Exam 1 Objectives: Pharmaceuticals and Respiratory Toxins Flashcards
Pharmaceuticals objectives
What is/are the major toxicities associated with the use of NSAIDs in companion animals?
ibuprofen
Ibuprofen
Acute toxicity can be seen in dogs at doses of 50-125 mg/kg: Vomiting, diarrhea, nausea, anorexia, gastric ulceration and abdominal pain.
Renal damage can be observed at doses >175 mg/kg.
At doses >400 mg/kg in dogs: CNS effects such as seizure, ataxia and coma may occur.
Pharmaceuticals objectives
What is/are the major toxicities associated with the use of NSAIDs in companion animals?
naproxen
Naproxen:
at doses close to what is needed for analgesia… GI toxicity at doses of 5 mg/kg/day
Pharmaceuticals objectives
What is/are the major toxicities associated with the use of NSAIDs in companion animals?
aspirin
Aspirin:
Dose required to control lameness in dogs is 23-86 mg/kg bid… resulting in plasma concentrations of 71-281 μg/ml. Toxic concentrations in the plasma are generally viewed as >300 μg/ml so……. Small safety margin but doses of 10-25 mg/kg every 8-12 hours can be used.
Mucosal erosions in the GI have been observed in 50% of dogs at a dose of 25 mg/kg plain aspirin… small safety margin
Buffered and coated preparations reduced the GI mucosal erosion.
Cats have a plasma half-life of aspirin that is ~5X longer than that of dogs. Why… aspirin is a phenol that is glucoronidated….. Doses of 10-20 mg/kg every 48 hours can be used.
No clinical signs of toxicosis were shown in one study where cats received aspirin at 25 mg/kg every 48 hours.
Pharmaceuticals objectives
What is/are the major toxicities associated with the use of NSAIDs in companion animals?
acetaminophen
Acetaminophen:
dogs: Toxic doses are in the range of 600 mg/kg acutely, with toxicity observed at lower doses with chronic exposure.
cats: Toxic doses are in the range of 50-100 mg/kg. Toxicoses has been observed at doses as low as 10 mg/kg.
Pharmaceuticals objectives
What phase II metabolizing system are felines deficient in?
limited glucoronyl-conjugating capacity
Pharmaceuticals objectives
What is/are the predominant toxic effects of acetaminophen in dogs? What about cats?
Hepatotoxicosis is first observed in dogs followed by methemoglobinemia during a higher exposure. in cats, methemoglobinemia is first observed followed by hepatotoxicosis at a higher exposure.
Pharmaceuticals objectives
Is there a specific treatment for acetaminophen toxicosis? In a general way, how does it work?
Prevent Additional Drug Absorption:
Induction of emesis or gastric lavage
Administer activated charcoal (2 g/kg PO) within first 4-6 hours
Provide Supportive Measures:
Administer oxygen and IV fluids
If anemia is severe enough, whole blood or packed red cells
Administer Drugs that Directly: Counteract the Toxic Mechanism
N-acetylcysteine administered IV at a dose of 140 mg/kg initially and then followed by 70 mg/kg q6h for 5-6 doses
If NAC is not available, then S-adenosylmethionine can be used at a dose of 40 mg/kg PO initially followed by 20 mg/kg PO q24h for 9 days in dogs. SAMe use in cats is not established
NAC serves as a thiol source in the face of GSH depletion caused by acetominophen.
Bottom Line – Dosing with NAC leads to increased GSH levels allowing for detoxification of reactive metabolites.
Pharmaceuticals objectives
Why are dogs generally more likely to be poisoned by pharmaceuticals? And, how does this same general behavior factor in to venlafaxine poisoning in cats?
Dogs generally explore things with their mouths. For some reason, cats are attracted to things with velafaxine.
Pharmaceuticals objectives
How do you treat amphetamine toxicity?
