Cholinergic Agonists (Parasympathomimetic)-Acetylcholinesterase Inhibitors

Name of the Acetylcholinesterase Inhibitors Drugs

1. Edrophonium
2. Neostigmine
3. Physostigmine

Mechanism of Action:

Edrophonium chloride is a synthetic quaternary ammonium cholinergic agent. It reversibly inhibits the hydrolysis of acetylcholine by binding to the anionic site of acetylcholinesterase, thereby causing accumulation of acetylcholine. This results in increased cholinergic responses including increased tonus of skeletal and intestinal muscles, bronchial and ureteral constriction, miosis, bradycardia, and increased sweat and salivary secretions.

Indications:

• Diagnosis of Myasthenia Gravis
• Anticholinesterase therapy evaluation
• Reversal of neuromuscular blockade.

Cautions& Contraindications:

• Mechanical Obstruction of GI or Genitourinary tract
• Caution:  in patients with bronchial asthma, Cardiac arrhythmias
• Pregnancy & Lactation

Metabolism and half- life:

Onset:  30-60 seconds (IV); 2-10 min (IM)

Duration: 5-10 min (IV); 5-30 min (IM)

Excreted mainly via urine.

Half –life: 126± 59min

Drug Interactions:

• Antagonised muscarinic effects with atropine.
• May cause an increased sensitivity of the heart to edrophonium when given with digitalis.
• May prolong the phase 1 blockade of depolarising muscle relaxants.
• May antagonise the effects of non-depolarising muscle relaxants.

Side-effects:

• Transient Bradycardia
• Cardiac and respiratory arrest
• Anticholinesterase insensitivity
• Cholinergic crisis
• Asthma
• Seizure
• Drowsiness
• Hypotension
• Syncope

Nursing Considerations:

• Vital signs, ECG, and ventilatory support; neuromuscular function
• May cause cholinergic crisis (IV atropine should be available)
• Resuscitation equipment should be readily available
• Not effective in reversing paralysis caused by succinylcholine
• Caution in patients with asthma or cardiac arrhythmias
• Supportive ventilation must be readily available in apnoeic patients
• Not recommended for maintenance therapy in myasthenia gravis due to short duration of action
• Contraindicated in intestinal and urinary obstruction of mechanical type
• Monitor pre- and post-injection strength, heart rate, respiratory rate, blood pressure, changes in fasciculations
• Dose may need to be reduced in chronic renal failure
• Patients may develop “anticholinesterase insensitivity” for brief or prolonged periods. During these periods the patients should be carefully monitored and may need respiratory assistance. Dosages of anticholinesterase drugs should be reduced or withheld until patients again become sensitive to them.

Mechanism of Action:

Inhibits enzyme acetylcholinesterase, leading to increased acetylcholine concentration at synapse and prolonged acetylcholine effects. Exerts direct cholinomimetic effect on skeletal muscle

Indications:

• Myasthenia gravis
• Postoperative distention and urinary retention
• To reverse effects of non-depolarizing neuromuscular blocking agents after surgery.

Cautions & Contraindications:

• Hypersensitivity to cholinergic or bromide
• Mechanical obstruction of GI or urinary tract
• Peritonitis
• Use cautiously in asthma, peptic ulcer, bradycardia, arrhythmias, recent coronary occlusion, vagotonia, hyperthyroidism, seizure disorder
• Pregnant or breastfeeding patients.

Metabolism and Half-life:

Onset: 1-20 min (IV); 20-30 min (IM); Duration: 2.5-4 hr (IM); 1-2 hr (IV)

Metabolized by Liver microsomal enzymes and hydrolysis by cholinesterase enzymes

Half-Life: 47-60 min (IV); 51-90 min (IM); 42-60 min (PO) ; Excretion: 50% urine

Drug Interactions:

• Aminoglycosides, anticholinergics, atropine, corticosteroids, local and general anaesthetics: reversal of anticholinergic effects
• Cholinergic: additive toxicity
• Succinylcholine: potentiation of neuromuscular blockade, prolonged respiratory depression

Side- Effects:

• Hives​
• Difficulty breathing​
• Swelling of your face, lips, tongue, or throat​
• New or increased muscle cramps, weakness, or twitching​
• New or increased difficulty swallowing​
• Slow, fast or irregular heartbeat​
• Dizziness​
• Shortness of breath​
• Headache​
• Seizures

Nursing Considerations:

