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:
 * short-acting ACHE inhibitors (reversible);
 * 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.

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.

Related Articles

 * Parasympathomimetics
 * Direct parasympathomimetics
 * Sympathomimetics
 * Sympatholytics