Atropine blocks the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the central nervous system.

It is used in the treatment of the following conditions:

• Atropine use as Antidote:

  • It is mostly used as an antidote for anticholinesterase poisoning (carbamate insecticides, nerve agents, organophosphate insecticides)
  • It can be used as an antidote for muscarine-containing mushroom poisoning.
  • It is also used along with anticholinesterases (eg, edrophonium, neostigmine) to lessen their adverse effects during the reversal of neuromuscular blockade.

• Atropine use in Cardiovascular conditions:

  • It is used in the treatment of symptomatic sinus bradycardia, atrioventricular (AV) nodal block.
  • It might not be effective for type II second-degree or third-degree AV block.
  • Its use is no longer recommended in the management of asystole or pulseless electrical activity.

• Atropine use in Respiratory tract medicine:

  • It is mostly used preoperative/ preanesthetic medication to stop salivation and secretions.

• Off Label Usage of Atropine In Adults:

  • Premedication in rapid sequence intubation.
  • It is also used as adjunct chronotropic agent in stress echocardiography.

Atropine Dose in Adults

Atropine Dosage for excessive salivation and secretions (preanesthesia):

Intramuscular, Intravenous, SubQ:

• It is given initially 0.4 to 1 mg 30 to 60 minutes preoperatively
• Then repeated every 4 to 6 hours as needed to a maximum total dose of 3 mg.

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Atropine Dose in the treatment of Bradycardia:

Intravenous, Intramuscular:

• 0.5 mg given every 3 to 5 minutes
• maximum total dose is 3 mg

  • Endotracheal:

• 1 to 2 mg given every 3 to 5 minutes
  • Atropine might not work in heart transplant patients due to a lack of vagal innervation.

---

Off label atropine Dose in the treatment of Muscarine-containing mushroom poisoning :

• 1 to 2 mg given Intravenous
• Titrate and repeat as needed

---

Atropine Dose in the treatment of Neuromuscular blockade reversal:

• 15 to 30 mcg/kg given  Intravenous administered with neostigmine

 or

• 7 to 10 mcg/kg given with edrophonium

---

Atropine Dose in the treatment of Organophosphate or carbamate insecticide or nerve agent poisoning:

• The dose of atropine required differs considerably with the severity of poisoning.
• The total amount of atropine used for carbamate poisoning is usually lower than with organophosphate insecticide or nerve agent poisoning.
• Severely poisoned patients may exhibit significant tolerance to atropine; sometimes higher doses may be needed.
• Titrate to pulmonary status (decreased bronchial secretions)
• Also, consider administration of atropine via continuous IV infusion in patients requiring large doses of atropine.
• Once the patient is stable, the dose/dosing frequency can be decreased.

Intravenous, Intramuscular, endotracheal:

• Initially, 1 to 6 mg is given
• Then repeat every 3 to 5 minutes as needed,
• Double the dose if the previous dose did not induce a response.
• Give repeat doses as needed for ≥2 to 12 hours based on the recurrence of symptoms

• Mild symptoms (≥2 mild symptoms):

  • Give 2 mg as soon as exposure is known or is strongly suspected.
  • If severe symptoms develop after the 1st dose then 2 additional doses should be repeated in rapid succession 10 minutes after the 1st dose
  • Do not give more than 3 doses.
  • If intense anticholinergic effects are seen in the absence of excessive bronchial secretions, then further doses of atropine should be withheld.

• Severe symptoms (≥1 severe symptom):

  • Immediately give three 2 mg doses in rapid succession.

