(Note: Combinations of pentobarbital with other agents (e.g., phenytoin) for euthanasia have a separate monograph listed under Euthanasia Agents)
Chemistry - Pentobarbital sodium occurs as odorless, slightly bitter tasting, white, crystalline powder or granules. It is very soluble in water and freely soluble in alcohol. The pKa of the drug has been reported to range from 7.85-8.03 and the pH of the injection is from 9-10.5. Alcohol or propylene 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 should not be used if it contains a precipitate. Because precipitates may occur, pentobarbital sodium should not be added to acidic solutions.
The following solutions and drugs have been reported to be compatible with pentobarbital sodium: dextrose IV solutions, Ringer’s injection, lactated Ringer’s injection, Saline IV solutions, dextrose-saline combinations, dextrose-Ringer’s combinations, dextrose-Ringer’s lactate combinations, amikacin sulfate, aminophylline, atropine sulfate(for at least 15 minutes, not 24 hours), 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, chlorpheniramine maleate, 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 streptomycin sulfate. 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 -See the monograph: Barbiturates, Pharmacology of.
Uses/Indications - Once pentobarbital was the principal agent used for general anesthesia in small animals, but has been largely superceded by the inhalant anesthetic agents. It is still commonly used as an anesthetic in laboratory situations, for rodents and occasionally as a sedative agent in dogs and cats.
Pentobarbital is considered to be a drug of choice in dogs and cats for treating intractable seizures secondary to convulsant agents (e.g., strychnine) or as a result of CNS toxins (e.g., tetanus). It should not be used to treat seizures caused by lidocaine intoxication.
Pentobarbital has been used as a sedative and anesthetic agent in horses, cattle, swine, sheep and goats. Often the drug is given after a preanesthetic agent to reduce pentobarbital dosages and side effects.
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 is absorbed quite rapidly from the gut after oral or rectal administration with peak plasma concentrations occurring between 30-60 minutes after oral dosing in humans. The onset of action usually occurs within 15-60 minutes after oral dosing and within 1 minute 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 less lipophilic than the ultra-short acting barbiturates (e.g., thiopental), pentobarbital is highly lipid soluble and patient fat content may alter the distributive qualities of the drug. All barbiturates cross the 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 not appreciably enhanced by increasing urine flow or alkalinizing the urine. Ruminants (especially sheep and goats) metabolize pentobarbital at a very rapid rate. The elimination half-life in the goat has been reported to be approximately 0.9 hrs. Conversely, the half-life in dogs is approximately 8 hours and ranges from 15-50 hours in man.
Contraindications/Precautions - Use cautiously in patients who are hypovolemic, anemic, have borderline hypoadrenal function, or cardiac or respiratory disease. Large doses are contraindicated in patients with nephritis or severe respiratory dysfunction. Barbiturates are contraindicated in patients with severe liver disease or who have demonstrated previous hypersensitivity reactions to them.
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 available when using anesthetic dosages. Pentobarbital may cause excitement in dogs during recovery from anesthetic doses. Hypothermia may develop in animals receiving pentobarbital if exposed to temperatures below 27°C (80.6°F). The barbiturates can be very irritating when administered SQ or perivascularly; 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 in dogs. Treatment of pentobarbital overdose consists of removal of ingested product from the gut if appropriate and offering respiratory and cardiovascular support. Forced alkaline diuresis is of little benefit for this drug. Peritoneal or hemodialysis may be of benefit in severe intoxications.
Drug Interactions - Most clinically significant interactions have been documented in humans with phenobarbital, however, these intreactions may also be of significance in animals receiving pentobarbital, 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 may effect the metabolism of phenytoin, monitoring of blood levels may be indicated.
Fatalities have been reported when dogs suffering from lidocaine induced seizures were treated with pentobarbital. Until this interaction is further clarified, it is suggested that lidocaine-induced seizures 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 be administered within the 24 hours before BSP retention tests.
Doses - Note: In order to avoid possible confusion, doses used for euthanasia are listed separately under the monograph for pentobarbital euthanasia solutions.
Horses: Note: Pentobarbital is generally not considered an ideal agent for use in the adult horse due to possible development of excitement and injury when the animal is “knocked down”.
a) 3 - 15 mg/kg IV (Robinson 1987)
b) 15 - 18 mg/kg IV for light anesthesia (Schultz 1986)
Monitoring Parameters -
1) Levels of consciousness and/or seizure control
2) Respiratory and cardiac signs
3) Body temperature
4) If using chronically, routine blood counts and liver function tests should be performed.
Client Information - This drug is best used in an inpatient setting or with close professional supervision. If dosage forms are dispensed to clients, they must be in instructed to keep away from children and should be dispensed in child-resistant packaging.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Pentobarbital Sodium for Injection 64.8 mg/ml (1 grain/ml) 100 ml vials
Generic; (Rx) Approved for use in dogs and cats.
Pentobarbital Sodium for Injection; 50 mg/ml in 1 & 2 ml syringes, 2 ml, 20 ml and 50 ml vials; (Rx)
Pentobarbital Sodium Oral Capsules; 50 mg, 100 mg capsules; (Rx)
Pentobarbital Sodium Rectal Suppositories; 30 mg, 60 mg, 120 mg, 200 mg in 12/pkg; (Rx)
A common trade name is Nembutal Sodium® (Abbott). May also be known as pentobarbitone sodium . Pentobarbital is a Class-II controlled substance and detailed records must be maintained with regard to its use and disbursement.
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