NSAID

Question 1

Non-steroidal anti-inflammatory drugs (NSAIDs)

Answer 1

• Analgesic , anti-inflammatory, antirevmatic properties
• Inhibition of cyclooxygenases (COX) – decrease in production of prostaglandins
• COX1 - constitutive form necessary for the regulation of physiological functions
• COX2 is mainly inducible form - synthesised at the place of inflammation, but also a constitutive enzyme in CNS, kidney and reproductive system
• Indogsproblemduetolowactivityofacetylation

Question 2

Big interspecies differences in pharmacokinetics (different toxicity to different species)
• Gastrointestinal ulceration

Answer 2

– due to inhibition of PGE2 synthesis (decrease in production of bicarbonates and mucus. Vasoconstriction contributes to the situation

Question 3

Big interspecies differences in pharmacokinetics (different toxicity to different species)

Nephrotoxicity

Answer 3

– due to inhibition of prostaglandins in kidneys (necessary for the regulation of salt and water balance, vascular tone, blood flow and renin secretion) – vasoconstriction and decreased renal blood flow lead to acute renal failure and death

Question 4

Big interspecies differences in pharmacokinetics (different toxicity to different species)

Decreased coagulation

Answer 4

• lack of thromboxane A2 in the platelets (which cannot aggregate - COX1 inhibitors) but on the other hand inhibition of prostacycline production by selective COX2 inhibitors (coxibs) - increased intravascular coagulation and higher risk of infarction

Question 5

Big interspecies differences in pharmacokinetics (different toxicity to different species)

Answer 5

• Leukotrienes, produced by lipoxygenase due to COX inhibition contribute to the gastrotoxicity of NSAIDs

Question 6

Ibuprofen:

Answer 6

• Typical poisoning in dogs - especially German shepherds are sensitive - and ferrets
• Causes renal impairment and gastrointestinal ulceration
• Signs in dogs at 25-125 mg/kg, LD 400 mg/kg. In cats
and ferrets toxic doses are 2x less

Question 7

Carprofen:

Answer 7

• Risk of hepatic and renal damage mainly in geriatric dogs, 1/3 of hepatic damage cases in Labrador retriever

Question 8

Acetylsalicylic acid:

Answer 8

• Irreversible effect on COX causes especially bleeding complications
• In overdose: hyperthermia, initial alkalosis followed by acidosis, muscular weakness, pulmonary and cerebral oedema, seizures and mineral imbalance

Question 9

Diclofenac:

Answer 9

• Approved for horses (some countries also for cattle)
• Toxic to birds - renal adverse effects
• Toxicity is highly species-dependent, in some birds doses even lower than therapeutic can be fatal

Question 10

Coxibs:

Answer 10

• Should be safer, but still can cause gastrointestinal adverse effects in higher doses and occasionally liver injury

Question 11

Treatment:

Answer 11

• Vomiting, charcoal, H2 antihistaminics, sucralfat, fluid therapy