Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

PENTOBARBITAL SODIUM

(Note: Combinations of pentobarbital with other agents (e.g., phenytoin) for euthanasia have aseparate monograph listed under Euthanasia Agents)
Chemistry - Pentobarbital sodium occurs as odorless, slightly bitter tasting, white, crystallinepowder or granules. It is very soluble in water and freely soluble in alcohol. The pKa of the drughas been reported to range from 7.85-8.03 and the pH of the injection is from 9-10.5. Alcohol orpropylene glycol may be added to enhance the stability of the injectable product.

Storage, Stability, Compatibility

The injectable product should be stored at room temperature;the suppositories should be kept refrigerated. The aqueous solution is not very stable and shouldnot be used if it contains a precipitate. Because precipitates may occur, pentobarbital sodium shouldnot be added to acidic solutions.
The following solutions and drugs have been reported to be compatible with pentobarbitalsodium: dextrose IV solutions, Ringer's injection, lactated Ringer's injection, Saline IV solutions, dextrose-saline combinations, dextrose-Ringer's combinations, dextrose-Ringer's lactatecombinations, amikacin sulfate, aminophylline, atropine sulfate(for at least 15 minutes, not 24hours), calcium chloride, cephapirin sodium, chloramphenicol sodium succinate, hyaluronidase, hydromorphone HCl, lidocaine HCl, neostigmine methylsulfate, scopolamine HBr, sodium bicarbonate, sodium iodide, thiopental sodium, and verapamil HCl.
The following drugs have been reported to be incompatible with pentobarbital sodium: benzquinamide HCl, butorphanol tartrate, chlorpromazine HCl, cimetidine HCl, chlorpheniraminemaleate, codeine phosphate, diphenhydramine HCl, droperidol, fentanyl citrate, glycopyrrolate, hydrocortisone sodium succinate, hydroxyzine HCl, insulin (regular), meperidine HCl, nalbuphine
HCl, norepinephrine bitartrate, oxytetracycline HCl, penicillin G potassium, pentazocine lactate, phenytoin sodium, prochlorperazine edisylate, promazine HCl, promethazine HCl, and streptomycinsulfate. Compatibility is dependent upon factors such as pH, concentration, temperature, anddiluents used and it is suggested to consult specialized references for more specific information.
Pharmacology -See the monograph: Barbiturates, Pharmacology of.
Uses, Indications - Once pentobarbital was the principal agent used for general anesthesia in smallanimals, but has been largely superceded by the inhalant anesthetic agents. It is still commonly usedas an anesthetic in laboratory situations, for rodents and occasionally as a sedative agent in dogsand cats.
Pentobarbital is considered to be a drug of choice in dogs and cats for treating intractable seizuressecondary to convulsant agents (e.g., strychnine) or as a result of CNS toxins (e.g., tetanus). Itshould not be used to treat seizures caused by lidocaine intoxication.
Pentobarbital has been used as a sedative and anesthetic agent in horses, cat le, swine, sheep andgoats. Often the drug is given after a preanesthetic agent to reduce pentobarbital dosages and sideeffects.
Pentobarbital is a major active ingredient in several euthanasia solutions. This indication is discussed later in this section in the monograph for pentobarbital euthanasia solutions.

Pharmacokinetics - PENTOBARBITAL SODIUM

Pentobarbital is absorbed quite rapidly from the gut after oral or rectal administration with peak plasma concentrations occurring between 30-60 minutes after oral dosing inhumans. The onset of action usually occurs within 15-60 minutes after oral dosing and within 1minute after IV administration.
Pentobarbital, like all barbiturates, distributes rapidly to all body tissues with highest concentrations found in the liver and brain. It is 35-45% bound to plasma proteins in humans. Although lesslipophilic than the ultra-short acting barbiturates (e.g., thiopental), pentobarbital is highly lipidsoluble and patient fat content may alter the distributive qualities of the drug. All barbiturates crossthe placenta and enter milk (at concentrations far below those of plasma).
Pentobarbital is metabolized in the liver principally by oxidation. Excretion of the drug is notappreciably enhanced by increasing urine flow or alkalinizing the urine. Ruminants (especiallysheep and goats) metabolize pentobarbital at a very rapid rate. The elimination half-life in the goathas been reported to be approximately 0.9 hrs. Conversely, the half-life in dogs is approximately 8hours and ranges from 15-50 hours in man.
Contraindications/Precautions - Use cautiously in patients who are hypovolemic, anemic, haveborderline hypoadrenal function, or cardiac or respiratory disease. Large doses are contraindicatedin patients with nephritis or severe respiratory dysfunction. Barbiturates are contraindicated inpatients with severe liver disease or who have demonstrated previous hypersensitivity reactions tothem.
When administering IV, give SLOWLY. It is not recommended to be used for cesarian section because of fetal respiratory depression. Cats tend to particularly sensitive to the respiratory depressant effects of barbiturates; use with caution in this species. Female cats are more susceptible to the effects of pentobarbital than male cats.

Adverse Effects, Warnings

Because of the respiratory depressant effects of pentobarbital, respiratory activity must be closely monitored and respiratory assistance must be readily availablewhen using anesthetic dosages. Pentobarbital may cause excitement in dogs during recovery fromanesthetic doses. Hypothermia may develop in animals receiving pentobarbital if exposed totemperatures below 27°C (80.6°F). The barbiturates can be very irritating when administered SQ orperivascularly; avoid these types of injections. Do not administer intra-arterially.
Overdosage - In dogs, the reported oral LD50 is 85 mg/kg and IV LD50 is 40 - 60 mg/kg.
Fatalities from ingestion of meat from animals euthanized by pentobarbital have been reported indogs. Treatment of pentobarbital overdose consists of removal of ingested product from the gut ifappropriate and offering respiratory and cardiovascular support. Forced alkaline diuresis is of littlebenefit for this drug. Peritoneal or hemodialysis may be of benefit in severe intoxications.

Drug Interactions

Most clinically significant interactions have been documented in humans withphenobarbital, however, these intreactions may also be of significance in animals receivingpentobarbital, especially with chronic therapy.
The following drugs may increase the effect of pentobarbital: Other CNS depressants(narcotics, phenothiazines, antihistamines, etc), valproic acid, and chloramphenicol.
Pentobarbital may decrease the effect of the following drugs: oral anticoagulants, corticosteroids, beta-Blockers (propranolol), quinidine, theophylline, metronidazole.
Pentobarbital with furosemide may cause or increase postural hypotension. Barbiturates mayeffect the metabolism of phenytoin, monitoring of blood levels may be indicated.
Fatalities have been reported when dogs suffering from lidocaine induced seizures were treatedwith pentobarbital. Until this interaction is further clarified, it is suggested that lidocaine-inducedseizures in dogs be treated initially with diazepam.
Drug/Lab Interactions - Barbiturates may cause increased retention of bromosulfopthalein (BSP;sulfobromopthalein) and give falsely elevated results. It is recommended that barbiturates not beadministered within the 24 hours before BSP retention tests.

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