Atropine

Pronunciation

(A troe peen)


U.S. Brand Names

AtroPen®; Atropine-Care®; Isopto® Atropine; Sal-Tropine™



Synonyms

Atropine Sulfate



Generic Available

Yes: Excludes tablet



Canadian Brand Names

Dioptic's Atropine Solution; Isopto® Atropine; Minim's Atropine Solution



Use

Injection: Preoperative medication to inhibit salivation and secretions; treatment of symptomatic sinus bradycardia; AV block (nodal level); ventricular asystole; antidote for organophosphate pesticide poisoning

Ophthalmic: Produce mydriasis and cycloplegia for examination of the retina and optic disc and accurate measurement of refractive errors; uveitis

Oral: Inhibit salivation and secretions

Use - Unlabeled/Investigational

Pulseless electric activity, asystole, neuromuscular blockade reversal; treatment of nerve agent toxicity (chemical warfare) in combination with pralidoxime



Restrictions

The AtroPen® formulation is available for use primarily by the Department of Defense.



Pregnancy Risk Factor

C



Pregnancy Implications

Animal reproduction studies have not been conducted. Atropine has been found to cross the human placenta.



Lactation

Enters breast milk (trace amounts)/use caution (AAP rates "compatible")



Contraindications

Hypersensitivity to atropine or any component of the formulation; narrow-angle glaucoma; adhesions between the iris and lens; tachycardia; obstructive GI disease; paralytic ileus; intestinal atony of the elderly or debilitated patient; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; hepatic disease; obstructive uropathy; renal disease; myasthenia gravis (unless used to treat side effects of acetylcholinesterase inhibitor); asthma; thyrotoxicosis; Mobitz type II block



Warnings/Precautions

Heat prostration can occur in the presence of a high environmental temperature. Psychosis can occur in sensitive individuals. The elderly may be sensitive to side effects. Use caution in patients with myocardial ischemia. Use caution in hyperthyroidism, autonomic neuropathy, BPH, CHF, tachyarrhythmias, hypertension, and hiatal hernia associated with reflux esophagitis. Use with caution in children with spastic paralysis.

AtroPen®: There are no absolute contraindications for the use of atropine in organophosphate poisonings, however, use caution in those patients where the use of atropine would be otherwise contraindicated. Formulation for use by trained personnel only.

Adverse Reactions

Severity and frequency of adverse reactions are dose related and vary greatly; listed reactions are limited to significant and/or life-threatening.

Cardiovascular: Arrhythmia, flushing, hypotension, palpitation, tachycardia

Central nervous system: Ataxia, coma, delirium, disorientation, dizziness, drowsiness, excitement, fever, hallucinations, headache, insomnia, nervousness

Dermatologic: Anhidrosis, urticaria, rash, scarlatiniform rash

Gastrointestinal: Bloating, constipation, delayed gastric emptying, loss of taste, nausea, paralytic ileus, vomiting, xerostomia

Genitourinary: Urinary hesitancy, urinary retention

Neuromuscular & skeletal: Weakness

Ocular: Angle-closure glaucoma, blurred vision, cycloplegia, dry eyes, mydriasis, ocular tension increased

Respiratory: Dyspnea, laryngospasm, pulmonary edema

Miscellaneous: Anaphylaxis

Overdosage/Toxicology

Symptoms of overdose include dilated, unreactive pupils; blurred vision; hot, dry flushed skin; dryness of mucous membranes; difficulty swallowing; foul breath; diminished or absent bowel sounds; urinary retention; tachycardia; hyperthermia; hypertension; and increased respiratory rate. For anticholinergic overdose with severe life-threatening symptoms, physostigmine 1-2 mg SubQ or I.V. slowly, may be given to reverse these effects.



Drug Interactions

Drugs with anticholinergic activity (including phenothiazines and TCAs) may increase anticholinergic effects when used concurrently.

Sympathomimetic amines may cause tachyarrhythmias; avoid concurrent use.

Stability

Store injection at controlled room temperature of 15°C to 30°C (59°F to 86°F); avoid freezing. In addition, AtroPen® should be protected from light.



