Atropine and pralidoxime

• It is used to treat poisoning from nerve gas or chemicals that kill insects.

In the face of life-threatening poisoning by organophosphorous nerve agents, there are no absolute contraindications for the use of the ATNAA (see WARNINGS).

Symptoms:

Atropine

Serious overdosage with atropine is characterized by widespread paralysis of parasympathetically innervated organs. Dry mucous membranes, widely dilated and nonresponsive pupils, tachycardia, fever, and cutaneous flush are especially prominent, as are mental and neurological symptoms.

Disorientation, mania, hallucinations, gait disturbances, and symptoms may last 48 hours or longer. In instances of severe intoxication, respiratory depression, coma, circulatory collapse, and death may occur.

The fatal dose of atropine is not known. In the treatment of organophosphorous poisoning, 200 mg doses have been used and doses as high as 1000 mg have been given.

In children, 10 mg or less may be fatal. With a dose as low as 0.5 mg, undesirable minimal symptoms or responses of overdosage may occur. These increase in severity and extent with larger doses of the drug (excitement, hallucinations, delirium, and coma with a dose of 10 mg or more). However, in the presence of organophosphate poisoning, higher doses of atropine may be tolerated.

Pralidoxime Chloride

Symptoms of pralidoxime chloride overdose have been observed in normal subjects only: dizziness, blurred vision, diplopia, headache, impaired accommodation, nausea, slight tachycardia. In therapy it has been difficult to differentiate side effects due to the drug from those due to effects of the poison.

Treatment:

Supportive treatment should be administered as indicated. If respiration is depressed, artificial respiration with oxygen is necessary. Ice bags, alcohol sponges or a hypothermia blanket may be required to reduce fever, especially in children. Catheterization may be necessary if urinary retention occurs. Since atropine elimination takes place through the kidney, urinary output must be maintained and increased if possible; intravenous fluids may be indicated. Because of the affected person's photophobia, the room should be darkened.

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 1 to 4 mg (0.5 to 1.0 mg in children), rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine has a short duration of action, the patient may again lapse into coma after one or two hours and repeated doses are likely to be required.

Neostigmine, pilocarpine, and methacholine are of little real benefit, since they do not penetrate the blood-brain barrier.

(A troe peen & pra li DOKS eem)

Atropine: Functions as a competitive antagonist of acetylcholine at muscarinic receptors in the peripheral and central nervous system, thus reducing the symptoms of parasympathetic overstimulation resulting from excess acetylcholine caused by organophosphate insecticide or nerve agent poisoning. The parasympatholytic action of atropine decreases oral and respiratory secretions, relieves airway constriction, and attenuates the bradycardia induced by organophosphate insecticides and nerve agents. Antagonizes acetylcholine accumulation at respiratory center and may reduce centrally-mediated respiratory paralysis.

Pralidoxime: An oxime which functions by way of nucleophilic attack on the ester site of the acetylcholinesterase enzyme which has been deactivated by phosphorylation. Displacement of the phosphoryl group allows reactivation of acetylcholinesterase’s hydrolytic activity, thus permitting renewed catalysis of accumulated acetylcholine. Destruction of accumulated acetylcholine allows for restoration of normal functioning at neuromuscular junctions and relief from respiratory muscle paralysis.

Organophosphate insecticide or nerve agent poisoning: IM: Note: If exposure is suspected, antidotal therapy should be given immediately as soon as symptoms appear (critical to administer immediately in case of soman exposure since its adverse effects develop within minutes). Definitive medical care should be sought after any injection given. One injection only may be given as self-aid. If repeat injections are needed, administration must be done by another trained individual. Emergency medical personnel who have self-administered a dose must determine their capacity to continue to provide care.

ATNAA:

Mild symptoms (some or all mild symptoms): Self-Aid or Buddy-Aid: 1 injection (wait 10-15 minutes for effect); if the patient is able to ambulate, and knows who and where they are, then no further injections are needed. If symptoms are still present: Buddy-Aid: May repeat 1-2 more injections

Severe symptoms (if most or all): Buddy-Aid: If no self-aid given, 3 injections in rapid succession; if 1 self-aid injection given, 2 injections in rapid succession

Maximum cumulative dose: 3 injections

Symptoms of organophosphate insecticide or nerve agent poisoning, as provided by manufacturer in the ATNAA product labeling to guide therapy:

Mild symptoms: Breathing difficulties, chest tightness, coughing, difficulty in seeing, drooling, headache, localized sweating and muscular twitching, miosis, nausea (with or without vomiting), runny nose, stomach cramps, tachycardia (followed by bradycardia), wheezing

Severe symptoms: Bradycardia, confused/strange behavior, convulsions, increased wheezing and breathing difficulties, involuntary urination/defecation, miosis (severe), muscular twitching/generalized weakness (severe), red/teary eyes, respiratory failure, unconsciousness, vomiting

Duodote:

Mild symptoms (≥2 mild symptoms): 1 injection (wait 10-15 minutes for effect); if after 10-15 minutes no severe symptoms emerge, no further injections are indicated; if any severe symptoms emerge at any point following initial injection, repeat dose by giving 2 additional injections in rapid succession. Transport to medical care facility.

