ANTICHOLINESTERASES

Question 1

Classify anticholinesterase drugs into reversible and irreversible
groups and state prototype for each group (neostigmine,
organophosphate agents)

Answer 1

Reversible inhibitors
Edrophonium: Bind by an electrostatic force, very short lived (max 10 mins)
Neostigmine: Bind by a stronger electrostatic force, prolonged duration (up to 6hrs)

Irreversible inhibitors
Organophosphate: Bind by a covalent bond

Question 2

State the prototype and essential examples for reversible
(*neostigmine, edrophonium) and irreversible
(organophosphates) anticholinesterases

Answer 2

Reversible inhibitors
Edrophonium: Bind by an electrostatic force, very short lived (max 10 mins)
Neostigmine: Bind by a stronger electrostatic force, prolonged duration (up to 6hrs)

Irreversible inhibitors
Organophosphate: Bind by a covalent bond

Question 3

Explain the mechanism of action of neostigmine.

Answer 3

• Neostigmine is a reversible AChE inhibitors.
• It is bind by a strong electrostatic force that can cause prolonged duration up to 6 hours
• Neostigmine will inhibit the AChE.
• This causes the ACh to be accumulated in the synaptic cleft
• ACh interaction with the cholino-ceptors will be increases
• However, if the amount of AChE is much more higher, the neostigmine will unable to inhibit the AChE.

Question 4

Explain the mechanism of action of organophosphate

Answer 4

• Organophosphate is an irreversible AChE inhibitor.
• It is bind by a covalent bond.
• Hence, organosphosphate will inhibit irreversibly AChE.
• This causes the ACh to be accumulated in the synaptic cleft.
• The interaction between the ACh and the cholino-ceptors is increasing.

Question 5

List the site where acetylcholine accumulation occurs.

Answer 5

Synaptic cleft

Question 6

Explain the pharmacological effects of anticholinesterases on
organs.

Answer 6

NMJ
- Increases the strength of contraction: more impulse is transmitted to the muscle - more muscle fibre stimulated
- NMJ blockade
CVS
- bradycardia
- low CO
- vasoconstriction
- high BP
CNS
- Increased alertness
- enhanced memory
- too much can cause convulsion which lead to coma and respiratory failure
EYES
- Miosis
RESPIRATORY
- Bronchoconstriction
GIT
- Increased motility and secretions
- Relaxed sphincter
URINARY BLADDER
- detrusor contracts
- sphincter relaxed

Question 7

Explain the pharmacological basis of the use of edrophonium in
the diagnosis of myasthenia gravis.

Answer 7

• Myasthenia gravis (MG) is an autoimmune disorder which causes weakness in and fatigue of certain muscles.
• MG have antibodies which, instead of preventing infection, attack nerves and muscles by mistake.
• Hence, to diagnose MG, edrophonium which is a short acting AChE inhibitor is used in Tensilon Test.
• This is because, edrophonium can provide temporary enhancement of impulse transmission by temporarily increase the amount of ACh in the synapse.

Question 8

Explain the pharmacological basis of the use of neostigmine in
the treatment of myasthenia gravis.

Answer 8

• MG is an autoimmune disorder that causes weakness and fatigue in certain muscles.
• To treat MG, it needs to improve the impulse transmission at the NMJ by increasing the amount of ACh available to interact with the limited number of nicotinic receptors.
• Hence, it has to inhibit the breakdown of released ACh from the neuron by blocking the AChE.
• Thus, neostigmine is the best medication to use to treat MG because it is a reversible AChE inhibitor.

Question 9

Differentiate between cholinergic crisis and myasthenic crisis

Answer 9

CHOLINERGIC CRISIS

• muscle weakness due to excessive ACh at the NMJ as a result of the inactivity of the AChE.
• Give edrophonium will worsen the weakness

MYASTHENIC CRISIS

• Muscle weakness due to severe form of myasthenia gravis that is severe enough to necessitate intubation
• give edrophonium will improve the weakness

Question 10

Explain the clinical uses of anticholinesterase drugs other than
myasthenia gravis.

Question 11

Discuss the symptoms and treatment of organophosphate

poisoning.

Answer 11

• Organophosphate poisoning: accumulation of ACh in the synapse that lead to excessive depolarisation and desensitisation of post- synaptic membrane.
• Mainly, farmers are effected.

SYMPTOMS
Diarrhea
Urination
Miosis
Bradycardia
Bronchospasm
Emesis
Lacrimation
Salivation

EFFECTS
NMJ: fasciculation, muscle weakness, paralysis
CNS: respiratory depression, lethargy, seizures, coma

TREATMENT

• ABCDE of resuscitation
• may need intubation but avoid succinylcholine
• ATROPINE
• PRALIDOXIME
• DECONTAMINATE: discard clothing,, aggresive dermal and ocular irrigation, activated charcoal

Question 12

Explain the rationale of the use of atropine & (*)pralidoxime in
the treatment of organophosphate poisoning.

Answer 12

• Atropine is a competitive antagonist of ACh at the muscarinic receptor
• It ables to cross the blood brain barrier and it is widely distributed
• It is a hepatic metabolism by 50% and another 50% excreted unchanged in urine.
• Pralidoxime is an AChE reactivating agent
• The binding of AChE with OP will phosphorylated the AChE.
• Hence, it will resists to hydrolysis
• Therefore phosphate grp is unable to remove
• The use of pralidoxime will help in removing the phosphate grp.
• Hence, enzyme will be regenerated.