Chemistry - A synthetic quaternary ammonium antimuscarinic agent, glycopyrrolate occurs as a bitter-tasting, practically odorless, white, crystalline powder with a melting range of 193 - 198°C. One gram is soluble in 20 ml of water; 30 ml of alcohol. The commercially available injection is adjusted to a pH of 2-3 and contains 0.9% benzyl alcohol as a preservative. Glycopyrrolate may also be known as glycopyrronium bromide .
Storage/Stability/Compatibility - Glycopyrrolate tablets should be stored in tight containers and both the injection and tablets should be stored at room temperature (15-30°C).
Glycopyrrolate is stable under ordinary conditions of light and temperature. It is most stable in solution at an acidic pH and undergoes ester hydrolysis at pH’s above 6.
Glycopyrrolate injection is physically stable in the following IV solutions: D5W, D5/half normal saline, Ringer’s injection, and normal saline. Glycopyrrolate may be administered via the tubing of an IV running lactated Ringer’s, but rapid hydrolysis will occur if it is added to an IV bag of LRS. The following drugs are reportedly physically compatible with glycopyrrolate: atropine sulfate, benzquinamide, chlorpromazine HCl, codeine phosphate, diphenhydramine HCl, droperidol, droperidol/fentanyl, hydromorphone, hydroxyzine HCl, lidocaine HCl, meperidine HCl, meperidine HCl/promethazine HCl, morphine sulfate, neostigmine methylsulfate, oxymorphone HCl, procaine HCl, prochlorperazine HCl, promazine HCl, promethazine HCl, pyridostigmine Br, scopolamine HBr, trimethobenzamide HCl.
The following drugs are reportedly incompatible with glycopyrrolate: chloramphenicol sodium succinate, dexamethasone sodium phosphate, diazepam, dimenhydrinate, methohexital sodium, methylprednisolone sodium succinate, pentazocine lactate, pentobarbital sodium, secobarbital sodium, sodium bicarbonate, and thiopental sodium. Other alkaline drugs (e.g., thiamylal) would also be expected to be incompatible with glycopyrrolate. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents used and it is suggested to consult specialized references for more specific information.
Pharmacology - An antimuscarinic with similar actions as atropine, glycopyrrolate is a quaternary ammonium compound and, unlike atropine, does not cross appreciably into the CNS. It, therefore, should not exhibit the same extent of CNS adverse effects that atropine possesses. For further information, refer to the atropine monograph.
Uses/Indications - Glycopyrrolate injection is approved for use in dogs and cats. The FDA approved indication for these species is as a preanesthetic anticholinergic agent. The drug is also used to treat sinus bradycardia, sinoatrial arrest, incomplete AV block where anticholinergic therapy may be beneficial. When cholinergic agents such as neostigmine or pyridostigmine are used to reverse neuromuscular blockade due to non-depolarizing muscle relaxants, glycopyrrolate may administered simultaneously to prevent the peripheral muscarinic effects of the cholinergic agent.
Pharmacokinetics - Quaternary anticholinergic agents are not completely absorbed after oral administration, but quantitative data reporting the rate and extent of absorption of glycopyrrolate is not available. In dogs, following IV administration, the onset of action is generally within one minute. After IM or SQ administration, peak effects occur approximately 30-45 minutes post injection. The vagolytic effects persist for 2-3 hours and the antisialagogue (reduced salivation) effects persist for up to 7 hours. After oral administration, the anticholinergic effects of glycopyrrolate may persist for 8-12 hours.
Little information is available regarding the distributory aspects of glycopyrrolate. Being a quaternary ammonium compound, glycopyrrolate is completely ionized. Therefore, it has poor lipid solubility and does not readily penetrate into the CNS or eye. Glycopyrrolate crosses the placenta only marginally; it is unknown if it is excreted into milk.
Glycopyrrolate is eliminated rapidly from the serum after IV administration and virtually no drug remains in the serum 30 minutes to 3 hours after dosing. Only a small amount is metabolized and the majority is eliminated unchanged in the feces and urine.
Contraindications/Precautions - The manufacturer (Robins) of the veterinary product lists contraindications to glycopyrrolate’s use in dogs and cats in animals hypersensitive to it and that it should not be used in pregnant animals. However, it would be prudent to refer to the recommendations listed in the atropine monograph regarding contraindications and precautions.
Adverse Effects/Warnings - With the exceptions of rare CNS adverse effects and being slightly less arrhythmogenic, glycopyrrolate can be expected to have a similar adverse effect profile as atropine. The manufacturer of the veterinary product (Robins) lists only mydriasis, tachycardia, and xerostomia as adverse effects in dogs and cats at the doses they recommend. For more information refer to the atropine monograph.
Overdosage - In dogs, the LD50 for glycopyrrolate is reported to be 25 mg/kg IV. Doses of 2 mg/kg IV daily for 5 days per week for 4 weeks demonstrated no signs of toxicity. In the cat, the LD50 after IM injection is 283 mg/kg. Because of its quaternary structure, it would be expected that minimal CNS effects would occur after an overdose of glycopyrrolate when compared to atropine. See the information listed in the atropine monograph for more information.
Drug Interactions - Glycopyrrolate would be expected to have a similar drug interaction profile as atropine. The following drugs may enhance the activity of glycopyrrolate and its derivatives: antihistamines, procainamide, quinidine, meperidine, benzodiazepines, phenothiazines.
The following drugs may potentiate the adverse effects of glycopyrrolate and its derivatives: primidone, disopyramide, nitrates, long-term corticosteroid use (may increase intraocular pressure). Glycopyrrolate and its derivatives may enhance the actions of nitrofurantoin, thiazide diuretics, sympathomimetics. Glycopyrrolate and its derivatives may antagonize the actions of metoclopramide.
For treatment of bradyarrhythmias due to increased parasympathetic tone:
a) 0.005 mg/kg IV (Muir and McGuirk 1987a)
As a bronchodilator:
a) Initially, 2 -3 mg IM bid-tid for a 450 kg animal (Beech 1987)
Monitoring Parameters - Dependent on route of administration, dose, and reason for use. See the atropine monograph for more information.
Client Information - Parenteral glycopyrrolate administration is best performed by professional staff and where adequate cardiac monitoring is available. If animal is receiving glycopyrrolate tablets, allow animal free access to water and encourage drinking if dry mouth is a problem
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Glycopyrrolate for Injection 0.2 mg/ml in 20 ml vials; Robinul®-V (Veterinary - 20 ml vial only); (Fort Dodge) (Rx) Approved for use in dogs and cats.
Glycopyrrolate Tablets 1 mg & 2 mg; Robinul® & Robinul Forte® (2 mg) (Robins); Generic; (Rx)
Glycopyrrolate for Injection 0.2 mg/ml in 1, 2, 5, & 20 ml vials; Robinul® (Robins); Generic; (Rx)
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