Page 396 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Over-the-Counter Drugs Chapter | 21 363

VetBooks.ir TABLE 21.1 An Incomplete List of Nonsteroidal toxicosis than other species (Roder, 2004a), and dogs are
very sensitive to ibuprofen (Rubin and Papich, 1990).
Antiinflammatory Drugs
Attempts should not be made to extrapolate the therapeu-
Carboxylic Acid Group Enolic Group tic dose from one species to another (Lees et al., 1991).
Individual factors also affect susceptibility to NSAIDs.
Salicylic Acid Derivatives Pyrazolone Young and aged animals do not have the same metabolic
Derivatives
capacity as mature animals. Drug excretion can be
Aspirin Azapropazone delayed in animals with poor hepatic or renal function
(Lees et al., 1991; Isaacs, 1996; Roder, 2004a).
Diflunisal Dipyrone
Dehydration and cardiac disease decrease renal circula-
Salicylates Isopyrin
tion, slowing drug excretion and promoting renal damage.
Oxyphenbutazone Preexisting gastrointestinal disease could predispose to
Phenylbutazone ulceration when NSAIDs are used.
Various drugs interact with NSAIDs. Changes in bio-
Acetic Acid Derivatives Oxicam Derivatives
availability are by inhibition of absorption, displacement
Etodolac Lornoxicam
from plasma- and tissue-binding proteins, and competition
Indomethacin Meloxicam for active renal secretion. Some drugs enhance or dimin-
ish metabolism of other drugs by hepatic cytochrome
Sulindac Piroxicam
P450 enzymes. An incomplete list of possible interactions
Tolmetin Tenoxicam
is provided in Table 21.2. NSAIDs also affect the bio-
Diclofenac availability of other drugs. There have been reports of
Fenamates/Anthranilic Acid Coxibs deaths in people using NSAIDs with methotrexate, and
Derivatives ibuprofen decreases renal clearance of digoxin and lith-
Flufenamic acid Celecoxib ium. The diuretic effects of furosemide and bumetanide,
which are mediated by prostaglandins (PGs), are inhibited
Meclofenamic acid Deracoxib
by NSAIDs. NSAIDs do not influence response to thia-
Mefenamic acid Firocoxib zide diuretics in this way, but decrease the hypotensive
Tolfenamic acid Robenacoxib response. NSAIDs can decrease the effectiveness of
angiotensin-converting enzyme (ACE) inhibitors such as
Propionic Acid Derivatives
captopril. NSAIDs have additive effects when used
Carprofen together, with decreased rates of metabolism and clear-
Ibuprofen ance for each (Lees et al., 1991; Verbeeck, 1990).
NSAIDs also have additive effects when used with corti-
Fenoprofen
costeroids, and such mixing should be avoided.
Flurbiprofen
Ketoprofen
Toxicity
Naproxen
There are species differences in NSAID tolerance, as
Suprofen
noted above. Dogs are more susceptible to ibuprofen and
Tiaprofenic acid naproxen toxicosis than many other species (Kore, 1990;
Flurbiprofen McKellar et al., 1991; Isaacs, 1996). Use of these drugs in
dogs should be avoided. Ibuprofen doses greater than
Aminonicotinic Acid Derivatives
5 mg/kg have been associated with adverse reactions in
Flunixin meglumine
dogs (Villar et al., 1998). Gastric lesions occurred in dogs
when 8 mg/kg/day ibuprofen was given over a 30-day
period, either PO or parenterally, although clinical signs
were not evident (McKellar et al., 1991; Godshalk et al.,
or anthranilic acid and propionic acid derivatives, as well as 1992; Boothe, 2001; Talcott, 2006). Clinical signs were
the enolic acid groups. An incomplete list of NSAIDs is evident in dogs dosed with 16 mg/kg/day for 8 weeks.
provided in Table 21.1. Single doses of 50 125 mg/kg have been associated with
The mechanism of action is similar for all drugs in gastrointestinal signs (Jackson et al., 1991; Murphy, 1994;
this classification. However, toxicity and pharmacokinetic Talcott, 2006), and a perforating gastric ulcer was
data vary markedly between the different compounds and reported in a dog given a cumulative dose of 110 mg/kg
species. Cats, e.g., are more susceptible to salicylate ibuprofen over a period of 48 h (Godshalk et al., 1992).