What are the characteristics of NSAIDs?
-commonly prescribed
-palatable
-human drugs generally more toxic
-toxicity from one-time overdose, chronic use, or administration of human form
What are the characteristics of COX inhibition?
-COX-1 interferes with stomach, kidney, endothelium, platelets, and physiologic functions
-COX-2 interferes with production of inflammatory mediators
-COX-2 specific NSAIDs are less toxic
-all NSAIDs toxic at high doses
-COX is responsible for prostaglandin production
What are the good effects of prostaglandins?
-decreased gastric acid production
-increased gastric mucus production
-increased gastric mucosal cytoprotection
-enhancement of renal blood flow
What are the toxic effects of NSAIDs?
-direct cellular injury
-decreased mucin quality and HCO3 content of mucous layer
-decreased mucosal blood flow
-decreased renal blood flow and GFR
-variable hepatotoxicity
Which body systems/organs are commonly affected by NSAIDs?
-GI tract
-kidney
-liver
-hemostatic system
-hematopoietic system
-CNS (large doses)
How is hospitalization duration determined for NSAIDs?
based on the half-life of the drug
What are the lab work findings with NSAID toxicity?
CBC:
-anemia
-changes in WBC counts; based on GI ulceration
CHEM:
-azotemia
-increased liver enzymes
-hyperbilirubinemia
UA:
-isosthenuria
-proteinuria
-urinary casts
What is the management for NSAID toxicity?
-emesis
-multi-dose activated charcoal
-cholestyramine
-GI protectants
-misoprostol (prostaglandins)
-antiemetics
-IV fluid diuresis for 3 drug half-lives
-IV lipids
-extracorporeal therapy
What are the characteristics of acetaminophen?
-analgesic, antipyretic, and weak anti-inflammatory
-therapeutic dose exists for dogs only
-tylenol-3 with codeine often used to break fevers in dogs
What are the characteristics of acetaminophen overdose?
-overwhelms glucuronidation and sulfation pathways
-depletes GSH stores and decreases GSH synthesis
-causes methemoglobinemia
-cats more susceptible due to decreased glucuronidation pathway to begin with
What are the consequences of acetaminophen toxicosis?
-hepatocellular protein damage
-lipid peroxidation
-oxidative RBC injury
-methemoglobinemia
What are the clinical signs of acetaminophen toxicity?
-anorexia
-vomiting
-lethargy
-abdominal pain
-icterus
-hepatic encephalopathy
-coma
-facial/paw edema
-KCS
What are the signs of methemoglobinemia?
-shock
-brown mucous membranes
-resp. distress
-cyanosis
-lethargy
-depression
-coma
What are the lab work findings with acetaminophen toxicity?
CBC:
-heinz body anemia
CHEM:
-increased liver enzymes
-inc. tbili
-dec. albumin
-hypoglycemia
COAG:
-inc. PT/PTT
CO-OXIMETRY:
-elevated metHgb (normal <2%)
What are the management steps for acetaminophen toxicosis?
-emesis
-activated charcoal
-N-acetylcysteine to bind NAPQI
-SAMe to promote glutathione production
What are the management steps for methemoglobinemia?
-ascorbic acid
-methylene blue
-packed RBC transfusion
What are the characteristics of serotonergic medications?
-used to treat depression, OCD, obesity, anxiety, and chronic pain
-lead to excess serotonin in CNS
-serotonin syndrome occurs with high doses or concurrent drug admin.
-serotonin syndrome causes mental changes, instability, and neuromuscular abnormalities
What are the effects of serotonin?
-regulation of temperature, appetite, sleep cycles, and emesis
-platelet aggregation
-vasoconstriction
-increased peristalsis
-bronchoconstriction
Which systems are impacted by serotonin syndrome?
-cardiovascular
-nervous
-GI
-metabolic
-respiratory
How is serotonin syndrome managed?
-emesis or gastric lavage
-AC
-sedation with acepromazine or propofol
-IV fluids
-cooling
-seizure control
-monitoring of BP and HR
-IV lipid therapy
-cyproheptadine
-chlorpromazine
What are the characteristics of muscle relaxant toxicity?
-enhance inhibition/reduce excitation in myocytes
-affect cortex, brainstem, spinal cord, and muscle
-peak absorption at 1 to 6 hours
-CNS, CV, and GI signs
Which muscle relaxant is of greatest concern for toxicity?
baclofen
What are the main signs of muscle relaxant toxicity?
-sedation
-ataxia
-resp depression
-resp failure
What is the management for muscle relaxant toxicity?
-emesis if very acute
-gastric lavage if large ingestion and symptomatic
-AC
-aggressive monitoring
-ILE therapy
-IV fluid therapy
-benzos for seizures
-intubation and ventilation
-extracorporeal therapy
