Name of the Indirect Cholinergic Drugs
- Neostigmine
- Physostigmine
- Pyridostigmine
- Ambenonium
- Organophosphorus compounds
1.Neostigmine
| Neostigmine |
| Availability Injection (methylsulfate): 2 mg/ml, 1 mg/ml, 0.5 mg/ml, 0.25 mg/ml Tablets (bromide): 15 mg |
| Indications and dosages ➣ Myasthenia gravis Adults: 15 mg/day P.O.; may increase p.r.n. up to 375 mg/day; average dosage is 150 mg/day. Or 1 ml of 1:2,000 solution (0.5 mg) subcutaneously or I.M. based on response and tolerance. ➣ Postoperative abdominal distention and bladder atony Adults: 0.5 to 1 mg I.M. or subcutaneously. If given for urinary retention and no response occurs within 1 hour, catheterize patient as ordered and repeat dose q 3 hours for five doses. ➣ Antidote for nondepolarizing neuromuscular blockers Adults: 0.5 to 2.5 mg I.V.; repeat p.r.n. up to 5 mg. Precede initial dose with 0.6 to 1.2 mg atropine sulfate I.V., as ordered |
Mechanism of Action
Competitive inhibitor of cholinesterase resulting in decreased hydrolysis of acetylcholine by cholinesterase; by reducing the breakdown of acetylcholine, neostigmine increases acetylcholine in the synaptic cleft which competes for the same binding site as nondepolarizing neuromuscular blocking agents, and reverses the neuromuscular blockade
Pharmacokinetics
- Bioavailability: 1-2% (PO); general PO:IV equivalence ~15 mg neostigmine bromide PO is equivalent to 0.5 mg neostigmine methylsulfate parenteral
- Peak plasma time: 30 min (IM); 1-2 hr (PO)
- Protein bound: 15-25% to albumin (PO)
- 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
Administration
- Before giving, ensure that atropine sulfate is available to treat cholinergic crisis.
- Know that atropine may be combined with usual neostigmine dose to decrease risk of adverse reactions.
- Give oral form 1 hour before or 2 hours after a meal.
- Administer I.V. dose undiluted directly into vein or I.V. line. Give 0.5-mg dose slowly over 1 minute.
- Keep resuscitation equipment nearby.
Contraindications
- Hypersensitivity to cholinergics or bromide
- Mechanical obstruction of GI or urinary tract
- Peritonitis
Precautions :
- Asthma, peptic ulcer, bradycardia, arrhythmias, recent coronary occlusion, vagotonia, hyperthyroidism, seizure disorder
- Pregnant or breastfeeding patients.
Adverse reactions
- CNS: dizziness, headache, drowsiness, asthenia, loss of consciousness
- CV: hypotension, tachycardia, bradycardia, atrioventricular (AV) block, cardiac arrest
- EENT: vision changes, lacrimation, miosis
- GI: nausea, vomiting, diarrhea, abdominal cramping, flatulence, increased peristalsis
- GU: urinary frequency
- Musculoskeletal: muscle cramps, spasms, and fasciculations; joint pain
- Respiratory: dyspnea, bronchospasm, respiratory depression, respiratory arrest, laryngospasm
- Skin: rash, urticaria, flushing
- Other: anaphylaxis
Patient monitoring
- 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 tablets 1 hour before or 2 hours after meals.
- 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.
- As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above
2.Physostigmine
| Physostigmine |
| Availability injectable solution1mg/mL |
| Indications and Dosages To counteract toxic anticholinergic effects (anticholinergic syndrome) Adults and adolescents. 0.5 to 2 mg at no more than 1 mg/min; then 1 to 4 mg, repeated every 20 to 30 min as needed and as prescribed. Children. 0.02 mg/kg I.V., at no more than 0.5 mg/min, repeated every 5 to 10 min as prescribed. Maximum: 2 mg/dose. |
Mechanism of Action
Inhibits destruction of acetylcholine by acetylcholinesterase. This action increases acetylcholine concentration at cholinergic transmission sites and prolongs and exaggerates effects of acetylcholine that are blocked by toxic doses of anticholinergics
Pharmacokinetics
Onset: 5-10 min
Duration: 30-60 min
Contraindications
Asthma; cardiovascular disease; diabetes mellitus; gangrene; GI or GU obstruction; hypersensitivity to physostigmine, sulfites, or their components
Adverse Reactions
- CNS: CNS stimulation, fatigue, hallucinations, restlessness, seizures (with too-rapid I.V. delivery), weakness
- CV: Bradycardia (with too-rapid I.V. delivery), irregular heartbeat, palpitations
- EENT: Increased salivation, lacrimation, miosis
- GI: Abdominal pain, diarrhea, nausea, vomiting
- GU: Urinary urgency
- MS: Muscle twitching
- RESP: Bronchospasm, chest tightness, dyspnea (with too-rapid I.V. administration), increased bronchial secretions, wheezing
- SKIN: Diaphoresis
Nursing Considerations
- Use physostigmine cautiously in patients with bradycardia, epilepsy, or Parkinson’s disease.
