Atropine Injection - Uses, Dosage, Side effects

Acetylcholine's function at parasympathetic locations in the central nervous system, secretory glands, and smooth muscle is blocked by atropine.

It is used in the therapy of the following conditions:

  • Atropine use as an Antidote:

    • In order to decrease the negative effects of anticholinesterases (such as edrophonium and neostigmine) during the restoration of neuromuscular blockade, it is also used in conjunction with them.
    • The main application is as a remedy for anticholinesterase poisoning (carbamate insecticides, nerve agents, organophosphate insecticides)
    • It serves as a remedy for poisoning brought on by muscarine-containing mushrooms.
  • Atropine use in Cardiovascular conditions:

    • Atrioventricular (AV) nodal block and symptomatic sinus bradycardia are both treated with it.
    • The treatment of asystole or pulseless electrical activity no longer calls for its usage.
    • For type II second-degree or third-degree AV block, it could not be effective.
  • Atropine use in Respiratory tract medicine:

    • It is often used as a preoperative or anaesthetic drug to reduce secretions and salivation.
  • Off-Label Usage of Atropine In Adults:

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

Atropine Dose in Adults

Atropine Dosage for excessive salivation and secretions (preanesthesia):

Intramuscular, Intravenous, SubQ:

  • An initial dose of 0.4 to 1 mg is administered 30 to 60 minutes before surgery.
  • Thereafter, as needed, it is repeated every 4 to 6 hours up to a maximum total dose of 3 mg.

Atropine Dose in the treatment of Bradycardia:

Intravenous, Intramuscular:

  • The maximum total dosage is 3 mg when administered at intervals of 0.5 mg every 3 to 5 minutes.
    • Endotracheal:

  • Every three to five minutes, 1 to 2 mg.
  • Due to a loss of vagal innervation, atropine may not be effective in individuals who have had heart transplants.

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

  • Intravenous titrate administered in doses of 1 to 2 mg; repeat as necessary

Atropine Dose in the treatment of Neuromuscular blockade reversal:

  • A dose of 15 to 30 mcg/kg neostigmine given intravenously or

  • Given with edrophonium, 7 to 10 mcg/kg


Atropine dosage for treating poisoning from organophosphate, carbamate, pesticide, or nerve agent:

  • The recommended atropine dose varies greatly depending on the degree of intoxication.
  • Compared to organophosphate insecticide or nerve agent poisoning, the overall amount of atropine utilised for carbamate poisoning is often smaller.
  • Patients who have been severely poisoned may have a strong tolerance to atropine; occasionally, greater dosages may be required.
  • Titrate to pulmonary state (reduced bronchial secretions) and take into account giving atropine as a continuous IV infusion to patients who need high dosages of the medication.
  • The dose and/or dosing frequency can be lowered after the patient is stabilised.

Intravenous, Intramuscular, endotracheal:

  • First, 1 to 6 mg are administered.
  • Repeat as necessary every 3 to 5 minutes, doubling the amount if the prior dose failed to elicit a reaction.
  • If the symptoms return, repeat the dosage and continue for 2 to 12 hours.
  • Mild symptoms (≥2 mild symptoms):

    • As soon as exposure is known or highly suspected, provide 2 mg.
    • 10 minutes after the first dose, two further doses should be given quickly if severe symptoms persist after the first dose.
    • Give no more than three doses.
    • Further dosages of atropine should be avoided if strong anticholinergic effects are observed in the absence of significant bronchial secretions.
  • Severe symptoms (≥1 severe symptom):

    • Give three 2 mg dosages in quick succession starting right away.
  • Symptoms of insecticide or nerve agent poisoning :

    • Mild symptoms:

      • Chest Tightness
      • Coughing
      • Tremor
      • Vomiting
      • Wheezing
      • Drooling
      • Blurred Vision
      • Bradycardia
      • Breathing Difficulties
      • Nausea
      • Runny Nose
      • Salivation Increased
      • Stomach Cramps
      • Tachycardia
      • Miosis
      • Muscular Twitching
      • Teary Eyes
  • Severe symptoms:
    • Defecation (Involuntary)
    • Muscular Twitching/Generalized Weakness (Severe)
    • Breathing Difficulties (Severe)
    • Confused/Strange Behavior
    • Unconsciousness
    • Urination (Involuntary)
    • Respiratory Secretions (Severe)
    • Seizure
  • Intravenous Infusion:
    • Start a continuous intravenous infusion of 10% to 20% of the total loading dosage needed to elicit the target response per hour.
    • Then make the necessary adjustments to ensure a sufficient response without atropine toxicity.

