Anticholinesterases. Short Notes

Anticholinesterases.

Anticholinesterases (AChE) are drugs that inhibit the enzyme cholinesterase. They are either esters of carbamic acid (carbamates) or derivatives of phosphoric acid (organophosphates).

They may be:

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Anticholinesterases Mechanism of action:

Anticholinesterases inhibit the enzyme cholinesterase and thereby increase ACh levels.

Anticholinesterases Physostigmine:

• An alkaloid from the plant Physostigma venenosum (Malabar bean)
• . It is a lipid-soluble, tertiary ammonium compound, hence has better penetration into tissues and also crosses the BBB.

Actions: Actions are like acetylcholine.

Anticholinesterases Uses:

1. Glaucoma: Physostigmine eye drops are used in glaucoma but can cause brow aches and, on long-term use, retinal detachment and cataracts.
2. Poisoning: Physostigmine IV in atropine and tricyclic antidepressant poisoning.

Anticholinesterases Neostigmine:

Synthetic quaternary ammonium compound—poorly absorbed from the gut and does not cross the BBB.

Physostigmine and Neostigmine:

Anticholinesterases  Skeletal muscle:

Neostigmine increases the skeletal muscle strength and force of contraction in myasthenia gravis by anticholinesterase activity, by direct stimulation of nicotine NM receptors, and by enhancing the amount of ACh released during each action potential.

Dose: 15–30 mg TDS-DID.

Uses of Reversible Anticholinesterases:

1. As a mitotic: Physostigmine causes meiosis, spasm of accommodation, and a decrease in IOP.

It is used:

• In glaucoma, physostigmine (0.1%) can be used with pilocarpine for better effect.
• Alternately, with a mydriatic to break the adhesions between the iris and lens.
• To reverse the effect of mydriatic, as they cause blurring of vision and photophobia.

2. Myasthenia gravis: Neostigmine, ambenonium, and pyridostigmine are used (see below).

3. Atropine poisoning:

• Physostigmine is the antidote in poisoning due to atropine and other drugs with anticholinergic activity like phenothiazines, tricyclic antidepressants, and antihistamines.
• Since physostigmine crosses the BBB, it reverses all the symptoms of atropine poisoning, including CNS effects.

4. Curare poisoning:

• Skeletal muscle paralysis by curare can be reversed by AntiChEs.
• Neuromuscular paralysis due to neuromuscular blockers used along with anesthesia may be reversed using reversible anti-ChEs.
• Neostigmine and pyridostigmine can be used. Though euphonium is faster acting, it is less effective than nesting
• Acetylcholine and reversible anticholinesterases bind to both anionic and static sites of
• AChE enzyme. Euphonium binds only to the anionic site and is short-acting because the binding is rapidly reversible.
• OP compounds bind only the esteratic site but the exception is echothiophate which binds both anionic and esteratic sites.

5. Postoperative paralytic ileus and urinary retention: Neostigmine given 0.5–1 mg SC.

6. Cobra bite: Cobra venom, a neurotoxin, causes skeletal muscle paralysis. The specific treatment is antivenom. Intravenous edrophonium prevents respiratory paralysis.

7. Alzheimer’s disease: To overcome the deficient cholinergic neurotransmission, rivastigmine, donepezil, and galantamine are tried.

Treatment of myasthenia gravis:

Myasthenia gravis (MG) is a chronic autoimmune disease characterized by progressive weakness with rapid and easy fatigability of the skeletal muscles. Antibodies to nicotine receptors destroy the nicotine receptors.

Symptoms resemble that of neuromuscular paralysis produced by tubocurarine—ptosis, diplopia, dysphagia and difficulty in speaking (dysarthria) with weakness of the extremities. In later stages, the disease involves all skeletal muscles.

• Drugs used are antiChE like neostigmine, pyridostigmine, ambenonium and edrophonium.
• Anticholinesterases increase ACh levels by preventing its destruction. They increase muscle power and provide symptomatic relief.
• Factors like infection, surgery, and stress can result in severe muscle weakness →

Myasthenia crisis.

• Severe weakness can also be due to an excess dose of anti-ChE → Cholinergic crisis.
• They can be differentiated by 2 mg IV edrophonium.

Organophosphorus Poisoning