NEOSTIGMINE METHYLSULFATE

(nee-oh-stig'meen)

Prostigmin
Classifications: cholinergic agent; cholinesterase inhibitor;
Therapeutic: cholinesterase inhibitor
Pregnancy Category: C

Availability

1:1000, 1:2000, 1:4000 injection

Action

Produces reversible cholinesterase inhibition or inactivation. Has direct stimulant action on voluntary muscle fibers and possibly on autonomic ganglia and CNS neurons. Allows intensified and prolonged effect of acetylcholine at cholinergic synapses (basis for use in myasthenia gravis).

Therapeutic Effect

Produces generalized cholinergic response including miosis, increased tonus of intestinal and skeletal muscles, constriction of bronchi and ureters, slower pulse rate, and stimulation of salivary and sweat glands.

Uses

To prevent and treat postoperative abdominal distension and urinary retention; for symptomatic control of and sometimes for differential diagnosis of myasthenia gravis; and to reverse the effects of nondepolarizing muscle relaxants (e.g., tubocurarine).

Contraindications

Hypersensitivity to neostigmine, cholinergics; cholinesterase inhibitor toxicity; GI obstruction; ileus; bradycardia, hypotension; mechanical obstruction of intestinal or urinary tract; peritonitis; administration with other cholinergic drugs; pregnancy (category C), lactation.

Cautious Use

Recent ileorectal anastomoses; epilepsy; bronchial asthma; hepatic disease; bradycardia, recent coronary occlusion; vagotonia; hyperthyroidism; cardiac arrhythmias; renal failure; renal impairment; renal disease; peptic ulcer; seizure disorder.

Route & Dosage

Diagnosis of Myasthenia Gravis
Adult: IM 0.02 mg/kg
Child: IM 0.04 mg/kg

Treatment of Myasthenia Gravis
Adult: IM/SC 0.5–2.5 mg q1–3h (max 10 mg/d)
Child: IM/SC 0.01–0.04 mg/kg q2–4h

Reversal of Nondepolarizing Neuromuscular Blockade
Adult: IV 0.5–2.5 mg slowly (max dose 5 mg)
Child: IV 0.025–0.08 mg/kg
Infant: IV 0.025–0.1 mg/kg

Postoperative Distention and Urinary Retention
Adult: IM/SC 0.25 mg q4–6h for 2–3 d

Renal Impairment
Cl_cr 10–50 mL/min: use 50% of dose; <10 mL/min: use 25% of dose

Administration

Intramuscular/Subcutaneous

Note: 1 mg = 1 mL of the 1:1000 solution; 0.5 mg = 1 mL of the 1:2000 solution; 0.25 mg = 1 mL of the 1:4000 solution.
Give undiluted.

Intravenous

PREPARE: Direct: Give undiluted.

ADMINISTER: Direct: Give at a rate of 0.5 mg or a fraction thereof over 1 min.

Adverse Effects (≥1%)

Body as a Whole: Muscle cramps, fasciculations, twitching, pallor, fatigability, generalized weakness, paralysis, agitation, fear, death. CV: Tightness in chest, bradycardia, hypotension, elevated BP. GI: Nausea, vomiting, eructation, epigastric discomfort, abdominal cramps, diarrhea, involuntary or difficult defecation. CNS: CNS stimulation. Respiratory: Increased salivation and bronchial secretions, sneezing, cough, dyspnea, diaphoresis, respiratory depression. Special Senses: Lacrimation, miosis, blurred vision. Urogenital: Difficult micturition.

Interactions

Drug: Succinylcholine decamethonium may prolong phase I block or reverse phase II block; neostigmine antagonizes effects of tubocurarine; atracurium, vecuronium, pancuronium; procainamide, quinidine, atropine antagonize effects of neostigmine.

Pharmacokinetics

Onset: 10–30 min IM or IV. Peak: 20–30 min IM or IV. Distribution: Not reported to cross placenta or appear in breast milk. Metabolism: In liver. Elimination: 80% of drug and metabolites excreted in urine within 24 h. Half-Life: 50–90 min.

Nursing Implications

Assessment & Drug Effects

Check pulse before giving drug to bradycardic patients. If below 60/min or other established parameter, consult physician. Atropine will be ordered to restore heart rate.
Monitor respiration, maintain airway or assisted ventilation, and give oxygen as indicated when used as antidote for tubocurarine or other nondepolarizing neuromuscular blocking agents (usually preceded by atropine). Respiratory assistance is continued until recovery of respiration and neuromuscular transmission is assured.
Monitor pulse, respiration, and BP during period of dosage adjustment in treatment of myasthenia gravis.
Report promptly and record accurately the onset of myasthenic symptoms and drug adverse effects in relation to last dose in order to assist physician in determining lowest effective dosage schedule.
Note carefully time of muscular weakness onset. It may indicate whether patient is in cholinergic or myasthenic crisis: Weakness that appears approximately 1 h after drug administration suggests cholinergic crisis (overdose) and is treated by prompt withdrawal of neostigmine and immediate administration of atropine. Weakness that occurs 3 h or more after drug administration is more likely due to myasthenic crisis (underdose or drug resistance) and is treated by more intensive anticholinesterase therapy.
Record drug effect and duration of action. S&S of myasthenia gravis relieved by neostigmine include lid ptosis; diplopia; drooping facies; difficulty in chewing, swallowing, breathing, or coughing; and weakness of neck, limbs, and trunk muscles.
Manifestations of neostigmine overdosage often appear first in muscles of neck and those involved in chewing and swallowing, with muscles of shoulder girdle and upper extremities affected next.
Report to physician if patient does not urinate within 1 h after first dose when used to relieve urinary retention.

Patient & Family Education

Be aware that regulation of dosage interval is extremely difficult; dosage must be adjusted for each patient to deal with unpredictable exacerbations and remissions.
Keep a diary of "peaks and valleys" of muscle strength.
Keep an accurate record for physician of your response to drug. Learn how to recognize adverse effects, how to modify dosage regimen according to your changing needs, or how to administer atropine if necessary.
Be aware that certain factors may require an increase in size or frequency of dose (e.g., physical or emotional stress, infection, menstruation, surgery), whereas remission requires a decrease in dosage.
Some patients become refractory to neostigmine after prolonged use and require change in dosage or medication.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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