Page 404 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Over-the-Counter Drugs Chapter | 21 371

VetBooks.ir toxicosis of products containing bismuth subsalicylate, an aspirin doses between 100 and 110 mg/kg in cats have
caused death within 7 days (McKellar et al., 1991).
OTC drug commonly used for gastrointestinal distress, are
Young cats, old cats, or cats with renal or hepatic disease
similar to those associated with other sources of salicylate,
thus these products will be further discussed in this section. are believed to be particularly sensitive (Kore, 1990).
However, lesions unique to bismuth subsalicylate are Aspirin can be used in cattle and goats, but they
described under gastroprotectants. require larger oral doses to reach appropriate plasma con-
Salicylates have been used since ancient times by centrations. A dose of 100 mg/kg PO given every 12 h in
Greek and Roman physicians, Hippocrates and Galen, by cattle maintains a therapeutic concentration of 30 μg/mL
South African tribes, and by North American Indians. (Davis, 1980; Boothe, 2001). IV dosing with 6.5 mg/kg
Reverend Edmund Stone wrote of the use of Salix alba hourly is associated with plasma concentrations of
bark in the journal of the Royal Philosophical Society in 50 20 μg/mL, 26 mg every 1.6 h yields plasma concen-
London in 1763. Salicylic acid was first isolated from the trations of 200 50 μg/mL, and 39 mg every 2 h yields
bark of willows (Salix spp.) and beech trees (Fagus spp.) concentrations of 300 50 μg/mL in the plasma. Horses
in the early 19th century (Lees et al., 1991). Bayer can be given 35 mg/kg aspirin IV, according to Davis
Pharmaceutical Company synthesized acetylsalicylic acid (1980). However, a single oral dose of 20 mg/kg was
in 1893, and aspirin has been marketed since 1899. associated with prolonged bleeding times (Boothe, 2001).
Contraindications for aspirin use include coagulation
disorders, recent (within 1 week) surgery, and concur-
rent use with certain drugs. See Table 21.2 for a list of Toxicokinetics
drugs that may interact with aspirin and other NSAIDs. Aspirin is lipophilic at acid pH, thus it is readily absorbed
Aspirin inhibits the diuretic effects of spironolactone from the stomach and duodenum in dogs and cats (Rubin
(Verbeeck, 1990). and Papich, 1990; Talcott, 2006). Aspirin is 68% 76%
bioavailable in dogs, with some variation based on the
formulation (Boothe, 2001). Enteric-coated and buffered
Toxicity products are used in humans and dogs (McKellar et al.,
The efficacy of aspirin is dose-dependent. Aspirin is used 1991; Murtaugh et al., 1993; Boothe, 2001). Buffered
in dogs at doses of 10 25 mg/kg every 8 12 h for anal- aspirin is more soluble and less ionized, thus slowing
gesia. Dogs dosed with 25 mg/kg aspirin every 8 h for up absorption and decreasing gastric irritation. Acid-resistant
to 3 weeks had no serious adverse effects, and peak forms are more readily absorbed at the relatively alkaline
plasma concentrations were .50 μg/mL in mature dogs pH range of the duodenum, and absorption is delayed up
(Lees et al., 1991). The half-life is likely to be increased to 12 h (Verbeeck, 1990). Ingestion of a fatty meal can
in pups less than 30 days old due to limited metabolic reduce aspirin bioavailability by 30% (Mazue ´ et al.,
capability (Waters et al., 1993). A study of dogs dosed 1982). Aspirin is 70% bioavailable in cattle, but absorp-
with 25 35 mg/kg aspirin every 8 h found increased fecal tion is relatively slow. Salicylates in bismuth subsalicylate
hemoglobin, and gastric ulcerations were visualized on are 97.5% absorbed in dogs and 85.4% absorbed in cats
endoscopy (McKellar et al., 1991). Seizures were reported (Papich et al., 1987).
in a dog given 37 mg/kg aspirin every 12 h for 2 weeks Peak serum concentrations occur 4 h after oral dosing
(Schubert, 1984). Clinical signs in dogs dosed with with buffered aspirin. Peak serum concentrations are
50 mg/kg aspirin every 12 h included emesis, and similar lower in immature dogs than in mature dogs after PO or
daily doses were associated with perforating gastric ulcers IV dosing. Circulating salicylate is 72% protein-bound in
within 4 weeks (Kore, 1990). One dose of 400 mg/kg humans and 45% protein-bound in dogs. There is more
caused hemorrhage, and daily dosing caused pyloric free and, therefore, bioavailable salicylate in the hypoal-
ulcers within 2 weeks (Mazue ´ et al., 1982). buminemic animal, but the excess is rapidly eliminated
Cats are more susceptible to the toxic effects of aspirin (Boothe, 2001). Aspirin is rapidly distributed to most tis-
than dogs and humans (Papich, 1990; Roder, 2004a). sues, including synovial fluid, peritoneal fluid, saliva, and
Doses of 25 mg/kg every 2 3 days are recommended to milk. Aspirin has a lower volume of distribution in cattle
control thromboembolic disease, and 10 mg/kg every compared to other domestic species (Davis, 1980).
other day can be used for analgesia and antipyresis Aspirin is rapidly hydrolyzed to salicylate by esterases
(Plumb, 2015). A dose of 10.5 mg/kg aspirin every 52 h in the gastrointestinal tract, liver, and erythrocytes. These
produced plasma concentrations ranging from 50 to enzymes are less efficient in immature dogs (Waters
20 μg/mL. No clinical signs were seen in cats dosed with et al., 1993). Most of the metabolism takes place in the
25 mg/kg aspirin every 48 h, and no severe signs were liver. Salicylate is bioactive, and responsible for most of
seen in cats dosed with 25 mg/kg aspirin every 24 h for the clinical effects of aspirin. Salicylate is conjugated to
2 3 weeks (Lees et al., 1991; Boothe, 2001). Daily glucuronide or glycine. The glucuronide pathway is