Compatibility

Y-site administration: Compatible: Etomidate, famotidine, heparin, hydrocortisone sodium succinate, inamrinone, meropenem, nafcillin, potassium chloride, propofol, sufentanil, vitamin B complex with C. Incompatible: Thiopental

Compatibility in syringe: Compatible: Butorphanol, chlorpromazine, cimetidine, dimenhydrinate, diphenhydramine, droperidol, fentanyl, glycopyrrolate, heparin, hydromorphone, hydroxyzine, hydroxyzine with meperidine, meperidine, meperidine with promethazine, metoclopramide, midazolam, milrinone, morphine, nalbuphine, ondansetron, pentazocine, perphenazine, prochlorperazine, promazine, promethazine, propiomazine, ranitidine, scopolamine, sufentanil. Incompatible: Cimetidine with pentobarbital. Variable (consult detailed reference): Pentobarbital

Compatibility when admixed: Compatible: Dobutamine, furosemide, meropenem, sodium bicarbonate, verapamil. Incompatible: Floxacillin, metaraminol, methohexital, norepinephrine

Mechanism of Action

Blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands and the CNS; increases cardiac output, dries secretions, antagonizes histamine and serotonin



Pharmacodynamics/Kinetics

Onset of action: I.V.: Rapid

Absorption: Complete

Distribution: Widely throughout the body; crosses placenta; trace amounts enter breast milk; crosses blood-brain barrier

Metabolism: Hepatic

Half-life elimination: 2-3 hours

Excretion: Urine (30% to 50% as unchanged drug and metabolites)

Dosage

Neonates, Infants, and Children: Doses <0.1 mg have been associated with paradoxical bradycardia.

Inhibit salivation and secretions (preanesthesia): Oral, I.M., I.V., SubQ:

<5 kg: 0.02 mg/kg/dose 30-60 minutes preop then every 4-6 hours as needed. Use of a minimum dosage of 0.1 mg in neonates <5 kg will result in dosages >0.02 mg/kg. There is no documented minimum dosage in this age group.

>5 kg: 0.01-0.02 mg/kg/dose to a maximum 0.4 mg/dose 30-60 minutes preop; minimum dose: 0.1 mg

Alternate dosing:

3-7 kg (7-16 lb): 0.1 mg

8-11 kg (17-24 lb): 0.15 mg

11-18 kg (24-40 lb): 0.2 mg

18-29 kg (40-65 lb): 0.3 mg

>30 kg (>65 lb): 0.4 mg

Bradycardia: I.V., intratracheal: 0.02 mg/kg, minimum dose 0.1 mg, maximum single dose: 0.5 mg in children and 1 mg in adolescents; may repeat in 5-minute intervals to a maximum total dose of 1 mg in children or 2 mg in adolescents. (Note: For intratracheal administration, the dosage must be diluted with normal saline to a total volume of 1-5 mL). When treating bradycardia in neonates, reserve use for those patients unresponsive to improved oxygenation and epinephrine.

Infants and Children: Nerve agent toxicity management (unlabeled use): See "Note" in Adults dosing.

Prehospital ("in the field"): I.M.:

Birth to <2 years: Mild-to-moderate symptoms: 0.05 mg/kg; severe symptoms: 0.1 mg/kg

2-10 years: Mild-to-moderate symptoms: 1 mg; severe symptoms: 2 mg

>10 years: Mild-to-moderate symptoms: 2 mg; severe symptoms: 4 mg

Hospital/emergency department: I.M.:

Birth to <2 years: Mild-to-moderate symptoms: 0.05 mg/kg I.M. or 0.02 mg/kg I.V.; severe symptoms: 0.1 mg/kg I.M. or 0.02 mg/kg I.V.

2-10 years: Mild-to-moderate symptoms: 1 mg; severe symptoms: 2 mg

>10 years: Mild-to-moderate symptoms: 2 mg; severe symptoms: 4 mg

Children: Organophosphate or carbamate poisoning:

I.V.: 0.03-0.05 mg/kg every 10-20 minutes until atropine effect, then every 1-4 hours for at least 24 hours

I.M. (AtroPen®): Mild symptoms: Administer dose listed below as soon as exposure is known or suspected. If severe symptoms develop after first dose, 2 additional doses should be repeated in 10 minutes; do not administer more than 3 doses. Severe symptoms: Immediately administer 3 doses as follows:

<6.8 kg (15 lbs): Use of AtroPen® formulation not recommended; administer atropine 0.05 mg/kg

6.8-18 kg (15-40 lbs): 0.5 mg/dose

18-41 kg (40-90 lbs): 1 mg/dose

>41 kg (>90 lbs): 2 mg/dose

Adults (doses <0.5 mg have been associated with paradoxical bradycardia):

Asystole or pulseless electrical activity:

I.V.: 1 mg; repeat in 3-5 minutes if asystole persists; total dose of 0.04 mg/kg.