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

  • You provide 0.01 to 0.02 mg/kg intravenously.
  • Minimum and maximum single doses are 0.1 mg and 0.5 mg, respectively.

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

  • Target is obtained when the intravenous dosage of 0.25 to 0.5 mg up to a total dose of 1 to 2 mg is administered.

Atropine Dose in Children

Atropine Dose in the treatment of Bradycardia:

  • Infants, Children, and Adolescents:

    • Intravenous, Intraosseous:

    • 0.02 mg/kg/dose is administered.
    • The smallest dosage is 0.1 mg per dose.
    • The maximum dosage per dose is 0.5 mg.
    • Use should only be made once every five minutes for individuals who do not respond to epinephrine and better oxygenation.
    • Endotracheal:

    • 0.04-0.06 mg/kg/dose is administered
    • Possibly once more if necessary

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

  • Infants and Children aged less than 12 yr:

    • Intramuscular, Intravenous, SubQ:

    • It contains 0.02 mg/kg.
    • The maximum dosage per dose is 0.5 mg.
    • Give the first dosage 30 to 60 minutes before operating, and then repeat as necessary every 4 to 6 hours.
    • One milligramme per operation is the maximum total dosage.
  • Children aged more than 12 years and Adolescents:

    • Intramuscular, Intravenous, SubQ:

    • 0.02 mg/kg/dose is administered.
    • There is a 1 mg/dose upper limit.
    • Preoperatively, provide the first dosage, and then repeat it every 4 to 6 hours as necessary.
    • The absolute maximum dosage is 2 mg per operation.

Atropine Premedication Dose in the emergency Intubation:

  • Atropine might be taken into consideration when there is a high risk of bradycardia, even though it is not frequently used as a pre-intubation drug in newborns and kids (eg, succinylcholine use)

    Infants and Children:

    • 0.02 mg/kg administered per dosage Intravenous
    • The maximum dosage per dose is 0.5 mg.
    • Due to the danger of bradycardia, it is often not advised for pre-intubation in babies and children.

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

  • Infants, Children, and Adolescents:

    • 0.02 mg/kg administered per dosage Intravenous
    • the 0.1 mg bare minimum.
    • Titrate, then repeat as necessary

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

  • Antidotal treatment should be administered as soon as symptoms start to manifest if exposure is known or suspected; do not wait for confirmation.
  • The amount of atropine that is needed depends on how bad the poisoning is.
  • Compared to the treatment of organophosphate pesticide or nerve agent poisoning, the total dosage of atropine administered to treat carbamate poisoning is often lower.
  • Patients who have been severely poisoned may have a strong atropine tolerance and need dosages that are two times higher than recommended.
  • Consider administering atropine by continuous intravenous infusion to individuals who require greater doses of the drug. Titrate to pulmonary status (decreased bronchial secretions).
  • Infants and Children:

    • Intravenous, Intramuscular, Intraosseous:

      • A dosage of 0.05 to 0.1 mg/kg is initially administered.
      • Then repeat as necessary every 5 to 10 minutes.
      • If the first dose does not result in atropinization, double it.
      • If symptoms return, continue atropinization by administering repeat doses as necessary for 2 to 12 hours.
    • Adolescents:

      • Intravenous, Intramuscular, Intraosseous:

        • At first, 1 to 3 mg/dose is administered.
          Repeat as necessary every 3 to 5 minutes after that.
        • If the first dose does not result in atropinization, double it.
        • In order to maintain atropinization, repeat doses should be given as necessary for 2 to 12 hours, depending on the return of symptoms.
  • Infants, Children, and Adolescents:

    • Continuous Intravenous infusion:

      • After atropinization, administer a continuous IV infusion of 10% to 20% of the total loading dosage used to cause atropinization per hour.
      • To maintain proper atropinization without harmful effects, make adjustments.
  • Infants, Children, and Adolescents:

    • Intramuscular (AtroPen): The number of dosages varies depending on the severity of the symptoms
    • Weight-directed dosing:

