Action And Clinical Pharmacology: Glycopyrrolate, like other anticholinergic (antimuscarinic) agents, competitively antagonizes the action of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine but lack cholinergic innervation.
Glycopyrrolate antagonizes muscarinic symptoms (e.g., bronchorrhea, bronchospasm, bradycardia and intestinal hypermotility) induced by cholinergic drugs such as the anticholinesterases.
As a premedicant, glycopyrrolate injectable reduces excessive pharyngeal, tracheal and bronchial secretions and, during anesthesia, it appears to protect the heart against excessive vagal stimulation.
Glycopyrrolate’s polar ammonium moiety limits its passage across lipid membranes, such as the blood-brain barrier in contrast to the belladonna alkaloids, which are nonpolar tertiary amines. Consequently, glycopyrrolate injectable does not cause CNS effects seen with the belladonna alkaloids.
The onset of action following i.m. glycopyrrolate injection is 20 to 40 minutes. Peak effects occur approximately 30 to 45 minutes after administration and the duration of action ranges from 4 to 6 hours. With i.v. injection, the onset of action is generally evident within 1 minute; the duration of action varies, as does that of all other anticholinergics. Following i.v. glycopyrrolate, the vagal blocking effects persist for 2 to 3 hours and the antisialagogue effects persist up to 7 hours.
Indications And Clinical Uses: The management of gastrointestinal disorders amenable to anticholinergic therapy when oral medication is not tolerated or a rapid anticholinergic effect is desired.
May also be used as a preanesthetic antimuscarinic agent. During reversal of neuromuscular blockade induced by nondepolarizing muscle relaxants, it protects against the peripheral muscarinic effects (e.g., bradycardia and excessive secretions) of cholinergic agents such as neostigmine and pyridostigmine.
Contra-Indications: Known hypersensitivity to glycopyrrolate and in treatment of gastrointestinal disorders in the presence of glaucoma, obstructive uropathy (e.g., bladder neck obstruction due to prostatic hypertrophy), obstructive disease of the gastrointestinal tract (e.g., pyloroduodenal stenosis), paralytic ileus, intestinal atony or chronic lung disease of the elderly or debilitated patient, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis.
Due to its benzyl alcohol content, Robinul Injectable should not be used in newborns.
Manufacturers’ Warnings In Clinical States: Pregnancy and Lactation: Use of glycopyrrolate in pregnancy, lactation or in the childbearing age requires that the drug’s potential benefits be weighed against the possible hazards to mother and child.
In the presence of a high environmental temperature, heat prostration can occur (fever, heat stroke due to decreased sweating) with all anticholinergic agents.
Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance, treatment with glycopyrrolate would be inappropriate and possibly harmful.
Occupational Hazards: Since glycopyrrolate may produce drowsiness or blurred vision, warn patients not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, and not to perform hazardous work while taking the drug.
Precautions: The i.v. administration of any anticholinergic in the presence of cyclopropane anesthesia can result in ventricular arrhythmias; therefore, observe caution if glycopyrrolate injectable must be used during cyclopropane anesthesia. If the drug is given in small incremental doses of 100 Âµg or less, the likelihood of producing ventricular arrhythmias is reduced.
Investigate any tachycardia before giving anticholinergic (atropine like) drugs since they may increase the heart rate.
With overdosage, a curare like action may occur, i.e., neuromuscular blockade leading to muscular weakness and possible paralysis. However, it has not yet been reported.
Use glycopyrrolate injectable with caution in elderly and in all patients with autonomic neuropathy; hepatic or renal disease; ulcerative colitis (large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason precipitate or aggravate the serious complication of toxic megacolon); hyperthyroidism; coronary heart disease; congestive heart failure; cardiac arrhythmias; hypertension; prostatic hypertrophy; hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition; incipient glaucoma (acute glaucoma can be precipitated in susceptible individuals).
Anticholinergic drugs used in the treatment of gastric ulcer may produce a delay in gastric emptying time and may complicate such therapy (antral stasis). Consider the use of an indwelling nasogastric tube whenever more than 2 doses in succession are to be administered.
Do not rely on the use of glycopyrrolate in the presence of complications of biliary tract disease.
