Chemicals / Complex Chemical Agents/ Chemical:

Pentobarbital Sodium (with notes on Hedgehogs, Elephants, Lagomorphs, Ferrets and Great Apes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
Barbiturate used for euthanasia but also used for anaesthesia and for control of seizures. (B201.6.w6, B205.5.w5)

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Names and Formulae
Type Barbiturate
Alternative Names
  • Pentobarbital. (B546)
  • Pentobarbitone sodium. (B201.6.w6, B205.5.w5)
  • 5-ethyl-5-(1-methylbutyl) barbiturate. (B205.5.w5)
  • "5-Ethyl-5-(1-methylbutyl)barbituric acid; 5-ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-Pyrimidinetrione; Pentobarbital; Pentabarbital." (W324)
Chemical Formula C11H18N2O3 (W324)
Chemical Structure
  • Racemic mixture. (B205.5.w5)
Molecular Weight 226.2748. (W324)
Related Chemicals --

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Physical Properties / Chemistry
Description
  • White crystalline powder/granules, odourless but with a slightly bitter taste. (B263)

Melting point --
Boiling point --
Density --
Water solubility
  • Very soluble. (B263)
Other solubility
  • Freely soluble in alcohol. (B263)
Acid/Base
  • pKa 7.85-8.03; pH of injectable product 9.0-10.5. (B263)

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Pharmacology & General Information
Pharmacology
  • Primarily a hypnotic (as with other barbiturates). (B205.5.w5)
  • Central nervous system depressant. (B205.5.w5)
    • Depresses the cerebral cortex; probably depresses the hypothalamus. (B205.5.w5)
    • Depresses the motor areas of the brain (therefore may be useful in control of seizures). (B205.5.w5)
    • Marked depression of the respiratory centre. (B205.5.w5)
    • Analgesic action is weak; relatively large doses required to alter perception of pain. (B205.5.w5)
    • Death from overdose is by depression of the medullary respiratory and vasomotor centres. (B201.6.w6)
  • One isomer causes transient excitement prior to central nervous system depression; the other isomer produces a smoother progressive hypnosis. (B205.5.w5)
  • In sheep: marked decrease in stroke volume and also in the acceleration of blood in the pulmonary artery, with resultant 64% decrease in cardiac output. (B205.5.w5)
  • Myocardial function and distribution of blood flow are generally altered. (B205.5.w5)
  • May inhibit diuresis, probably by causing release of antidiuretic hormone from the pituitary. (B205.5.w5)
Storage / Stability
  • Store injectable product at room temperature. (B263)
  • Keep suppositories refrigerated. (B263)
  • Do not add to acidic solutions as precipitation may occur. (B263)
Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5); Gracia Vila-Garcia (V.w67)
Referees Suzanne I. Boardman (V.w6); Becki Lawson (V.w26); Susan Mikota (V.w72)

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Therapeutic Information

Uses/Indications
Activity
  • Primarily a hypnotic (as with other barbiturates). (B205.5.w5)
  • Central nervous system depressant. (B205.5.w5)
    • Depresses the motor areas of the brain (therefore useful in control of seizures). (B205.5.w5)
    • Markedly depresses respiration. (B205.5.w5)
Appropriate Use
  • For euthanasia. (B201.6.w6, B205.5.w5)
  • To treat intractable seizures. (B205.5.w5)
    • A drug of choice for treatment of intractable seizures secondary to convulsant agents such as strychnine and CNS toxins such as in tetanus. (B201.6.w6, B263)
    • Treatment of status epilepticus. (B201.6.w6)
  • As a sedative/anaesthetic. (B205.5.w5, B263)
    • Now mainly used in laboratories. (B205.5.w5, B263)
    • Has been used as a sedative in the treatment of hypomagnesaemic tetany in large animals. (B201.6.w6)
Limitations
  • Should not be used to treat seizures due to lignocaine intoxication. (B263)
Notes --

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability
  • Following intravenous injection an appreciable time is required to cross the blood-brain barrier. (B205.5.w5)
    • Onset of action within one minute. (B263)
  • Quite rapid absorption following oral or rectal administration. (B263)
    • Onset of action within 15-60 minutes following oral administration. (B263)
    • Human: peak plasma concentration 30-60 minutes after oral administration. (B263)
Distribution
  • Rapid distribution to all body tissues. (B263)
  • Crosses the blood-brain barrier. (B205.5.w5)
    • Relatively slow to cross the blood-brain barrier. (B201.6.w6)
  • Highest levels in liver and brain. (B263)
  • Crosses the placenta and enters the fetal circulation. (B205.5.w5)
  • Enters milk (low concentrations). (B263)
  • Highly lipid soluble: distribution may be affected by the body fat content of the individual. (B263)
Plasma Protein binding / Storage
  • Human: 35-45% plasma protein-bound. (B263)
Elimination Route
  • Mainly hepatic. (B205.5.w5, B263); principally metabolised by oxidation. (B263)
  • Part of the administered dose is excreted in urine; this may be increased by giving fluids to produce a diuresis. (B205.5.w5)
    • Increasing urine flow rate does not appreciably enhance drug excretion. (B263)
    • Alkalinisation of urine does not appreciably enhance drug excretion. (B263)
Elimination half-life / Clearance Rate
  • Slow; recovery from pentobarbital anaesthesia is slow. (B205.5.w5)
  • Horses, sheep and goats metabolise the barbiturate faster than do pigs, dogs and cats. (B205.5.w5)

