Action and Spectrum

Actions and Spectrum:

atropine and pralidoxime are two drugs commonly used in managing organophosphate poisoning, which can occur due to exposure to certain insecticides, herbicides, and nerve gases. atropine is a competitive antagonist of acetylcholine at muscarinic receptors. In cases of organophosphate poisoning, the excess acetylcholine leads to excessive stimulation of these receptors, causing symptoms such as

salivation, lacrimation, urination, defecation, and bradycardia. atropine acts by blocking these receptors, thereby reducing the cholinergic effects of acetylcholine. This results in a reversal of some of the symptoms of organophosphate poisoning, particularly those related to the parasympathetic nervous system, such as bradycardia, bronchospasm, and excessive secretions. pralidoxime, on the other hand, is a cholinesterase reactivator.

It works by binding to the organophosphate-inhibited acetylcholinesterase enzyme and displacing the organophosphate molecule. This allows the enzyme to regain its normal function of breaking down acetylcholine, reducing the excess acetylcholine levels that lead to symptoms of organophosphate poisoning. pralidoxime is effective only if administered within a few hours of exposure to the organophosphate before the organophosphate has irreversibly bound to the acetylcholinesterase enzyme.

Drug Interaction

Adverse Reaction

Frequency not defined

Reaction at the injection site (pain, muscle tightness)

Atropine

Blurred vision

Photophobia

Headache

Dizziness

Dry mouth

Dry eyes

Confusion

Pralidoxime

Dizziness, headache

Nausea

Increased blood pressure

Dry mouth

Rash

Decreased renal function

Transient elevation of LFTs

Vision changes

Drowsiness

Tachycardia

Muscular weakness

Emesis

Dry skin

Hyperventilation

Manic behavior

Black Box Warning

None

Contraindication / Caution

Contraindications/caution:

Contraindications:

None

Caution:

• Allergies: Both atropine and pralidoxime can cause allergic reactions in some individuals. Caution should be exercised in patients with known allergies to these medications or related substances. Signs of an allergic reaction may include rash, itching, swelling, difficulty breathing, or severe dizziness.
• Dose and Administration: The appropriate dosage and route of administration of atropine and pralidoxime should be carefully followed per the specific guidelines and recommendations of the treating physician or medical professional. Overdose or incorrect administration can result in adverse effects.
• Side Effects: atropine and pralidoxime can cause various side effects, including dry mouth, blurred vision, increased heart rate, urinary retention, constipation, and confusion. Elderly patients and patients with pre-existing medical conditions, such as glaucoma, urinary retention, or cardiovascular disease, may be more susceptible to these side effects. Close monitoring is necessary, and dose adjustments may be required.
• Drug Interactions: atropine and pralidoxime may interact with other medications, potentially leading to adverse effects or reduced effectiveness. To avoid potential drug interactions, it is essential to inform the treating physician or medical professional about all other medications being taken, including prescription, over-the-counter, and herbal supplements.
• Pregnancy and Breastfeeding: The safety of atropine and pralidoxime during pregnancy and breastfeeding is not well established.
• Timing of Administration: pralidoxime is most effective when administered early, within a few hours of organophosphate exposure, before irreversible binding of the organophosphate to acetylcholinesterase occurs. Delayed administration of pralidoxime may result in reduced effectiveness.
• Underlying Medical Conditions: atropine and pralidoxime may not be appropriate for all patients, particularly those with certain underlying medical conditions such as glaucoma, myasthenia gravis, or cardiac arrhythmias. Close monitoring and caution are required in such cases.

Individual Variability: Response to atropine and pralidoxime can vary among individuals. Dosing and administration should be tailored to the patient’s specific needs, considering factors such as age, weight, and severity of poisoning.

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available

Lactation: Excretion of the drug in human breast milk is unknown

Pregnancy category:

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:

atropine is a competitive antagonist of acetylcholine at muscarinic receptors. It binds to the muscarinic receptors in place of acetylcholine, thereby blocking the effects of excess acetylcholine. At therapeutic doses, atropine predominantly affects the parasympathetic nervous system, resulting in dilation of the pupils, inhibition of salivation and secretion, and relaxation of bronchial smooth muscle. It also has cardiovascular effects, including increased heart rate and cardiac output.

pralidoxime is a cholinesterase reactivator that binds to the organophosphate-inhibited acetylcholinesterase enzyme and displaces the organophosphate molecule. This allows the enzyme to regain its normal function of breaking down acetylcholine, reducing the excess acetylcholine levels that lead to symptoms of organophosphate poisoning.

