RBC Oxidants Flashcards
describe acetaminophen
- OTC analgesic, antipyretic
-tylenol, generic - prescription meds: lortab, vicodin
- dogs and humans:
-toxicity: 100-900 mg/kg - cats:
-lower dose for toxicity!
-40-60mg/kg (deaths at 10mg/kg reported)
describe toxicokinetics of acetaminophen
- rapid absorption
- biotransformation!
-phase II conjugation
-dogs: 50-75% glucuronide
-cats <3%
-phase I oxidation
-deacetylation
- excretion: urine
- targets: GOOGLE
-liver: 1ry target
-dogs and cats: RBCs
–dogs lack NAT 1, 2
–cats: NAT1 slow (low glucoronidate)
describe acetaminophen mechanism
- redox recycling of PAP oxidized Hb to MetHb
- reduced activity of reductase
- GSH depletion
describe clinical presentation of acetaminophen toxicity
- 3-12 hours post exposure
- decreased O2 transport and hemolytic anemia:
-cyanosis or dark MM, dyspnea, tachypnea
-hypothermia, tachycardia
-hematuria, hemoglobinuria
-edema and swelling of face and front paws (cats)
-death - labs:
-chocolate brown blood
-methemoglobinemia, heinz bodies
-elevated liver enzymes
describe treatment of acetaminophen toxicity
- transfusion, O2 therapy
- emesis, activate charcoal with sorbitol
- antidote:
-N-acetylcytseine (glutathione precursor)
-8 hours post ingestion - others: antidotes with some success
-sodium sulfate
-ascorbic acid
-cimetidine (cytP450 inhibtor)
-SAMe
-silymarin
describe nitrate/nitrites
- nitrate (NO3-); nitrite (NO2-)
- found in soil, plants, water: stems and stalks
- hay and forage:
-alfalfa, fescue, sorghum, sudan grass
-corn, soybean - many poisonous plants
- FERTILIZERS:
-nitrate-based
-phenoxy herbicides: 2,4 D (dichlorophenoxy acetic acid)
describe target site, species, toxicity, and MOA of nitrate/nitrite
- target site: hemoglobin
- species:
-nitrate: CATTLE, horses
-rumen microflora can convert nitrate to nitrite, which then forms MetHb and interferes with O2-carrying capacity of blood - toxicity:
>10,000 ppm dry weight
<5000 ppm safe
5000-10,000: not safe for pregnant cows
<1,000 ppm in wtaer toxic - MOA:
-rumen microflora convert, see above
describe clinical presentation of nitrite tox
- acute: 1-4 hr following rapid ingestion of material high in nitrate
- respiratory distress: exercise intolerance, cyanosis, tachypnea, gasping
-ataxia, tachycardia, seizures, death (6-24hr) - GI distress: salivation, diarrhea
- abortion: 3-7 days after sublethal ingestion
describe diagnostics for nitrite tox
- discolored blood, tissues
- Methemoglobinemia
-may not be evident in animals dead more than a few hours - nitrate/nitrite:
-blood, urine, ocular fluid
-hay, water
describe treatment and prevention of nitrite tox
- reduce MetHgb!!
-antidote: methylene blue
-not currently allowed in livestock - reduce ruminal nitrite:
-cold water lavage
-ruminal antibiotics: penicillin
-proprionic bacteria - prevention
-testing
-adaptation
-dilution
-ensiling
describe onions (and friends)
- family amaryllidaceae
-genus allium
-onions, garlic, shallots, leeks
-more than 400 species - toxicity:
-N-propyl disulfides: potent odor
-varies with plant type, growing conditions, processing, species
-greater in areas with higher soil SULFUR content: LA, TX, CO, NV, WY, CA - reported poisonings:
-wild or cultivated
-raw: fresh or culled
-dried or dehydrated: minced, flakes
-cooked: onion souffle, meatloaf
-powders: baby foods - species:
-dogs, cats, cattle, horse
-small ruminants are more resistant
describe onion toxicity MOA
- plants high in sulfur, when chewed release thiosulfinates
- thiosulfinates are converted to disulfides and back and forth
- n-propyl disulfides: greatest toxicity
- redox recycling of disulfides releases free radicals
-n-propyl disulfides are oxidants
-decrease NADPH and GSH
-RBCs are most sensitive; oxidation of hemoglobin!
