Usage
Neostigmine is prescribed for:
- Myasthenia Gravis: A chronic autoimmune neuromuscular disease characterized by weakness and fatigability of skeletal muscles.
- Reversal of Nondepolarizing Neuromuscular Blockade: Used after surgery to reverse the muscle relaxation induced by drugs like rocuronium, vecuronium, etc.
- Postoperative Urinary Retention and Paralytic Ileus: Helps restore bladder and bowel function after surgery.
Pharmacological Classification: Cholinesterase inhibitor, parasympathomimetic.
Mechanism of Action: Neostigmine increases the concentration of acetylcholine (ACh) at the neuromuscular junction by reversibly inhibiting acetylcholinesterase (AChE), the enzyme that breaks down ACh. This increased ACh concentration stimulates nicotinic receptors on skeletal muscle, improving muscle contraction.
Alternate Names
While “neostigmine” is the generic name, it is often used in conjunction with the salt form, such as neostigmine methylsulfate or neostigmine bromide.
Brand Names: Prostigmin, Bloxiverz.
How It Works
Pharmacodynamics: Neostigmine primarily acts at the neuromuscular junction by inhibiting AChE. It also has effects on muscarinic receptors, leading to parasympathetic stimulation.
Pharmacokinetics:
- Absorption: Administered intravenously (IV), intramuscularly (IM), or subcutaneously (SC). Oral absorption is variable and incomplete.
- Metabolism: Primarily metabolized in the liver by microsomal enzymes and by AChE in the plasma.
- Elimination: Excreted primarily through the kidneys.
Mode of Action: Neostigmine binds reversibly to AChE, preventing the breakdown of ACh. This results in accumulation of ACh at the synaptic cleft, prolonging its action on nicotinic receptors at the neuromuscular junction, leading to increased muscle strength and improved neuromuscular transmission.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Neostigmine acts as a reversible competitive inhibitor of AChE. At higher doses, it can also weakly stimulate nicotinic receptors directly.
Elimination Pathways: Primarily renal excretion. Some hepatic metabolism also occurs.
Dosage
Standard Dosage
Adults:
- Myasthenia Gravis: 15-375 mg orally per day, divided into multiple doses. IM/SC: 1-2.5 mg as needed, with a total daily dose of 5-20 mg. IV: Reserved for myasthenic crisis.
- Reversal of Neuromuscular Blockade: 0.03-0.07 mg/kg IV, administered slowly over 1 minute. Maximum dose: 5 mg.
Children:
- Myasthenia Gravis (Oral): <6 years: Start with 7.5 mg/day, titrating based on response (max 90 mg/day); 6-12 years: Start with 15 mg/day, titrating based on response (max 90 mg/day). IM/SC: 0.2-0.5 mg for children >1 month to 11 years. Adolescents (12-17 years): Same as adult dose.
- Reversal of Neuromuscular Blockade: 0.03-0.07 mg/kg IV, administered slowly over 1 minute. Maximum dose: 2.5 mg.
Special Cases:
- Elderly Patients: Monitor closely; they may experience prolonged drug effects.
- Patients with Renal Impairment: Dose adjustment may be needed.
- Patients with Hepatic Dysfunction: Dose adjustment may be needed.
- Patients with Comorbid Conditions: Use with caution in patients with bronchial asthma, cardiovascular disease, epilepsy, peptic ulcer, or hyperthyroidism.
Clinical Use Cases
- Intubation: Used to reverse neuromuscular blockade after intubation.
- Surgical Procedures: Reversal of neuromuscular blockade post-surgery.
- Mechanical Ventilation: May be used to improve muscle strength in patients weaning from mechanical ventilation.
- Intensive Care Unit (ICU) Use: Similar to mechanical ventilation usage.
- Emergency Situations: Not typically used in emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
Adjustments are necessary based on patient-specific factors such as renal or hepatic dysfunction, age, and concurrent medications.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, abdominal cramps, increased salivation, sweating, miosis (constricted pupils), increased urination.
Rare but Serious Side Effects:
Bradycardia, hypotension, bronchospasm, respiratory depression, seizures, allergic reactions (including anaphylaxis), cholinergic crisis (excessive muscle weakness and respiratory paralysis).
