GI and Reproductive Toxins Flashcards
NSAIDs
- Include aspirin, ibuprofen, naproxen
- absorbed well from the stomach and intestinal mucosa
- Dogs are sensitive to ibuprofen (25 mg/kg)
- Cats are sensitive to aspirin (25 mg/kg) due to lack of glucuronidation
MOA of NSAIDs
- Inhibit COX-1 and COX-2 which make prostaglandins
-
Uncouple oxidative phosphorylation at high doses
- increase lactic acid, metabolic acidosis
COX-1 actions
Create prostaglandins that protect gastric mucosa and help with hemostasis
COX-2 actions
Create prostaglandins that mediate pain, inflammation, and fever
MOA of NSAID toxicity
- GI and RENAL
- Cause gastric ulceration
-
Cause renal toxicity mainly by the inhibition of prostaglandin synthesis and renal blood flow (analgesic nephropathy)
- vasoconstructive acute renal failure
- acute interstitial nephritis
- fluid and electrolyte imbalanes
- renal papillary necrosis
- chronic renal failure
clinical signs of acute aspirin toxicity
- Nausea, vomiting (may be blood tinged), anorexia
- Fever and respiratory stimulation with high doses
- Depression (muscle weakness, ataxia), lethargy, seizure, coma
- Acidosis with anion gap
- Reduced renal flow, renal failure
clinical signs of chronic aspirin toxicity
- Gastric irritation and ulceration most common
- Anemia, bone marrow depression
- Heinz bodies, thrombocytopenia in cats
- toxic dose for dogs is 50 mg/kg/day
- toxic dose for cats is 25 mg/kg/day
Naproxen clinical signs
- Vomiting (sometimes bloody)
- black tarry stool
- diarrhea
- anorexia, weakness, lethargy
- painful abdomen
- pale gums
- more rare: facial twitching (cats), seizures, depression, coma
diagnosis of NSAID toxicity
-
Hx and clinical signs
- GI irritation, lethargy, anemia
- in cases of perforation due to ulcers, signs will include abdominal pain, shock, dark red mm, tachycardia
- Anion gap due to acidosis (for salicylates)
- Increased liver enzymes, jaundice
- Increased blood clotting time
-
Acute renal failure
- renal tubular casts in urine sediment (incr. BUN, creat)
treatment of NSAID toxicity
- Induced emesis and activated charcoal several times
-
Address GI ulceration and acute renal failure as necessary
- use ranitidine or similar H2-blocker, or sucralfate and misoprostol for a few weeks to heal or prevent ulcers
- Supportive care (watch for and treat acidosis, hyperkalemia, correct electrolyte and glucose levels, increase renal blood flow and maintain urine flow)
- Consider transfusion for animals with significant hemorrhage/severe anemia
arsenic
- The #1 priority pollutant
- Sources:
- insecticides
- medicine
- food production (chicken and swine feed additive)
- electronics
- shellfish
- water
inorganic arsenicals
- mechanism of action depends on form
- Pentavalent
- Trivalent
- Causes serious toxicity to GI epithelium and capillary endothelium leading to enteritis and shock
pentavalent MOA
- *Reduced and metabolized in the rumen** and:
1. reduces available metabolic energy
2. some gets converted to the trivalent form, producing toxicosis
trivalent MOA
- binds to -SH groups and disrupts cellular metabolism and inhibits oxidative phosphorylation enzymes, reducing metabolism
clinical signs of inorganic arsenic poisoning
- Depends on dose
-
Acute/sub-acute exposure
- intense abdominal pain, gastroenteritis
- weakness, staggering gait
- salivation, trembling
- vomiting (dogs)
- PU/PD progressing to oliguria and anuria
- dehydration, thirst
- posterior paresis
- cold extremities due to poor perfusion
- subnormal temps
- may live for 1-3 days
Lesions associated with inorganic arsenic toxicity
- At very high exposure, may not see any lesions
- Brick red gut (abomasum in ruminants)
- Fluid GI contents, sometimes foul smelling
- Soft yellow liver, red congested lungs
- Damage to glomerulus and tubules in kidney
diagnosis of inorganic arsenic toxicity
- Consider whenever there is sudden onset of gastroenteritis or sudden death, especially dead animals found in or near water
- Liver or kidney arsenic > 5ppm
- Should also examine stomach contents or vomitus for arsenic
-
Readily absorbed from GI tract, rapidly excreted
- take samples early
Treatment of inorganic arsenic toxicity
-
GI decontamination
- if no symptoms, emesis followed by activated charcoal with a cathartic
-
Begin chelation therapy
- the classic chelating antidote for arsenic toxicosis is dimercaprol: compete with -SH groups for available arsenic
- sodium thiosulfate before clinical signs
-
Supportive therapy
- demulcents (sucralfate or kaopectate)
- fluids for dehydration ,shock, reduced renal function
- Prognosis is poor once symptoms occur
zinc
- Found in all galvanized metals: nuts, bolts, wire (hardware ingestion)
-
Post-1982 pennies
- 96% zinc
- big problems in zoos
- one of the most common household hazards called into ASPCA
MOA of zinc
- When zinc enters the stomach’s acidic environment, free zinc is released, forming zinc salts
- zinc salts have a direct corrosive effect to stomach and intestinal mucosa
- Oxidative damage that leads to hemolysis
- Toxicity usually seen in dogs and aquatic organisms (seal at the zoo)
clinical signs of acute zinc toxicity
- occurs within a few days
- vomiting (especially with ointment)
- depression, anorexia
- hemolytic anemia
- jaundice
- pancreatitis
