontaneous recovery of cholinesterase activity after stopping the drug

Q30. Which of the following drug interactions is most likely with echothiophate?

• Reduced warfarin anticoagulant effect
• Enhanced effect of anticholinergic drugs like atropine
• Prolonged action of succinylcholine and increased risk of bradycardia with beta-blockers
• Increased clearance of digoxin

Correct Answer: Prolonged action of succinylcholine and increased risk of bradycardia with beta-blockers

Q31. In cases of severe organophosphate poisoning, benzodiazepines (e.g., diazepam) are given primarily to:

• Reverse muscarinic effects
• Reactivate acetylcholinesterase
• Control seizures and provide neuroprotection
• Decrease bronchial secretions directly

Correct Answer: Control seizures and provide neuroprotection

Q32. Which statement about the systemic absorption of topical echothiophate is true?

• Systemic absorption is impossible due to ocular barriers
• Systemic absorption can occur and cause generalized cholinergic effects if dosing is excessive or barriers are compromised
• Systemic absorption leads to immediate renal failure
• Systemic absorption always leads to permanent CNS damage

Correct Answer: Systemic absorption can occur and cause generalized cholinergic effects if dosing is excessive or barriers are compromised

Q33. Which of the following best explains why echothiophate can precipitate a cholinergic crisis?

• It blocks acetylcholine receptors
• It causes excessive accumulation of acetylcholine by inhibiting acetylcholinesterase irreversibly
• It acts as a nicotinic antagonist at the neuromuscular junction
• It stimulates adrenergic receptors excessively

Correct Answer: It causes excessive accumulation of acetylcholine by inhibiting acetylcholinesterase irreversibly

Q34. Which sign is more indicative of muscarinic rather than nicotinic toxicity?

• Muscle weakness
• Bradycardia and bronchorrhea
• Paralysis of respiratory muscles
• Fasciculations

Correct Answer: Bradycardia and bronchorrhea

Q35. Which structural feature of echothiophate contributes to its water solubility compared to many nerve agents?

• Presence of a large lipophilic alkyl chain
• Quaternary ammonium salt form (iodide)
• Absence of phosphorus atom
• High degree of aromatic substitution

Correct Answer: Quaternary ammonium salt form (iodide)

Q36. Which of the following is NOT a typical responsibility of a B.Pharm student or pharmacist when dispensing echothiophate?

• Counseling the patient on ocular administration technique and systemic signs of toxicity
• Checking for contraindications such as uncontrolled asthma
• Advising on storage and avoiding expired stock
• Prescribing a systemic antidote dose for overdose without physician instruction

Correct Answer: Prescribing a systemic antidote dose for overdose without physician instruction

Q37. Which factor accelerates the aging process of phosphorylated acetylcholinesterase, making reactivation more difficult?

• Presence of bulky substituents on the organophosphate that slow dealkylation
• Low pH and high temperature conditions promoting dealkylation
• Administration of atropine after exposure
• Co-administration of neostigmine

Correct Answer: Low pH and high temperature conditions promoting dealkylation

Q38. Echothiophate’s therapeutic effect in glaucoma is primarily due to which change in aqueous humor dynamics?

• Increased production of aqueous humor
• Increased trabecular outflow of aqueous humor
• Decreased uveoscleral outflow
• Blockage of Schlemm’s canal

Correct Answer: Increased trabecular outflow of aqueous humor

Q39. Which population requires special caution when using echothiophate due to increased risk of systemic effects?

• Patients with localized conjunctivitis only
• Children and elderly with thin ocular barriers or multiple comorbidities
• Patients with well-controlled glaucoma on one drug
• Healthy young adults with no comorbidities

Correct Answer: Children and elderly with thin ocular barriers or multiple comorbidities

Q40. Which best describes the initial pharmacodynamic effect of echothiophate at neuromuscular junctions?

• Immediate paralysis due to receptor blockade
• Transient stimulation (fasciculations) followed by muscle weakness due to persistent acetylcholine excess
• Selective inhibition of presynaptic calcium channels
• Permanent increase in acetylcholine synthesis

Correct Answer: Transient stimulation (fasciculations) followed by muscle weakness due to persistent acetylcholine excess

Q41. In monitoring occupational exposure to organophosphates, which preventative measure should pharmacists emphasize?

