Neostigmine: Formula, Presentation, Mechanism of Action, Dosage, Side Effects and Interactions

It is a parasympathomimetic agent or cholinergic agonist (anticholinesterase and antimiasthenic), of oral and parental administration.

Neostigmine is an anticholinesterase that is constituted by quaternary ammonium molecules.

The primary use of this drug is in anesthetic practice and causes the reversal of the neuromuscular block produced by drugs such as non-depolarizing neuromuscular relaxants.

Chemical formula

  • C12H19N2O2.
  • 3-(dimetilcarbamoiloxi)-N,N,N-trimetilbenzenaminio.

Presentation

  1. Neostigmine bromide: In 15 mg tablets for oral administration.
  2. Neostigmine Methylsulfate: In 0.5 mg / ml ampoules containing 1 ml and 0.5 mg / ml containing 5 ml for parenteral administration.

Indications

  • Neostigmine is indicated in cases of bloating, intestinal atony, bladder atony, paroxysmal tachycardia .
  • It acts as an antagonist of tubocurarine and other non-depolarizing synthetic type relaxants.
  • It is indicated in cases of myasthenia gravis and in the paralysis of the locomotor system.

Mechanism of action

Neostigmine inhibits the hydrolysis of acetylcholine by its competitive action with acetylcholinesterase, an enzyme in nerve tissues.

It interferes with the enzymatic destruction of acetylcholine, neostigmine to potentiate the action of acetylcholine on the cholinergic receptors of skeletal muscle (nicotinic receptors) and the gastrointestinal tract (muscarinic receptors).

Neostigmine Methylsulfate is recommended as an antagonist for the effects of non-depolarizing neuromuscular blocking agents, such as tubocurarine and pancuronium.

It is also used in the treatment of non-obstructive urinary incontinence and cases of non-obstructive abdominal distention before and after surgery.

Dose

In the case of Myasthenia gravis

Oral administration
  • In adults, the first recommended doses are 15 mg, 3 times daily. This dose should be increased progressively in intervals of 1 day or more.
  • The dose for prescribed maintenance varies from 15 to 375 mg per day.
  • Some patients may require 30 to 40 mg orally every 2 to 4 hours.
  • In children the dose of 0.333 mg / kg or 10 mg / m 2 to 6 times daily.
  • Some recommendations are initial doses of 7.5 to 15 mg tablets 3 to 4 times daily.
  • Doses greater than 45 mg orally every 2 hours are rarely required.
 Intravenous, subcutaneous or intramuscular administration

In intravenous administration, high parenteral doses should be performed intravenously accompanied by atropine in order to compensate for the possible adverse effects of Neostigmine.

  • In adults, administer 0.5 to 2.5 mg intravenously, every 1 to 3 hours.
  • In children administer from 0.01 to 0.04 mg / kg, intravenously, every 2 to 4 hours.
In intramuscular administration
  • In adults, doses of 1.5 mg (0.022 mg / kg) are prescribed in a single dose.
  • If a cholinergic reaction occurs, it should be discontinued and atropine should be administered.
  • In children, doses of 0.025 to 0.04 mg / kg or 1 mg / m2 are prescribed in a single dose.

Reversal of nondepolarizing neuromuscular block

In intravenous administration
  • In adults, a dose of 0.5 to 2.5 mg is recommended in a slow intravenous bolus.
  • Repeat as required by the patient up to a maximum dose of 5 mg.
  • To perform the parallel administration of atropine, the dose should be from 0.6 to 1.2 mg intravenously or glycopyrrolate in doses of 0.2 to 0.6 mg, in an approximate ratio of 0.2 mg of glycopyrrolate for each 1 mg of Neostigmine and should be administered a few minutes before administering Neostigmine.
  • In children, doses of 0.025 to 0.08 mg / kg in slow application are recommended, with the concomitant administration of atropine in a dose of 0.01 mg / kg subcutaneously or intramuscularly, with each dose.
  • In infants, 0.025-0.1 mg / kg is recommended intravenously in combination with atropine or glycopyrrolate.
Administration by intramuscular or subcutaneous route:
  • In adults, doses of 0.5 to 1 mg are recommended, repeating it every four to six hours if necessary.
  • If in this case, no answers are presented within 1 hour after the first dose, the patient should be catheterized.
  • After observing the cessation of urinary retention, continue with the treatment every three hours for at least five doses.
  • To prevent, it must be administered subcutaneously or intramuscularly
  • In adults a dose of 0.25 mg every four to six hours for 2 or 3 days.

