Indirect parasympathomimetics

General Features

• Indirectly acting parasympathomimetics are substances that inhibit ACHE (they do not act on the receptor, but on ACHE – acetylcholinesterase).
• We distinguish:
  1. short-acting ACHE inhibitors (reversible);
  2. long-term ACHE inhibitors (irreversible).

Effects and Uses

• ACH builds up as a result of ACHE inhibition.
• It is used in postoperative atonia, to induce miosis and reduce intraocular pressure, to increase stimulation on the neuromuscular disc (in the treatment of Myasthenia gravis) .

Side effects

• Confusion, ataxia, convulsions and eventual coma can occur from excessive stimulation of the CNS by acetylcholine.
• From excessive stimulation of the N receptor in the sympathetic ganglia, a paradoxical increase in blood pressure, tachycardia can occur.

Short-acting acetylcholinesterase inhibitors

They act on both the N receptor (nicotinic) and the M receptor (muscarinic).

Therapeutic use

1. Myasthenia gravis.
2. Antidote for competitive peripheral myorelaxants.
3. Postoperative atony of the GIT and bladder.
4. Miotic and antiglaucomatic.

Substances used

Physostigmine

• Natural alkaloid.
• Crosses the blood-brain barrier.
• Antidote for poisoning parasympatholytics (eg atropine).
• Used in ophthalmology - miosis, reduces intraocular pressure.

Neostigmine

• Does not cross the blood-brain barrier.
• Use in myasthenia gravis (increases ACh on the neuromuscular disc).
• Antidote to disc blockers (myorelaxants).

Edrophonium

• Very fast onset of effect.
• It is used to diagnose myasthenia gravis (the condition improves after administration, the patient was underdosed and the dose needs to be increased).

Long-term acetylcholinesterase inhibitors

Today, they are no longer used therapeutically. They have only toxicological significance - organophosphates.

Intoxication

• Proceeding quickly.
• Permanently phosphorylate ACHE.
• Manifests as nausea, convulsions, vomiting, increased salivation, bradycardia, lacrimation, anorexia, skeletal muscle weakness, decreased breathing and even death (respiratory arrest or circulatory collapse).

Intoxication therapy

• Prevention of absorption.
• Controlled breathing, anticonvulsant treatment.
• Administration of atropine (block of M receptors).
• Preventive short-term inhibitors (Neostigmine).
• Cholinesterase reactivation – oximes'.

Oximes

They are able to bind the organophosphate, which has all the side structures, and tear it away from ACHE. Once it loses them, it forms a covalent bond with ACHE, the bond is irreversible. Oximes must be administered in a timely manner (e.g. trimedoxime, pralidoxime).

Substances used

Tabun, Sarin, Soman.

Links

Related Articles

• Parasympathomimetics
• Direct parasympathomimetics
• Sympathomimetics
• Sympatholytics

Source

• HYNIA, Sixtus. Pharmacology in a Nutshell. 2. edition. Triton, 2001. ISBN 80-7254-181-1.