Phenobarbital

Phenobarbital In Dogs & Cats: Uses, Dosage and Side Effects

Overview

• It has an antiepileptic effect through affinity for the GABAA receptor, resulting in a GABA-ergic effect; GABA is the major inhibitory mammalian neurotransmitter with prolonged chloride channel opening.
• Phenobarbital also blocks the AMPA receptor, inhibiting the release of the excitatory
  neurotransmitter glutamate.
• This combined potentiation of GABA and inhibition of glutamate leads to reduced neuronal excitability.

Uses of Phenobarbital

• Phenobarbital and imepitoin are primary choices for treating idiopathic epilepsy in dogs, with phenobarbital being cost-effective and highly effective. In contrast, imepitoin offers a faster onset of action, doesn’t require steady-state levels, and has a milder side effect profile.
• They are also approved for managing seizures caused by structural brain disease in dogs and are utilized for treating seizures in cats.
• Additionally, phenobarbital, in combination with propranolol and behaviour modification, can be used in dogs to control fears and anxieties, particularly those influenced by physiological factors.

Dose of Phenobarbital in Dogs and Cats

Dogs

• Epilepsy treatment: the recommended initial oral dose is 1–2.5 mg/kg every 12 hours, but due to concerns about achieving therapeutic serum levels, an initial dose of 2.5–3 mg/kg every 12 hours is often suggested, with subsequent adjustments based on serum concentrations.
• In emergencies like status epilepticus: a loading dose of 18–24 mg/kg is advised for dogs not on maintenance phenobarbital, administered in three stages, while dogs on maintenance phenobarbital may receive 4–6 mg/kg intravenously or intramuscularly for slight blood level elevation.
• In cases of fear and anxiety control: a dose of 2–3 mg/kg every 12 hours is recommended along with propranolol at the same dosage.

Cats:

• Initial therapy: 1.5–3 mg/kg p.o. q12h.
• Emergency management: doses as for dogs.

Side Effects of Phenobarbital in Dogs and Cats

• Sedation, ataxia, polyphagia, and polyuria/polydipsia are common side effects.
• Polyphagia and polyuria/polydipsia may persist throughout treatment.
• Ataxia and sedation are common initially but typically resolve within a week, potentially continuing with high doses.
• Hepatic toxicity is rare but may occur at high serum concentrations or as an idiosyncratic reaction within two weeks of starting treatment.
• Hyperexcitability has been reported at subtherapeutic doses.
• Hematological abnormalities, including neutropenia, anemia, and thrombocytopenia, may occur.
• Superficial necrolytic dermatitis is a rare side effect.
• Long-term use without hepatotoxicity may show a moderate increase in liver size on radiographs, with no changes in echogenicity or architecture on ultrasonography.
• Morphological liver damage is typically absent on histology, but there may be a significant increase in ALP and, to a lesser extent, ALT activity.
• Albumin may be transiently decreased up to six months after starting therapy, and GGT may increase.
• Other parameters like serum AST, bilirubin, and bile acid assay, as well as ultrasonographic examination, should be assessed for liver function.
• Phenobarbital treatment does not affect adrenal function tests but does lead to a decrease in total T4 and free T4, while cholesterol levels tend to increase toward the upper limits of the normal range

Contraindications of Phenobarbital in Dogs and Cats

• Avoid administration to animals with impaired hepatic function.
• Not recommended for use in pregnant animals and nursing bitches, although the risk of uncontrolled seizures may outweigh the potential risks associated with phenobarbital.
• Do not use for controlling seizures resulting from hepatic disease (e.g., portosystemic shunt), hypoglycemia, or toxic causes where clinical signs are mediated through GABA channels (e.g., ivermectin and moxidectin toxicity) as it may worsen seizures.
• Avoid administering high doses via intravenous (i.v.) or intramuscular (i.m.) injection in animals with marked respiratory depression.
• When used in combination with propranolol, adhere to the normal contraindications associated with propranolol.

Some Notes: