Page 1380 - Cote clinical veterinary advisor dogs and cats 4th

696 Nonsteroidal Antiinflammatory Drug Toxicosis

RISK FACTORS ○ Cyclooxygenase 2 (COX2) inhibitors: ○ Liver (if persistent enzyme elevation;
• Pre-existing GI, renal, cardiovascular, or celecoxib, firocoxib (Previcox),* deracoxib rarely performed): multifocal to bridging
†
VetBooks.ir • Dehydration, hypotension, and concurrent ○ Prostaglandin E 2 EP4 receptor blocker: (apoptosis), with mild to moderate
hepatocellular degeneration and necrosis
(Deramaxx),* robenacoxib (Onisor)*
hepatic disease may increase severity of signs.
periportal inflammation (neutrophils and
use of other potentially nephrotoxic drugs
grapiprant (Galliprant)*
can potentiate signs.
• Concurrent use of NSAIDs with other • NSAIDs inhibit COX enzymes, blocking lymphocytes)
prostaglandin (PG) production. PGs formed
NSAIDs or glucocorticoids can lead to by COX1 are important for normal physi- TREATMENT
life-threatening complications. ologic function (GI protection, renal med-
• Hypoproteinemia or concurrent use of other ullary blood flow). PGs formed by COX2 Treatment Overview
highly protein-bound drugs can result in mediate inflammation. Adverse effects are Treatment goals are decontamination (acute
higher active drug levels. generally fewer when COX2 is selectively ingestion; induce vomiting and potentially
inhibited; however, in overdose situations, repeated doses of activated charcoal); preventing/
Clinical Presentation selectivity is lost. managing/monitoring GI, renal, hepatic and
DISEASE FORMS/SUBTYPES • Platelet aggregation can be affected by hematologic effects; and supportive care
• Acute toxicosis: single, large ingestion (usually NSAIDs because they inhibit the forma-
5-10 times the recommended dose) tion of platelet thromboxane through COX Acute General Treatment
• Chronic toxicosis: in sensitive animals after inhibition. • Decontamination (p. 1087):
NSAID use for days, weeks, or months at • NSAID hepatopathy is thought to result ○ Induction of emesis (p. 1188): indicated
recommended doses from formation of antigenic proteins that in the first 1-2 hours in acute overdose
trigger an immune-mediated attack against patient not showing clinical signs
HISTORY, CHIEF COMPLAINT the liver. ○ Activated charcoal 1-2 g/kg PO (or as
• History of exposure (acute or chronic) to labeled) with a cathartic if over a potential
an NSAID DIAGNOSIS renal toxic dose, repeated (one-half dose) q
• Clinical signs can begin within hours after 6-8h to reduce enterohepatic recirculation
acute exposure, or days to weeks later with Diagnostic Overview of NSAID if indicated
repeated/chronic therapeutic use or when In most cases, exposure is known (whether acute • Prevent and/or manage GI effects with
hepatopathy develops. overdose or ongoing therapeutic administra- combination therapy (sucralfate + proton
• Vomiting (± hematemesis), anorexia, lethargy, tion). In acute overdoses, history and clinical pump inhibitor [PPI] + misoprostol):
diarrhea (melena) due to GI irritation/ulcer signs may be sufficient to make the diagnosis. In ○ For dogs, misoprostol 2-5 mcg/kg PO q
• Polyuria, polydipsia due to kidney disease/ chronic treatment-associated toxicosis, detailed 8-12h; prostaglandin analog helps replace
kidney injury diagnostic testing and/or drug discontinuation NSAID-induced PG depletion.
• CNS signs are possible. for regression of signs is needed to distinguish ○ PPI: omeprazole 0.5-1 mg/kg PO q 12-24h
NSAID toxicosis from other naturally occurring (dogs, cats), or esomeprazole 0.5-1 mg/kg
PHYSICAL EXAM FINDINGS disorders mimicking NSAID toxicosis. PO q 12-24h, or pantoprazole 0.7-1 mg/
Varies from minor GI signs to signs caused by kg IV over 15 minutes q 24h
life-threatening GI perforation or kidney injury Differential Diagnosis ○ Sucralfate 0.25-1 g PO q 6-12h (dogs,
• Minor to moderate toxicosis: signs of Any disease process that can cause GI, cats), given in addition to PPI
abdominal pain, vomiting, diarrhea, lethargy renal, hepatic, CNS, or hematologic adverse • Prevent and/or manage renal effects.
• Severe toxicosis: dehydration, pallor, tachycar- effects ○ Fluid diuresis (2-3 times maintenance rate,
dia, icterus, bruising (aspirin), hyperthermia barring cardiovascular disease; monitor
(aspirin), sudden death Initial Database renal output) to enhance NSAID excre-
• CNS signs (lethargy, ataxia, coma, seizures) • CBC: anemia from GI hemorrhage (usually tion and maintain renal perfusion for 48
can be seen with large doses of some NSAIDs regenerative), leukocytosis (stress or perito- hours if potential renal toxic dose has been
(ibuprofen, phenylbutazone). nitis) is possible. ingested (72 hours for naproxen due to
• Neither hematemesis or melena is reli- • Serum chemistry profile: azotemia (prerenal long half-life)
ably linked to GI perforation. Absence of or primary renal insult [usually within 24-48 • Manage hepatic effects.
hematemesis does not indicate absence of hours after exposure in acute toxicosis]) ○ Discontinue use of NSAID.
perforation. or elevated liver enzymes and bilirubin ○ IV fluids
(hepatopathy) ○ Administer vitamin K 1 1-5 mg/kg PO if
Etiology and Pathophysiology • Urinalysis: hematuria, glycosuria, pyuria, evidence of coagulation disruption.
• Examples of commonly implicated NSAIDs: proteinuria, casts, and isosthenuria possible ○ S-adenosyl-l-methionine (SAMe) 18 mg/
○ Acetic acid derivatives: diclofenac, etodolac with renal injury kg PO q 24h for 1-3 months
(EtoGesic),* indomethacin, nabumetone, • Abdominal radiographs: free air in peritoneal • Supportive care
ketorolac cavity strongly suggests GI tract perforation. ○ Control vomiting with maropitant 1 mg/kg
○ Fenamic acids: meclofenamic acid SQ q 24h or metoclopramide 0.2-0.5 mg/kg
†
○ Oxicams: meloxicam (Metacam),* Advanced or Confirmatory Testing q 6-8 h PO, SQ, or IM or 0.01-0.09 mg/
piroxicam • Usually, serum/plasma drug levels are not kg/hr IV as constant-rate infusion
○ Propionic acids: carprofen (Rimadyl),* useful clinically. ○ Correct fluid losses and electrolyte changes.
flurbiprofen, ibuprofen, ketoprofen, • Endoscopy (with persistent nonspecific GI ○ Control seizures with diazepam 0.5-1 mg/
naproxen signs to rule out GI ulceration/irritation/ kg IV.
○ Azole derivatives: phenylbutazone, perforation) ○ Blood transfusion if needed (p. 1169)
tepoxalin • Histopathologic evaluation of tissues ○ Treat GI tract perforation or enteropathy
○ Salicylic acid derivatives: aspirin, flunixin ○ Stomach (endoscopic or surgical): (laparotomy, antibiotics) if suspected.
meglumine irritation/duodenal ulceration/hemorrhage;
peritonitis if gastric perforation Nutrition/Diet
○ Kidneys (postmortem): renal tubular or Use appropriate prescription diets for patients
*Approved for use in dogs in the United States.
† Approved for use in cats in the United States papillary necrosis or interstitial nephritis with kidney or liver dysfunction.
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