Phenobarbital

(phenobarbital)

Brand

Barbita

(phenobarbital sodium)

Brand

Luminal Sodium

Availability

  • Tablets: 15 mg, 16 mg, 30 mg, 60 mg, 100 mg
  • Elixir: 15 mg/5mL, 20 mg/5mL
  • Injectable: 30 mg/mL

Pharmacology

An antileptic agent, phenobarbital is of the barbiturate class of drugs. It is a central nervous system depressant, and works by facilitating the action of GABA (a neurotransmitter), suppressing the spread of seizure activity, and increasing seizure threshold.

Phenobarbital is one of the least toxic of the antileptics. It has a slow onset and long duration of action. Although it is the least toxic of this classification of drugs, it is considered to have a narrow margin of safety when used in rats and mice due to its link to hepatic and thyroid changes over lifetime use. However, in many of these studies, doses were given at toxic levels to determine what effect it might have on various organs when used in humans.

Phenobarbital is distributed widely throughout the body. Its rate of distribution into the central nervous system is slower than other barbiturates due to its low lipid solubility. It is also slowly absorbed in the GI tract.

The class of barbiturates can cause fetal damage and should not be used during pregnancy if possible.

Phenobarbital is metabolized in the liver and excreted partially unchanged in the kidneys. It has also been shown to be excreted in breast milk.

Indications

Used to treat generalized tonic-clonic, or focal type seizures.

Drug Interactions or Contraindications

  • An increased risk of hepatotoxicity can occur when acetaminophen (e.g., Tylenol) is given with long term (chronic) use of phenobarbital.
  • The effects of phenobarbital may increase if used with other CNS depressants such as:
    • antihistamines
    • diazepam (valium)
    • opiate narcotics
    • phenothiazines (e.g., Phenergan)
    • valproic acid (e.g., Depakote)
  • Phenobarbital may lower serum concentrations of the following drugs thereby decreasing their effects:
    • anticoagulants
    • Beta-Blockers (e.g., atenolol)
    • chloramphenicol
    • corticosteroids
    • doxycycline
    • griseoflvin
    • metronidazole
    • theophylline

Adverse Reactions

CV: slow heartrate (bradycardia), low blood pressure (hypotension).

CNS: lethargy, sedation, ataxia, or paradoxical excitement. Often dose related, these signs may subside with continued therapy. Monitor closely.

Resp: breathing depressed

GI: polydipsia (increase thirst)

GU: polyuria (increased urine output)

Skin: abscess or necrosis at injection site

Dosage Recommendations

Initial dose is 2 mg/kg, PO, BID (twice a day or every 12 hours), and gradually increasing to 4 mg/kg , PO, BID (twice a day or every 12 hours), depending on effectiveness in controlling seizure activity. 12, 16

or

Example of treatment regimen in seizures:

  • Initiate phenobarbital at 2 mg/kg BID, and increase to control by 0.5 mg/kg to maximum of 3.5 mg/kg. If seizures not controlled in three days add Potassium Bromide at 35 mg/kg once a day. If seizures controlled continue regimen for two weeks to maintain level. If seizures continued to be controlled phenobarbital can begin to be decreased allowing for meds to trough approximately 5 days before each decrease change until phenobarbital is stopped, and the rat able to be maintained on the Potassium Bromide at prescribed dose. 18

*Note: instruct pet owner to observe their pet rat closely, and report increased lethargy, increased excitability, bleeding, or changes in frequency, duration, and appearance of seizures.

Considerations

  • Do not skip doses, or stop drug suddenly, as this may initiate a seizure or cause seizures to worsen. Consult with veterinarian.
  • Encourage increase fluid intake by providing fresh fruit that is juicy.
  • Give with food, if possible, to decrease chance of distress to GI tract.
  • Injections may cause sterile abscesses with sloughing of tissue. Oral dosing is the preferred method for rats.
  • Do not use solutions that are discolored or that contains precipitates.
  • *Note: phenobarbital may be combined with potassium bromide(KBr), or gabapentin where seizures are refractory to phenobarbital treatment alone; or where the reduction of phenobarbital is desired due to side effects.

References
  1. Kolaja, K., Stevenson, D., Johnson, J., Walborg, E., & Klaunig, J. (1996). Subchronic effects of dieldrin and phenobarbital on hepatic DNA synthesis in mice and rats. Fundam Appl Toxicol, 29(2), 219-28. Retrieved December 15, 2008, from the PubMed database.

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