Limit Absorption: Emitics, activated charcoal and cathartics
Supportive and symptomatic treatment: Acepromazine or chlorpromazine for agitation, Barbiturates to control seizure, Cyproheptadine as a serotonin antagonist, Propranolol to treat tachycardia
Increase elimination: Intravenous fluids, Ammonium chloride, or ascorbic acid to acidify urine….. How does that work? A formal charge on the drug leads to increased urinary elimination due to decreased reabsorption from the proximal tubule
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
ammonia
Ammonia: Animal facilities, especially common where excrement can decompose on a solid floor
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
carbon dioxide
Carbon dioxide: End product of metabolism… we breathe it out. Fuel burning heaters, Decomposing manure
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
carbon monoxide
Carbon monoxide: Odorless, colorless poisonous gas that results from incomplete combustion of hydrocarbons. Primary source is car exhaust, Fires are also an important source.
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
methane
Methane: Product of microbial degradation. Formed by rumen microflora in cows, goats, sheep and other ruminants.
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
hydrogen sulfide
Hydrogen sulfide: Potentially lethal gas formed by anaerobic bacterial decomposition of protein and other sulfur containing organic matter. Heavier than air and thus accumulates in manure pits, holding tanks. Greatest threat to livestock and other animals are liquid manure holding pits….. Is rapidly released when waste slurry is agitated and can generate high concentrations in the range of 1000 ppm.
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
nitrogen dioxide
Nitrogen dioxide: A poisonous gas with a yellow or yellow-brown color and a bleach-like smell. The most important agricultural source is the fermentation process of ensiled forages. Is heavier than air and thus will concentrate as a layer on top of silage. Will accumulate in enclosed spaces at the bottom of the chute and can flow into an adjoining building and potentially expose animals in a feeding area.
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
Environmental tobacco smoke
Environmental tobacco smoke: in the home, from humans
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
PTFE
PTFE: from overheating cookware
Respiratory Toxins objectives
What is the source and potential exposure for each of the respiratory toxins?
non-volatile trypt and perilla mint
Non volatile agents that cause pulmonary damage:
Tryptophan-3 methyl indole (3-MI) : Associated with cattle consuming tryptophan in lush green forages
Perilla Mint: Cows that consume several pounds of green forage containing 4-ipomeanol can also suffer lung toxicity that may be fatal.
Respiratory Toxins objectives
What are three factors that can influence respiratory toxicosis across species?
- Variability in metabolizing enzymes (species-specific P450 reactions)
- Regional variation in cell populations (different cell populations in affected areas)
- Anatomic configuration (more complex nasopharynx, airways in birds)
Respiratory Toxins objectives
What factors are associated with Hydrogen Sulfide production and release that make it potentially dangerous?
At concentrations above 200 ppm H2S has a paralyzing effect on the olfactory sensory apparatus and thus blocks detection of the warning odor
Respiratory Toxins objectives
What is the mechanism of action of Carbon Monoxide and how is that related to observed toxicities and treatments?
- Rapidly absorbed through the lungs.
- Competes with oxygen for binding sites on a variety of proteins….. Including hemoglobin.
- The affinity of CO for hemoglobin is 250X greater than that of oxygen.
- Binds to hemoglobin to form carboxy-hemoglobin that has a severely reduced ability to carry oxygen.
- Increase oxygen affinity at remaining sites → preventing the release of oxygen to tissues
Respiratory Toxins objectives
Why does Nitrogen Dioxide cause considerable damage to the lungs but may not cause as much damage in the upper respiratory tract?
Remember that this is a heavy gas, so it goes down. NO2 is relatively insoluble in water and thus may pass through the upper respiratory tract with little effect BUT produce considerable damage to the lungs where the duration of contact is longer and the moisture content is greater.
Respiratory Toxins objectives
What kind of animal is susceptible to toxicosis caused by overheating of cookware?
birds, overheating teflon pans (PTFE).
Respiratory Toxins objectives
How can cows eating forage high in tryptophan possibly lead to lung damage?
Cytochrome P450s convert the 3-MI to reactive intermediates that cause lung damage including pulmonary edema, emphysema and potentially death.