Intratracheal: Administer 2-2.5 times the recommended I.V. dose; dilute in 10 mL NS or distilled water. Note: Absorption is greater with distilled water, but causes more adverse effects on PaO2.

Inhibit salivation and secretions (preanesthesia):

I.M., I.V., SubQ: 0.4-0.6 mg 30-60 minutes preop and repeat every 4-6 hours as needed

Bradycardia: I.V.: 0.5-1 mg every 5 minutes, not to exceed a total of 3 mg or 0.04 mg/kg; may give intratracheally in 10 mL NS (intratracheal dose should be 2-2.5 times the I.V. dose)

Neuromuscular blockade reversal: I.V.: 25-30 mcg/kg 60 seconds before neostigmine or 7-10 mcg/kg in combination with edrophonium

Organophosphate or carbamate poisoning:

I.V.: 2 mg, followed by 2 mg every 5-60 minutes until adequate atropinization has occurred; initial doses of up to 6 mg may be used in life-threatening cases

I.M. (AtroPen®): Mild symptoms: Administer 2 mg as soon as exposure is known or suspected. If severe symptoms develop after first dose, 2 additional doses should be repeated in 10 minutes; do not administer more than 3 doses. Severe symptoms: Immediately administer three 2 mg doses.

Nerve agent toxicity management (unlabeled use): I.M.: See Note. Prehospital ("in the field") or hospital/emergency department: Mild-to-moderate symptoms: 2-4 mg; severe symptoms: 6 mg

Note: Pralidoxime is a component of the management of nerve agent toxicity; consult pralidoxime monograph for specific route and dose. For prehospital ("in the field") management, repeat atropine I.M. (children: 0.05-0.1 mg/kg; adults: 2 mg) at 5-10 minute intervals until secretions have diminished and breathing is comfortable or airway resistance has returned to near normal. For hospital management, repeat atropine I.M. (infants 1 mg; all others: 2 mg) at 5-10 minute intervals until secretions have diminished and breathing is comfortable or airway resistance has returned to near normal.

Mydriasis, cycloplegia (preprocedure): Ophthalmic (1% solution): Instill 1-2 drops 1 hour before procedure.

Uveitis: Ophthalmic:

1% solution: Instill 1-2 drops 4 times/day

Ointment: Apply a small amount in the conjunctival sac up to 3 times/day; compress the lacrimal sac by digital pressure for 1-3 minutes after instillation

Elderly, frail patients: Nerve agent toxicity management (unlabeled use): I.M.: See "Note" in Adults dosing.

Prehospital ("in the field"): Mild-to-moderate symptoms: 1 mg; severe symptoms: 2-4 mg

Hospital/emergency department: Mild-to-moderate symptoms: 1 mg; severe symptoms: 2 mg

Administration

I.M.: AtroPen®: Administer to outer thigh. May be given through clothing as long as pockets at the injection site are empty. Hold auto-injector in place for 10 seconds following injection; massage the injection site.

I.V.: Administer undiluted by rapid I.V. injection; slow injection may result in paradoxical bradycardia.

Intratracheal: Dilute in NS or distilled water. Absorption is greater with distilled water, but causes more adverse effects on PaO2. Pass catheter beyond tip of tracheal tube, stop compressions, spray drug quickly down tube. Follow immediately with several quick insufflations and continue chest compressions.

Monitoring Parameters

Heart rate, blood pressure, pulse, mental status; intravenous administration requires a cardiac monitor



Patient Education

Take oral forms exactly as directed, 30 minutes before meals. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. Void before taking medication. You may experience dizziness, blurred vision, sensitivity to light (use caution when driving or engaging in tasks requiring alertness until response to drug is known); dry mouth, nausea, or vomiting (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); orthostatic hypotension (use caution when climbing stairs and when rising from lying or sitting position); constipation (increased exercise, fluids, fruit, or fiber may help; if not effective, consult prescriber); increased sensitivity to heat and decreased perspiration (avoid extremes of heat, reduce exercise in hot weather); or decreased milk if breast-feeding. Report hot, dry, flushed skin; blurred vision or vision changes; difficulty swallowing; chest pain, palpitations, or rapid heartbeat; painful or difficult urination; increased confusion, depression, or loss of memory; rapid or difficult respirations; muscle weakness or tremors; or eye pain.

