physostigmine salicylate

physostigmine sulfate

Pharmacologic classification: cholinesterase inhibitor
Therapeutic classification: antimuscarinic antidote, antiglaucoma
Pregnancy risk category C

Available forms
Available by prescription only
Injection: 1 mg/ml
Ophthalmic ointment: 0.25%

Indications and dosages
 Tricyclic antidepressant and anticholinergic poisoning. Adults: 0.5 to 2 mg I.M. or I.V. given slowly (not to exceed 1 mg/minute I.V.). Dosage individualized and repeated, p.r.n., q 10 minutes.
Children: Reserve for life-threatening situations only. Initial pediatric I.V. or I.M. dose of physostigmine salicylate is 0.02 mg/kg. Dose may be repeated at 5- to 10-minute intervals to maximum of 2 mg if no adverse cholinergic signs are present.
 Postanesthesia care. Adults: 0.5 to 1 mg I.M. or I.V. given slowly (not to exceed 1 mg/minute I.V.). Dosage individualized and repeated, p.r.n., q 10 to 30 minutes.
 Open-angle glaucoma. Adults: Apply ointment to lower fornix up to t.i.d.

Antimuscarinic action: Competitively blocks acetylcholine hydrolysis by cholinesterase, resulting in acetylcholine accumulation at cholinergic synapses; that antagonizes the muscarinic effects of overdose with antidepressants and anticholinergics. With ophthalmic use, miosis and ciliary muscle contraction increase aqueous humor outflow and decrease intraocular pressure.

Absorption: Well absorbed from GI tract, mucous membranes, and S.C. tissues when given I.M. or I.V. After ophthalmic use, may be absorbed orally after passage through nasolacrimal duct.
Distribution: Distributed widely; crosses blood-brain barrier.
Metabolism: Cholinesterase hydrolyzes drug relatively quickly.
Excretion: Only small amount excreted in urine. Exact mode of excretion unknown.

Route Onset Peak Duration
I.V. 3-5 min 5 min 1/2-5 hr
I.M. 3-5 min 20-30 min 1/2-5 hr
Ophthalmic 10-30 min Unknown 12-48 hr

Contraindications and precautions
Injected form contraindicated in patients hypersensitive to drug or its components and in patients allergic to sulfites (one commercial product contains sodium bisulfite). Also contraindicated in patients with mechanical obstruction of the intestine or urogenital tract, asthma, gangrene, diabetes, CV disease, or vagotonia and in those receiving choline esters or depolarizing neuromuscular blockers.
  Ophthalmic form is contraindicated in patients with intolerance to physostigmine and in those with active uveitis or corneal injury. Use injectable form cautiously during pregnancy.

Drug-drug. Succinylcholine: Prolongs respiratory depression. Monitor patient closely.
Systemic cholinergic drugs: Causes additive toxicity. Monitor patient for toxicity.
Drug-herb. Jaborandi tree, pill-bearing spurge: Causes additive effects. Discourage use together.

Adverse reactions
CNS: weakness; headache (ophthalmic form); seizures, restlessness, excitability (injected form).
CV: slow or irregular heartbeat (ophthalmic form); bradycardia, hypotension (injected form).
EENT: blurred vision, eye pain, burning, redness, stinging, eye irritation, twitching of eyelids, watering of eyes (ophthalmic form); miosis (injected form).
GI: nausea, vomiting, diarrhea; epigastric pain, excessive salivation (injected form).
GU: loss of bladder control (ophthalmic form); urinary urgency (injected form).
Respiratory: bronchospasm, bronchial constriction, shortness of breath, dyspnea (injected form).
Skin: diaphoresis.

Effects on lab test results
None reported.

Overdose and treatment
Toxicity may cause headache, nausea, vomiting, diarrhea, blurred vision, miosis, myopia, excessive tearing, bronchospasm, increased bronchial secretions, hypotension, incoordination, excessive sweating, muscle weakness, bradycardia, excessive salivation, restlessness or agitation, and confusion.
 Support respiration; bronchial suctioning may be performed. Discontinue drug immediately. Atropine may be given to block muscarinic effects. Avoid atropine overdose because it may cause bronchial plug formation.

Special considerations
 ALERT Watch closely for adverse reactions, particularly CNS disturbances. Raise side rails if patient becomes restless or hallucinates. Adverse reactions may indicate drug toxicity.
Injectable form
• Effectiveness is typically immediate and dramatic but it may be transient.
• Observe solution for discoloration. Don’t use if darkened, which may indicate loss of potency.
• Give I.V. at controlled rate; use direct injection at no more than 1 mg/minute in adults or 0.5 mg/minute in children.
• Atropine sulfate injection should always be available as an antagonist and antidote for most of physostigmine’s effects.
• The commercially available formulation of physostigmine salicylate injection contains sodium bisulfite, a sulfite that can cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes in susceptible individuals.
Ophthalmic form
• After applying ointment, have patient close eyelids and roll eyes.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Safety and efficacy in breast-feeding women haven’t been established.
Geriatric patients
• Use cautiously when administering to elderly patients because they may be more sensitive to drug’s effects.

Patient education
• Teach patient how to administer ophthalmic ointment.
• Instruct patient not to close his eyes tightly or blink unnecessarily after instilling ointment.
• Warn patient that he may experience blurred vision and difficulty seeing after initial instillation.
• Instruct patient to report abdominal cramps, diarrhea, or excessive salivation.
• Remind patient to wait 10 minutes after instillation before using another eye preparation.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use