      • 7-18 kg (15-40 lb):

        • 0.5 mg/dose is given (blue pen)
      • less than 7 kg (less than 15 lb):

        • 0.25 mg/dose is given (yellow pen)
      • more than 41 kg (more than 90 lb):

        • 2 mg/dose is given (green pen)
      • more than 18-41 kg (more than 40-90 lb):

        • 1 mg/dose is given (dark red pen)
  • Mild symptoms (≥2 mild symptoms):

    • As soon as exposure is known or highly suspected, provide the weight-directed dosage as specified above.
    • Two extra doses should be administered quickly 10 minutes after the first dosage if severe symptoms persist after the initial dose.
    • Give no more than three doses.
    • Additional dosages of atropine should be avoided if significant anticholinergic effects develop without the presence of excessive bronchial secretions.
    • Mild symptoms of insecticide or nerve agent poisoning,  include:
      • Chest tightness
      • Coughing
      • Bradycardia
      • Breathing Difficulties
      • Drooling
      • Miosis
      • Salivation increased
      • Stomach cramps
      • Blurred Vision
      • Muscular Twitching
      • Nausea
      • Teary eyes
      • Tremor
      • Vomiting
      • Wheezing.
      • Runny nose
      • Tachycardia
  • Severe symptoms (≥1 severe symptom):

    • Give three weight-directed dosages in quick succession right away.
    • Insecticide or nerve agent overdose can cause severe symptoms like:
      • Defecation (involuntary)
      • Muscular twitching/generalized weakness 
      • Respiratory Secretions 
      • Breathing difficulties 
      • Confused/strange behaviour
      • Urination (involuntary)
      • Seizure
      • Unconsciousness
  • Infants who have muscular floppiness as opposed to muscle twitching may become sleepy or comatose.

Endotracheal:

  • The dosage should be two to three times that of intravenous administration.
    • After combining with 3 to 5 ml of ordinary saline, give.
    • Follow a 3 to 5 ml flush with normal saline by five-aided manual ventilations.

Atropine Pregnancy Risk Factor B/C

  • Adverse effects were not seen in animal reproductive trials.
  • Atropine crosses the placental barrier in humans.
  • Only after receiving a clear indication should pregnant women obtain antidotes.
  • They shouldn't be withheld out of concern that they could be teratogenic.
  • The same drugs that are prescribed for women who are not pregnant are also utilised to treat cardiac arrest in pregnant women.
  • You should base your treatment choices on the Advanced Cardiovascular Life Support Guidelines.
  • We must not withhold necessary drugs due to worries about embryonic teratogenicity.

Atropine use during breastfeeding:

  • Atropine is not found in very much breast milk.
  • Atropine can affect breastfeeding infants by reducing or causing issues with lactation.
  • The producer advises women who are nursing to use atropine with caution.

Atropine dose in kidney disease:

  • The labelling provided by the manufacturer does not mention dose modifications.

Atropine dose in liver disease:

  • The labelling provided by the manufacturer does not mention dose modifications.

Side effects of atropine:

  • Cardiovascular:

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

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

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

    • Dehydration
    • Hyperglycemia
    • Hypoglycemia
    • Hypokalemia
    • Hyponatremia
    • Increased Thirst
    • Loss Of Libido
  • Neuromuscular & Skeletal:

    • Laryngospasm
    • Muscle Twitching
    • Weakness
  • Gastrointestinal:

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

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

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

    • Injection Site Reaction
  • Hematologic & Oncologic:

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

    • Hypersensitivity Reaction
  • 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

Contraindications to Atropine:

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

Warnings and precaution

 

  • Anaphylaxis

    • Can occur.
  • Arrhythmias:

    • Avoid depending on atropine for type II second-degree and third-degree AV blockages (with or without a broad QRS complex).
    • Routine usage is not advised in bradycardic PEA and asystole.
  • Hyperthermia

    • Hyperthermia can be caused by high ambient temperatures.
  • Psychosis:

    • Psychosis may develop in sensitive individuals or following heavy usage.
  • Autonomic neuropathy:

    • Autonomic neuropathy patients need to exercise caution.
  • Gastrointestinal Disease:

