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Cholinergic medications are a category of pharmaceutical agents that act upon the neurotransmitter acetylcholine, the primary neurotransmitter within the parasympathetic nervous system (PNS). There are two broad categories of cholinergic drugs: direct-acting and indirect-acting. The direct-acting cholinergic agonists work by directly binding to and activating the muscarinic receptors. Examples of direct-acting cholinergic agents include choline esters (acetylcholine, methacholine, carbachol, bethanechol) and alkaloids (muscarine, pilocarpine, cevimeline). Indirect-acting cholinergic agents increase the availability of acetylcholine at the cholinergic receptors. These include reversible agents (physostigmine, neostigmine, pyridostigmine, edrophonium, rivastigmine, donepezil, galantamine) and irreversible agents (echothiophate, parathion, malathion, diazinon, sarin, soman). This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of cholinergic agents, which is a topic of significant complexity and with far-reaching clinical implications, as is pertinent for members of the interprofessional team in dealing with the effects of these agents, both therapeutic and toxic. Objectives: Outline indications for cholinergic medications. Summarize the presentation of a patient with cholinergic medication toxicity. Describe the potential contraindications for cholinergic drugs. Review the importance of improving care coordination amongst interprofessional team members to improve outcomes for employees who handle organophosphates or patients receiving cholinergic medications. Access free multiple choice questions on this topic.

Anticholinesterases are readily available and extensively used as agricultural, and household insecticides (malathion, parathion); accidental as well as suicidal and homicidal poisoning is common, which may present as severe cholinergic toxicity following ingestion or cutaneous exposure to the substances.[10][11] Some of these agents have also seen use in chemical warfare, such as nerve gases (sarin, soman). Anticholinesterases have medical use for the treatment of myasthenia gravis, reversal of neuromuscular blockade, Alzheimer disease. Acute toxicity from organophosphate agents presents with manifestations of cholinergic excess. Primary toxic effects involve the neuromuscular junction, autonomic nervous system, and the central nervous system. The clinical features of acute cholinergic toxicity include miosis, salivation, lacrimation, emesis, bradycardia, bronchospasm, bronchorrhea, urination, and diarrhea. Sympathetic activation of postganglionic muscarinic receptors regulates the sweat glands causing diaphoresis. As sympathetic ganglia contain nicotinic receptors, at times, however, mydriasis and tachycardia may be observed. The nicotinic effects include muscle weakness, fasciculations, and paralysis through acetylcholine stimulation of receptors at the neuromuscular junction. Muscarinic and nicotinic receptors have been identified in the brain also and may contribute to lethargy, seizures, central respiratory depression, and coma. Cardiac arrhythmias, including QTc prolongation and heart block, are sometimes observed in organophosphorus agent poisoning. Mortality from acute poisoning generally results from respiratory failure due to a combination of neuromuscular weakness, depression of the CNS respiratory center, bronchoconstriction, and excessive respiratory secretions. Oxidative stress causes overstimulation of the cholinergic and glutamatergic nervous system, causing some chronic adverse health effects.[12][13] Organophosphorus agents bind to acetylcholinesterase and turn the enzyme non-functional. The acetylcholinesterase-organophosphorus compound becomes resistant to reactivation by antidote after some time, a process known as 'aging.'[14] Hence, the treatment should initiate as early as possible. Intoxication Management

Acute toxicity from organophosphate agents presents with manifestations of cholinergic excess. Primary toxic effects involve the neuromuscular junction, autonomic nervous system, and the central nervous system. The clinical features of acute cholinergic toxicity include miosis, salivation, lacrimation, emesis, bradycardia, bronchospasm, bronchorrhea, urination, and diarrhea. Sympathetic activation of postganglionic muscarinic receptors regulates the sweat glands causing diaphoresis. As sympathetic ganglia contain nicotinic receptors, at times, however, mydriasis and tachycardia may be observed. The nicotinic effects include muscle weakness, fasciculations, and paralysis through acetylcholine stimulation of receptors at the neuromuscular junction. Muscarinic and nicotinic receptors have been identified in the brain also and may contribute to lethargy, seizures, central respiratory depression, and coma. Cardiac arrhythmias, including QTc prolongation and heart block, are sometimes observed in organophosphorus agent poisoning. Mortality from acute poisoning generally results from respiratory failure due to a combination of neuromuscular weakness, depression of the CNS respiratory center, bronchoconstriction, and excessive respiratory secretions. Oxidative stress causes overstimulation of the cholinergic and glutamatergic nervous system, causing some chronic adverse health effects.[12][13] Organophosphorus agents bind to acetylcholinesterase and turn the enzyme non-functional. The acetylcholinesterase-organophosphorus compound becomes resistant to reactivation by antidote after some time, a process known as 'aging.'[14] Hence, the treatment should initiate as early as possible. Intoxication Management Medical personnel should terminate exposure by complete removal of the patient's clothes, irrigation of the skin, and mucous membranes. Patients with altered mental status require 100 percent oxygen and endotracheal intubation. Maintain positive-pressure respiration if the patient has respiratory distress. Supportive measures like hydration, maintenance of blood pressure, and use diazepam for control of convulsions. Prophylactic diazepam has also been shown to prevent impairment of cognitive function after organophosphorus poisoning. Treatment for cholinergic toxicity due to organophosphate agents is with atropine and pralidoxime.[14] Atropine competes with acetylcholine at muscarinic receptors, preventing cholinergic activation. Pralidoxime is a cholinesterase reactivating agent that is effective in treating both muscarinic and nicotinic symptoms. Pralidoxime works as a specific antidote for organophosphate poisoning. An intramuscularly administered dosage form is available which contains both atropine and pralidoxime.

Cholinergic medications are useful for a variety of medical conditions. Healthcare professionals, including pharmacists and nurses, need to be aware of the common adverse effects of cholinergic medications. Patients who are on a cholinesterase inhibitor should be seen for follow-up at three and six months to assess drug response, tolerance, and to prevent any symptoms of cholinergic excess. Stringent measures should be in place for agricultural employers to avoid accidental exposure to insecticides with cholinergic properties. Upon establishing a baseline, periodic blood tests should be done to check cholinesterase concentrations. Timely intervention can help prevent cases of overexposure and poisoning. All emergency department personnel, as well as primary care physician, should be trained and have easy access to drug intoxication procedures at all institutions receiving presentations of intoxication. Patients should receive education, in detail, regarding the common potential adverse effects of all new medications. When prescribing cholinergic drugs, an interprofessional team approach is essential. As outlined above, the adverse effect profile of these agents mandates such. Clinicians need to be aware of the benefits and limitations of cholinergic drugs when prescribing them. A pharmacist consult is beneficial; the pharmacist can verify dosing, look for drug-drug interactions, and perform medication reconciliation, and report back to the prescriber is there are issues. Nurses will need to be familiar with the adverse effect profile as they will often have the first contact with patients on subsequent visits. They can monitor for these adverse effects as well as evaluate medication compliance as well as therapeutic effectiveness. An interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, is essential in cholinergic therapy to achieve optimal patient outcomes. [Level V]