Adverse Reactions: Symptoms of CNS effects have not been observed with glycopyrrolate injectable. Adverse reactions to anticholinergics may include xerostomia; urinary hesitancy and retention; blurred vision due to mydriasis and cycloplegia; photophobia; increased ocular tension including acute glaucoma; tachycardia; palpitation; decreased sweating and heat prostration; loss of taste; headache; nervousness; drowsiness; weakness; dizziness, insomnia, nausea; vomiting; impotence; suppression of lactation; constipation; bloated feeling; severe allergic reaction or drug idiosyncrasies including anaphylaxis, urticaria and other dermal manifestations; some degree of mental confusion and/or excitement, especially in elderly persons.
Symptoms And Treatment Of Overdose: Symptoms: Widespread paralysis of organs innervated by parasympathetic nerves should create a suspicion of poisoning by antimuscarinic agents. Dry mucous membranes, widely dilated and unresponsive pupils, tachycardia, cutaneous flush and fever are significant. A curariform neuromuscular block may occur and lead to respiratory paralysis.
Treatment: To combat peripheral anticholinergic effects, a quaternary ammonium anticholinesterase such as neostigmine methylsulfate may be given in a dose of 1.0 mg for each 1.0 mg of glycopyrrolate injectable known to have been administered.
To combat hypotension, pressor amines may be tried. To combat respiratory depression, administer oxygen and respiratory stimulant or artificial respiration. Catheterization sometimes is necessary.
Dosage And Administration: May be administered by i.m. or i.v. routes without dilution. Not for use in newborns. Children with disorders such as Down’s syndrome should not have anticholinergics, or if they are necessary, the usual dose should be reduced by half.
Gastroenterology: Usual adult dose is 0.1 mg administered at 4 hour intervals 3 or 4 times daily. Where more profound effect is required, 0.2 mg may be given. Frequency of administration depends upon individual patient response, but a 4 hour interval between injections is recommended. Some patients may need only a single dose, others may require administration 2, 3, or 4 times a day.
Data on the use of glycopyrrolate injectable in the management of gastrointestinal disorders in children are not available.
Preanesthetic medication: Adults and children: 0.005 mg/kg may be given by i.m. injection 30 to 60 minutes prior to the anticipated time of induction of anesthesia or at the time the preanesthetic narcotic and/or sedative are administered.
Note: Children (up to 12 years of age) may require up to 0.010 mg/kg of body weight.
The timing of administration of glycopyrrolate injectable with relation to the time of anesthetic induction is not as critical as with the belladonna alkaloids, since glycopyrrolate has a prolonged duration of action, providing protection 2 to 3 times as long as that provided by atropine or scopolamine.
Intraoperative Medication: Glycopyrrolate injectable may be used during surgery to counteract drug induced or vagal traction reflexes with the associated arrhythmias (e.g., bradycardia). The usual attempts should be made to determine the etiology of the arrhythmia and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed. It should be administered i.v. to adults as single doses of 0.1 mg and repeated, as needed, at intervals of 2 to 3 minutes. The pediatric dose is 0.005 mg/kg i.v., not to exceed 0.1 mg in a single dose which may be repeated, as needed, at intervals of 2 to 3 minutes.
Reversal of Neuromuscular Blockade: The recommended adult and pediatric dose is 0.2 mg of glycopyrrolate for each 1 mg of neostigmine or 5 mg of pyridostigmine. In order to minimize the appearance of cardiac side effects, the drugs may be administered simultaneously by i.v. injection and may be mixed in the same syringe. Mixtures containing more than 5 mg of neostigmine or 25 mg of pyridostigmine plus 1 mg of glycopyrrolate are not recommended.
Compatibility with Other Agents: Drug Interaction during anesthesia: Glycopyrrolate has been used clinically with at least the following medications: a barbiturate (sodium thiopental); narcotic analgesics (morphine, alphaprodine, fentanyl); sedative/tranquilizers (droperidol, diazepam); gaseous anesthetics (diethyl ether, halothane, methoxyflurane, enflurane); parenteral anesthetics (ketamine); peripherally-acting skeletal muscle relaxants (succinyl choline, gallamine, d-tubocurarine, pancuronium); cholinergic agents (neostigmine, pyridostigmine); and other anticholinergics (atropine).
There are no known unique or unanticipated drug-drug interactions with other agents except that glycopyrrolate injectable should be used with caution, if at all, during cyclopropane anesthesia (see Precautions).
Availability And Storage: Each mL of solution contains: glycopyrrolate 0.2 mg. Nonmedicinal ingredients: benzyl alcohol, hydrochloric acid, sodium hydroxide and water for injection. Vials of 2 mL. Multiple dose vials of 20 mL.
ROBINUL® INJECTABLE Wyeth-Ayerst Glycopyrrolate Anticholinergic