- 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.
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.
3.Pyridostigmine
| Pyridostigmine |
| Availability injection, IV solution 5mg/mL (Mestinon, Regonol) tablet, extended-release 105mg,180mg (Mestinon) Tablet,30mg,60mg (Mestinon) oral solution 60mg/5mL (473-mL bottle; Mestinon) |
| Indications and Dosages To treat symptoms of myasthenia gravis Adults and adolescents. 180 to 540 mg once or twice daily (at least 6 hr between doses). Adults and adolescents. Initial: 30 to 60 mg every 3 to 4 hr, adjusted as needed. Maintenance: 60 mg to 1.5 g daily. Children. 7 mg/kg daily in 5 or 6 divided doses. Adults and adolescents. 2 mg every 2 to 3 hr. I.M. INJECTION Neonates of myasthenic mothers. 0.05 to 0.15 mg/kg every 4 to 6 hr. To reverse the effects of neuromuscular blockers Adults and adolescents. 10 to 20 mg after 0.6 to 1.2 mg of I.V. atropine has been given. |
Mechanism of Action
Improves muscle strength compromised by myasthenia gravis or neuromuscular blockade by competing with acetylcholine for its binding site on acetylcholinesterase. This action potentiates the effects of acetylcholine on skeletal muscle and the GI tract. Inhibited destruction of acetylcholine allows freer transmission of nerve impulses across the neuromuscular junction.
Pharmacokinetics
Bioavailability: 10-20%
Undergoes hydrolysis by cholinesterases and is metabolized in liver
Excretion: Urine (80-90%)
Contraindications
Hypersensitivity to pyridostigmine or its components, mechanical obstruction of GI or urinary tract
Adverse Reactions
- EENT: Increased salivation, lacrimation, miosis
- GI: Abdominal cramps, diarrhea, increased peristalsis, nausea, vomiting
- GU: Urinary frequency, incontinence, or urgency
- MS: Fasciculations, muscle spasms or weakness
- RESP: Increased tracheobronchial secretions
- SKIN: Diaphoresis
Nursing Considerations
- Use pyridostigmine cautiously in patients with renal disease because drug is mainly excreted unchanged by kidneys. Monitor BUN and serum creatinine levels
- Observe for cholinergic reactions when administering drug I.V. or I.M
- Be aware that reversal of neuromuscular blockade usually occurs in 15 to 30 minutes. Be prepared to maintain patent airway and ventilation until normal voluntary respiration returns completely. Assess respiratory measurements and muscle tone with peripheral nerve stimulator device, as indicated.
Patient Teaching
- Instruct patient to take pyridostigmine as directed and on schedule. Explain that a late or missed dose can precipitate a crisis. Suggest the use of a battery-operated alarm clock as a reminder.
- Tell patient to take drug with a full glass of water or with food or milk if GI distress occurs.
- Warn patient not to crush or chew E.R. tablets.
- Ask patient to record pyridostigmine dosage, times taken, and drug effects to help determine optimal dosage and schedule.
- Urge patient to carry medical identification describing her condition and drug regimen.
4.Ambenonium
| Ambenonium |
| Availability: Tablet 10 mg |
| Indications and Dosages Myasthenia Gravis Adult Initial: 5 mg orally every 6-8 hours |
Contraindications
- Hypersensitivity
- Mechanical obstruction of intestinal or urinary tracts
- Concurrent administration with belladona derivatives or ganglionic blocking agents such as mecamylamine
Warnings
- This medication contains ambenonium. Do not take Mytelase if you are allergic to ambenonium or any ingredients contained in this drug.
Cautions
- May develop anticholinergic insensitivity (withhold or reduce dosages until the patient becomes sensitive again
- Use caution in patients with intestinal obstruction, asthma, urinary tract obstruction, or Parkinson’s disease
- The narrow therapeutic index may increase the risk of overdosage
REFERENCES
- Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
- McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
- April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
- Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
- Nursebro.com, Search – Nursebro
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