-
lesions
- enteritis
- renal, hepatic, and pancreatic necrosis
clinical signs of chronic toxicity
- Occurs most often in cattle
- Onset time is several weeks
-
Signs include
- PU/PD
- diarrhea
- anorexia
- hemolytic anemia
- lameness
- lesions (gastric ulcers, renal tubular necrosis, hepatic necrosis)
diagnosis of zinc toxicity
-
Serum zinc levels >10 ppm
- use blue top tube for collecting blood and syringes without rubber due to zinc in lubricant
- liver zinc > 200 ppm
- decreased PCV, regenerative anemia, thrombocytopenia
- Heinz bodies reported in 33% of canine patients
- elevated liver, kidney, and pancreatic enzymes
- hemoglobinuria
- radiographs for hardware ingestion
treatment of zinc toxicity
- Removal of foreign bodies
- Emesis if not contraindicated
-
Primarily symptomatic
- fluids for renal failure, dehydration
- blood products for hemolytic anemia
-
Initiate treatment with proton pump inhibitors, or H2 blockers
- will help to decrease systemic absorption of zinc salts
- can also administer gastroprotectants for irritation/ulceration
soap and shampoo clinical signs
vomiting and diarrhea
soap and shampoo treatment
dilution with milk or water
rarely ever fatal
scouring powder/bleach toxicity
due to alkalinity-corrosive effect on skin and mucous membranes
MOA of scouring powder/bleach
causes liquefactive necrosis that penetrates deep layers of mucous membranes
clinical signs of scouring powder/bleach
vomiting and abdominal pain
treatment of scouring powder/bleach
- Diluting with milk or water
- Emesis and lavage not good
- activated charcoal and cathartics except with very caustic exposures
phenol disinfectants MOA
Phenol denatures and precipitates cellular proteins thus destroying all contacted cells
pine oil disinfectant MOA
- Pine oil disinfectant MOA
- Directly irritating to mucous membranes.
- Detoxified by glucuronidation so cats are more susceptible
phenol toxicity clinical signs
- Corrosive burns or oral-esophageal pathway, vomiting, hypersalivation, ataxia, panting
- Progresses to shock, cardiac, arrhythmias, methemoglobinemia, hepatic and renal damage, coma
pine oil toxicity clinical signs
Nausea, hyersalivation, bloody vomit, abdominal pain, ataxia, hypotension, respiratory depression, acute renal failure, pulmonary edema
phenol toxicity treatment
- Demulcents (milk or eggs)
- Not gastric lavage or emesis or activated charcoal
- Supportive therapy including IV fluids and resp support
- 1% methylene blue for methemoglobinemia
pine oil treatment
- Dilute with milk, egg whites, or water
- Because of aspiration pneumonia, emesis and lavage are contraindicated
- Follow dilution with activated charcoal or cathartic
- Supportive therapy including renal perfusion, acid-base and electrolyte balance
automatic dishwater detergent toxicity
Due mostly to high alkalinity (pH >10.5)
clinical signs of automatic dishwasher detergent
vomiting, diarrhea, salivation, GI pain, and oral, esophageal, gastric erosions
treatment of automatic dishwasher detergent
Dilution with milk or water, analgesics and possibly steroids for inflammation
toilet bowel cleaner toxicity
they are acidic - containing sulfuric acid or hydrochloric acid
clinical signs of toilet bowl cleaner toxicity
vomiting, salivation, dyspnea, dysphagia, abdominal pain, GI ulceration
treatment of toilet bowel cleaner toxicity
- dilution with milk or water, steroids if stricture possible, symptomatic
- emesis, lavage, activated charcoal and catharsis CONTRAINDICATED
ammonia, oven cleaners, drain cleaner toxicity
alkaline products that cause caustic ulceration at pH around 12
clinical signs of ammonia, oven cleaners, and drain cleaner toxicity
vomiting, salivation, dysphagia, abdominal pain, GI ulceration, dyspnea
treatment of ammonia, oven cleaners, and drain cleaner toxicity
dilution with milk or water, steroids if stricture possible, symptomatic
phytoestrogens
- Large animal toxins
- most affect reproductive system
- Found in foods like lentils, beans, clover
zearalenone
- mycotoxin
- metabolite of Fusarium spp, often found with deoxynivalenol
- Most grains can be affected, toxin production occurs mostly during storage
- Heat stable and resistant to most mold retardants
animals affected by zearalenones
most animals: pigs, cattle, sheep
chickens are resistant
MOA of zearalenones
- estrogen receptor agonists
- alpha-zearalenol has a higher affinity for estrogen receptors than endogenous estrogen
clinical signs of zearalenol
- “hyperestrogen” syndrome
-
In pigs and ferrets: symptoms depend on sex and maturity
- decrease male libido, infertility
- enlarged, swollen uteri
- shrunken and/or cystic ovaries
- necrosis or reddening of the tail
- vulva swelling and reddening
- vaginal and rectal prolapse
- immunosuppression and liver damage
- decreased litter size and birth weights
- similar signs in cattle and sheep: males regressed testis and feminization, females have abortions and pseudopregnancy
diagnosis of zearalenol toxicity
- presence of greater than 1-2 ppm zearalenone in swine feed
- Reversal of symptoms when feed is changed
- may take 7-10 days due to long half life of zearalenone
treatment of zearalenol toxicity
activated charcoal or high fiber may reduce elimination times due to extensive enterohepatic recycling
