GLYCOPYRROLATE

Chemistry - A synthetic quaternary ammonium antimuscarinic agent, glycopyrrolate occurs as abitter-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 isadjusted to a pH of 2-3 and contains 0.9% benzyl alcohol as a preservative. Glycopyrrolate mayalso be known as glycopyrronium bromide.

Storage, Stability, Compatibility

Glycopyrrolate tablets should be stored in tight containers andboth 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 insolution 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 normalsaline, Ringer's injection, and normal saline. Glycopyrrolate may be administered via the tubing ofan 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 sodiumsuccinate, dexamethasone sodium phosphate, diazepam, dimenhydrinate, methohexital sodium, methylprednisolone sodium succinate, pentazocine lactate, pentobarbital sodium, secobarbitalsodium, sodium bicarbonate, and thiopental sodium. Other alkaline drugs (e.g., thiamylal) wouldalso be expected to be incompatible with glycopyrrolate. Compatibility is dependent upon factorssuch as pH, concentration, temperature, and diluents used and it is suggested to consult specializedreferences for more specific information.

Pharmacology - GLYCOPYRROLATE

An antimuscarinic with similar actions as atropine, glycopyrrolate is a quaternaryammonium 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 furtherinformation, 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 - GLYCOPYRROLATE

Quaternary anticholinergic agents are not completely absorbed after oraladministration, but quantitative data reporting the rate and extent of absorption of glycopyrrolate isnot available. In dogs, following IV administration, the onset of action is generally within oneminute. 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 aquaternary ammonium compound, glycopyrrolate is completely ionized. Therefore, it has poor lipidsolubility and does not readily penetrate into the CNS or eye. Glycopyrrolate crosses the placentaonly marginally; it is unknown if it is excreted into milk.
Glycopyrrolate is eliminated rapidly from the serum after IV administration and virtually no drugremains in the serum 30 minutes to 3 hours after dosing. Only a small amount is metabolized andthe 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 slightlyless arrhythmogenic, glycopyrrolate can be expected to have a similar adverse effect profile asatropine. The manufacturer of the veterinary product (Robins) lists only mydriasis, tachycardia, andxerostomia as adverse effects in dogs and cats at the doses they recommend. For more informationrefer to the atropine monograph.
Overdosage - In dogs, the LD50 for glycopyrrolate is reported to be 25 mg/kg IV. Doses of 2mg/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 thatminimal 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 asatropine. 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 intraocularpressure).
Glycopyrrolate and its derivatives may enhance the actions of nitrofurantoin, thiazide diuretics, sympathomimetics.
Glycopyrrolate and its derivatives may antagonize the actions of metoclopramide.