Severe symptoms (≥1 severe symptom): 3 injections in rapid succession. Transport to medical care facility.

Maximum cumulative dose: 3 injections unless medical care support (eg, hospital, respiratory support) is available

Symptoms of organophosphate insecticide or nerve agent poisoning, as provided by manufacturer in the Duodote™ product labeling to guide therapy:

Mild symptoms: Airway secretions increased, blurred vision, bradycardia, breathing difficulties, chest tightness, drooling miosis, nausea, vomiting, runny nose, salivation, stomach cramps (acute onset), tachycardia, teary eyes, tremors/muscular twitching, wheezing/coughing

Severe symptoms: Breathing difficulties (severe), confused/strange behavior, convulsions, copious secretions from lung or airway, involuntary urination/defecation, muscular twitching/generalized weakness (severe)

Concerns related to adverse effects:

• Atropinization: Signs of atropinization (eg, flushing, mydriasis, tachycardia, dryness of mouth or nose) may occur earlier than expected with the use of a combination product as compared to atropine alone. Monitor effects closely when administering subsequent injections as necessary. The presence of these effects is not indicative of the success of therapy. Reversal of bronchial secretions is the preferred indicator of success.

• Hyperthermia: Atropine may inhibit sweating and possibly lead to heat-related injury or hyperthermia in patients exposed to warm environments or exercise.

Disease-related concerns: The following diseases are relative precautions only when symptoms of poisoning are not severe:

• Cardiovascular disease: Use with caution in patients with heart disease, arrhythmias (eg, atrial flutter), severe CAD, or history of recent MI; treatment-related blood pressure increases and tachycardia may lead to ischemia, precipitate an MI, or increase arrhythmogenic potential.

• Chronic lung disease: Use with caution in patients with chronic lung disease patients; may cause inspiration of bronchial secretions and formation of dangerous viscid plugs.

• Hepatic impairment: Use with caution in patients with hepatic impairment; effects of atropine may be prolonged in severe hepatic impairment.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may precipitate myasthenic crisis.

• Narrow-angle glaucoma: Use with caution in patients with severe narrow-angle glaucoma; may precipitate acute glaucoma.

• Prostatic hyperplasia: Use with caution in patients with prostatic hyperplasia; may cause urinary retention.

• Pyloric stenosis: Use with caution in patients with pyloric stenosis; may cause complete pyloric obstruction.

• Renal impairment: Use with caution in renal impairment; pralidoxime is excreted renally and the effects of atropine may be prolonged in severe renal impairment.

Special populations:

• Elderly: Elderly patients may be more sensitive to the anticholinergic effects of atropine.

• Pediatric: Children may be more sensitive to the anticholinergic effects of atropine.

Other warnings/precautions:

• Appropriate use: Clinical symptoms consistent with highly-suspected organophosphate insecticide or nerve agent poisoning should be treated with antidote immediately; administration should not be delayed for confirmatory laboratory tests. Treatment should always include proper evacuation and decontamination procedures; medical personnel should protect themselves from inadvertent contamination. Antidotal administration is intended only for initial management; definitive and more extensive medical care is required following administration. Individuals should not rely solely on antidote for treatment, as other supportive measures (eg, artificial respiration) may still be required. Continued administration of additional doses in asymptomatic patients may result in atropine toxicity.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience muscle rigidity, injection site pain, nasal dryness, vision changes, dry eyes, sensitivity to light, enlarged pupils, dizziness, flushing, constipation, abdominal pain, stomach edema, nausea, vomiting, lack of sweating, fatigue, muscle weakness, dry skin, or dry mouth. Have patient report immediately to prescriber fast breathing, severe dizziness, severe headache, confusion, difficult urination, decreased libido, passing out, sexual dysfunction, urinary retention, change in amount of urine passed, abnormal heartbeat, angina, or tachycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

Data not available

No more than three doses of atropine-pralidoxime (DuoDote) should be administered unless definitive medical care (e.g., hospitalization, respiratory support) is available.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).