Drugs- NSAID/ acetaminophen Flashcards
Important information to gather when animal ingests drug
-active ingredient
-strength/composition (rapid release, extended release/long lasting)
-estimated amount ingested
-time ingested
Common NSAIDs in vet med
-meloxicam
-robenacoxib (onsior)
-carprofen (Rimadyl)
-phenylbutazone
-Banamine
Exposure scenarios of NSAIDs
-overdose of prescribed med
-combination therapy
-accidental ingestion of improperly stored medications
-well meaning owner gives human NSAID OTC
What are the most common NSAID toxicities in animals?
- OTC NSAIDs
- Ibuprofen and naproxin
What are the target organs for NSAIDs?
-GI tract
-kidneys
-CNS
-sometimes hepatotoxicity
*worse with dehydration
NSAID mechanism of toxicity
Inhibits the COX expression resulting in decreased prostaglandin production
-decreased GI mucosal and renal blood flow
-decreased mucosal barrier repair and cell turnover
-decreased GI immune function
-decreased GI mucosal protection (bicarbonate and mucus secretion)
Toxicokinetics of NSAIDs
-highly protein bound
-undergoes enterohepatic recirculation
NSAID toxicity small animal species differences
-cats twice as sensitive as dogs because poor glucuronide conjugation
-cats with renal failure, dogs with GI ulcers
-ferrets very sensitive to ibuprofen
NSAID toxicity large animal species differences
-horses= narrow margin of safety; ponies and foals more sensitive
-uncommon in cattle and small ruminants
NSAID toxicity onset
Within hours to days (dose dependent)
GI clinical signs from NSAID toxicity
-anorexia, abdominal pain
-vomiting, diarrhea +/- blood, (coffee grounds)
-dehydration, hypovolemia
-ulcers; perforatinos, septic peritonitis
-pale MM
-tachypnea and tachycardia
Horse GI clinical signs from NSAID toxicity
-colic
-diarrhea
-fever
-anorexia
Renal clinical signs from NSAID toxicity
-painful abdomen
-PU/PD
-acute renal insufficiency secondary to hypoperfusion
-PM lesion= renal papillary necrosis and in horses right dorsal colitis
CNS clinical signs from NSAID toxicity
-depression
-ataxia
-stupor or obtundation
-seizures
What in NSAID toxicity results in death?
-GI perforation secondary to ulceration
-acute kidney injury and renal failure
-CNS toxicosis
Clinical pathology of NSAID toxicity
-dehydration
-normocytic, normochromic, regenerative
-leukocytosis with left shift= peritonitis
-renal dysfunction (azotemia, decreased USG, tubular casts, acidosis)
-horses with right dorsal colitis= hypoalbuminemia
Carprofen
Aspirin
NSAID management
-no antidote
-decontamination if not contraindicated
-symptomatic and supportive care (GI protectants, renal support, anticonvulsants, monitoring)
May consider:
-therapeutic plasma exchange due to high protein binding
-IV lipid emulsion
-horses: low stress, low bulk diet, reduced work
Diagnosis of NSAID toxicity
-history of exposure
-quantification in bloodwork
-imaging: loss of serosal details
DDx for NSAID toxicity
-bleeding: anticoagulant rodenticides
-GI ulcers/erosions: corrosive products (bleach)
-AKI: grapes/raisins, lilies, mushrooms, vit D, ethylene glycol, soluble oxalates
-CNS depression: ethylene glycol, acetone, xylitol, ivermectin, opioids, bezodiazepines
Prognosis for NSAID toxicity
Typically good in companion animals with prompt medical attention
-if perforation from long term dose= grave prognosis
Acetaminophen
Common OTC pain reliever and antipyretic in human med
*COX-3 inhibitor in hypothalamus
Acetaminophen exposure
-accidental ingestion
-lack of owner knowledge
*common reason for presentation to the ER at VMC
Mechanism of Acetaminophen toxicity
Bioactivation rxn leading to a production of reactive metabolite. Results in depletion of cellular glutathione and oxidative injury
*damage to proteins and cell membranes
Target organs for acetaminophen
Cats= blood, liver
Dogs= liver
Species differences for acetaminophen toxicity
Greater effect on cats, ferrets than on dogs
*because poor glucuronidation capacity, greater sulfation capacity
Dose response impact for cats vs dogs for acetaminophen toxicity
Cats= no safe dose!
Dogs= more than 50mg needs decontamination and monitoring
Acetaminophen toxicity clinical signs in first 4-12hrs of ingestion
-vomiting, anorexia, dairrhea
-depression, lethargy
-tachypnea, tachycardia
-chemosis, facial edema, paw swelling
Acetaminophen toxicity clinical signs in 24-36hrs of ingestion
-hepatic necrosis
-methemoglobinemia
-oxidative damage hemolytic anemia
-yellow, brown, cyanotic MM
-jaundice, abdominal pain
-CNS- tremors, seizures, coma
Clinical pathology from acetaminophen toxicity
-regenerative anemia
-heinz bodies on blood smear
-metabolic acidosis
-(Met) hemoglobinuria
-PM hepatomegaly with enhanced reticular pattern/ jaundice
Histology of acetaminophen toxicity
Severe centrilobular hepatic necrosis and renal tubular necrosis
Management of acetaminophen toxicity
-decontamination if not indicated
-Antidote= N-acetylcysteine
-supportive care (fluids, oxygen, blood transfusion for anemia, hepatoprotectants, methylene blue for MetHb)
-sometimes can give cimetidine, vit C, bioflavonoids
How does N-acetylcystein work as antidote?
Increased hepatic glutathione synthesis and enhances sulfation
-might also directly bind to NAPQI
Diagnosis of acetaminophen toxicity
-history of exposure
-clin path findings
DDx for metHb/ acetaminphen toxicity
-from oxidizing agents (mothballs, phenolic compounds, garlic/onion)
-heinz bodies: zinc, skunk musk, mothballs, phenolics in cats, garlic/onion
-liver damage: sago palm, death cap mushrooms, alfatoxin, microcystin
Prognosis of acetaminophen toxicity
Variable
-guarded to grave in cats
-severe liver damage with no response to treatment= grave
