Page 1108 - Clinical Small Animal Internal Medicine

1046 Section 9 Infectious Disease

experimental dogs given four times the recommended including vomiting and diarrhea after oral administra-
VetBooks.ir dose of ofloxacin. The use of fluoroquinolones is gener- tion. Clindamycin capsules have been associated with
esophageal strictures in cats. Stricture formation is
ally avoided in young puppies (<8 months), but in an
experimental study in young beagles (13–16 weeks old),
mucosal contact of the capsule if administration is not
an oral dose of ciprofloxacin 10 mg/kg/day for 14 days thought to occur secondary to prolonged esophageal
did not induce joint lesions. preceded or followed by food or liquid.
A species‐specific side‐effect of the fluoroquinolones Potential drug interactions associated with some
is dose‐dependent retinal toxicity in cats. Cats are func- macrolides are their ability to inhibit the metabolism of
tionally deficient in the ATP‐binding cassette subfamily other drugs which are substrates of the CYP3A subfam-
G member 2 (ABCG2) protein, encoded by the ABCG2 ily of the microsomal cytochrome P450 enzyme system.
gene. This membrane‐associated protein functions at Erythromycin and clarithromycin are inhibitors of
the blood–retinal barrier to limit xenobiotics (e.g., fluo- CYP3A (i.e., CYP3A4 in people) which will inhibit the
roquinolone) from entering the retina. When fluoroqui- metabolism of CYP3A substrate drugs (e.g., theophyl-
nolones are administered to cats, the photosensitive line), leading to toxicity when prescribed concurrently.
fluoroquinolones have access to the retina, leading to Azithromycin is not a cytochrome P450 inhibitor.
retinal degeneration and blindness. All fluoroquinolones
have the potential to cause retinal lesions with a modest Nitroimidazoles (e.g., Metronidazole)
overdose in cats, although there are differences between
the fluoroquinolones. Retinal toxicity has been reported Metronidazole has activity against anaerobes to include
for enrofloxacin at 4-times the label dose and orbifloxa- Bacteroides (B. fragilis), Fusobacterium, and Clostridium
cin at 18-times the label dose. In contrast, marbofloxacin species. Other organisms susceptible to metronidazole
and pradofloxacin did not cause retinal lesions when include Giardia and Trichomonas. An overdose of metro-
administered at 20-times and 10-times the label dose, nidazole is associated with neurotoxicity leading to cere-
respectively. To minimize retinal toxicity in cats, the rec- bellovestibular ataxia in dog and cats. The mechanism of
ommended label dose should not be exceeded, rapid IV toxicity is thought to be inhibition of the gamma‐amin-
infusions and prolonged treatment durations should be obutyric acid (GABA) neurotransmitter. At toxic doses,
avoided, and dose adjustment in patients with underly- clinical signs include ataxia, nystagmus, and propriocep-
ing kidney disease should be considered. tive deficits which are reversible once the drug is discon-
Two important drug–drug interactions are associated tinued. To avoid toxicity in patients with impaired liver
with clinical use of fluoroquinolones. Orally adminis- function, dose reduction is recommended (e.g., an empiri-
tered fluoroquinolones chelate with di‐ or tri-valent cal dose reduction to 7.5 mg/kg twice a day for metronida-
cations (e.g., calcium, aluminum, or magnesium), result- zole in patients with underlying liver failure or cirrhosis).
ing in decreased absorption. The co‐administration of
fluoroquinolones with antacids containing aluminum Potentiated Sulfonamides
or magnesium, or sucralfate should be avoided. If co‐
administration is necessary, separate the administration The potentiated sulfonamides provide broad‐spectrum
times by at least two hours (e.g., give the fluoroquinolone activity against gram‐positive and gram‐negative
at least two hours before any products that contain di‐ or organisms and some activity against Coccidia and
tri-valent cations). Fluoroquinolones inhibit the hepatic Toxoplasma. Pseudomonas aeruginosa is not susceptible
microsomal cytochrome P450 enzyme system, specifi- to the potentiated sulfonamides. Many Staphylococcus
cally CYP1A2 in people. CYP1A inhibition will decrease spp., including methicillin‐resistant Staphylococcus
the elimination of substrate drugs, like theophylline, pseudintermedius (MRSP), remain susceptible to the
resulting in clinical signs of theophylline toxicity potentiated sulfonamides. The major limitation of the
( tachycardia, excitability, tremors, or seizures). In clini- use of potentiated sulfonamides in veterinary medicine,
cal practice, it would be best to avoid the concurrent and specifically in dogs, is the risk of an idiosyncratic
therapy of a fluoroquinolone (e.g., ciprofloxacin) with and/or dose‐dependent side‐effect.
theophylline. Alternatively, a significant reduction in the Sulfonamide‐induced side‐effects in dogs may be
theophylline dose can be considered to avoid toxicity. in part due to the dog’s inability to metabolize the sul-
fonamides via acetylation (the major metabolic pathway
for sulfonamides in people). The underlying pathophys-
Lincosamides and Macrolides
iology is not well understood but in part involves
The lincosamides and macrolides have a similar spectrum immune‐mediated mechanisms. For example, sulfona-
of activity to include most gram‐positive organisms. mide metabolites may play a role in triggering a T cell‐
The most common side‐effects are gastrointestinal signs, mediated response to haptenated proteins.