Long-Term Effects:
With long-term use for myasthenia gravis, dose adjustments may be needed due to disease progression or tolerance.
Adverse Drug Reactions (ADR):
Any signs of cholinergic crisis or severe allergic reactions require immediate intervention.
Contraindications
- Hypersensitivity to neostigmine.
- Peritonitis.
- Mechanical obstruction of the intestinal or urinary tract.
Drug Interactions
- Depolarizing muscle relaxants (e.g., succinylcholine): Prolongs the action.
- Certain antibiotics (e.g., aminoglycosides): May enhance neuromuscular blockade.
- Anticholinergics (e.g., atropine): Antagonizes muscarinic effects.
- Beta-blockers: Can worsen bradycardia.
- Other drugs affecting neuromuscular transmission: Use with caution.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not assigned. Use only if clearly needed and the potential benefits outweigh the risks. Can potentially induce premature labor if given IV near term.
- Breastfeeding: Neostigmine is excreted in breast milk in small amounts. Monitor infants for potential side effects (e.g., abdominal cramps).
Drug Profile Summary
- Mechanism of Action: AChE inhibitor.
- Side Effects: Nausea, vomiting, diarrhea, bradycardia, bronchospasm, respiratory depression.
- Contraindications: Hypersensitivity, peritonitis, bowel/urinary obstruction.
- Drug Interactions: Aminoglycosides, succinylcholine, beta-blockers.
- Pregnancy & Breastfeeding: Use with caution.
- Dosage: Varies by indication and age.
- Monitoring Parameters: Respiratory rate, heart rate, blood pressure, muscle strength.
Popular Combinations
Neostigmine is frequently used in combination with atropine (or glycopyrrolate) to reduce muscarinic side effects when reversing neuromuscular blockade.
Precautions
- General Precautions: Assess for respiratory and cardiovascular function. Have atropine readily available. Monitor for cholinergic crisis.
- Specific Populations: Use with caution in pregnancy, during breastfeeding, in children and the elderly.
- Lifestyle Considerations: May impair ability to drive or operate machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Neostigmine?
A: The dosage varies depending on the indication, patient age, and other factors. Please refer to the detailed dosage guidelines provided above.
Q2: What is the mechanism of action of Neostigmine?
A: Neostigmine reversibly inhibits acetylcholinesterase, leading to increased acetylcholine at the neuromuscular junction and improved muscle contraction.
Q3: What are the common side effects of Neostigmine?
A: Common side effects include nausea, vomiting, diarrhea, increased salivation, sweating, miosis, and increased urination.
Q4: What are the serious side effects of Neostigmine?
A: Serious side effects include bradycardia, hypotension, bronchospasm, respiratory depression, seizures, and allergic reactions.
Q5: What are the contraindications to using Neostigmine?
A: Neostigmine is contraindicated in hypersensitivity, peritonitis, and mechanical bowel or urinary obstruction.
Q6: Can Neostigmine be used during pregnancy?
A: Use with caution during pregnancy only if clearly needed, as it can potentially induce premature labor. It is unknown if it can cause fetal harm.
Q7: Can Neostigmine be used during breastfeeding?
A: It is excreted in breast milk in small amounts. Monitor the infant for possible side effects, such as abdominal cramps.
Q8: How should Neostigmine be administered for reversal of neuromuscular blockade?
A: Administer 0.03-0.07 mg/kg IV slowly over at least 1 minute, with a maximum dose of 5 mg in adults or 2.5 mg in children. Atropine should be given prior to or concurrently to reduce muscarinic side effects.
Q9: What is a cholinergic crisis, and how is it treated?
A: A cholinergic crisis is a condition characterized by excessive muscle weakness and respiratory paralysis due to overstimulation of cholinergic receptors. It can be caused by an overdose of neostigmine. Treatment involves respiratory support and administration of atropine.
Q10: How is Neostigmine used in the treatment of myasthenia gravis?
A: Neostigmine improves muscle strength in myasthenia gravis patients by increasing acetylcholine levels at the neuromuscular junction. Dosing is individualized based on patient needs and response, and it can be administered orally, IM, or SC.
