Nephrotoxicity - 11

 Explain the mechanism by which the toxins in oak leaves and acorns cause gastrointestinal irritation and nephrotoxicity in ruminants o Rumen microfilaria metabolize gallotannins to acid  Know which is more toxic to ruminants: Older oak leaves and brown (older) acorns or younger oak leaves and green (young) acorns o Young leaves and green acorns  Recognize which animal is most susceptible to kidney damage from oral exposure to lilies o cats  Know the common clinical, laboratory findings associated with lily intoxication in cats o Vomiting, anorexia, lethargy, dehydration, CNS signs o Increased BUN, creatinine, phosphorus, potassium  Know which animal is more commonly reported to experience nephrotoxicity from grape/raisin ingestion o Dogs  List the two compounds that are currently “suspected” to be the nephrotoxicants in grapes/raisins o Tartaric acid and potassium bitartrate?  In addition to a clinical finding of azotemia, know what predominating clinical sign is often associated with grape/raisin toxicosis in dogs o Acute vomiting  Describe the difference between the mechanisms of action of prostaglandins with respect to COX-1 and COX-2 enzyme pathways o COX-2: inflammation o COX-1: protects GI tract, decreases stomach acid, maintains renal perfustion and vasodilation  Describe the consequences of inhibiting the COX-1 pathway o Inhibition of mucous production and mucosal blood flow, increased stomach acid secretion NSAIDs are acidic drugs, unopposed constriction of arterioles/decreased GFR  Explain why the protein-binding characteristic of NSAIDs predisposes animals to toxicity if the patient is hypoproteinemic o Less NSAID binding to proteins so increasing NSAIDs will increase the anti- inflammatory effect which increases the risk for detrimental side effects  Describe why melena and the presence of occult blood can occur with NSAID toxicosis o Bleeding ulcers  Know the mechanism by which NSAID-induced, nephrotoxicity occurs and how prostaglandins are involved o Prostaglandins dilate renal blood vessels to counteract vasocontriction cause by the SNS  toxicity occur from hypotension, renal vasoconstriction and NSAIDs block COX-1 o Contriction of vessels supply kidney with oxygen and nutrients  decreased blood flow to the renal medulla and low oxygen to tissues  Know why cats are more prone to NSAID toxicosis than other species o They have a Glucuronyltransfersae deficiency 2