Physostigmine

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Physostigmine is a natural product made from the seeds of the calabar bean. It increases the activity of the parasympathetic nervous system by inhibiting enzymes, so it is a parasympathomimetic. This effect is used, among other things, in the treatment of the central anticholinergic syndrome. Read more about the use, effects and possible side effects of physostigmine here.

This is how physostigmine works

Physostigmine stimulates the activity of the parasympathetic nervous system. This part of the autonomic nervous system is involved in the control of the internal organs, the heartbeat, breathing and digestion.

Physostigmine is a so-called cholinesterase inhibitor: it blocks the enzyme acetylcholinesterase, which breaks down the neurotransmitter acetylcholine. Acetylcholine is an important signaling substance of the parasympathetic nervous system. If too little acetylcholine is released due to poisoning or a congenital disorder, this can lead to movement disorders and defective organ functions.

As physostigmine inhibits the breakdown of the messenger substance, more acetylcholine is available in the body for a longer period of time. This increases the parasympathetic activity: Physostigmine can lower the heart rate, narrow the pupil in the eye, constrict the bronchi and stimulate the intestines to be more active. In addition, the secretion of saliva, gastric juice and sweat is increased.

The active ingredient can cross the blood-brain barrier and thus also increase the acetylcholine concentration in the central nervous system.

Physostigmine is therefore suitable as an antidote to anticholinergic substances such as herbal poisons (for poisoning) or certain drugs.

Uptake, breakdown and excretion of physostigmine

The active ingredient is injected directly into a vein. In this way it can spread quickly in the tissue and develop its effect. After just two hours, it is completely broken down by an enzyme (cholinesterase). It is excreted in the urine.

When is physostigmine used?

Physostigmine is used as an antidote for poisoning with anticholinergic substances. These include, for example, alkaloids (in deadly nightshade, thorn apple, etc.), antidepressants, strong pain relievers from the opiate group and most anesthetics.

Such substances can (even in therapeutic doses) lead to a so-called central anticholinergic syndrome (ZAS). The potentially life-threatening ZAS manifests itself in symptoms such as extreme excitability (hyperactivity, restlessness, fear) or coma as well as a rise in temperature, racing heart, dilation of the pupils (mydriasis), dry, hot skin and inability to empty the bladder (urinary retention).

This is how physostigmine is used

The active ingredient physostigmine is administered directly into a vein, usually as an injection (syringe). Adults initially receive around two milligrams. If necessary, another dose of one to four milligrams can be given after 15 to 20 minutes. The active ingredient must be injected slowly to reduce the risk of side effects.

Very rarely is it necessary to give a patient a continuous infusion of physostigmine over a long period of time.

What side effects does physostigmine have?

Possible physostigmine side effects include nausea, vomiting, a slow heartbeat (bradycardia), profuse sweating, narrowing of the bronchi (bronchoconstriction), or even a cerebral seizure.

What should be considered when using physostigmine?

In certain cases, physostigmine must not be administered under any circumstances. These absolute contraindications include:

Poisoning with organic cholinesterase inhibitors
Myotonic dystrophy (hereditary muscle disorder)

In the case of some diseases, the benefits and risks of the application must first be carefully weighed before the drug is administered. Only if the expected benefit outweighs the active ingredient may be given. These relative contraindications include a very slow heartbeat (bradycardia), low blood pressure (hypotension), asthma and chronic obstructive pulmonary disease, and Parkinson's disease.

Physostigmine is administered very strictly because the active ingredient is very toxic. The lethal dose for humans is only about ten milligrams.

Interactions

Physostigmine and other representatives of its class of active ingredients (indirectly acting parasympathomimetics: distigmine, neostigmine) interact with various other drugs. For example, they influence the effect of muscle relaxing substances (muscle relaxants): The effect of so-called non-depolarizing muscle relaxants is weakened, while that of depolarizing muscle relaxants is prolonged.

In addition, physostigmine and its related compounds in combination with cardiovascular drugs of the beta blocker type can lead to low blood pressure and conduction disorders in the heart.

pregnancy and breast feeding period

There is little experience with the use of physostigmine during pregnancy and breastfeeding. Use in pregnant women is possible if absolutely necessary. To be on the safe side, the development of the unborn child can be precisely monitored using ultrasound.

A necessary, short-term use of physostigmine during breastfeeding seems acceptable. However, the customer should be carefully observed.