CROPINE

Injection, USP is a sterile, nonpyrogenic isotonic solution of atropine sulfate monohydrate in water for injection with sodium chloride sufficient to render the solution isotonic.

It is administered parenterally by intravenous injection.

Each milliliter (mL) contains 0.4 mg or 1 mg of atropine sulfate monohydrate equivalent to 0.332 mg or 0.83 mg of atropine, and sodium chloride, 9 mg. May contain sodium hydroxide and/or sulfuric acid for pH adjustment. 0.308 mOsmol/mL (calc). pH (3.0 to 5.0).

The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended for use only as a single-dose injection.

When smaller doses are required the unused portion should be discarded.

Sulfate, USP is chemically designated 1α H, 5α H-Tropan-3-α-ol (±)-tropate (ester), sulfate (2:1) (salt) monohydrate, (C17H23NO3)2 ∙ H2SO4 ∙ H2O, colorless crystals or white crystalline powder very soluble in water.

It has the following structural formula

Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d.

• and 1-hyocyamine, whose activity is due almost entirely to the levo isomer of the drug.

& USAGE Atropine Sulfate Injection, USP, is indicated for temporary blockade of severe or life threatening muscarinic effects, e.g., as an antisialagogue, an antivagal agent, an antidote for organophosphorus or muscarinic mushroom poisoning, and to treat bradyasystolic cardiac arrest.

Arrhythmia Intestinal atony of the elderly High degree atrial cell Chronic Bronchitis Diarrhoea Child under 15 years of age Unstable cardiovascular condition Fever Hypertension Hyperthyroidism Benign prostate hypertrophy Congestive heart failure Coronary heart failure Hepatic impairment Renal impairment Cardiac surgery Parkinson's disease Myasthenia Infants under 30 months of age Esophagitis due to gastroesophageal reflux Brain pathology Elderly Subject over 40 years Subject subject to high heat Down syndrome Tachyarrhythmia Tachycardia.

Atropine is an antimuscarinic agent since it antagonizes the muscarine-like actions of acetylcholine and other choline esters.

Atropine inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves, and on smooth muscles which respond to endogenous acetylcholine but are not so innervated.

As with other antimuscarinic agents, the major action of atropine is a competitive or surmountable antagonism which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g., by using anticholinesterase agents which inhibit the enzymatic destruction of acetylcholine).

The receptors antagonized by atropine are the peripheral structures that are stimulated or inhibited by muscarine (i.e., exocrine glands and smooth and cardiac muscle).

Responses to postganglionic cholinergic nerve stimulation also may be inhibited by atropine, but this occurs less readily than with responses to injected (exogenous) choline esters. 12.2 Pharmacodynamics Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control.

Atropine exerts a more potent and prolonged effect on heart, intestine and bronchial muscle than scopolamine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of scopolamine.

Unlike the latter, atropine in clinical doses does not depress the central nervous system but may stimulate the medulla and higher cerebral centers.

Although mild vagal excitation occurs, the increased respiratory rate and (sometimes) increased depth of respiration produced by atropine are more probably the result of bronchiolar dilatation.

Accordingly, atropine is an unreliable respiratory stimulant and large or repeated doses may depress respiration.

Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole.

The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus.

Atropine also may lessen the degree of partial heart block when vagal activity is an etiologic factor.

In some patients with complete heart block, the idioventricular rate may be accelerated by atropine; in others, the rate is stabilized.

Occasionally a large dose may cause atrioventricular (A-V) block and nodal rhythm.

Injection, USP in clinical doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters.

However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure.

Systemic doses slightly raise systolic and lower diastolic pressures and can produce significant postural hypotension.

Such doses also slightly increase cardiac output and decrease central venous pressure.

Occasionally, therapeutic doses dilate cutaneous blood vessels, particularly in the "blush" area (atropine flush), and may cause atropine "fever" due to suppression of sweat gland activity in infants and small children.

The effects of intravenous atropine on heart rate (maximum heart rate) and saliva flow (minimum flow) after intravenous administration (rapid, constant infusion over 3 min). are delayed by to 8 minutes after drug administration and both effects are non-linearly related to the amount of drug in the peripheral compartment.

Changes in plasma atropine levels following intramuscular administration (0.5 to 4 mg doses) and heart rate are closely overlapped but the time course of the changes in atropine levels and behavioral impairment indicates that pharmacokinetics is not the primary rate-limiting mechanism for the central nervous system effect of atropine. 12.3 Pharmacokinetics Atropine disappears rapidly from the blood following injection and is distributed throughout the body.

Exercise, both prior to and immediately following intramuscular administration of atropine, significantly increases the absorption of atropine due to increased perfusion in the muscle and significantly decreases the clearance of atropine.

