ANTICHOLINESTERASES

KANAV BHANOT
ROLL NO. 5
 CONTENTS
• GENERAL- Anticholinesterases
• MECHANISM OF ACTION
• THERAPEUTIC USES
• ADVERSE DRUG REACTIONS
• ORGANOPHOSPHOROUS POISONING
(TREATMENT)
 ANTICHOLINESTERASES

The Indirectly-acting CHOLINERGIC DRUGS are also

known as ANTICHOLINESTERASES.
Anticholinesterases are drugs that increase the level
of acetylcholine after it is released from cholinergic
nerve endings by inhibiting both
acetylcholinesterase and butyrylcholinesterase.
They increase the level of Acetylcholine.
They act where Ach is physiologically released.
 MECHANISM OF ACTION

They act by increasing the concentration of Ach at

cholinoceptors by inhibiting AchE. Thus they prevent
the degradation of Ach into choline and acetate.
The anti-ChEs react with the enzyme essentially in the
same way as ACh.
The carbamates and phosphates respectively
carbamylate and phosphorylate the esteratic site of
the enzyme.
 CONTD.
 The acetylated enzyme reacts with water extremely
rapidly and the esteratic site is freed in a fraction of a
millisecond, whereas THE CARBAMYLATED ENZYME
(REVERSIBLE INHIBITORS) REACTS SLOWLY AND THE
PHOSPHORYLATED ENZYME (IRREVERSIBLE INHIBITORS)
REACTS EXTREMELY SLOWLY.
 It is noteworthy that edrophonium and tacrine attach only
to the anionic site and do not form covalent bonds with
the enzyme(REVERSIBLE INHIBITION), while
organophosphates attach only to the esteratic site
forming covalent bonds (IREVERSIBLE INHIBITION).
 THERAPEUTIC USES
I. EYES
1. Glaucoma
Acute congestive glaucoma: Pilocarpine is the preferred
cholinergic drug (pilocarpine eye drops 0.5-4% every 4-6
hourly), the main action is that they improve the aqueous
outflow. Physostigmine (0.1%) is used to supplement action
of pilocarpine in closed angle glaucoma.

2. Pilocarpine or Physostigmine is used alternate with a

mydriatic in iritis, uveitis or corneal ulcer.
II. ALZHEIMER’S DISEASE
Treatment: Cholinergic replacement using cholinesterase
inhibitors such as:
Donepezil 5-10 mg/day (drug of choice)
Rivastigmine 1.5 mg BID (max: 12 mg/day)

III. POST-OPERATIVE AND NEUROGENIC ILEUS AND

URINARY RETENTION
Neostigmine: 0.5-2mg SC
IV. MYAESTHENIA GRAVIS

DIAGNOSIS- Edrophonium is used for Tensilon test .

TREATMENT-
Anti-cholinesterase agent (increase Ach)
1.Pyridostigmine 60-120 mg 3-4 times/day orally
[less frequent dosing compared to Neostigmine]
2. or Pyridostigmine 2 mg IM
3. Or Neostigmine 15 mg q 6hourly
V. POST-OPERATIVE DECURARIZATION
Neostigmine: 0.5-2mg IV Or Edrophonium

VI. COBRA BITE (release a ‘curare-like neuro-toxin’ )

Treatment: Neostigmine/pyridostigmine

VII. BELLADONNA POISONING (Atropine poisoning)

Physostigmine 0.5-2mg is used by IV route.
 ADVERSE DRUG REACTIONS
1. Nausea, Increased Salivation, Increased
Sweating
2. Flushing, Bradycardia
3. Bronchospasm
4. Abdominal Pain, Diarrhoea
5. Increased Urination
6. At High Dose: Convulsions ; Skl. Muscle
weakness
7. ADR On Eyes When Used As Eye Drops:
Miosis, Decrease Vision In Dim-light, Impaired
Accommodation.
 ORGANOPHOSPHOROUS POISONING
(TREATMENT)

1. Termination of further exposure to the poison— fresh

air, wash the skin and mucous membranes with soap
and water, gastric lavage according to need.
2. Maintain patent airway, positive pressure respiration if
it is failing.
3. Supportive measures—maintain BP, hydration, control
of convulsions with judicious use of diazepam.
4. Specific antidotes—
(a)Atropine
(b)Cholinesterase reactivators
(A) ATROPINE
 It is highly effective in counteracting the muscarinic
symptoms, but higher doses are required to antagonize
the central effects.
 It does not reverse peripheral muscular paralysis which
is a nicotinic action.
 All cases of anti-ChE (carbamate or organophosphate)
poisoning must be promptly given ATROPINE 2 mg I.V.
REPEATED EVERY 10 MIN till dryness of mouth or other
signs of atropinization appear
 Continued treatment with maintenance doses may be
required for 1–2 weeks.
(B) CHOLINESTERASE REACTIVATORS
 Oximes are used to restore neuromuscular transmission
only in case of organophosphate anti-ChE poisoning.
 The phosphorylated ChE reacts very slowly or not at all
with water. However, if more reactive OH groups in the
form of oximes are provided, reactivation occurs more
than a million times faster.
 Pralidoxime 1-2 mg (30mg/kg), IV as 15-30 min infusion
[max 12g]
 Oximes improve action at nicotinic sites.
 It should be administered within 48 hours of
organophosphorus poisoning; otherwise when ageing
occurs; the phosphorylated enzyme becomes resistant to
hydrolysis (following loss of an alkyl group).