• Be aware that 15 mg oral neostigmine bromide is equivalent to 0.5 mg parenteral neostigmine methylsulfate.
• If also giving atropine, be sure to administer it before neostigmine, as prescribed.
• When giving neostigmine I.V., make sure patient is well ventilated and airway remains patent until normal respiration is assured.
• If patient has myasthenia gravis, give drug night and day, as ordered, with larger portions of daily dose during periods of increased fatigue. If patient’s condition becomes refractory to neostigmine, expect to reduce dosage or discontinue drug, as prescribed, for a few days.
• Monitor patient for evidence of neostigmine overdose, which can cause possibly fatal cholinergic crisis (increased
• Muscle weakness, including respiratory muscles). Expect to stop neostigmine and atropine, as ordered.

Intervention/evaluation:

• Monitor vital signs.
• Assess patient for hypotension, bradycardia or tachycardia, AV block, and evidence of impending cardiac arrest.
• Evaluate respiratory and neurologic status.

Patient teaching

• Instruct patient to take neostigmine exactly as prescribed.
• Advise patient to take drug with food or milk to reduce adverse GI reactions. Instruct patient to take tablets 1 hour before or 2 hours after meals.
• Suggest that patient with myasthenia gravis keep a daily record of doses and adverse reactions during therapy.
• Instruct patient to schedule activities to minimize fatigue.
• Tell patient drug may alter his respiratory and cardiac status. Teach him to recognize and immediately report warning signs.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration,
• Vision, muscle function, and alertness.

Mechanism of Action​:

Physostigmine Salicylate Injection is a reversible anticholinesterase which effectively increases the concentration of acetylcholine at the sites of cholinergic transmission. The action of acetylcholine is normally very transient because of its hydrolysis by the enzyme, acetylcholinesterase. Physostigmine Salicylate Injection inhibits the destructive action of acetylcholinesterase and thereby prolongs and exaggerates the effect of the acetylcholine.​

Indications:

• Antidote used to reverse the effect of anticholinergic toxicity. 
• Certain types of glaucoma.

Cautions & contraindications:

• Asthma
• Cardiovascular disease
• Diabetes mellitus
• Gangrene
• GI or GU obstruction
• Hypersensitivity to physostigmine, sulfites, or their components

Metabolism & Half- life:

Onset: 3- 8 min

Duration: 30-60 min

Drug interactions:

• Choline esters: Enhanced effects of carbachol and bethanechol with concurrent use of physostigmine, enhanced effects of acetylcholine and methacholine with prior use of physostigmine
• Succinylcholine: Prolonged neuromuscular paralysis

Side- effects:

• CNS stimulation, fatigue, hallucinations, restlessness, seizures (with too-rapid I.V. delivery), weakness
• Bradycardia (with too-rapid I.V. delivery), irregular heartbeat, palpitations
• Increased salivation, lacrimation, miosis
• Abdominal pain, diarrhea, nausea, vomiting
• Urinary urgency
• Bronchospasm, chest tightness, dyspnea (with too-rapid I.V. administration)
• Increased bronchial secretions, wheezing
• Diaphoresis

   Nursing Considerations

• Use physostigmine cautiously in patients with bradycardia, epilepsy, or Parkinson’s disease.
• Intravenous administration should be at a slow, controlled rate, no more than 1 mg per minute. Avoid rapid I.V. delivery, which may lead to bradycardia, respiratory distress, or seizures.
• Check pulse and respiratory rates, blood pressure, and neurologic status often.
• Monitor ECG tracing during I.V. use.
• Closely monitor patient with asthma for asthma attack because physostigmine may precipitate attack by causing bronchoconstriction.
• Watch for seizures in patient with a history of seizures because physostigmine can induce seizures by stimulating CNS.
• Be alert for life-threatening cholinergic crisis, which may indicate physostigmine overdose and may include confusion, diaphoresis, hypotension, miosis, muscle weakness, nausea, paralysis (including respiratory paralysis), salivation, seizures, sinus bradycardia, and vomiting. If you detect such signs, prepare to give atropine (the antidote) and use resuscitation equipment. Keep in mind that atropine counteracts only muscarinic cholinergic effects; paralytic effects may continue.

Patient teaching

• Reassure patient that vital signs will be monitored often to help prevent or detect adverse reactions.
• Instruct patient to notify prescriber at once about evidence of cholinergic crisis.

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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