How physostigmine works
Physostigmine stimulates the activity of the parasympathetic nervous system. This part of the autonomic nervous system is involved in controlling the internal organs, 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, for example, this can lead to movement disorders and faulty organ functions.
As physostigmine inhibits the breakdown of the neurotransmitter, more acetylcholine is available in the body over a longer period of time. This increases parasympathetic activity: physostigmine can lower the heart rate, cause the pupil of the eye to constrict, constrict the bronchi and stimulate the intestines to become more active. It also increases the secretion of saliva, gastric juice and sweat.
The active ingredient can easily cross the blood-brain barrier and thus also increase the concentration of acetylcholine in the central nervous system.
Absorption, breakdown and excretion
The active ingredient is injected directly into a vein or muscle. This allows it to spread quickly in the tissue and develop its effect. It is half degraded by an enzyme (cholinesterase) after just a quarter of an hour. It is excreted in the urine.
When is physostigmine used?
Physostigmine is approved in Germany and Austria for the treatment of:
- Poisoning with anticholinergic substances* such as alkaloids (in belladonna, datura, etc.), ingredients of some mushrooms (such as panther and fly agaric), tricyclic antidepressants (such as amitriptyline, imipramine), strong painkillers from the opiate group and various anesthetics
- Alcohol withdrawal delirium (form of delirium)
- Delayed awakening after an operation (only approved in Germany)
- Cold tremors, also known as “shivering” (only approved in Germany)
There are no medicines containing physostigmine on the market in Switzerland.
How Physostigmine is used
Physostigmine is administered directly into a vein or muscle. Adults usually receive two milligrams initially. If necessary, a further dose of one to four milligrams can be given after 15 to 20 minutes. The active substance must be injected slowly in order to reduce the risk of side effects.
Very rarely it is necessary to give a patient a continuous infusion of physostigmine over a longer period of time.
What are the side effects of physostigmine?
Possible side effects include nausea, vomiting, a slowed heartbeat (bradycardia), heavy sweating, narrowing of the bronchi (bronchoconstriction) and even a cerebral seizure (= seizure originating in the brain).
What should be considered when using physostigmine?
Contraindications
Physostigmine must not be administered in certain cases. These absolute contraindications include
- Poisoning with irreversible cholinesterase inhibitors
- Myotonic dystrophy (a hereditary muscle disease)
- Depolarization block after administration of depolarizing muscle relaxants
- Closed craniocerebral trauma
There are also relative contraindications, i.e. circumstances in which the benefits and risks of administering physostigmine must first be weighed up very carefully. The drug may only be administered if the expected benefits outweigh the risks.
This applies to severely slowed heartbeat (bradycardia), low blood pressure (hypotension), bronchial asthma, diabetes, ulcerative colitis and Parkinson’s disease.
The administration of physostigmine is handled very strictly, as the active substance is very toxic. The lethal dose for humans is only about ten milligrams.
Interactions
Physostigmine and other members of its active substance class (indirect-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 (Rocuronium, Atracurium etc.) is weakened, while that of depolarizing muscle relaxants is prolonged.
In addition, physostigmine and related compounds in combination with cardiovascular drugs of the beta-blocker type can lead to low blood pressure and cardiac conduction disorders.
Age restriction
Pregnancy and breastfeeding
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 closely monitored by ultrasound. There are no reports of congenital defects following the administration of physostigmine during pregnancy.
Necessary, short-term use of physostigmine during breastfeeding appears to be acceptable. However, the infant should be carefully observed.
How to obtain medication with physostigmine
Physostigmine is only available on prescription in Germany and Austria and is administered by a doctor.
There are no medicines with the active substance physostigmine on the market in Switzerland.
