Toxicology Lecture 17A Nsaid-Acetaminophine

Front 1

NSAIDs is the #_____ most common small animal toxin.

Back 1

4th

Front 2

What is the strongest NSAID?

Back 2

Aspirin

Front 3

Why don't you want to administer ketoprofen to a dog getting ready to undergo surgery?

Back 3

Has most potent effects on platelets

Front 4

What was the first nonsteroidal anti-inflammatory drug to be sold commercially?

Back 4

Aspirin (acetylsalicylic acid)

Front 5

Aspirin reduces inflammation by the inhibition of the _______ system.

Back 5

Cyclooxygenase (COX) enzyme system

Front 6

Plasma elimination of aspirin depends on Phase II conjugation with ______.

Back 6

Glucaronic acid

Front 7

Compare the half lives of aspirin in dogs and cats.

Back 7

8 hours in dogs
38 hours in cats -due to relative deficiency of glucuronate

Front 8

What is the mode of action of aspirin?

Back 8

Inhibits prostaglandins
-COX mediates production of cyclic endoperoxides from arachidonic acid to yield prostaglandins

Front 9

**What are the 3 primary clinical signs of aspirin toxicosis (main systems affected)?

Back 9

1) GI symptoms
2) Neurological symptoms
3) Acute kidney failure

Front 10

What are the 3 GI symptoms of aspirin toxicity?

Back 10

1) Loss of appetite
2) Diarrhea & vomiting
3) Spontaneous bleeding & black tarry stools

Front 11

What are the 5 neurological symptoms of aspirin toxicosis?

Back 11

1) Restlessness
2) Anxiety
3) Depression
4) Incoordination
5) Seizures (rarely)

Front 12

What are 3 signs of kidney failure from aspirin toxicosis that are observed?

Back 12

1) Lighter urine
2) Extreme thirty
3) Lethargy

Front 13

Toxic quantities of aspirin may adversely affect what 4 systems?

Back 13

1) Digestive system
2) Circulatory system
-impaired clotting of blood
3) Neurological system
4) Renal system

Front 14

What is the toxic dose of aspirin in CATS?

Back 14

80 to 120 mg/kg for 10 days

Front 15

What is the toxic dose of aspirin in dogs?

Back 15

100-300 mg/kg daily for 1-4 weeks

Front 16

How long can you give aspirin to a cat for?

Back 16

ONLY 24 hours

Front 17

What are the clinical pathologies seen due to renal failure from aspirin toxicosis?

Back 17

Elevated BUN & creatinine
-may also have elevated Na & K

Front 18

What clinical pathologies will see in the circulatory system due to aspirin toxicosis?

Back 18

-CBC shows:
thrombocytopenia
Anemia
-Heinz bodies present in chronic exposure

Front 19

_____ ______ levels may confirm aspirin exposure, but correlates poorly with signs of toxicosis.

Back 19

Serum salicylate levels

Front 20

**What are the 2 main components of treating aspirin toxicosis?

Back 20

1) Stop administration
2) Decontamination

Front 21

What is the prognosis of an animal that receives 45 mg/kg of aspirin?

Back 21

Good <50 mg/kg

Front 22

What is the prognosis of an animal that receives 60 mg/kg of aspirin?

Back 22

Poor > 50 mg/kg

Front 23

How can you prevent aspirin toxicosis?

Back 23

Keep in proper storage

Front 24

What is the prognosis of an animal that receives 45 mg/kg of aspirin?

Back 24

Good <50 mg/kg

Front 25

What is the chemical classification of ibuprofen?

Back 25

NSAID in the classification of propionic acids
-includes carprofen, fenoprofen, ketoprofen, naproxen

Front 26

What is the mode of action of ibuprofen?

Back 26

COX-1 and Cox-2 inhibitor but mainly COX-2
-Inhibition of COx-1 responsible for effects on platelet aggregation and GI signs

Front 27

What is the prognosis of an animal that receives 60 mg/kg of aspirin?

Back 27

Poor > 50 mg/kg

Front 28

How can you prevent aspirin toxicosis?