Ophthalmic: Instill as often as recommended. Wash hands before using. Sit or lie down, open eye, look at ceiling, and instill prescribed amount of solution. Do not blink for 30 seconds, close eye and roll eye in all directions, and apply gentle pressure to inner corner of eye for 1-2 minutes. Do not let tip of applicator touch eye; do not contaminate tip of applicator (may cause eye infection, eye damage, or vision loss). Temporary stinging or blurred vision may occur.

Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Nursing Implications

Observe for tachycardia if patient has cardiac problems



Anesthesia and Critical Care Concerns/Other Considerations

Atropine, at usual recommended cardiovascular doses, causes blockade of muscarinic receptors at the cardiac SA-node and is parasympatholytic (ie, blocks vagal activity increasing heart rate). A dose 0.5-1 mg is recommended for the treatment of bradyarrhythmias. In administering atropine, it is important to recognize that lower doses (<0.5 mg) may have vagalmimetic effects (ie, increase vagal tone causing paradoxical bradycardia). A total dose of 3 mg (0.04 mg/kg) results in full vagal blockade in humans. In the absence of vascular access, atropine can be administered intratracheally.



Cardiovascular Considerations

Atropine, at usual recommended cardiovascular doses, causes blockade of muscarinic receptors at the cardiac SA-node and is parasympatholytic (ie, blocks vagal activity increasing heart rate). A dose 0.5-1 mg is recommended for the treatment of bradyarrhythmias. In administering atropine, it is important to recognize that lower doses (<0.5 mg) may have vagalmimetic effects (ie, increase vagal tone causing paradoxical bradycardia). It is likely that the vagal tonic effects of atropine are mediated by blockade of muscarinic receptors at the level of the brain. Thus, it is important that the recommended dose of atropine be administered by rapid intravenous injection. Slow injection may result in paradoxical bradycardia. Atropine is also recommended as part of the ACLS protocol. In this situation, in the absence of vascular access, atropine can be administered intratracheally. For intratracheal administration, the dosage must be diluted with normal saline to a total volume of 10 mL.



Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), dry throat, and nasal dryness.



Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions



Mental Health: Effects on Mental Status

Use of injectable dosage form may cause ataxia, hallucinations, dizziness, amnesia, difficulty concentrating, agitation, delirium, paranoia, anxiety, and mania.



Mental Health: Effects on Psychiatric Treatment

May decrease the effects of phenothiazines; concurrent use with psychotropics may result in additive anticholinergic side effects (dry mouth, blurred vision, constipation)



Dosage Forms

Injection, solution, as sulfate: 0.05 mg/mL (5 mL); 0.1 mg/mL (5 mL, 10 mL); 0.4 mg/mL (0.5 mL, 1 mL, 20 mL); 0.5 mg/mL (1 mL); 1 mg/mL (1 mL)

AtroPen® [prefilled auto-injector]: 0.5 mg/0.7 mL (0.7 mL); 1 mg/0.7 mL (0.7 mL); 2 mg/0.7 mL (0.7 mL)

Ointment, ophthalmic, as sulfate: 1% (3.5 g)

Solution, ophthalmic, as sulfate: 1% (5 mL, 15 mL)

Atropine-Care®: 1% (2 mL)

Isopto® Atropine: 1% (5 mL, 15 mL)

Tablet, as sulfate (Sal-Tropine™): 0.4 mg

References

"American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,"Pediatrics, 2001, 108(3):776-89.

Eisenberg MS and Mengert TJ, "Cardiac Resuscitation,"N Engl J Med, 2001, 344(17):1304-13.

Emergency Cardiac Care Committee and Subcommittees, American Heart Association, "Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care, III: Adult Advanced Cardiac Life Support" and "VI: Pediatric Advanced Life Support,"JAMA, 1992, 268(16):2199-241 and 2262-75.

"Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: Advanced Cardiovascular Life Support: Section 5: Pharmacology I: Agents for Arrhythmias,"Circulation, 2000, 102(8):I112-128.

"Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 10: Pediatric Advanced Life Support,"Circulation, 2000, 102(8):I291-342.

"Medical Management Guidelines (MMGs) for Nerve Agents: Tabun (GA); Sarin (GB); Soman (GD); and VX." Available at: www.atsdr.cdc.gov/MHMI/mmg166.html. Accessed January 8, 2003.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings,"Chest, 2003, 123(3):897-922.

International Brand Names

Atromed® (RU); Atropina Apolo® (AR); Atropina Braun® (ES); Atropina® (BR, EC, IT, RO); Atropina Llorens® (ES); Atropina Lux® (IT); Atropina Nicolich® (CL); Atropina Poen® (AR); Atropina Solfato® (IT); Atropina Solucion Oftalmica® (CL); Atropina Sulfato® (AR, CL); Atropina Sulfato Ecar® (CO); Atropina Sulfato Serra® (ES); Atropina Sulfurica [inj.] (RO); Atropin® (CZ, FI, HR, NO, SE, YU); Atropin Dak® (DK); Atropin Dispersa® (CH, DE, LU); Atropine® (AU); A-Tropine® (BD); Atropine® (BE, GB, IL, NZ); Atropine Covan® (ZA); Atropine Dispersa® (CH); Atropin EDO® (DE); Atropine Faure® (CH, FR); Atropine FNA® (NL); Atropine Injection® (GB); Atropine-Jayson® (BD); Atropine Minims® (NL); Atropine Novartis Ophthalmics® (SG); Atropine Novartis® (TH); Atropine-OSL® (BD); Atropine Sulfate® (AU, RU); Atropine Sulfate Demo® (TH); Atropine Sulfate Injection BP® (AU, NZ); Atropine Sulfate Lavoisier® (FR); Atropine Sulphate Atlantic® (SG, TH); Atropine-Sulphate-Fresenius® (ZA); Atropine Sulphate® (IL); Atropin® [inj.] (TR); Atropini sulfas® (HR, ID, SI); Atropinium sulfuricum Streuli® (CH); Atropin Minims® (NO); Atropin NM Pharma® (SE); Atropinol® (DE, RO); Atropin-POS® (DE); Atropin PS® (DK); Atropin SAD® (DK); Atropinsulfat Braun® (DE, LU); Atropinsulfat® (DE); Atropinsulfat IMS® (CH, DE); Atropinsulfat Lannacher® (AT); Atropinsulfatloesung Fresenius® (LU); Atropin Sülfat® (TR); Atropin sulfat® (YU); Atropinum sulfuricum Eifelfango® (DE); Atropinum Sulfuricum Nycomed® (AT); Atropinum Sulfuricum® (PL); Atropt® (AU, NZ); Atrosol® (TR); Beecham Atropine Sulphate® (ZA); Bellafit N® (CH); Bellapan® (PL); Bell Pino-Atrin® (IN); Cendo Tropine® (ID); Colircusi Atropina® (ES); Colirio Ocul Atropina® (ES); Dioptic's Atropine Solution (CA); Dysurgal® (DE); Endotropina® (AR); G-Atropine® (BD); Intramed Atropine Sulphate Injection® (ZA); Isopto Atropina® (AR); Isopto® Atropine (CA); Isopto Atropine® (GB, IE, SG, TH, ZA); Isopto-Atropin® (SE); Isotic Cycloma® (ID); Midrisol® (TR); Min-I-Jet Atropine Sulphate® (GB); Minims Atropine® (BE, IE); Minim's Atropine Solution (CA); Minims Atropine Sulphate® (FI, GB, NZ, ZA); Minims Atropinsulfat® (AT); Mydriatropine® (BD); Oftan Atropin® (FI); Oft Cusi Atropina® (ES); Q-Med Atropine® (ZA); Ryuato® (JP); Sabax Atropine® (ZA); Stellatropine® (BE, LU); Sulfat de Atropina Renaudin® (RO); Sulfat de Atropina® (RO); Sulfate d'Atropine-Chauvin® (LU); Sulfate d'Atropine® (FR); Sulfato de Atropina® (AR, BR); Sulfato de Atropina Biol® (AR); Sulfato de Atropina Larjan® (AR); Tropyn Z® (MX); Ximex Optitrop® (ID)



Review Date: 1969-12-31 Reviewed By: Keywords: ,
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