PYRIDOSTIGMINE BROMIDE

Chemistry - An anticholinesterase agent, pyridostigmine bromide is a synthetic quaternary ammonium compound that occurs as an agreeable smelling, bitter-tasting, hygroscopic, white orpractically white, crystalline powder. It is freely soluble in water and in alcohol. The pH of thecommercially available injection is approximately 5.

Storage, Stability, Compatibility

Unless otherwise instructed by the manufacturer, store pyridostigmine products at room temperature. The oral solution and injection should be protected fromlight and freezing. Pyridostigmine tablets should be kept in tight containers.
The extended-release tablets may become mottled with time, but does not affect their potency.
Pyridostigmine injection is unstable in alkaline solutions. It is reportedly compatible with glycopyrrolate, heparin sodium, hydrocortisone sodium succinate, potassium chloride, and vitamin B-complex with C. Compatibility is dependent upon factors such as pH, concentration, temperatureand diluents used. It is suggested to consult specialized references (e.g., Handbook on Injectable
Drugs by Trissel; see bibliography) for more specific information.

Pharmacology - PYRIDOSTIGMINE BROMIDE

Pyridostigmine inhibits the hydrolysis of acetylcholine by directly competingwith acetylcholine for attachment to acetylcholinesterase. Because the pyridostigmine-acetyl-cholinesterase complex is hydrolyzed at a much slower rate than the acetylcholine-acetyl-cholinesterase complex, acetylcholine tends to accumulate at cholinergic synapses with resultantcholinergic activity.
At usual doses, pyridostigmine does not cross into the CNS (quaternary ammonium structure), butoverdoses can cause CNS effects.

Uses, Indications

Pyridostigmine is used in the treatment of myasthenia gravis (MG) in dogs(and rarely in cats). It is considered to be much more effective in acquired MG, rather than congenital MG.

Pharmacokinetics - PYRIDOSTIGMINE BROMIDE

Pyridostigmine is only marginally absorbed from the GI tract and absorptionmay be more erratic from the sustained-release tablets than with the regular tablets. The onset ofaction after oral dosing is generally within one hour.
At usual doses, pyridostigmine is apparently distributed to most tissues, but not to the brain, intestinal wall, fat or thymus. The drug crosses the placenta.
Pyridostigmine is both metabolized by the liver and hydrolyzed by cholinesterases.

Contraindications, Precautions, Reproductive Safety

Pyridostigmine is contraindicated inpatients hypersensitive to this class of compounds or bromides, or those who have mechanical orphysical obstructions of the urinary or GI tract.
The drug should be used with caution in patients with bronchospastic disease, epilepsy, hyperthyroidism, bradycardia or other arrhythmias, vagotonia, or GI ulcer diseases.

Adverse Effects, Warnings

Adverse effects associated with pyridostigmine are generally doserelated and cholinergic in nature. Although usually mild and easily treatable with dosage reduction, severe adverse effects are possible (see Overdosage below).
Overdosage, Acute Toxicity - Overdosage of pyridostigmine may induce a cholinergic crisis.
Symptoms of cholinergic toxicity can include GI effects (nausea, vomiting, diarrhea), salivation, sweating (in animals able to do so), respiratory effects (increased bronchial secretions, bronchospasm, pulmonary edema, respiratory paralysis), ophthalmic effects (miosis, blurred vision, lacrimation), cardiovascular effects (bradycardia or tachycardia, cardiospasm, hypotension, cardiacarrest), muscle cramps and weakness.
Overdoses in myasthenic patients can be very difficult to distinguish from the effects associatedwith a myasthenic crisis. The time of onset of symptoms or an edrophonium challenge may help todistinguish between the two.
Treatment of pyridostigmine overdosage, consists of both respiratory and cardiac supportivetherapy and atropine if necessary. Refer to the atropine monograph for more information on its usefor cholinergic toxicity.

Drug Interactions

Anticholinesterase therapy may be antagonized by administration of parenteral magnesium therapy, as it can have a direct depressant effect on skeletal muscle. Drugsthat possess some neuromuscular blocking activity (e.g., aminoglycoside antibiotics, someantiarrhythmic and anesthetic drugs) may necessitate increased dosages of pyridostigmine intreating or diagnosing myasthenic patients.
Corticosteroids may decrease the anticholinesterase activity of pyridostigmine. After stoppingcorticosteroid therapy, neostigmine may cause increased anticholinesterase activity.
Pyridostigmine may prolong the Phase I block of depolarizing muscle relaxants (e.g., succinylcholine, decamethonium). Pyridostigmine antagonizes the actions of non-depolarizingneuromuscular blocking agents (pancuronium, tubocurarine, gallamine, etc.).
Atropine will antagonize the muscarinic effects of pyridostigmine, but concurrent use should beused cautiously as atropine can mask the early symptoms of cholinergic crisis.
Theoretically, dexpanthenol may have additive effects when used with pyridostigmine.