GI and Reproductive Toxins

Question 1

NSAIDs

Answer 1

• 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

Question 2

MOA of NSAIDs

Answer 2

• Inhibit COX-1 and COX-2 which make prostaglandins
• Uncouple oxidative phosphorylation at high doses
  
  • increase lactic acid, metabolic acidosis

Question 3

COX-1 actions

Answer 3

Create prostaglandins that protect gastric mucosa and help with hemostasis

Question 4

COX-2 actions

Answer 4

Create prostaglandins that mediate pain, inflammation, and fever

Question 5

MOA of NSAID toxicity

Answer 5

• 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

Question 6

clinical signs of acute aspirin toxicity

Answer 6

• 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

Question 7

clinical signs of chronic aspirin toxicity

Answer 7

• 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

Question 8

Naproxen clinical signs

Answer 8

• Vomiting (sometimes bloody)
• black tarry stool
• diarrhea
• anorexia, weakness, lethargy
• painful abdomen
• pale gums
• more rare: facial twitching (cats), seizures, depression, coma

Question 9

diagnosis of NSAID toxicity

Answer 9

• 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)

Question 10

treatment of NSAID toxicity

Answer 10

• 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

Question 11

arsenic

Answer 11

• The #1 priority pollutant
• Sources:
  
  • insecticides
  • medicine
  • food production (chicken and swine feed additive)
  • electronics
  • shellfish
  • water

Question 12

inorganic arsenicals

Answer 12

• mechanism of action depends on form
  
  • Pentavalent
  • Trivalent
• Causes serious toxicity to GI epithelium and capillary endothelium leading to enteritis and shock

Question 13

pentavalent MOA

Answer 13

• *Reduced and metabolized in the rumen** and:
  1. reduces available metabolic energy
  2. some gets converted to the trivalent form, producing toxicosis

Question 14

trivalent MOA

Answer 14

• binds to -SH groups and disrupts cellular metabolism and inhibits oxidative phosphorylation enzymes, reducing metabolism

Question 15

clinical signs of inorganic arsenic poisoning

Answer 15

• 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

Question 16

Lesions associated with inorganic arsenic toxicity

Answer 16

• 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

Question 17

diagnosis of inorganic arsenic toxicity

Answer 17

• 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

Question 18

Treatment of inorganic arsenic toxicity

Answer 18

• 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

Question 19

zinc

Answer 19

• 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

Question 20

MOA of zinc

Answer 20

• 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)

Question 21

clinical signs of acute zinc toxicity

Answer 21

• occurs within a few days
• vomiting (especially with ointment)
• depression, anorexia
• hemolytic anemia
• jaundice
• pancreatitis
• lesions
  
  • enteritis
  • renal, hepatic, and pancreatic necrosis

Question 22

clinical signs of chronic toxicity

Answer 22

• 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)

Question 23

diagnosis of zinc toxicity

Answer 23

• 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

Question 24

treatment of zinc toxicity

Answer 24

• 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

Question 25

soap and shampoo clinical signs

Answer 25

vomiting and diarrhea

Question 26

soap and shampoo treatment

Answer 26

**dilution with milk or water** **rarely ever fatal**

Question 27

scouring powder/bleach toxicity

Answer 27

due to **alkalinity**-**corrosive effect** on skin and mucous membranes

Question 28

MOA of scouring powder/bleach

Answer 28

causes **liquefactive necrosis** that **penetrates deep layers of mucous membranes**

Question 29

clinical signs of scouring powder/bleach

Answer 29

vomiting and abdominal pain

Question 30

treatment of scouring powder/bleach

Answer 30

* **Diluting with milk or water** * **Emesis and lavage not good** * **activated charcoal and cathartics** except with very caustic exposures

Question 31

phenol disinfectants MOA

Answer 31

**Phenol denatures and precipitates cellular proteins** thus destroying all contacted cells

Question 32

pine oil disinfectant MOA

Answer 32

* **Pine oil disinfectant MOA** * **Directly irritating** to mucous membranes. * Detoxified by **glucuronidation** so cats are more susceptible

Question 33

phenol toxicity clinical signs

Answer 33

* **Corrosive burns** or **oral-esophageal pathway,** vomiting, hypersalivation, ataxia, panting * **Progresses** to shock, cardiac, arrhythmias, methemoglobinemia, hepatic and renal damage, coma

Question 34

pine oil toxicity clinical signs

Answer 34

Nausea, hyersalivation, bloody vomit, abdominal pain, ataxia, hypotension, respiratory depression, acute renal failure, pulmonary edema

Question 35

phenol toxicity treatment

Answer 35

* **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

Question 36

pine oil treatment

Answer 36

* **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

Question 37

automatic dishwater detergent toxicity

Answer 37

Due mostly to high alkalinity (pH \>10.5)

Question 38

clinical signs of automatic dishwasher detergent

Answer 38

vomiting, diarrhea, salivation, GI pain, and oral, esophageal, gastric erosions

Question 39

treatment of automatic dishwasher detergent

Answer 39

**Dilution** with milk or water, **analgesics** and possibly **steroids** for inflammation

Question 40

toilet bowel cleaner toxicity

Answer 40

they are **acidic** - containing sulfuric acid or hydrochloric acid

Question 41

clinical signs of toilet bowl cleaner toxicity

Answer 41

vomiting, salivation, dyspnea, dysphagia, abdominal pain, GI ulceration

Question 42

treatment of toilet bowel cleaner toxicity

Answer 42

* **dilution** with milk or water, **steroids** if stricture possible, **symptomatic** * **emesis, lavage, activated charcoal and catharsis CONTRAINDICATED**

Question 43

ammonia, oven cleaners, drain cleaner toxicity

Answer 43

**alkaline products** that cause **caustic ulceration at pH around 12**

Question 44

clinical signs of ammonia, oven cleaners, and drain cleaner toxicity

Answer 44

vomiting, salivation, dysphagia, abdominal pain, GI ulceration, dyspnea

Question 45

treatment of ammonia, oven cleaners, and drain cleaner toxicity

Answer 45

dilution with milk or water, steroids if stricture possible, symptomatic

Question 46

phytoestrogens

Answer 46

* **Large animal toxins** * most affect **reproductive** **system** * Found in foods like **lentils, beans, clover**

Question 47

zearalenone

Answer 47

* **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**

Question 48

animals affected by zearalenones

Answer 48

**most animals:** pigs, cattle, sheep ## Footnote **chickens are resistant**

Question 49

MOA of zearalenones

Answer 49

* **estrogen receptor agonists** * alpha-zearalenol has a **higher affinity for estrogen** receptors than endogenous estrogen

Question 50

clinical signs of zearalenol

Answer 50

* **"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

Question 51

diagnosis of zearalenol toxicity

Answer 51

* 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

Question 52

treatment of zearalenol toxicity

Answer 52

**activated charcoal or high fiber** may reduce elimination times due to **extensive enterohepatic recycling**