• Symptoms of insecticide or nerve agent poisoning :

  • Mild symptoms:

    • Blurred Vision
    • Bradycardia
    • Breathing Difficulties
    • Chest Tightness
    • Coughing
    • Drooling
    • Miosis
    • Muscular Twitching
    • Nausea
    • Runny Nose
    • Salivation Increased
    • Stomach Cramps
    • Tachycardia
    • Teary Eyes
    • Tremor
    • Vomiting
    • Wheezing

• Severe symptoms:
  • Breathing Difficulties (Severe)
  • Confused/Strange Behavior
  • Defecation (Involuntary)
  • Muscular Twitching/Generalized Weakness (Severe)
  • Respiratory Secretions (Severe)
  • Seizure
  • Unconsciousness
  • Urination (Involuntary)

• Intravenous Infusion:
  • Start 10% to 20% of the total loading dose required to induce the desired response as a continuous Intravenous infusion per hour
  • Then adjust as required to maintain adequate response without atropine toxicity

---

Off label atropine Dose in the Rapid sequence intubation (premedication):

• 0.01 to 0.02 mg/kg Intravenous is given
• The minimum dose is 0.1 mg
• a maximum single dose is 0.5 mg

---

Off label atropine Dose in the treatment of Stress echocardiography (adjunct chronotropic agent):

• 0.25 to 0.5 mg Intravenous given up to a total dose of 1 to 2 mg
• Target is 85% of the target heart rate achieved.

Atropine Dose in Childrens

Atropine Dose in the treatment of Bradycardia:

• Infants, Children, and Adolescents:

  • Intravenous, Intraosseous:

  • 0.02 mg/kg/dose is given
  • The minimum dose is 0.1 mg/dose
  • Maximum dose is 0.5 mg/dose
  • Can repeat once in 5 minutes
  • use should be reserved for those patients unresponsive to improved oxygenation and epinephrine.

  • Endotracheal:

  • 0.04 to 0.06 mg/kg/dose is given
  • Can repeat once if needed

---

Atropine Dosage in the treatment to Inhibit salivation and secretions (preoperative/ intraoperative):

• Infants and Children aged less than 12 years:

  • Intramuscular, Intravenous, SubQ:

  • Dose is 0.02 mg/kg
  • Maximum dose is  0.5 mg/dose
  • Administer first dose 30 to 60 minutes before operating and then repeat every 4 to 6 hours as needed
  • The maximum total dose is 1 mg/procedure.

• Children aged more than 12 years and Adolescents:

  • Intramuscular, Intravenous, SubQ:

  • 0.02 mg/kg/dose is given
  • The maximum dose is 1 mg/dose
  • Give the first dose 30 to 60 minutes preoperatively and then repeat every 4 to 6 hours as needed
  • The maximum total dose is 2 mg/procedure.

---

Atropine Premedication Dose in the emergency Intubation:

• It is not used routinely for pre-intubation in infants and children
• atropine can be considered in situations with a high-risk of bradycardia (eg, succinylcholine use)

• Infants and Children:

  • 0.02 mg/kg/dose given Intravenous
  • Maximum dose is 0.5 mg/dose
  • It is usually not recommended for pre-intubation in infants and children due to the risk of bradycardia.

---

Atropine Dose in the treatment of Muscarine-containing mushroom poisoning: 

• Infants, Children, and Adolescents:

  • 0.02 mg/kg/dose given Intravenous
  • The minimum dose of 0.1 mg.
  • Titrate and repeat as required

---

Atropine Dose in the treatment of Organophosphate or carbamate insecticide or nerve agent poisoning:

• If exposure is known or suspected then antidotal therapy should be given as soon as symptoms appear; do not wait for confirmation.
• The dose of atropine required differs from the severity of poisoning.
• The total amount of atropine used for the treatment of carbamate poisoning is usually less than with organophosphate insecticide or nerve agent poisoning.
• Severely poisoned patients may exhibit significant tolerance to atropine& require ≥2 times the suggested doses.
• Titrate to pulmonary status (decreased bronchial secretions)
• Consider giving atropine via continuous Intravenous infusion in patients requiring higher doses of atropine.

• Infants and Children:

  • Intravenous, Intramuscular, Intraosseous:

    • Initially, a dose of 0.05 to 0.1 mg/kg is given
    • Then repeat every 5 to 10 minutes as needed
    • Double the dose if the previous dose does not induce atropinization.
    • Maintain atropinization by giving repeat doses as needed for ≥2 to 12 hours based on the recurrence of symptoms

  • Adolescents:

    • Intravenous, Intramuscular, Intraosseous:

      • Initially, 1 to 3 mg/dose is given
      • Then repeat every 3 to 5 minutes as needed
      • Double the dose if the previous dose does not induce atropinization.
      • Maintain atropinization by administering repeat doses as needed for ≥2 to 12 hours based on the recurrence of symptoms.

