atropine sulfate

Pharmacologic classification: anticholinergic, belladonna alkaloid
Therapeutic classification: antiarrhythmic, vagolytic
Pregnancy risk category C


Available forms
Available by prescription only
Injection: 0.05 mg/ml, 0.1 mg/ml, 0.3 mg/ml, 0.4 mg/ml, 0.5 mg/ml, 0.8 mg/ml, and 1 mg/ml
Ophthalmic ointment: 1%
Ophthalmic solution: 0.5%, 1%, 2%
Tablets: 0.4 mg

Indications and dosages
 Symptomatic bradycardia, bradyarrhythmia (junctional or escape rhythm). Adults: Usually 0.5 to 1 mg by I.V. push; repeat q 3 to 5 minutes, to maximum of 0.03 mg/kg in patients with mild bradycardia or 2.5 mg (0.4 mg/kg) in patients with severe bradycardia or ventricular asystole. Lower doses (less than 0.5 mg) may cause bradycardia.
Children: 0.02 mg/kg I.V. up to maximum 1 mg; or 0.3 mg/m2; may repeat q 5 minutes.
Adults and children: Note: Dose may be administered at 2 1/2 times the I.V. dose and diluted in 10 ml of normal saline solution (adults) or 1 to 2 ml of half-normal or normal saline solution (child) and administered via the endotracheal tube during cardiopulmonary resuscitation if I.V. access unavailable.
 Preoperatively for diminishing secretions and blocking cardiac vagal reflexes. Adults and children who weigh more than 20 kg (44 lb): 0.4 mg I.M. or S.C. 30 to 60 minutes before anesthesia.
Children who weigh less than 20 kg: 0.1 mg I.M. for 3 kg (6.6 lb), 0.2 mg I.M. for 4 to 9 kg (8.8 to 20 lb), 0.3 mg I.M. for 10 to 20 kg (22 to 44 lb) 30 to 60 minutes before anesthesia.
 To block adverse muscarinic effects of anticholinesterase agents when these agents are used to reverse neuromuscular blockade produced by curariform agents. Adults: 0.6 to 1.2 mg for each 0.5 to 2.5 mg of neostigmine or 10 to 20 mg of pyridostigmine administered; administer I.V. a few minutes before the anticholinesterase agent.
 Antidote for anticholinesterase insecticide poisoning. Adults: 1 to 2 mg I.M. or I.V. repeated q 5 to 60 minutes until muscarinic symptoms disappear. In severe cases, 2 to 6 mg may be given initially, repeating doses every 5 to 60 minutes.
Children: 0.05 mg/kg I.V. or I.M. repeated every 10 to 30 minutes until muscarinic signs and symptoms disappear.
 Hypotonic radiograph of the GI tract. Adults: 1 mg I.M.
 Short-term treatment or prevention of bronchospasm. Adults: 0.025 mg/kg administered via nebulizer t.i.d. or q.i.d. to maximum dose of 2.5 mg.
Children: 0.05 mg/kg t.i.d. or q.i.d.
 Acute iritis, uveitis. Adults: 1 to 2 drops (0.5% or 1% solution) into the eye t.i.d. (in children use 0.5% solution) or a small amount of ointment in the conjunctival sac t.i.d.
 Cycloplegic refraction. Adults: 1 drop (1% solution) 1 hour before refraction.
Children: 1 to 2 drops (0.5% solution) into each eye b.i.d. for 1 to 3 days before eye examination and 1 hour before examination.

Pharmacodynamics
Antiarrhythmic action: An anticholinergic (parasympatholytic) agent with many uses, atropine remains the mainstay of pharmacologic treatment for bradyarrhythmias. It blocks the effects of acetylcholine on the SA and AV nodes, thereby increasing SA and AV node conduction velocity. It also increases sinus node discharge rate and decreases the effective refractory period of the AV node. These changes result in an increased heart rate (both atrial and ventricular).
Atropine has variable-and clinically negligible-effects on the His-Purkinje system. Small doses (below 0.5 mg) and occasionally larger doses may lead to a paradoxical slowing of the heart rate, which may be followed by a more rapid rate.
Anticholinergic action: As a cholinergic blocking agent, atropine decreases the action of the parasympathetic nervous system on certain glands (bronchial, salivary, and sweat), resulting in decreased secretions. It also decreases cholinergic effects on the iris, ciliary body, and intestinal and bronchial smooth muscle.
Antidote for cholinesterase poisoning: Atropine blocks the cholinomimetic effects of these pesticides.

