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Anticholinesterases
Dr. S. Parthasarathy
MD., DA., DNB, MD (Acu), Dip. Diab.
DCA, Dip. Software statisticsPhD ( physiology), IDRA
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
Cholinesterase means acetyl
cholinesterase – true
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Opc
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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
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.
Drugs – structure
Neostigmine
Edrophonium
Pyridostigmine
No
NH4+
Crosses
membranes
Physostigmine
Organophosphorous
compounds – lipid
soluble – cross BBB
Systems
CVS
• Vagal influence of conducting tissue
• Bradycardia
• Decreased BP and output
Respiratory system
• cause bronchial smooth muscle contraction leading
to bronchospasm and hypoxia,
• aggravated by an increase in secretions
GIT
• Oesophageal motility, gastric motility and
production of gastric secretions are enhanced
• Rarely vomiting
Local application on eye
• Miosis
• Loss of accommodation
• 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.
Edrophonium
• Dose 0.5 to 1 mg / kg
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Onset 1 minute
Duration 10 minutes
Need spontaneous recovery
Atropine
Neostigmine
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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 ??
Pyridostigmine
• Derivative of neostigmine
• Onset - 16 minutes
• duration - 6 hours
• Not for reversal
• Myaesthenia
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
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.
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
Pharmacokinetics- neostigmine
• Metabolism
• Liver microsomal enzymes and hydrolysis by
cholinesterase enzymes
• Elimination
• Half-Life: 47-60 min (IV); 51-90 min (IM); 4260 min (PO)
• Excretion: 50% urine
Tensilon test
• Discontinue all anticholinesterase agents for >8
hr
• Give atropine 0.011 mg/kg IV (if IM give 30
minutes before) with neostigmine 0.022 mg/kg
IM
• If cholinergic response, stop test and give 0.4-0.6
mg atropine IV
• If inconclusive, retest another day with
neostigmine 0.031 mg/kg IM preceded by 0.016
mg/kg atropine
• 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
Myasthenia gravis
• Acute: 0.5-2.5 mg IV/IM/SC q Day
• Maintenance: 15-375 mg/day PO divided q68hr
• Use injectable with 0.6-1.2 mg atropine IV to
counteract muscarinic effects
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
Alzheimer’s disease
• A deficiency of structurally intact cholinergic
neurones leads to progressive dementia in
patients with Alzheimer’s disease
• Donezipil
• Rivastigmine
Post op urinary retention
• Prevention: Neo -- 0.25mg IM after surgery.
Repeat q4-6hr for 2-3 days
• Treatment: 0.5-1 mg IM and up to q3hr PRN
(for 5 doses for retention)
• Colonic Pseudo-obstruction
Central anticholinergic syndrome
• . It can be reversed by intravenous
physostigmine 2 mg followed by additional
doses as required.
• Chemical warfare
• Oximes and atropine
Side effects
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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,
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
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
• Possible intraarticular neostigmine – used for
analgesia
Summary
• Ach – cholinesterase – anticholinesterase –
pour Ach every where
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Types
Anionic – esteritic sites –
Uses
Side effects