• Infants, Children, and Adolescents:

  • Continuous Intravenous infusion:

    • Following atropinization, give 10% to 20% of the total loading dose used to induce atropinization as a continuous IV infusion per hour
    • Adjust to maintain adequate atropinization without atropine toxicity.

• Infants, Children, and Adolescents:

  • Intramuscular (AtroPen): Number of doses differs with symptom severity:

  • Weight-directed dosing:

    • <7 kg (<15 lb):

      • 0.25 mg/dose is given (yellow pen)

    • 7 to 18 kg (15 to 40 lb):

      • 0.5 mg/dose is given (blue pen)

    • >18 to 41 kg (>40 to 90 lb):

      • 1 mg/dose is given (dark red pen)

    • >41 kg (>90 lb):

      • 2 mg/dose is given (green pen)

• Mild symptoms (≥2 mild symptoms):

  • Give the weight-directed dose described above as soon as exposure is known or strongly suspected.
  • If severe symptoms develop after the 1st dose then 2 additional doses should be repeated in rapid succession 10 minutes after the first dose
  • Do not give more than 3 doses.
  • If significant anticholinergic effects occur in the absence of excessive bronchial secretions further doses of atropine should be withheld.
  • Mild symptoms of insecticide or nerve agent poisoning,  include:
    • Blurred Vision
    • Bradycardia
    • Breathing Difficulties
    • Chest tightness
    • Coughing
    • Drooling
    • Miosis
    • Muscular Twitching
    • Nausea
    • Runny nose
    • Salivation increased
    • Stomach cramps
    • Tachycardia
    • Teary eyes
    • Tremor
    • Vomiting
    • Wheezing.

• Severe symptoms (≥1 severe symptom):

  • Immediately give three weight-directed doses in rapid succession.
  • Severe symptoms of insecticide or nerve agent poisoning, include:
    • Breathing difficulties (severe)
    • Confused/strange behavior
    • Defecation (involuntary)
    • Muscular twitching/generalized weakness (severe
    • Respiratory Secretions (severe)
    • Seizure
    • Unconsciousness
    • Urination (involuntary)
• Infants may become drowsy or unconscious with muscle floppiness as opposed to muscle twitching.

Endotracheal:

• The dose should be by 2 to 3 times the usual Intravenous dose.
  • Mix with 3 - 5 ml of normal saline and then administer.
  • Flush with 3 - 5 ml of normal saline and follow with 5 assisted manual ventilation.

Atropine Pregnancy Risk Factor B/C

• In animal reproduction studies, adverse events were not observed
• Atropine passes the human placental barrier.
• Pregnant women should only receive antidotes if they have been given a clear indication. They should not be withheld due to fears of teratogenicity.
• The same medications are used to treat cardiac arrest during pregnancy as for women who are not pregnant.
• The Advanced Cardiovascular Life Support Guidelines should guide you in your treatment decisions.
• Because of concerns about fetal teratogenicity, it is important to not withhold appropriate medications.

Atropine use during breastfeeding:

• Breast milk contains very little atropine.
• Atropine can cause lactation problems or decreases in infants who are breastfeed.
• The manufacturer suggests that breastfeeding mothers be cautious when using atropine.

Atropine dose in kidney disease:

• There are no dosage adjustments given in the manufacturer’s labeling.

Atropine dose in liver disease:

• There are no dosage adjustments given in the manufacturer’s labeling.

Side effects of atropine:

• Cardiovascular:

  • Asystole
  • Atrial Arrhythmia
  • Atrial Fibrillation
  • Atrioventricular Dissociation (Transient)
  • Bigeminy
  • Bradycardia
  • Chest Pain
  • Decreased Blood Pressure
  • ECG Changes (Prolonged P Wave
  • Shortened PR Segment
  • R On T Phenomenon
  • Shortened RT Duration
  • Prolonged QT Interval
  • Widening Of QRS Complex
  • Flattened T Wave
  • Repolarization Abnormalities
  • ST Segment Elevation
  • Retrograde Conduction)
  • Ectopic Beats (Atrial)
  • Extrasystoles (Nodal
  • Ventricular
  • Supraventricular)
  • Flushing
  • Increased Blood Pressure
  • Left Heart Failure
  • Myocardial Infarction
  • Nodal Arrhythmia (No P Wave On ECG)
  • Palpitations
  • Sinus Tachycardia
  • Supraventricular Tachycardia (Including Junctional Tachycardia)
  • Tachycardia
  • Trigeminy
  • Ventricular Arrhythmia (Including Flutter)
  • Ventricular Fibrillation
  • Ventricular Flutter
  • Ventricular Premature Contractions
  • Ventricular Tachycardia
  • Weak Pulse (Or Impalpable Peripheral Pulses)

• Central Nervous System:

  • Abnormal Electroencephalogram (Runs Of Alpha Waves
  • Increase In Photic Stimulation
  • And Signs Of Drowsiness)
  • Agitation (Children)
  • Amnesia
  • Anxiety
  • Ataxia
  • Behavioral Changes
  • Coma
  • Confusion
  • Decreased Deep Tendon Reflex
  • Delirium
  • Dizziness
  • Drowsiness
  • Dysarthria
  • Dysmetria
  • Emotional Disturbance
  • Excitement
  • Feeling Hot
  • Hallucination (Visual Or Aural)
  • Headache
  • Hyperpyrexia
  • Hyperreflexia
  • Hypertonia
  • Insomnia
  • Intoxicated Feeling
  • Irritability (Children)
  • Lack Of Concentration
  • Lethargy (Children)
  • Mania
  • Myoclonus
  • Neurologic Abnormality
  • Nocturnal Enuresis
  • Opisthotonus
  • Paranoia
  • Positive Babinski Sign
  • Restlessness
  • Seizure (Generally Tonic-Clonic)
  • Stupor
  • Vertigo

• Dermatologic:

  • Anhidrosis
  • Cold Skin
  • Dermatitis
  • Dry And Hot Skin
  • Erythematous Rash
  • Hyperhidrosis
  • Macular Eruption
  • Maculopapular Rash
  • Papular Rash
  • Scarlatiniform Rash
  • Skin Rash

• Endocrine & Metabolic:

  • Dehydration
  • Hyperglycemia
  • Hypoglycemia
  • Hypokalemia
  • Hyponatremia
  • Increased Thirst
  • Loss Of Libido

• Gastrointestinal:

  • Abdominal And Bladder Distension
  • Abdominal Pain
  • Constipation
  • Delayed Gastric Emptying
  • Diminished Bowel Sounds
  • Dry Mucous Membranes
  • Dysphagia
  • Malabsorption
  • Nausea
  • Oral Lesion
  • Paralytic Ileus
  • Salivation
  • Vomiting
  • Xerostomia

• Genitourinary:

  • Difficulty In Micturition
  • Impotence
  • Urinary Hesitancy
  • Urinary Retention
  • Urinary Urgency

• Hematologic & Oncologic:

  • Abnormal Erythrocytes (Increased)
  • Decreased Hemoglobin
  • Increased Hemoglobin
  • Leukocytosis
  • Petechiae

• Hypersensitivity:

  • Hypersensitivity Reaction

• Local:

  • Injection Site Reaction

• Neuromuscular & Skeletal:

  • Laryngospasm
  • Muscle Twitching
  • Weakness

• Ophthalmic:

  • Abnormal Eye Movements (Cyclophoria And Heterophoria)
  • Angle-Closure Glaucoma  (Acute)
  • Blepharitis
  • Blindness
  • Blurred Vision
  • Conjunctivitis
  • Crusted Of Eyelid
  • Cycloplegia
  • Decreased Accommodation
  • Decreased Visual Acuity
  • Dry Eye Syndrome
  • Eye Irritation
  • Keratoconjunctivitis Sicca
  • Lacrimation
  • Mydriasis
  • Photophobia
  • Strabismus