Elimination half-life:

  • Goat: approximately 0.9 hours. (B263)
  • Dog: approximately eight hours.
  • Human: 15-50 hours. (B263)
Drug Interactions
  • Effect of pentobarbital may be increased by: other CNS depressants (including narcotics, phenothiazines, antihistamines etc.), valproic acid, chloramphenicol. (B263)
  • May decrease the effects of: oral anticoagulants, corticosteroids, beta-blockers (such as propanolol), quinidine, theophylline, metronidazole. (B263)
  • In combination with furosamide, may cause/increase postural hypotension. (B263)
  • May affect phenytoin metabolism: blood level monitoring may be indicated. (B263)
  • Fatalities have been reported following treatment of lignocaine-induced seizures with pentobarbitone. (B263)
  • Reported physically incompatible with: benzquinamine hydrochloride, butorphanol tartrate, chlorpromazine hydrochloride, cimetidine hydrochloride, chlorpheniramine maleate, codeine phosphate, diphenhydramine hydrochloride, droperidol, fentanyl citrate, glycopyrrolate, hydrocortisone sodium succinate, hydroxyzine hydrochloride, insulin (regular), meperidine hydrochloride, nalbuphine hydrochloride, norepinephrine bitartrate, oxytetracycline hydrochloride, penicillin G potassium, pentazocine lactate, phenytoin sodium, prochlorperazine edisylate, promazine hydrochloride, promethazine hydrochloride, streptomycin sulphate. (B263)
  • Reported physically compatible with: intravenous dextrose solutions, Ringer's injection, lactated Ringer's injection, saline intravenous solution, dextrose-saline combinations, dextrose-Ringer's combinations, dextrose-Ringer's lactate combinations, amikacin sulphate, aminophylline, atropine sulphate (for at least 15 minutes, but not for 24 hours), calcium chloride, cephapirin sodium, chloramphenicol sodium succinate, hyaluronidase, hydromorphone hydrochloride, lignocaine Hydrochloride, neostigmine methylsulphate, scopolamine HBr, sodium bicarbonate, sodium iodide, thiopental sodium, verapamil Hydrochloride. (B263)
  • Compatibility may vary depending on factors such as pH, concentration, temperature and diluents. (B263)

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Administration
Formulations available
  • 20% solution (200 mg/mL) for injection, non-sterile, for euthanasia. (B201.6.w6, B205.5.w5)
  • 6.5% solution containing propylene glycol. (B205.5.w5)
  • Powder in gelatine capsules. (B205.5.w5)

In UK:

  • Available products include (but are not limited to):
    • Dolethal (Vetoquinol UK Ltd.) non-sterile solution, containing 20% w/v Pentobarbital Sodium PhEur and 1.04% w/v benzyl alcohol as preservative. (B266)
    • Euthatal (Merial Animal Health Ltd.). Contains 20% w/v Pentobarbitone Sodium BP(Vet). (B266)
    • Lethobarb (Fort Dodge Animal Health) UK. Contains 20% w/v Pentobarbitone Sodium BP. (B266)
    • Pentobarbital Solution 20% for Euthanasia (J.M. Loveridge p.l.c.). Contains 20% w/v Pentobarbital Sodium PhEur. (B266)
Doses / Administration Routes / Frequencies

Use of Drugs (Medication):

  • Before administration of any pharmaceutical product the manufacturer's datasheet must be consulted regarding operator safety, relevant withdrawal times etc.
  • Many drugs are not registered for use in particular species and additional care should be taken in their use, with proper regard for possible toxic effects. 
  • Consideration should be given to relevant legislation regarding the use of drugs.
  • In the UK, guidelines regarding the use of drugs are set out in the Royal College of Veterinary Surgeons' Guide to Professional Conduct 2000: (See: LCofC1 - RCVS Guide to Professional Conduct 2000 - Choice of Medicinal Products).

For euthanasia:

  • 120-200 mg/kg, as necessary. (B201.6.w6)
    • Rapid intravenous injection is the preferred route. (B201.6.w6)
    • Intraperitoneal injection is also acceptable. (B201.6.w6)
    • Intracardiac injection is acceptable in unconscious animals. (B201.6.w6)
Atelerix albiventris - Four-toed hedgehog:
  • 2.0-4.0 ml [Editor's note: formulation not given] per animal, intraperitoneally or intracardiac. (J204.59.w1)

For anaesthesia:

Erinaceus europaeus - West European Hedgehog:

  • Dose described: 25 mg/kg intraperitoneally. "usually effective and, in the authors' experience, safe." (B156.7.w7) [Editors' note: other anaesthetic agents are now considered safer and preferable; this information is included for interest.]