The pharmacokinetics of atropine is nonlinear after intravenous administration of 0.5 to 4 mg. Atropine's plasma protein binding is about 44% and saturable in the to 20 mcg/mL concentration range.

Atropine readily crosses the placental barrier and enters the fetal circulation, but is not found in amniotic fluid.

Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from to 50% is excreted unchanged in the urine.

Traces are found in various secretions, including milk.

The major metabolites of atropine are noratropine, atropin-n-oxide, tropine, and tropic acid.

The metabolism of atropine is inhibited by organophosphate pesticides.

The elimination half-life of atropine is more than doubled in children under two years and the elderly (>65 years old) compared to other age groups.

There is no gender effect on the pharmacokinetics and pharmacodynamics (heart rate changes) of atropine.

Mechanism of action

L-atropine is an antispasmodic.

It is competitively opposed to the muscarinic effects of acetylcholine.

Spasmolytic, l-atropine is an antidote of anticholinesterases.

By ophthalmic way: atropine blocks responses to cholinergic stimulations of the irian sphincter and the ciliary muscle responsible for accommodation.

It thus produces dilatation of the pupil (mydriase) and paralysis of the accommodation (cycloplegia).

• Anhidrosis (Very common)
• Rash (Very common)
• Urticaria (Very common)
• Dry skin Hyperthermia (Common)
• Anaphylactic reaction (Common)
• Hypersensitivity (Rare)
• Dysphagia (Common)
• Polydipsy
• Vision disorder (Very common)
• Glaucoma (Common)
• Mydriase Blurty vision Photophobia
• Accommodation disorder Lacrymal hyposecretion Vertigo (Uncommon)
• Dysgueusia (Very common)
• Nasal congestion (Uncommon)
• Hyposialia Psychotic episode (Uncommon)
• Hallucination (Common)
• Agitation Irritability Mental confusion Insomnia Hot flash (Common)
• Bradycardia (Common)
• Ventricular fibrillation (Very rare)
• Angor (Very rare)
• Hypertensive crisis (Very rare)
• Palpitation Bradycardia (exacerbation)
• Tachycardia Arrhythmia Gastroesophageal reflux (Very common)
• Parasympathic inhibition of the gastrointestinal tract (Very common)
• Vomiting (Common)
• Nausea (Very common)
• Ball-down (Very common)
• Paralytic ileus (Common)
• Constipation
• Glutation disorder Gastric hyposecretion Ataxia (Common)
• Convulsions (Rare)
• Somnolence (Rare)
• Headache Speech Disorder Bronchial hyposecretion (Very common)
• Hyperviscosity of bronchial secretions
• Inhibition of parasympathetic bladder control (Common)
• Impower (Uncommon)
• Urinary retention
• Dysuria.

Excessive dosing may cause palpitation, dilated pupils, difficulty in swallowing, hot dry skin, thirst, dizziness, restlessness, tremor, fatigue and ataxia.

Toxic doses lead to restlessness and excitement, hallucinations, delirium and coma.

Depression and circulatory collapse occur only with severe intoxication.

In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma.

The fatal adult dose of atropine is not known.

In pediatric populations, 10 mg or less may be fatal.

In the event of toxic overdosage, a short acting barbiturate or diazepam may be given as needed to control marked excitement and convulsions.

Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in atropine poisoning.

Central stimulants are not recommended.

Physostigmine, given as an atropine antidote by slow intravenous injection of to 4 mg (0.5 to 1 mg in pediatric populations), rapidly abolishes delirium and coma caused by large doses of atropine.

Since physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and repeated doses may be required.

Artificial respiration with oxygen may be necessary.

Ice bags and alcohol sponges help to reduce fever, especially in pediatric populations.

Atropine is not removed by dialysis.

& ADMINISTRATION 2.1 General Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not administer unless solution is clear and seal is intact.

Each vial is intended for single dose only.

Discard unused portion.

Intravenous administration.

Titrate based on heart rate, PR interval, blood pressure and symptoms. 2.2 Adult Dosage 2.3 Pediatric Dosage Dosing in pediatric populations has not been well studied.

Usual initial dose is 0.01 to 0.03 mg/kg. 2.4 Dosing in Patients with Coronary Artery Disease Limit the total dose of atropine sulfate to 0.03 to 0.04 mg/kg.

Injection, USP 1 mg/mL is supplied in 1 mL, single-dose glass vial.

NDC 51662-1626-1 ATROPINE SULFATE INJECTION, USP 1mg/mL 1mL VIAL Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C and 30°C (59°F and 86°F).

LLC, DBA HealthFirst 11629 49th Pl W. Mukilteo, WA 98275.