Physostigmine: Formula, Indications, Mechanism of Action, Dosage, Side Effects, Warnings, Contraindications and Interactions

It is a choline esterase that acts indirectly and has a double mechanism of action.

Physostigma differs from pharmacologically similar drugs, such as neostigmine and pyridostigmine, due to its tertiary amine structure, facilitating entry into the central nervous system.

The effects of skeletal muscle are the same as those of direct-acting drugs, producing a state of depolarization and improving lean muscle strength.

Chemical formula

  • C15H21N3O2.


Its presentation on the market is a 2 ml injectable solution, with a concentration of 1 mg of physostigmine per ml.


Physostigmine is used to treat glaucoma and to treat severe anticholinergic toxicity.

It has also been shown to be effective in treating Myasthenia Gravis.

Mechanism of action

It interferes with acetylcholine metabolism and indirectly stimulates nicotinic and muscarinic receptors due to the consequent increase in acetylcholine at the synapse.



Pediatric dose

The recommended dose is 0.02 mg per kg, administered intramuscularly or by slow intravenous injection, no more than 0.5 mg per minute.

If toxic effects persist and there are no signs of cholinergic effects, dosing can be repeated at 5 to 10-minute intervals until a therapeutic effect is obtained or a maximum dose of 2 mg is reached.

Adult dose

  • The recommended dose is 0.5 to 1.0 mg intramuscularly or intravenously.
  • Intravenous administration should be at a controlled slow rate of no more than 1 mg per minute.
  • If the desired patient response is not obtained, the dose can be repeated at 10 to 30-minute intervals.
  • Physostigmine must be administered slowly.

Respiration, blood pressure, oxygen levels, and other vital signs should be watched closely while the patient is receiving physostigmine.

Side effects

If, when administering physostigmine, symptoms of an allergic reaction such as cigarillo, difficulty breathing, swelling of the face, lips, tongue, or throat occur, with the use of physostigmine, the doctor should be informed immediately.

Other symptoms are:

  • Increased urination or bowel movements.
  • Stomach cramps, diarrhea, and severe or worsening nausea or vomiting.
  • Increased sweating.
  • Excessive salivation.
  • Difficulty breathing.
  • Slow or irregular heartbeat, tiredness, and chest tightness or wheezing.
  • Muscle weakness
  • Blurred vision or change in near or far vision, and eye pain.

Warnings and Contraindications

Physostigmine should not be used if you are allergic to it or if you have:

  • Asthma.
  • Diabetes.
  • Seizures
  • Symptoms of Parkinson’s disease.
  • Blockage of nerve function that affects regular muscle action.
  • Bladder obstruction or some other urination problem.
  • Blockage in the digestive tract (stomach or intestines).
  • Diseases of the heart and blood vessels.
  • Gangrene (damaged skin and muscle tissue caused by infection or lack of blood supply).

Before the patient receives physostigmine, the doctor should be informed if:

  • You have a sulfite allergy.
  • You recently took Ultracet (acetaminophen with tramadol).
  • Take bupropion regularly (Wellbutrin, Zyban, Aplenzin, Forfivo, among others).

Safe use in pregnancy and lactation has not been established; therefore, help in pregnant women, nursing mothers, or women who may become pregnant requires that the possible benefits be weighed against the potential risks to the mother and child.

Therefore, the doctor should be informed if the patient is pregnant, breastfeeding, or planning to become pregnant.

Nor should physostigmine be used if the patient has had allergies to the components of the formula or to:

  • Salicylates.
  • Non-steroidal anti-inflammatory drugs.
  • Cholinesterase inhibitors (Carbamate).


The doctor’s instructions regarding any food, drink, or activity restrictions should be followed.

Other drugs can interact with physostigmine, including prescription and nonprescription medications, vitamins, and herbal products.

The risk or severity of side effects may be increased when physostigmine is combined with acetylcholine and alclometasone.

Physostigmine can increase the bradycardic activities of Acebutolol.

The therapeutic efficacy of Aclidinium may decrease when used in combination with physostigmine.