• Frequent handwashing and use of personal protective equipment to avoid dermal absorption
• Only inhalation protection is necessary
• Exposure is harmless at low levels so no measures are needed
• Only ingestion prevention is required

Correct Answer: Frequent handwashing and use of personal protective equipment to avoid dermal absorption

Q42. Which of the following best characterizes the difference between acetylcholinesterase located at synapses and butyrylcholinesterase in plasma?

• Both are identical enzymes with same substrate specificity
• Acetylcholinesterase is membrane-bound and critical for synaptic transmission; butyrylcholinesterase is a plasma enzyme with broader substrate range
• Butyrylcholinesterase is exclusively found in the CNS
• Acetylcholinesterase is not inhibited by organophosphates

Correct Answer: Acetylcholinesterase is membrane-bound and critical for synaptic transmission; butyrylcholinesterase is a plasma enzyme with broader substrate range

Q43. Which clinical action would you expect after topical administration of echothiophate to the eye?

• Immediate dilation of the pupil
• Prolonged miosis and reduced intraocular pressure
• Increased tear production with no IOP change
• Systemic hypertension

Correct Answer: Prolonged miosis and reduced intraocular pressure

Q44. A patient treated with echothiophate develops severe bronchospasm. Which immediate treatment is indicated?

• Topical beta-blocker in the eye
• Systemic atropine to counter muscarinic bronchoconstriction
• Oral acetylcholinesterase inhibitor
• Activated charcoal

Correct Answer: Systemic atropine to counter muscarinic bronchoconstriction

Q45. Which of the following best explains why echothiophate may be preferred over shorter-acting miotics for some glaucoma patients?

• It has no risk of systemic side effects
• Prolonged duration reduces dosing frequency and may improve compliance
• It is the safest drug for patients with respiratory disease
• It increases aqueous production leading to pressure reduction

Correct Answer: Prolonged duration reduces dosing frequency and may improve compliance

Q46. During a pharmacology exam scenario, which statement about echothiophate’s reversibility is correct?

• Echothiophate causes reversible competitive inhibition like atropine
• Echothiophate causes irreversible inhibition by covalent phosphorylation of the enzyme
• Echothiophate noncompetitively blocks acetylcholine receptors
• Echothiophate is an allosteric activator of acetylcholinesterase

Correct Answer: Echothiophate causes irreversible inhibition by covalent phosphorylation of the enzyme

Q47. Which preventive counseling point should be given to patients applying echothiophate drops?

• Expect immediate relief of systemic symptoms
• Apply drops and then firmly press the inner corner of the eye (punctal occlusion) to reduce systemic absorption
• Remove contact lenses only after several days of therapy
• Use nasal decongestants to enhance drug absorption

Correct Answer: Apply drops and then firmly press the inner corner of the eye (punctal occlusion) to reduce systemic absorption

Q48. Which experimental finding supports that echothiophate binds irreversibly to acetylcholinesterase?

• Enzyme activity returns immediately after dialysis
• Enzyme activity remains suppressed after removal of free drug until new enzyme synthesis occurs
• Enzyme inhibition is reversed by increasing substrate concentration
• The drug shows competitive antagonism in binding assays

Correct Answer: Enzyme activity remains suppressed after removal of free drug until new enzyme synthesis occurs

Q49. Which of the following statements about echothiophate and pregnancy is most appropriate for counseling?

• It is universally safe and requires no risk discussion
• Use only if clearly needed and under specialist supervision due to potential fetal risk from systemic cholinergic effects
• It enhances fetal development and is recommended
• It should be used at double the usual dose during pregnancy

Correct Answer: Use only if clearly needed and under specialist supervision due to potential fetal risk from systemic cholinergic effects

Q50. From a medicinal chemistry perspective, the quaternary ammonium group in echothiophate primarily affects which pharmacological parameter?

• Increases CNS penetration
• Confers permanent enzyme activation
• Limits membrane permeability and CNS entry while enhancing aqueous solubility
• Makes the molecule volatile and inhalable

Correct Answer: Limits membrane permeability and CNS entry while enhancing aqueous solubility

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