Page 1130 - Small Animal Internal Medicine, 6th Edition

1102 PART IX Nervous System and Neuromuscular Disorders

necessitates subsequent increases in dose to maintain trough features of significant hepatotoxicity include anorexia, seda-
serum concentration in the therapeutic range. Cats may be tion, ascites, and occasionally icterus. Laboratory testing
VetBooks.ir more susceptible to the sedative effects of PB, so a lower dose typically reveals a large increase in ALT compared with
ALP, decreased serum albumin, abnormal bile acids, and
(1-2 mg/kg twice daily) might be used to initiate therapy.
After 2 to 3 weeks of therapy, the fasted morning pre-
administered dose. All animals receiving chronic PB therapy
pill (trough) blood PB concentration should be deter- an increasing PB concentration despite no increase in the
mined. This should be in the therapeutic range of 25 to should be evaluated every 6 months to assess the effective-
35 µg/mL (107-150 µmol/L) in dogs and 20 to 30 µg/mL ness of their drug regimen, serum concentration of PB, liver
(90-129 µmol/L) in cats. Many references allow a wider enzyme activities, and serum albumin concentration. Liver
therapeutic range in dogs (15 to 35 µg/mL) but report that function testing should be performed if ALT levels suddenly
seizure control is improved at serum concentrations greater increase or if serum albumin levels start to decrease. When
than 25 µg/mL. If the measured serum concentration is too chronic hepatotoxicity is suspected, PB should be discon-
low, the dose of PB should be increased by approximately tinued, the patient should be rapidly switched to an alterna-
25% (see Box 62.6) and the trough serum concentration tive AED, and supportive measures should be initiated for
determined again 2 to 3 weeks later. If the serum concentra- liver failure. The hepatotoxicity is occasionally reversible if
tion is still inadequate, the dose of PB should be increased discovered early.
in 25% increments every 2 to 3 weeks while the blood con- PB increases the biotransformation of drugs metabolized
centration is monitored. Once the measured blood concen- by the liver, decreasing the systemic effects of many drugs
tration of PB is within the therapeutic range, the dog or cat administered concurrently. PB also increases the rate of
should be observed by the owner for a long enough period of thyroid hormone elimination, decreasing measured serum
time (time required for two or three cycles of seizures), and, total and free T 4 and increasing serum thyroid-stimulating
if control is acceptable, therapy is maintained at that dosage. hormone concentrations, but this is rarely associated with
Blood PB concentrations should be reevaluated routinely clinical signs of hypothyroidism (see Chapter 48). PB
every 6 months, 2 weeks after any change in dosage, and administration does not alter endogenous ACTH concen-
whenever two or more seizures occur between scheduled trations, the response to exogenous ACTH, or results of
PB evaluations. Serum separator tubes should not be used to low-dose dexamethasone suppression testing. Drugs that
collect serum for this purpose, because their use will under- inhibit microsomal enzymes (e.g., chloramphenicol, tet-
estimate the concentration of PB. racycline, cimetidine, ranitidine, enilconazole) may dra-
PB is well tolerated in most dogs and cats at therapeutic matically inhibit the hepatic metabolism of PB, resulting
serum concentrations. Sedation and ataxia may be pro- in increased serum concentrations of PB and potentially
nounced for the first 7 to 10 days of therapy or after an causing toxicity.
increase in dosage, but these adverse effects resolve with time Seizures are controlled in 70% to 85% of dogs and most
(10-21 days) as the animal acquires a tolerance for the seda- cats treated with PB monotherapy if serum PB concentra-
tive effects of the drug. Transient (7 days) hyperexcitability tions are maintained within the target range. If seizures con-
occurs as an idiosyncratic effect in up to 40% of dogs and tinue to occur at an unacceptable frequency or severity
cats. The most common persistent adverse effects of PB despite adequate serum concentrations, therapy with addi-
include polyuria, polydipsia, and polyphagia. Owners should tional drugs must be considered.
be advised to refrain from overfeeding dogs receiving PB,
even though their pet may seem ravenous. Neutropenia or POTASSIUM BROMIDE
thrombocytopenia has been recognized in a few dogs within The addition of potassium bromide (KBr) to already estab-
the first 6 months of starting PB, but in most cases these lished PB therapy in dogs with poorly controlled seizures
blood dyscrasias are immune-mediated and they resolve despite adequate serum concentrations of PB effectively
when the PB is discontinued. Acute idiosyncratic hepato- decreases seizure numbers by 50% or more in 70% to 80%
toxic reactions with rapid elevations of alanine aminotrans- of dogs (see Box 62.6). KBr is also effective as a single agent
ferase (ALT) are rare, but should prompt immediate and is considered by many to be the initial AED of choice in
transition to an alternative AED. PB may also be a risk factor dogs with hepatic dysfunction and in large-breed dogs and
for the development of superficial necrolytic dermatitis in working dogs that have unacceptable side effects from PB.
dogs. The drug should not be administered to cats because it can
The most life-threatening potential complication of cause severe progressive bronchitis in that species that can
chronic PB therapy is drug-induced hepatotoxicity. PB is be fatal.
a potent inducer of hepatic enzymes, and mild to moder- Bromide is excreted unchanged by the kidney. It is not
ate elevations in serum alkaline phosphatase (ALP) and metabolized by the liver and does not cause hepatotoxic-
alanine transaminase (ALT) activities are seen in virtually all ity. KBr is typically administered as an inorganic salt dis-
dogs receiving PB; significant hepatotoxicity is uncommon. solved in double distilled water to achieve a concentration
Significant chronic hepatotoxicity is most likely to occur of 200 to 250 mg/mL. Administration of the salt in gelatin
when peak serum PB concentrations are at the high end of capsules is also possible, but the concentrated drug in this
the therapeutic range (>35 µg/mL; >150 µmol/L). Clinical form is more likely to cause gastric irritation and vomiting.