• Renal:

  • Increased Blood Urea Nitrogen

• Respiratory:

  • Bradypnea
  • Changes In Respiration (Labored Respiration)
  • Cyanosis
  • Dyspnea
  • Laryngitis
  • Pulmonary Edema
  • Respiratory Failure
  • Stridor (Inspiratory)
  • Tachypnea

• Miscellaneous:

  • Failure To Thrive
  • Fever (Secondary To Decreased Sweat Gland Activity)
  • Swelling (Children)

Contraindications to Atropine:

• The manufacturer's labeling does not contain any contraindications.

Warnings and precaution

 

• Anaphylaxis

  • Can occur.

• Hyperthermia

  • Hyperthermia can be caused by high ambient temperatures.

• Psychosis:

  • Psychosis can occur in sensitive people or after excessive use.

• Arrhythmias:

  • For type II second-degree and third-degree AV blocks (with or without a wide QRS complex), avoid relying upon atropine.
  • In asystole and bradycardic PEA, routine use is not recommended.

• Autonomic neuropathy:

  • Patients with autonomic neuropathy should be cautious.

• Cardiovascular disease

  • Patients with heart failure, myocardial ischemia, heart disease, tachyarrhythmias (including sin tachycardia) and hypertension should be cautious.
  • Tachycardia can cause blood pressure to rise, which could lead to ischemia, MI, or an increase in arrhythmogenic potential.

• Gastrointestinal Disease:

  • It could cause partial organic pyloric obstruction.
  • Patients with severe ulcerative colitis, paralytic ileus, or intestinal atony for the elderly or disabled should not use this product.

• Glaucoma:

  • It could lead to acute glaucoma.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious
  • Atropine's effects are more severe in those with severe hepatic impairment.

• Hiatal hernia

  • Patients with hiatal hernia and reflux esophagitis should be cautious.

• Hyperthyroidism:

  • Patients with hyperthyroidism should be cautious.

• Myasthenia gravis:

  • Avoid using acetylcholinesterase inhibition side effects.

• Renal impairment

  • Patients with impaired renal function should be cautious.
  • In severe renal impairment, the effects of atropine can be extended.

• Respiratory impairment

  • Patients with chronic lung disease may experience thickening of the bronchial secretions or viscid plugging.

• Urinary retention

  • Patients with prostatic hypertrophy may experience complete urinary retention.
  • Patients with obstructive or other conditions that cause urinary retention should avoid using it if at all possible

Monitor:

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

Organophosphate or carbamate insecticide or nerve agent poisoning:

• Heart rate, blood pressure, respiratory status, oxygenation secretions.
• Maintain atropinization with repeated dosing according to clinical status.
• Crackles in lung bases, or continuation of cholinergic signs, are signs of inadequate dosing.
• Pulmonary improvement is not parallel to other signs of atropinization.
• Look for signs and symptoms of atropine toxicity (eg, fever, muscle fasciculations, delirium)
• If toxicity occurs, discontinue atropine and monitor closely.

How to administer Atropine?

Intramuscular: AtroPen:

• Administer it in the outer thigh.
• Firmly grasp the autoinjector with the green tip (0.5 mg, 1 mg, and 2 mg autoinjector) or black tip (0.25 mg autoinjector) pointed downwards
• remove the yellow safety release (0.5 mg, 1 mg, and 2 mg autoinjector) or gray safety release (0.25 autoinjector).
• Jab the green tip against the outer thigh at a 90° angle
• It may be administered through clothing as long as pockets at the injection site are empty.
• In thin patients, bunch up the thigh before injection.
• Hold the autoinjector in place for 10 seconds after the injection
• remove the autoinjector and massage the injection site.
• After administration, the needle will be visible
• if the needle is not visible, then repeat the above steps.
• After use, bend the needle against a hard surface (needle does not retract) to avoid accidental injury.