For the control of seizures:

Elephas maximus - Asian Elephant

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 20 - 45 mg/kg intraperitoneally or intravenously. As an anaesthetic "Marginal analgesia; autonomic depression; not recommended.". (B548.w8)
  • For euthanasia: 150 mg/kg intravenously or intraperitoneally, as rapidly as possible or to effect. (B546)

Ferrets - Mustela putorius furo - Ferret:

  • In the control of seizures:
    • 1 - 2 mg/kg orally every 12 hours. Oral elixir for control of seizures. (B602.41.w41)
    • 1 - 2 mg/kg orally once or twice daily. Adjust dose as required for maintenance. (B626.App.w22)
    • 1 - 2 mg/kg orally every 8 - 12 hours. (B631.21.w21)
  • For euthanasia:
    • 25 - 30 mg/kg intramuscularly, subcutaneously or intravenously. (B626.App.w22)

Great Apes

  • Adult Pan troglodytes - Chimpanzee: 100 mg initial dose intravenously, at a rate not exceeding 50 mg per minute. 150-200 mg/kg intramuscularly. (W768.Jun2012.w1)
Monitoring parameters --

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Withdrawal period / Withholding time
Notes Before the use of any pharmaceutical product in food-producing animals the label instructions for the product should be consulted regarding withdrawal requirements.

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Euthanasia solutions are not necessarily sterile and are not suitable for use as general anaesthetic agents. (B201.6.w6)
  • Caution in individuals with hypovolaemia, anaemia, borderline hypoadrenal function, cardiac disease, respiratory disease.
  • Large doses are contraindicated in individuals with nephritis or with severe respiratory dysfunction. (B263)
  • Barbiturates are contraindicated in individuals with previous hypersensitivity reactions to barbiturates. (B263)
  • Barbiturates are contraindicated in individuals with severe hepatic disease/impairment. (B201.6.w6, B263)
  • Not recommended for anaesthesia for caesarean section due to respiratory depression of the fetus(es). (B263)
  • In cats: caution is required as these animals are particularly sensitive to the respiratory depressant effect of barbiturates; female cats are particularly susceptible to this drug. (B263)
  • Do not administer intra-arterially. (B263)
  • With intravenous administration, slow injection is required for assessment of the effects and avoidance of overdose. (B205.5.w5)
  • For euthanasia:
    • Intracardiac injection should not be used for euthanasia of conscious animals, as it is painful. (B201.6.w6)
    • In horses: excitement may occur; if pentobarbitone sodium is used for euthanasia it should be preceded by a short-acting barbiturate or a sedative (e.g. an alpha2-adrenoceptor agonist). (B201.6.w6)
    • Animals given 200mg/ml pentobarbital sodium should not be used for animal or human consumption. (B201.6.w6)
Adverse Effects / Side Effects / Warnings
  • In use as an anaesthetic:
    • Excitement may occur during induction. (B201.6.w6)
    • Marked respiratory and cardiovascular depression. (B201.6.w6)
    • Recovery from pentobarbitone anaesthesia is slow. (B201.6.w6, B205.5.w5)
    • In recovery from pentobarbitone anaesthesia, convulsive movements, paddling and vocalization may occur. (B205.5.w5);  these signs may be suppressed using analgesics or tranquillisers. (B205.5.w5)
    • In dogs: excitement may occur during recovery from pentobarbitone anaesthesia. (B263)
    • Close monitoring of respiration is required during anaesthesia with respiratory assistance readily available. (B263)
    • Hypothermia commonly occurs due to the long recovery period. (B201.6.w6)
  • In small animals, exposure to temperatures below 27C (80.6F) during pentobarbital anaesthesia may lead to hypothermia. (B263)
  • If administering intravenously, inject slowly (except for euthanasia). (B263)
    • Barbiturates may be very irritant if administered subcutaneously or perivascularly; sloughing may result. (B201.6.w6, B263)
  • In use for the treatment of status epilepticus:
    • Avoid overmedication; administer only a sufficient amount to suppress the seizures. (B201.6.w6)
Operator Warnings
  • Before the use of any pharmaceutical product the label instructions for the product should be consulted regarding operator safety/warnings.
  • "Accidental contact through skin, eyes, or ingestion or self-injection may be fatal in humans. Contact area should be washed or irrigated with water and medical aid obtained. In case of accidental self-injection seek urgent medical attention, advising medical services of barbiturate poisoning. Do not leave patient unattended. Maintain airways and give symptomatic and supportive treatment." (B201.6.w6)
Overdose / Acute Toxicity
  • In individuals with liver damage, large doses may cause further hepatic damage. (B205.5.w5)
  • Ingestion of meat from animals euthanased with pentobarbital may be fatal. (B263)
    • Treatment: remove ingested product if appropriate. Provide respiratory and cardiovascular support. (B263)
    • Haemodialysis or peritoneal dialysis may be beneficial in individuals with severe intoxication. (B263)

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Detailed Toxicological Information
Classification  
Acute Toxicity
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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