Side effects

The most common side effects or unwanted side effects of Neostigmine are:

  • Sickness.
  • Vomiting
  • Increase in peristalsis.
  • Abdominal cramps.
  • Miosis.
  • Hipersalivation.
  • Diaforesis .
  • Sinus bradycardia
  • Bronchial and laryngeal spasms.
  • Sweating
  • Bronchial hypersecretion.
  • Myasthenia
  • Muscle cramps.
  • Fasciculations and hypotension .

All these symptoms usually present in different degrees and are not necessarily indicative of cholinergic crisis.

In crises caused by overdose can occur very serious adverse reactions, such as respiratory paralysis and even the occurrence of cardiac arrest.

Atropine can be used concomitantly to decrease adverse muscarinic effects, but it may happen that this conceals the early symptoms of the actual crisis.

Warnings and contraindications

Neostigmine is contraindicated for patients with ileus , gastrointestinal obstruction, and obstruction of the urinary tract, because it increases muscle contractions.

Neostigmine also stimulates the secretion of gastric acids and should be used with caution in cases of peptic ulcers.

In cases of cholinesterase toxicity, the use of Neostigmine is not recommended.

The differential diagnosis of a myasthenic crisis and a cholinergic crisis is very important, because these two conditions are exposed with analogous symptoms.

However, the myasthenic crisis demands a treatment with anticholinesterase drugs, but in the case of the cholinergic crisis (due to an overdose of anticholinesterase) it requires the disturbance of the treatment with the administration of cholinesterase inhibitors.

Neostigmine should be used with caution in patients who have bradycardia and hypotension, since it can reduce the levels of heart rate and blood pressure by increasing the vagal tone.

Neostigmine has exciting effects on the myocardium, and this can increase the oxygen demand of the heart and may be dangerous to administer in patients with heart disease, coronary artery disease and in cases of cardiac arrhythmias .

Neostigmine should be used with caution in patients with epilepsy or hyperthyroidismclinics , because conditions can be weighted through stimulation of the central nervous system.

Neostigmine in patients with asthma symptoms should be used with caution, as it may cause bronchoconstriction.

The administration of Neostigmine has certain risks during pregnancy, it is not known with certainty if it can cause abnormalities in the fetus.

But anticholinesterase drugs cause uterine irritations that can cause premature births if administered directly into the intravenous lines.

It should not be administered during the pregnancy period, it should only be indicated when the attending physician considers that the potential benefits to be obtained with the administration of the treatment outweigh the possible risks that may exist for the fetus.

Interactions

The muscarinic effects of Neostigmine are frequently counteracted by atropine.

It is recommended to avoid the frequent use of atropine in the administration of daily treatment in myasthenia gravis, since atropine can conceal the signs of excessive doses of Neostigmine.

Because atropine is frequently used in treatments with Neostigmine, to reverse the non-depolarizing neuromuscular blockade and under these circumstances, atropine manages to control muscarinic cholinergic effects that are not desired.

As used properly, this combination of atropine with neostigmine results in a beneficial interaction.

Cholinesterase inhibitor drugs, such as neostigmine, are suitable for restoring the action of nondepolarizing neuromuscular blockers.

They can not be indicated to reverse the depolarizing neuromuscular blocking effects.

The administration of drugs such as neostigmine can contradictorily prolong the relaxing activity of the skeletal muscle.

The effects produced by Neostigmine are additive to the effects of other parasympathomimetics.

Therefore, regardless of the type of combination should be administered with great care because it can increase the risk of the occurrence of any adverse reaction, including a cholinergic crisis

Quinine has been prescribed as a skeletal muscle relaxant and its effect is pharmacologically opposite to that of Neostigmine.

Trimetaphan or mecamylamine, ganglionic blockers, may antagonize the effects of Neostigmine.

Neostigmine can reduce the effects of these drugs as hypotensive drugs.

Disopyramide has anticholinergic properties, although it is not clear if it can interfere with the chymomimetic activity of neostigmine.

Antiarrhythmics should be used with caution in patients with myasthenia gravis.

When used as abdominal irrigators during surgery, aminoglycoside antibiotics can cause a neuromuscular block and although this risk of blockage is very remote with parenteral aminoglycosides.

This type of antibiotic will be used with great caution in patients with myasthenia.

Local anesthetics can also antagonize the consequences of cholinesterase inhibitors since they inhibit neuronal transmission in skeletal muscle, especially if they are used in high doses.