Back 28

Keep in proper storage

Front 29

What is the chemical classification of ibuprofen?

Back 29

NSAID in the classification of propionic acids
-includes carprofen, fenoprofen, ketoprofen, naproxen

Front 30

What is the mode of action of ibuprofen?

Back 30

COX-1 and Cox-2 inhibitor but mainly COX-2
-Inhibition of COx-1 responsible for effects on platelet aggregation and GI signs

Front 31

When are peak plasma concentrations of ibuprofen reached?

Back 31

30 min to 3 hours

Front 32

What is the mean elimination half-life of ibuprofen?

Back 32

~4.6 hours

Front 33

Ibuprofen is metabolized in the liver and mainly excreted in the urine after ____ hours.

Back 33

24 hours

Front 34

What is the major metabolic pathway of ibuprofen elimination?

Back 34

Conjugation w/ Glucaronic acid

Front 35

Cats are susceptible to ibuprofen toxicosis at _______ the dosage required to cause toxicosis in dogs.

Back 35

1/2

Front 36

What are 6 clinical signs of ibuprofen toxicosis observed in both cats & dogs?

Back 36

1) Nausea, vomiting
2) Depression or stupor
3) Diarrhea
4) Anorexia
5) Polyuria
6) Polydipsia

Front 37

What is a clinical sign of ibuprofen toxicosis only seen in cats?

Back 37

Tachypnea and panting

Front 38

Why do stomach ulcers form with ibuprofen toxicosis?

Back 38

Because it inhibits prostaglandin symthesis---> decreases secretion of protective mucous layer in stomach & small intestine

Front 39

What are the 5 ways that ibuprofen affects the renal system?

Back 39

1) Decrease renal blood flow
2) Glomerular filtration rate
3) Tubular ion transport
4) Renin release
5) Water homeostasis

Front 40

What occurs in a dog that receives 50-100 mg/kg of ibuprofen?

Back 40

Mild to severe GI upset**

Front 41

What happens to a dog that receives b/w 100-250 mg/kg of ibuprofen?

Back 41

Renal** compromise to renal failure

Front 42

What happens to a dog that receives > 300 mg/kg of ibuprofen?

Back 42

Fatalities* (treated & untreated animals)
CNS effects*

Front 43

Cats are considered to be ______ times as sensitive as dogs to ibuprofen toxicity.

Back 43

Twice

Front 44

What will you see in a cat that receives 25-50 mg/kg of ibuprofen?

Back 44

GI signs

Front 45

What is the primary way ibuprofen toxicosis is diagnosed?

Back 45

HISTORY*

Front 46

How can gastric ulceration from ibuprofen administration be monitored?

Back 46

Using PCV or fecal occult blood

Front 47

How can you determine whether or not an animal has developed renal issues due to ibuprofen administration?

Back 47

Increased BUN & creatinine

Front 48

What are some post mortem lesions associated with ibuprofen administration?

Back 48

Perforations, erosion & ulceration and hemorrhage of the upper and occasionally lower GI tract

Front 49

What is the primary component of treating ibuprofen toxicosis?

Back 49

Decontamination***

Front 50

What is the active ingredient of aleve?

Back 50

Naproxen

Front 51

For ______, naproxen can easily exceed toxic levels.

Back 51

Dogs
-usually given to dog by owner

Front 52

Is inhibition of COX-1 or COX-2 thought to be association w/ GI and renal toxicity?

Back 52

COX-1
-generates PGs necessary for normal GI and renal function
-Inhibition of COX-2= anti-inflammatory effect

Front 53

What is the mode of action of naproxen?

Back 53

Inhibits prostaglandin formation

Front 54

What is different about elimination of naproxen in dogs compared to other species?

Back 54

Dogs= primarily eliminated through bile
-in other species primary route of elimination is through kidneys

Front 55

Why does naproxen have such a long half life in dogs?

Back 55

Enterohepatic recirculation

Front 56

**What is the initial toxic effect of naproxen?

Back 56

Bleeding stomach ulcers

Front 57

What are the 8 clinical signs of naproxen toxicity?

