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Phenobarbital: Adverse Effects/Toxicosis 783.e3

Phenobarbital: Adverse Effects/Toxicosis Client Education
Sheet
VetBooks.ir Diseases and Disorders

BASIC INFORMATION
acid (GABA), inhibition of glutamate
(excitatory neurotransmitter) and increasing TREATMENT
Definition the motor cortex’s threshold for electrical Treatment Overview
Adverse effects result from chronic dosing stimulation. Discontinue phenobarbital and substitute
of phenobarbital for seizure control or an • Sedation, ataxia: direct central nervous system another anticonvulsant (p. 903); treat complica-
acute overdose (ingestion or injection). See (CNS) effects occur early in treatment, tions symptomatically.
the Barbiturates Toxicosis chapter for more usually resolve within 1 week, but can recur
information. with increase in dose. Acute General Treatment
• Polyuria, polydipsia, polyphagia: likely to • The Barbiturates Toxicosis chapter describes
Epidemiology persist throughout therapy treatment for acute toxicosis.
SPECIES, AGE, SEX • Hepatic enzymes: alkaline phosphatase • With neurologic signs
All species, sexes, and ages are at risk. (ALP) elevation in 50% of dogs; elevated ○ Discontinue medication.
alanine aminotransferase (ALT) in 25% ○ Activated charcoal 1-2 g/kg PO once with
RISK FACTORS of dogs within weeks to months; can sorbitol or other cathartic can help reduce
Human or animal in household taking phe- be due to benign induction of enzymes blood levels; repeating charcoal (one-half
nobarbital for seizure control (upregulation) or liver injury; hepato- of the original dose, omitting the cathartic)
toxicosis is rare and usually associated with q 6-8h until improvement of CNS depres-
Clinical Presentation months to years of therapy with high drug sion helps decrease severity and duration
DISEASE FORMS/SUBTYPES concentrations of signs. Monitor for hypernatremia
Chronic exposure: • Hyperactivity: associated with low serum and associated signs (tremor, ataxia,
• Elevated liver enzymes associated with levels of phenobarbital seizures).
upregulation or rare hepatotoxicity • Decreased T 4 : increased metabolism and ○ Hemodialysis, charcoal hemoperfusion,
• Sedation, ataxia; rarely agitation excretion of thyroid hormones; 40% of dogs or plasma exchange may be considered
• Polyuria, polydipsia within weeks if available.
• Polyphagia, weight gain • Blood dyscrasias: rare; neutropenia, ○ IV lipid emulsion: IV administration of
• Neutropenia, anemia, thrombocytopenia (can thrombocytopenia, anemia within weeks lipid emulsion may decrease severity and
be selective or pancytopenia) (idiosyncratic or immune) duration of signs and may be considered
• Decreased total T 4 and free T 4 in severe cases with coma and at risk of
• Hypercholesterolemia DIAGNOSIS developing apnea. This potentially can
• Dermatologic reactions enhance elimination of lipophilic barbitu-
○ Crusting of footpad and hyperkeratosis Diagnostic Overview rates; however, efficacy varies significantly
(canine superficial necrolytic dermatitis – With chronic dosing, liver enzymes, CBC, between cases. Risk of hyperlipidemia,
progressive disorder associated with liver and serum phenobarbital levels should be pancreatitis, and hemolysis from therapy
disease) monitored. (p. 1127)
○ Mucocutaneous eruptions • With chronic exposure and increased liver
Acute overdose: Differential Diagnosis enzymes
• Ataxia, sedation, hypotension, coma, • Depends on adverse effects ○ If ALP is elevated but other hepatic
hypothermia, respiratory depression, death • Chronic hepatopathy (pp. 174 and 452) enzymes and indicators of liver function
are normal, monitor serum phenobarbital
HISTORY, CHIEF COMPLAINT Initial Database concentration, and rule out other causes
• History of accidental overdose (ingestion • Chemistry panel: increase in ALP is an of elevated ALP (e.g., glucocorticoid use,
or injection) or chronic treatment with expected consequence of treatment, but hyperadrenocorticism)
phenobarbital increase in ALT or reduction of synthetic ○ If both ALP and ALT are elevated but
• Ataxia, lethargy, weight gain or loss functions (hypoalbuminemia, hypocholes- there is no indication of hepatic dysfunc-
• Complaints typical of hepatic cirrhosis terolemia, hypoglycemia, low blood urea tion, change to different antiepileptic
(p. 174) nitrogen [BUN]) or hyperbilirubinemia or reduce dose (if serum concentration
• Laboratory evidence of toxicity discovered suggests hepatotoxicity. suggests dose is excessive).
incidentally or during routine screening for • CBC: if (rare) blood dyscrasias, pancytopenia ○ If hepatotoxicosis is likely; discontinue
toxicity recognized medication, and address hepatopathy
• Serum phenobarbital level directly (pp. 174, 442, and 452).
PHYSICAL EXAM FINDINGS • Abdominal radiography (liver enlargement or • Blood dyscrasias or dermatologic signs:
• Chronic: sedation, ataxia, agitation (rare), microhepatica), ultrasonography (no changes discontinue medication and treat symp-
abdominal pain, enlarged liver, icterus, in echogenicity with enzyme induction; tomatically.
ascites, footpad crusting and hyperkeratosis, changes with hepatotoxicosis)
ecchymosis; exam can be unremarkable • Bile acids to assess hepatic function Drug Interactions
• Acute: ataxia, sedation, weakness, hypother- • Coagulation profile (p. 1325) before liver • Increased CNS depression: antihistamine,
mia, hyporeflexia, hypotension, hypothermia, biopsy narcotics, phenothiazine, benzodiazepines
coma, respiratory depression • Enhanced metabolism: glucocorticoids,
Advanced or Confirmatory Testing beta-blockers, metronidazole, theophylline,
Etiology and Pathophysiology • Histopathology of liver, biopsy (p. 1128) tricyclic antidepressants
• Antiepileptic effect is thought to be from • Bone marrow aspirate if blood dyscrasias • Decreased absorption: griseofulvin
enhancing responsiveness to inhibitory (p. 1068) • Increased phenobarbital levels: cimetidine,
postsynaptic effects of gamma-aminobutyric • Skin biopsy if dermal lesions (p. 1091) ketoconazole, chloramphenicol

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