Intravenous:

• Administer undiluted by rapid Intravenous injection.
• A slow injection may result in paradoxical bradycardia.
• Atropine administration should not delay treatment with external pacing in patients with bradycardia.

Intraosseous (IO):

• It may be administered intraosseous if needed.

Endotracheal:

• Dilute in ≤10 mL NS or sterile water.
• Absorption might be greater with sterile water.
• Stop compressions & spray the drug quickly down the tube during CPR.
• Follow immediately with several quick insufflations and continue chest compressions.

SubQ

•  May administer subcutaneous if needed.

Mechanism of action of Atropine:

• It prevents acetylcholine from acting at parasympathetic locations in smooth muscle, secretory and CNS.
• It increases cardiac output and dries secretions.
• Atropine acts as a competitive antagonist to acetylcholinesterase inhibitor activities and inhibits cholinergic poisoning's muscarinic effects.
• Cholinergic poisonings are primarily designed to reverse bronchorrhea or bronchoconstriction.
• It does not affect the nicotinic nerves that are responsible for paralysis, muscle weakness, fasciculations and paralysis.

The onset of action:

Inhibition of salivation: Intramuscular:

• Within 30 minutes
• The maximum effect is seen 30 to 60 minutes

Increased heart rate: Intramuscular:

• Within 15 to 30 minutes
• The maximum effect is seen after 45 to 60 minutes

Intravenous: Immediate;

• The maximum effect is seen in  0.7 to 4 minutes

Duration:

• Inhibition of salivation: IM: less than 4 hours.

Absorption:

• Rapid and well absorbed from all dosage forms

Distribution:

• Widely throughout the body; can cross the blood-brain barrier

Protein binding:

• 14% - 44%

Metabolism:

• Hepatic route via enzymatic hydrolysis

Half-life elimination:

• Children <2 years: 6.9 hours
• Children >2 years: 2.5  hours
• Adults: 3  hours
• Elderly 65 - 75 years of age: 10 hours

Time to peak: Intramuscular: 30 minutes Intramuscular auto-injector: 3 minutes

Excretion:

• Via Urine (13% to 50% as unchanged drug and metabolites)  

International Brands of Atropine:

• Nespin
• Atren
• Atro
• Atropa
• Atropan
• Atropin
• Atropin Biotika
• Atrosol
• Bellafit
• Bellafit N
• Cholspas Atropin
• Ciratro
• Dysurgal
• Endotropina
• Estropin
• Santropina
• Stellatropine
• Tropyn

Atropine brand names in Pakistan:

Atropine (Sulphate) Injection 1 Mg/Ml
Atropine	P.D.H. Pharmaceuticals (Pvt) Ltd.
Atropine Sulphate	Shifa Laboratories.(Pvt) Ltd.
Elitopine	Elite Pharma

Atropine (Sulphate) Eye Drops 1 %W/V
Atropine	Lahore Chemical & Pharmaceutical Works (Pvt) Ltd
Atropine	Harmann Pharmaceutical Laboratories (Pvt) Ltd.
Atropine Sulphate	Shifa Laboratories.(Pvt) Ltd.
Atropisole	Lahore Chemical & Pharmaceutical Works (Pvt) Ltd
Ethiatropine	Ethical Laboratories (Pvt) Ltd.
Eytropine	Orient Laboratories
Ophth-Atropine	Ophth-Pharma (Pvt) Ltd.
Opta Atropine	Remington Pharmaceutical Industries (Pvt) Ltd.
Optapine	Harmann Pharmaceutical Laboratories (Pvt) Ltd.
Orbatropin	Zafa Pharmaceutical Laboratories (Pvt) Ltd.

Atropine (Sulphate) Eye Oint 1 %W/W
Atropine	Lahore Chemical & Pharmaceutical Works (Pvt) Ltd
Litropina	Neo Medix
Ophth-Atropine	Ophth-Pharma (Pvt) Ltd.

Atropine (Sulphate) Tabs 0.02 Mg
Fymotil	Fynk Pharmaceuticals