Back 57

1) Poor appetite
2) Vomiting
3) Black tarry stools
4) Vomiting blood
5) Abdominal pain
6) Dehydration
7) Weakness
8) Lethargy

Front 58

What will you see in a dog that receives 5 mg/kg of naproxen?

Back 58

GI signs

Front 59

What will you see in a dog that receives 25 mg/kg of naproxen?

Back 59

>25 mg/kg= acute renal failure

Front 60

What is the primary way to diagnose naproxen toxicosis?

Back 60

HISTORY

Front 61

What is the primary component of treating naproxen toxicosis?

Back 61

DETOXIFICATION

Front 62

What is the prognosis of naproxen toxicosis?

Back 62

Depends on dose ingested

Front 63

What are the 5 veterinary NSAIDs?

Back 63

1) Carprofen (Rimadyl)
2) Deracoxib (Deramaxx)
3) Ketoprofen (Ketofen)
4) Meloxicam (Metacam)
5) Phenylbutazone

Front 64

Do Carprofen, deracoxib, and meloxicam have a higher affinity for COX-1 or COX-2 inhibition?

Back 64

CoX-2 inhibitors
-only inhibit Cox-1 at high levels

Front 65

Does ketoprofen have a higher affinity for Cox-1 or Cox-2 inhibition?

Back 65

Nonselective inhibitor of COX enzymes

Front 66

What are the 3 primary systems affected by toxicosis caused by veterinary NSAIDs?

Back 66

1) GI Signs
2) Kidney damage
3) CNS symptoms

Front 67

What are the 4 GI signs associated with toxicosis from veterinary NSAIDs?

Back 67

1) Vomiting
2) Abdominal pain
3) Melena
4) Diarrhea

Front 68

What are the 4 clinical signs associated with renal failure from NSAID toxicity?

Back 68

1) PU/PD
2) Anorexia
3) Lethargy
4) Vomiting

Front 69

What causes the CNS symptoms associated to toxicity from vet NSAIDs?

Back 69

From severe ingestion
-Weakness
-Ataxia
-Icterus from liver damage

Front 70

The toxic dose of vet NSAIDs in dogs is _____ times the therapeutic dose.

Back 70

5 Xs

Front 71

True or false. The dosage of veterinary NSAIDs used in a cat is enough to cause toxicosis.

Back 71

True

Front 72

What are the clinical pathologies seen on a CBC of an animal with vet NSAID toxicosis?

Back 72

Blood loss- anemia decreased total protein

Front 73

What are the 3 primary findings on a chemistry profile of a dog with veterinary NSAID toxicosis?

Back 73

1) Azotemia
2) Liver enzyme, bilirubin and protein increase
3) Low albumin

Front 74

What are the 2 abnormalities detected on UA of veterinary NSAID toxicosis?

Back 74

Inappropriate specific gravity
Urinary casts

Front 75

What is the mode of action of phenylbutazone?

Back 75

Prostaglandin inhibitor

Front 76

What are the 5 primary signs of phenylbutazone toxicosis?

Back 76

1) GI toxicity
2) Nephrotoxicity
-PU/PD, oliguria
3) Hepatotoxicity
-Icterus, lethargy, encephalopathy
4) Aplastic anemia
5) Platelet dysfunction

Front 77

Overdoses of phenylbutazone can cause ____ failure effects and _______. Early signs of toxicity include _____ and _____.

Back 77

Renal failure
GI ulceration /perforation
Early signs: anorexia, depression

Front 78

What are the most common side effects of phenylbutazone toxicosis in horses?

Back 78

Ulceration of mouth & GI tract

Front 79

What drugs should you avoid combining phenylbutazone with?

Back 79

Other anti-inflammatory drugs that tend to cause GI ulcers such as corticosteroids and other NSAIDs

Front 80

What are the diagnostic tests that detect GI ulceration from phenylbutazone toxicosis?

Back 80

-Decreased hematocrit and total protein
-Increased blood urea nitrogen due to GI hemorrhage

Front 81

What are the clinical pathologies associated with renal toxicity due to phenylbutazone toxicosis?