Pharmacokinetics
Absorption: I.V. administration is the most common route for bradyarrhythmia treatment. With endotracheal administration, atropine is well absorbed from the bronchial tree; drug has been used in 1-mg doses in acute bradyarrhythmia when an I.V. line hasn’t been established.
Distribution: Well distributed throughout the body, including the CNS. Only 18% of drug binds with plasma protein (clinically insignificant).
Metabolism: Metabolized in the liver to several metabolites. About 30% to 50% of a dose is excreted by the kidneys as unchanged drug.
Excretion: Excreted primarily through the kidneys; however, small amounts may be excreted in the feces and expired air. Elimination half-life is biphasic, with an initial 2-hour phase followed by a terminal half-life of about 12-1/2 hours.

Route Onset Peak Duration
P.O. 1/2-2 hr 1-2 hr 4 hr
I.V. Immediate 2-4 min 4 hr
I.M. 5-40 min 20-60 min 4 hr
S.C. Unknown Unknown Unknown
Ophthalmic Unknown 1/2-3 hr 7-10 days


Contraindications and precautions
Contraindicated in patients hypersensitive to drug or sodium metabisulfite and in those with acute angle-closure glaucoma, obstructive uropathy, obstructive disease of the GI tract, paralytic ileus, toxic megacolon, intestinal atony, unstable CV status in acute hemorrhage, asthma, or myasthenia gravis.
  Ophthalmic form is contraindicated in patients with glaucoma or hypersensitivity to drug or belladonna alkaloids and in those who have adhesions between the iris and lens. Atropine shouldn’t be used during the first 3 months after birth because of the possible association between cycloplegia produced and development of amblyopia.
 Use cautiously in patients with Down syndrome. Ophthalmic form should be used cautiously in elderly patients and patients with increased intraocular pressure.

Interactions
Drug-drug. Amantadine: May increase anticholinergic adverse effects. Monitor patient carefully.
Anticholinergics, drugs with anticholinergic effects: Causes additive effects. Monitor patient carefully.
Drug-herb. Betel palm: May cause reduced temperature, increasing effects and enhancing CNS effects. Discourage use together.
Jaborandi tree products: Decrease atropine effects. Monitor patient closely.
Jimsonweed: Adversely affects CV function. Discourage use together.
Pill-bearing spurge: Choline in herb may decrease atropine effects. Tell patient to use together cautiously.
Squaw vine: Tannic acid may decrease metabolic breakdown of atropine. Monitor patient.

Adverse reactions
CNS: headache, restlessness, ataxia, disorientation, hallucinations, delirium, insomnia, dizziness, excitement, agitation, confusion, especially in geriatric patients (with systemic or oral form); confusion, somnolence, headache (with ophthalmic form).
CV: palpitations and bradycardia following low-dose atropine, tachycardia after higher doses (with systemic or oral form), tachycardia (with ophthalmic form).
EENT: photophobia, increased intraocular pressure, blurred vision, mydriasis, cycloplegia (with systemic or oral form), ocular congestion with long-term use, conjunctivitis, contact dermatitis of eye, ocular edema, eye dryness, transient stinging and burning, eye irritation, hyperemia (with ophthalmic form).
GI: dry mouth, thirst, constipation, nausea, vomiting (with systemic or oral form); dry mouth, abdominal distention in infants (with ophthalmic form).
GU: urine retention, impotence (with systemic or oral form).
Hematologic: leukocytosis (with systemic or oral form).
Skin: dryness (with ophthalmic form).
Other: severe allergic reactions, including anaphylaxis and urticaria (systemic or oral form).

Effects on lab test results
None reported.

Overdose and treatment
Signs of overdose reflect excessive anticholinergic activity, especially CV and CNS stimulation.
 Treatment includes administering physostigmine to reverse excessive anticholinergic activity and providing general supportive measures, as needed.

Special considerations
• With I.V. administration, drug may cause paradoxical initial bradycardia, which usually disappears within 2 minutes.
• High doses may cause hyperpyrexia, urinary retention, and CNS effects, including hallucinations and confusion (anticholinergic delirium). Other anticholinergic drugs may increase vagal blockage.
• Atropine sulfate injection is physically incompatible with norepinephrine bitartrate, metaraminol bitartrate, and sodium bicarbonate injection. A haze or precipitate will form within 15 minutes of mixing with methohexital solutions.
• If patient has a cardiac disorder, watch for tachycardia.
• Monitor patient’s fluid intake and output; drug causes urine retention and hesitancy. If possible, patient should void before taking drug.
• Store drug at 59° to 86° F (15° to 30° C) and protect from heat, light, and air.
Geriatric patients
• Watch closely for urine retention in elderly men with BPH.

Patient education
• Tell patient to report serious adverse reactions promptly.
• Teach patient how to instill eye medication.
• Warn patient to avoid hazardous activities until blurry vision subsides.
• Advise patient to ease photophobia by wearing dark glasses.

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