Pharmacodynamics:

atropine is a competitive antagonist of acetylcholine at muscarinic receptors located in various organs and tissues throughout the body. By binding to these receptors, atropine blocks the effects of excess acetylcholine, released due to the inhibition of acetylcholinesterase by organophosphates. This results in the following pharmacodynamic effects:

• Muscarinic receptor blockade: atropine antagonizes the muscarinic receptors in various organs, leading to the relaxation of smooth muscles, including bronchial smooth muscle, resulting in bronchodilation. It also inhibits salivary and sweat gland secretions, leading to dry mouth and decreased sweating. atropine also causes pupillary dilation by blocking the muscarinic receptors in the iris sphincter muscle, resulting in mydriasis (dilated pupils).
• Cardiovascular effects: atropine increases heart rate by blocking the inhibitory effect of acetylcholine on the cardiac muscarinic receptors, resulting in increased heart rate and cardiac output. It can also cause mild vasodilation, which may result in a slight decrease in blood pressure.

pralidoxime reactivates the inhibited acetylcholinesterase enzyme, which is essential for breaking acetylcholine. The pharmacodynamic effects of pralidoxime include:

• Reactivation of acetylcholinesterase: pralidoxime binds to the organophosphate-inhibited acetylcholinesterase enzyme, displacing the organophosphate molecule and allowing the enzyme to regain its normal function of breaking down acetylcholine. This helps to restore standard cholinergic transmission and reduce the excess acetylcholine levels that lead to symptoms of organophosphate poisoning.
• Limited central nervous system penetration: pralidoxime cannot penetrate the blood-brain barrier, so its effects are mainly peripheral, targeting acetylcholinesterase in the peripheral nervous system, such as neuromuscular junctions, and not the central nervous system.

Pharmacokinetics:

Absorption

atropine is well-absorbed after oral, intramuscular, or intravenous administration. The onset of action is usually rapid, with peak effects occurring 30-60 minutes after intramuscular injection and 5-10 minutes after intravenous injection. pralidoxime is rapidly absorbed after intravenous or intramuscular injection, with peak plasma concentrations reached within 10-30 minutes after injection.

Distribution

atropine is distributed widely throughout the body, including the central nervous system, due to its ability to cross the blood-brain barrier. It is also highly protein-bound, which limits its distribution to tissues. pralidoxime is distributed widely throughout the body, including the central nervous system. Still, its ability to penetrate the blood-brain barrier is limited. It is also highly protein-bound, which limits its distribution to tissues.

Metabolism

atropine is metabolized primarily in the liver by hydrolysis, and the metabolites are excreted in the urine. The half-life of atropine is relatively short, ranging from 2-4 hours, depending on the dosage and route of administration.

Hydrolysis metabolizes pralidoxime in the liver, and the metabolites are excreted in the urine. The half-life of pralidoxime is relatively short, ranging from 1-2 hours, depending on the dosage and route of administration.

Elimination and Excretion

atropine and its metabolites are eliminated primarily through renal excretion, with a small amount excreted in the feces.

pralidoxime and its metabolites are eliminated primarily through renal excretion.

Adminstartion

Administration:

• Route of administration: atropine can be administered intravenously (IV), intramuscularly (IM), or subcutaneously (SC). IV administration is preferred for severe cases, while IM or SC administration can be used if IV access is not readily available. pralidoxime is typically administered intravenously (IV) for severe cases of organophosphate poisoning.
• Dosage: The dosage of atropine is typically based on the severity of symptoms and the patient’s weight. The initial adult dose is usually 2 to 5 mg IV, repeated every 5 to 10 minutes until symptoms improve or the desired effect is achieved. The maximum total dose of atropine for adults is typically 100 mg in 24 hours. The dosage of pralidoxime is typically based on the severity of the poisoning and the patient’s weight. The usual adult dose is 1 to 2 grams IV over 15 to 30 minutes, followed by a continuous infusion of 0.5 to 1 gram per hour. The total duration of pralidoxime therapy may vary depending on the severity of the poisoning.

Titration: atropine should be titrated carefully to avoid over-dosage, especially in elderly patients or those with pre-existing cardiovascular conditions. The goal is to relieve symptoms of excess acetylcholine without causing excessive anticholinergic side effects, such as dry mouth, tachycardia, or urinary retention. pralidoxime should be closely monitored for signs of adverse effects, such as hypersensitivity or infusion site reactions.

Patient Information Leaflet

Patient information leaflet

Generic Name: atropine and pralidoxime

Why do we use atropine and pralidoxime?

atropine and pralidoxime are medications used to manage organophosphate poisoning, which can occur due to exposure to certain insecticides, pesticides, or nerve agents. Both drugs have specific uses in the treatment of organophosphate poisoning as follows:

atropine:

• Antidote for organophosphate poisoning: atropine is used to manage organophosphate poisoning. It works by blocking the action of acetylcholine, a neurotransmitter that is excessively released in cases of organophosphate poisoning, leading to cholinergic overstimulation. atropine acts as a competitive antagonist to acetylcholine receptors, reducing excess acetylcholine symptoms and helping restore normal physiological function.
• Symptomatic relief of cholinergic symptoms: atropine is also used to relieve cholinergic symptoms such as excess salivation, bronchoconstriction, miosis (pupil constriction), bradycardia (slow heart rate), and gastrointestinal hyperactivity that can occur in cases of organophosphate poisoning.

pralidoxime:

• Reactivation of acetylcholinesterase: pralidoxime, also known as 2-PAM (2-pyridine aldoxime methyl chloride), is used as an antidote in organophosphate poisoning to reactivate acetylcholinesterase, the enzyme that is inhibited by organophosphates. pralidoxime works by binding to the enzyme and displacing the organophosphate, allowing acetylcholinesterase to regain its regular activity and break down acetylcholine, which helps to restore normal neuromuscular function.

Treatment of muscarinic and nicotinic symptoms: pralidoxime is also used to treat the muscarinic and nicotinic symptoms associated with organophosphate poisonings, such as excess salivation, bronchoconstriction, muscle weakness, and paralysis.