Back 81

-increased BUN, creatinine
-Decreased urine specific gravity

Front 82

What does treatment of phenylbutazone toxicosis consist of?

Back 82

Supportive care
Gi protectant drugs
-Misoprostol, cimetidine, omeprazole, ranitidine or sucralfate

Front 83

True or false. Acetaminophen is an NSAID.

Back 83

False, acts via different mechanisms

Front 84

How is acetaminophen similar to NSAIDs? How is it different?

Back 84

Shares analgesic & antipyretic properties
Not anti-inflammatory or antithrombolic

Front 85

What is the active drug of excedrin?

Back 85

Acetaminophen
-also tylenol & equate

Front 86

True or false. Acetaminophen is lethal if ingested by a dog or cat.

Back 86

True

Front 87

How quickly is acetaminophen absorbed in dogs?

Back 87

Complete in 1 hour

Front 88

How is elimination of acetaminophen in a dog different from NSAID elimination?

Back 88

Acetaminophen is broken down by liver, NSAIDs are removed via the kidneys

Front 89

How is acetaminophen metabolized in the liver?

Back 89

By p450 enzymes via conjugation w/ glucuronides
-excreted in bile & urine ~5% unchanged

Front 90

Why is acetaminophen more toxic to cats?

Back 90

Deficient in UDP-glucuronyl transferase --> more readily available acetaminophen which is oxidized to reactive intermediates

Front 91

What is the mode of action of acetaminophen toxicity in dogs and cats?

Back 91

When sulfation and glucirinidation pathways are oveloaded--> prolonged high concentrations of acetyl-p-aminophenol (APAP) & increases the amount of APAP which bioactivates the toxic intermediate
- Levels of glutathione become exhausted allowing reactive metabolites to react with cellular molecules --> cellular necrosis and/or lysis

Front 92

what is n-acetyl-p-benzoquinoneimine?

Back 92

Acetminophen is oxidized into the reactive intermediate= - acetyl-p-benzoquinoneimine
-these reactive intermediates are scavenged by glutathione and excreted as inactive derivatives

Front 93

What are the 2 targets of cellular necrosis and/or lysis of acetaminophen toxicity?

Back 93

Erythrocytes and liver

Front 94

**Are erythrocytes or the liver the main target of acetaminophen toxicity in cats?

Back 94

-Major effects is on the RBCs --> methemoglobin formation & hypoxia
-Higher the exposure dose the greater the chance of effecting liver

Front 95

**What is the primary clinical sign of acetaminophen toxicity in cats?

Back 95

Methemoglobinemia/ heinz body anemia- hemolysis/ hemoglobinemia (uria)

Front 96

Is the liver or RBCs more affected by acetaminophen toxicity in dogs?

Back 96

Signs generally associated w/ acute centrilobular necrosis
-renal necrosis too

Front 97

What causes hepatic damage due to acetaminophen toxicity?

Back 97

Hepatobiliary binding of N-acetyl-para-benzoquinoneimine (NAPQI) to hepatocyte membranes leads to hepatocellular death & central lobular necrosis

Front 98

What is the toxic dose of acetaminophen in cats?

Back 98

NO AMOUNT IS SAFE FOR A CAT****

Front 99

Is two regular strength tablets toxic to dogs?

Back 99

Yes= 325 mg
-toxic dose = 150-200 mg/kg

Front 100

Is one extra strength tablet of acetaminophen toxic to a 10lb dog?

Back 100

Yes= 500 mg

Front 101

How do you diagnose acetaminophen toxicity?

Back 101

HISTORY of potential exposure
-*chocolate brown blood

Front 102

What is the primary component of treating acetaminophen toxicity?

Back 102

Decontamination
-emetic, activated charcoal often too late (2-4 hour)

Front 103

What is the prognosis of acetaminophen toxicity in cats?

Back 103

GRAVE

Front 104

What is the prognosis of dogs with acetaminophen toxicity?

Back 104

Less GRAVE, but still POOR