Cholinergic Agonists
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
The clinical uses of anti-ChEs are as follows: Neostigmine: At the end of an operation, it reverses the action of nondepolarizing neuromuscular blockers.Pyridostigmine or neostigmine: Treatment of myasthenia gravis.Edrophonium: A short-acting drug, given intravenously in the management of myasthenia gravis and to differentiate between muscle paralysis due to myasthenia gravis or cholinergic crisis at the motor end plate.Donepezil: In Alzheimer’s disease.Ecothiopate: In glaucoma, as an eye drops (Katzung et al., 2009).
Physiology, Biochemistry, and Pathology of Neuromuscular Transmission
Marc H. De Baets, Hans J.G.H. Oosterhuis in Myasthenia Gravis, 2019
There are three classes of substances that block AChE. The first class blocks in a competitive manner at the anionic site of the enzyme. Edrophonium, which is used as a diagnostic test in myasthenia gravis, belongs to this class. The second class are the carbamates, for instance neostigmine and pyridostigmine, which react chemically with the active center of the enzyme. The carbamyl group of these drugs gets covalently attached to the active site; the active site is regenerated by hydrolysis only very slowly (cf. Figure 10). The third class is formed by the organophosphates which comprises compounds that are produced as insecticides (e.g., parathion) and nerve gases (e.g., tabun). These substances also react with the reactive center of the AChE in the same way as carbamates (a phosphate derivative is attached to the active center), the main difference being that the enzyme-phosphate bond cannot be hydrolyzed spontaneously, so that the enzyme activity does not recover (see Figure 10).
Medical Countermeasures for Intoxication by Botulinum Neurotoxin
Brian J. Lukey, James A. Romano, Salem Harry in Chemical Warfare Agents, 2019
In a wound botulism case, a 13-year-old boy developed wound botulism following a football injury (de Jesus and Slater, 1973). He was hospitalized after paralysis of the face and tongue, drooping of the eyelids (ptosis), ophthalmoplegia, depressed gag reflex, and dysphonia; limb strength, however, was normal. The short-acting ACh inhibitor edrophonium (normally used in the diagnosis of myasthenia gravis) was administered intravenously (i.v.) early in the course of his hospitalization on two occasions. In the first, a 3 mg dose enabled the patient to open his eyes approximately 90%, and a 5 mg dose led to improvements in eye movements and speech quality. These improvements were transient, consistent with the short-acting nature of edrophonium. The patient’s condition continued to deteriorate, and he subsequently developed shortness of breath and limb weakness requiring artificial ventilation. At this time, administration of 10 mg edrophonium (i.v.) or 1 mg neostigmine was only able to reverse ptosis by 50%, and there was no consistent improvement in ocular movement, indicating a reduction in efficacy of AChE inhibitors as a function of disease progression.
Myasthenic crisis as an initial presentation of myasthenia gravis in an 81-year-old following endoscopic myotomy for Zenker’s diverticulum
Published in Baylor University Medical Center Proceedings, 2023
Daniel Tran, Lucas Fair, Bryana Baginski, Bola Aladegbami, Steven Leeds, Marc Ward
Physical examination may reveal muscle weakness, ptosis, or impaired extraocular movements. However, physical examination may reveal normal muscle strength due to a fluctuating disease pattern. In these cases, repeated muscle use can demonstrate weakness. In a patient with suspected MG, serum testing for AChR antibodies is the first recommended step in diagnosis.7 Multiple other diagnostic tests can be performed. Electrodiagnostic techniques, such as nerve conduction studies and routine needle electromyography, can be performed to exclude alternative diagnoses or to confirm a concomitant disorder.7 Pharmacologic testing with edrophonium can be used, but is associated with serious adverse reactions.8 The ice pack test is a quick and simple bedside method that can be used. If there is improvement in ptosis after ice is placed on a closed lid for 2 minutes, it is a positive test result.9
A cluster of tetrodotoxin poisoning in Oman
Published in Clinical Toxicology, 2022
Badria Alhatali, Sultan Al Lawatia, Faryal Khamis, Sandeep Kantur, Seif Al-Abri, Vikas Kapil, Jerry Thomas, Rudolph Johnson, Elizabeth I. Hamelin, Rebecca M. Coleman, Ziad Kazzi
There is no specific antidote for TTX intoxication. The management is mainly based on supportive care. This includes intubation and mechanical ventilation for respiratory failure, intravenous fluids and vasopressors for hypotension, atropine for bradycardia, and hypersalivation [18]. Acetylcholinesterase inhibitors such as neostigmine or edrophonium have been used in tetrodotoxin-induced respiratory failure. They inhibit the breakdown of acetylcholine at the neuromuscular junction and may overcome the blockade of the nicotinic receptor at the neuromuscular junction [16,19]. The recommended dose of neostigmine is 1.5–2.5 mg IV every 6 h for a total duration of 24 h [11,16,19]. Pretreatment with edrophonium 10 mg before neostigmine appears to accelerate recovery of muscle power [20]. Neostigmine does not cross the blood-brain barrier and would not affect the medullary respiratory center in the Central Nervous System in which the toxin exerts inhibition of respiration in addition to its effect at the neuromuscular junction [19]. Unfortunately, there is currently insufficient evidence to support or refute the use of neostigmine in patients with tetrodotoxin-associated respiratory failure. Most data consist of case series [16].
Quantification of Cover Test Prior and Post Pyridostigmine in Diagnosis of Myasthenia Gravis
Published in Journal of Binocular Vision and Ocular Motility, 2021
Marta Saint-Gerons, Miguel Angel Rubio, Ana Martinez, Ana Matheu
The most accepted pharmacological test for the diagnosis of MG is the Tensilon® test with edrophonium chloride, another reversible acetylcholinesterase (AChE) inhibitor.14 The sensitivity of the edrophonium test for the detection of OMG is 88–97% and the sensitivity around 50–83%.2 Edrophonium test can cause adverse cardiovascular effects and should be used with precaution in patients with heart disease or in patients taking atrioventricular node-blocking drugs. The test may also be complicated by cholinergic side effects. Consequently, the edrophonium test has been increasingly replaced by the noninvasive rest/sleep and ice bedside tests.1 Kubis et al.15 reported a sensitivity of 50% for the rest test although its specificity was high 100%. M Benatar13 estimates a sensitivity of 95% (90–99%) and a sensitivity of 97% (94–100%) of seven studies that describe the accuracy of the ice test in ocular and generalized myasthenia, even if the value is questionable given the heterogeneity between studies.
Related Knowledge Centers
- Acetylcholinesterase
- Acetylcholinesterase Inhibitor
- Cholinergic Crisis
- Neuromuscular Junction
- Neurotransmitter
- Acetylcholine
- Approved Drug Products With Therapeutic Equivalence Evaluations
- Tensilon Test
- Myasthenia Gravis
- Lambert–Eaton Myasthenic Syndrome