1. MD., DA., DNB, MD (Acu), Dip. Diab. DCA, Dip. Software statistics-
Anticholinesterases
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu), Dip. Diab. DCA, Dip. Software statistics-
PhD ( physiology), IDRA

2. What are these ?
These agents are used in clinical practice to inhibit the action of acetylcholinesterase at the neuromuscular junction, thus prolonging the half-life of acetylcholine
So it antagonizes
neuromuscular blockade

5. Cholinesterase means acetyl cholinesterase – true
Edrophoni
Phos
Acetylate
Neo
Opc

6. Pouring acetyl choline in junctions
Antagonizes neuro muscular blockers
Initiate depolarization
Start contraction
Also presynaptic action
If we don’t have blockers at the site , it may cause persistent depolarization to cause weakness

7. Its pouring acetyl choline !!
The anticholinesterases produce effects equivalent to excessive stimulation of the cholinergic system,
i.e. stimulation of muscarinic receptor responses at the autonomic effector organs,
and stimulation of cholinergic receptors in the CNS.

9. Drugs – structure Neostigmine Pyridostigmine Edrophonium Physostigmine
No NH4+
Crosses membranes
Edrophonium
Physostigmine

10. Organophosphorous compounds – lipid soluble – cross BBB

11. Systems

12. CVS Vagal influence of conducting tissue Bradycardia
Decreased BP and output

13. Respiratory system
cause bronchial smooth muscle contraction leading to bronchospasm and hypoxia,
aggravated by an increase in secretions

14. GIT
Oesophageal motility, gastric motility and production of gastric secretions are enhanced
Rarely vomiting

15. Local application on eye
Miosis
Loss of accommodation

16. Tacrine is a short-acting anticholinesterase that can cross the blood–brain barrier producing central effects.
used in the past to extend the duration of action of succinylcholine.
Currently, it is used in the management of Alzheimer’s disease.

17. Edrophonium Dose 0.5 to 1 mg / kg Onset 1 minute Duration 10 minutes
Need spontaneous recovery
Atropine

18. Neostigmine 50 – 60 mic/ kg 1 minute 20 – 30 minute Glyco
15 mg neostigmine bromide PO is equivalent to 0.5 mg neostigmine methylsulfate parenteral
Nausea
Intestinal obstruction
Phase 2 block ??

19. Pyridostigmine Derivative of neostigmine Onset - 16 minutes
duration - 6 hours
Not for reversal
Myaesthenia

20. Physostigmine
Physostigmine (also known as eserine from éséré, the West African name for the Calabar bean) is a parasympathomimetic alkaloid,
Physostigmine is metabolized by plasma esterases;
elimination does not depend on renal excretion, but others depend

21. Uses of physo
Physostigmine is used to treat glaucoma, Alzheimer's disease, and delayed gastric emptying. It has been shown to improve long term memory.
Recently, it has begun to be used in the treatment of orthostatic hypotension.

22. Physostigmine
Because it is a tertiary amine, it can cross the blood–brain barrier, and physostigmine salicylate is used to treat the central nervous system effects of atropine, scopolamine, and other anticholinergic drug overdoses.
Physostigmine is the antidote of choice for Datura stramonium poisoning. It is also an antidote for Atropa belladonna poisoning, the same as for atropine

23. Pharmacokinetics- neostigmine
Metabolism
Liver microsomal enzymes and hydrolysis by cholinesterase enzymes
Elimination
Half-Life: min (IV); min (IM); min (PO)
Excretion: 50% urine

24. Tensilon test Discontinue all anticholinesterase agents for >8 hr
Give atropine mg/kg IV (if IM give 30 minutes before) with neostigmine mg/kg IM
If cholinergic response, stop test and give mg atropine IV
If inconclusive, retest another day with neostigmine mg/kg IM preceded by mg/kg atropine

25. Edrophonium is used mainly to diagnose myasthenia gravis.
A test dose of 2 mg followed 30 s later by 8 mg i.v. causes transient improvement in muscle power.
Myesthenic crisis or cholinergic crisis

26. Myasthenia gravis Acute: 0.5-2.5 mg IV/IM/SC q Day
Maintenance: mg/day PO divided q6-8hr
Use injectable with mg atropine IV to counteract muscarinic effects

27. Nondepolarizing Neuromuscular Blockade, Reversal
30 – 70 mic./kg
Dose varies with type of drug,
time duration after NMBs
Administer an IV anticholinergic (eg, atropine, glycopyrrolate) prior to, or concomitantly with neostigmine for NMB reversal; if bradycardia present, give anticholinergic before neostigmine

28. Alzheimer’s disease
A deficiency of structurally intact cholinergic neurones leads to progressive dementia in patients with Alzheimer’s disease
Donezipil
Rivastigmine

29. Post op urinary retention
Prevention: Neo mg IM after surgery. Repeat q4-6hr for 2-3 days
Treatment: mg IM and up to q3hr PRN (for 5 doses for retention)
Colonic Pseudo-obstruction

30. Central anticholinergic syndrome
. It can be reversed by intravenous physostigmine 2 mg followed by additional doses as required.
Chemical warfare
Oximes and atropine

31. Side effects Allergic: Allergic reactions and anaphylaxis Neurologic:
Dizziness, convulsions, loss of consciousness, drowsiness, headache, dysarthria, miosis and visual changes
Cardiovascular:
Cardiac arrhythmias (including bradycardia, A-V block and nodal rhythm) and nonspecific EKG changes have been reported,

32. Side effects Respiratory:
Increased oral, pharyngeal and bronchial secretions, and dyspnea;
respiratory depression, respiratory arrest and bronchospasm have been reported following the use of the injectable form

33. Frequency of side effects not studied
Dermatologic: Rash and urticaria
Gastrointestinal: Nausea, emesis, flatulence, and increased peristalsis and salivation
Genitourinary: Urinary frequency
Musculoskeletal: Muscle cramps and spasms, arthralgia
Miscellaneous: Diaphoresis, flushing and weakness

35. Possible intraarticular neostigmine – used for analgesia

36. Summary
Ach – cholinesterase – anticholinesterase – pour Ach every where
Types
Anionic – esteritic sites –
Uses
Side effects