    • It could result in organic pyloric partial blockage.
    • The elderly or those with disabilities who have intestinal atony, paralytic ileus, or severe ulcerative colitis should not use this medication.
  • Cardiovascular disease

    • Patients who have hypertension, myocardial ischemia, cardiac illness, tachyarrhythmias (especially sin tachycardia), or heart failure should exercise caution.
    • Blood pressure increases brought on by tachycardia may result in ischemia, MI, or an increase in arrhythmogenic potential.
  • 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 reflux esophagitis and hiatal hernia should exercise caution.
  • 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.
    • Atropine's effects might be prolonged in cases of severe renal impairment.
  • Respiratory impairment

    • The bronchial secretions of patients with chronic lung illness may thicken or viscid clog.
  • Urinary retention

    • Complete urine retention may occur in prostatic hypertrophy patients.
    • If at all possible, patients with obstructive or other diseases that result in urine retention should refrain from taking it.

Monitor:

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

Organophosphate or carbamate insecticide or nerve agent poisoning:

  • Blood pressure, respiratory condition, oxygenation secretions, and heart rate.
  • Recurring doses in accordance with the clinical state will maintain atropinization.
  • An inadequate dose is indicated by crackles in the lung bases or a continuance of cholinergic symptoms.
  • The healing of the lungs does not coincide with other atropinization symptoms.
  • Look for the warning signs and symptoms of atropine toxicity, such as fever, confusion, and muscular fasciculations.
  • If toxicity develops, stop taking atropine and keep a careful eye on the patient.

How to administer Atropine?

Intramuscular: AtroPen:

  • Apply it on the outside of the thigh.
  • Remove the yellow safety release (0.5 mg, 1 mg, and 2 mg autoinjector) or grey safety release by firmly grasping the autoinjector with the green tip (0.5 mg, 1 mg, and 2 mg autoinjector) or black tip (0.25 mg autoinjector) pointing downward (0.25 autoinjector).
  • At a 90° angle, whack the green tip on the outer thigh.
  • As long as the pockets closest to the injection site are free of objects, it can be given via clothes.
  • Bunch up the thigh before the injection in thin people.
  • After the injection, keep the autoinjector in place for 10 seconds before removing it and massaging the injection site.
  • The needle will be visible after administration; if it is not, repeat the previous procedure.
  • To prevent inadvertent harm, bend the needle after usage against a hard surface (the needle does not retract).

Intravenous:

  • Give an intravenous infusion quickly and without dilution.
  • It's possible for a gradual injection to cause paradoxical bradycardia.
  • When treating individuals with bradycardia with external pacing, atropine delivery shouldn't be postponed.

Intraosseous (IO):

  • If necessary, it can be given intraosseously.

Endotracheal:

  • Add 10 mL of sterile water or NS to dilute.
  • With sterile water, absorption can be increased.
  • During CPR, halt compressions and swiftly spray the medication down the tube.
  • Continue chest compressions and provide numerous fast insufflations after that.

SubQ

  •  May administer subcutaneously if needed.

Mechanism of action of Atropine:

  • It stops acetylcholine from functioning at parasympathetic sites in smooth muscle, secretory tissue, and the central nervous system.
  • Both the cardiac output and secretion drying are increased.
  • Atropine blocks the muscarinic effects of cholinergic poisoning by acting as a competitive antagonist to acetylcholinesterase inhibitor actions.
  • The main goal of cholinergic poisonings is to relieve bronchospasm or bronchorrhea.
  • The nicotinic nerves, which are in charge of paralysis, muscular weakness, fasciculations, and paralysis, remain unaffected.

The onset of action:

Duration:

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

Increased heart rate: Intramuscular:

  • Within 15-30 mins
  • The greatest effect is seen after 45-60 mins

Inhibition of salivation: Intramuscular:

  • Within 30 mins
  • The greatest effect is seen in 30-60 minutes

Intravenous: Immediate;

  • The greatest effect is seen in  0.7-4 mins

Absorption:

  • Rapid and well absorbed from all dosage forms

Protein binding:

  • 14% - 44%

Distribution:

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

Metabolism:

  • Hepatic route via enzymatic hydrolysis

Half-life elimination:

  • Children under 2 years: 6.9hrs
  • Children over 2 years: 2.5hrs
  • Adults: 3hrs
  • Elderly 65-75 years of age: 10hrs

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

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