Glycopyrrolate/neostigmine Disease Interactions

Patients with tachycardia should be supervised closely during treatment with anticholinergic agents. Tachycardia is produced by blocking normal vagal inhibition of the SA node. Paradoxically, bradycardia may occur due to central vagal stimulation which may occur prior to peripheral cholinergic blockade.

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Agents with anticholinergic activity can exacerbate many of the manifestations of autonomic neuropathy, including tachycardia, anhidrosis, bladder atony, obstipation, dry mouth and eyes, cycloplegia and blurring of vision, and sexual impotence in males. Therapy with antimuscarinic agents and higher dosages of antispasmodic agents (e.g., dicyclomine or oxybutynin) should be administered cautiously in patients with autonomic neuropathy.

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Anticholinergics are contraindicated in patients with obstructive diseases such as achalasia, esophageal stricture or stenosis, pyloroduodenal stenosis, stenosing peptic ulcer, pyloric obstruction, and paralytic ileus. Anticholinergics may further suppress intestinal motility with resultant precipitation or aggravation of toxic megacolon.

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Anticholinergic agents are contraindicated in patients with primary glaucoma, a tendency toward glaucoma (narrow anterior chamber angle), or adhesions (synechiae) between the iris and lens, as well as for the elderly and others in whom undiagnosed glaucoma or excessive pressure in the eye may be present. Because anticholinergics cause mydriasis, they may exacerbate these conditions.

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In general, the use of anticholinergic agents is contraindicated in patients with urinary retention and bladder neck obstruction caused by prostatic hypertrophy. Dysuria may occur and may require catheterization. Also, anticholinergic drugs may aggravate partial obstructive uropathy. Caution is advised even when using agents with mild to moderate anticholinergic activity, particularly in elderly patients.

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Anticholinergic agents and agents with secondary anticholinergic activity may aggravate tardive dyskinesia or induce previously suppressed symptoms. Therapy with these agents should be avoided, if possible, or administered cautiously in patients with preexisting tardive dyskinesia, particularly in the elderly. If tardive dyskinesia symptoms develop or worsen during treatment with an anticholinergic agent, prompt withdrawal of therapy will provide better chances of improving the condition.

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The use of drugs with antiperistaltic activity (primarily antidiarrheal and antimuscarinic agents, but also antispasmodic agents such as dicyclomine or oxybutynin at high dosages) is contraindicated in patients with diarrhea due to pseudomembranous enterocolitis or enterotoxin-producing bacteria. These drugs may prolong and/or worsen diarrhea associated with organisms that invade the intestinal mucosa, such as toxigenic E. coli, Salmonella and Shigella, and pseudomembranous colitis due to broad-spectrum antibiotics. Other symptoms and complications such as fever, shedding of organisms and extraintestinal illness may also be increased or prolonged. In general, because antiperistaltic agents decrease gastrointestinal motility, they may delay the excretion of infective gastroenteric organisms or toxins and should be used cautiously in patients with any infectious diarrhea, particularly if accompanied by high fever or pus or blood in the stool. Some cough and cold and other combination products may occasionally include antimuscarinic agents for their drying effects and may, therefore, require careful selection when necessary.

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Due to their pharmacological action, cholinesterase inhibitors can have a vagotonic effect on the sinoatrial and atrioventricular nodes producing bradycardia or heart block. Therapy with cholinesterase inhibitors should be administered cautiously in patients with preexisting bradycardia or underlying cardiac conduction abnormalities. Syncopal episodes have been reported in patients with and without cardiac abnormalities. Atropine may be used to reverse bradycardia produced by cholinesterase inhibitors.

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Cholinesterase inhibitors inhibit the hydrolysis of acetylcholine. The enhanced effect of acetylcholine produces constriction of the bronchi, increased bronchial secretions, and bronchospasm. Therapy with cholinesterase inhibitors should be administered cautiously in patients with respiratory dysfunction, history of asthma or obstructive pulmonary disease. Monitoring respiratory function during dosage initiation and adjustment is recommended. Use of atropine along with discontinuation of the cholinesterase inhibitor may be required for serious respiratory distress. Neostigmine may produce more severe muscarinic side effects than does pyridostigmine and ambenonium. However, the duration of action is longest for ambenonium and shortest for edrophonium. Echothiophate iodide ophthalmic may be systemically absorbed and cautious use is recommended in these patients.

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The use of cholinesterase inhibitors has been associated with a constriction of coronary arteries. Therapy with cholinesterase inhibitors should be administered cautiously in patients with coronary artery disease.

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Cholinesterase inhibitors should be used with caution in patients with parkinsonism. Some of these drugs might be contraindicated in these patients (refer to specific prescribing information). Symptoms of Parkinson's disease may be exacerbated with the increase in cholinergic activity. Caregivers and patients should be advised.

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The use of cholinesterase inhibitors is associated with an increase in gastric acid secretion and gastric contractions. Therapy with cholinesterase inhibitors should be administered cautiously in patients with peptic ulcer disease.

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Cholinesterase inhibitors have been associated with convulsions and tremor. Therapy with cholinesterase inhibitors should be administered cautiously in patients with seizure disorders.

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The use of glycopyrrolate is contraindicated in patients with myasthenia gravis.

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Glycopyrrolate is contraindicated in patients with severe ulcerative colitis and toxic mega-colon complicating ulcerative colitis.

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Neostigmine is contraindicated in mechanical obstruction of the urinary or intestinal tract and peritonitis.

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Toxic psychosis manifested as confusion, disorientation, agitation, excitation, memory impairment, delusions and hallucinations may develop at toxic and therapeutic dosages of antimuscarinic agents. Therapy with these agents should be administered cautiously in patients with mental disorders receiving antimuscarinic agents for control of drug-induced extrapyramidal effects, especially at the beginning of therapy or during dosage adjustment. Psychiatric deterioration and psychotic flare-ups have also been reported following withdrawal of therapy. Symptoms include delusions, hallucinations, aggression or violent behavior, and suicidal tendencies. In high dosages, antimuscarinic agents may sometimes produce euphorigenic effects. For this reason, it can be a drug of abuse.

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Many of the manifestations of hyperthyroidism may be exacerbated by increased levels of acetylcholine produced by cholinesterase inhibitors. Therapy with cholinesterase inhibitors should be administered cautiously to patients with hyperthyroidism. Monitoring of thyroid levels is recommended.

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Anticholinergics may cause increased side effects in pediatric patients with Down's syndrome, spastic paralysis, and other brain anomalies.

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The pharmacokinetics of glycopyrrolate in hepatically impaired patients is unknown, however, caution is advised since anticholinergics can worsen this condition.

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Elimination of glycopyrrolate may be severely impaired in renal failure. Use caution when administering glycopyrrolate to patients with impaired renal function, and they should be closely monitored while under the effect of the neuromuscular blocking agent.

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Neostigmine is metabolized by microsomal enzymes in the liver, and the effect of hepatic impairment on pharmacokinetics has not been evaluated. Patients should be carefully monitored if hepatically cleared neuromuscular blocking agents are used, as their duration of action may be prolonged due to hepatic insufficiency.

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Cardiovascular effects of anticholinergics may exacerbate hypertension. Therapy with anticholinergic agents should be administered cautiously in patients with hypertension.

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Atropine-like agents may increase the risk of hyperthermia in patients with fever by producing anhidrosis. Therapy with atropine-like agents should be administered cautiously in febrile patients.

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