describe clinical presentation of onion toxicosis
- hemolytic anemia
-acute to delayed onset
-pale MM, tachypnea, tachycardia, weakness, icterus, hematuria
-possible vomiting, diarrhea, anorexia - labs: anemia, hemoglobinemia, HEINZ BODIES
describe treatment of onion toxicosis
- blood transfusion
- fluids
- GI decontamination
-emesis: if NOT vomiting
-activated charcoal - monitor hematocrit for several days!
describe zine
- an essential nutrient
- sources:
-pennies before 1982
-skin ointments
-galvanized metals: bolts, nails
-paints (55%)
-dietary excess - monogastrics: dogs and pigs
- birds
describe toxicokinetics of zinc
- absorption:
-upper small intestine: Zn2+
-increased by dietary Zn deficiency
-acidic pH - distribution:
-transport proteins
-liver: release back to circulation
-accumulation: liver, pancreas, muscle, bone - excretion:
-feces: bile, pancreatic fluids, GI mucosa
describe zinc MOA and toxicosis
MOA:
-oxidative damage
-Heinz bodies
-RBC hemolysis
toxicosis:
-initial: gastroenteritis
-hemolytic anemia: icterus, tachycardia, hemoglobinuria, renal failure
describe treatment of zinc toxicosis
- fluids, transfusions
- remove source
- antacids: metallic Zn
- H2 antagonists: increase pH, decrease absorption
5, chelation!
-Ca2+ disodium EDTA
describe methylxanthines
- origin:
-plant alkaloids found in chocolate, coffee, tea, cola
-3 alkaloids: theobromine, caffeine, theophylline - other sources:
-cocoa bean shell mulch
-OTC meds/stimulants, herbal
-human and veterinary medications!
describe chocolate
80% theobromine, 20% caffeine
-baking chocolate has highest levels of theobromine!! followed by dark chocolate, then milk chocolate
describe methylxanthine toxicosis in dogs and cats
- LD50: 80-200mg/kg
-mild signs: 20 mg/kg
-severe signs: 40-50 mg/kg
-seizures: 60 mg/kg
AKA toxicity with
1 ounce milk chocolate per pound BW or
0.1oz backers chocolate per pound body weight
longer half life in dogs = bigger window of opportunity
describe toxicokinetics of methylxanthines
- absorption/distribution:
-readily absorbed
-widely distributed
-crosses placenta - elimination:
-biotransformation: phase I and II to inactive metabolites - excretion:
-bile; reabsorption
-urine: reabsorption from bladder
-milk
describe methylxanthine MOA
- complete antagonists of adenosine receptors
adenosine: nucleoside,
-in ATP for energy transfer
-in cAMP for signal transduction as phosphodiesterae inhibitors (non-competitive, regulate cAMP level)
-inhibitory neurotransmitter to allow sleep
- adenosine binds to
A1 receptors: decrease HR, decrease force of atrial contraction, and respond to epinephrine
-decrease CNS excitability, inhibit EAA release
-anti-diuretic
A2 receptors: regulate vascular tone, dilate coronary arteries
describe clinical presentaion of methylxanthine toxicosis
depends on what ingested and how much!!
dogs and cats:
-1-12 hours post ingestion
-polydipsia, vomiting, bloating, diarrhea
-hyperactivity, polyuria, tremors, seizures
-tachycardia, arrhythmias, tachypnea, cyanosis, hypertension
-hyperthermia, coma
-death (cardiac failure) is rare
describe treatment of methylxanthine toxicosis
- stabilize:
-tremors and seizures: methocarbamol, diazepam
-antiarrhythmia drusg!!
- GI decontamination:
-emetics or gastric lavage
-activate charcoal, repeated
-1x cathartic - fluid therapy
- urinary catheter to prevent reabsorption from bladder
- severe cases:
-72 hours to resolve
-24-72 hours: pancreatitis could follow due to increased fat consumption from original ingestion (choccy)
describe TCAs
- antidepressants used for chronic pain
-amitryptiline, nortriptyline, imipramine
-min LD <15 mg/kg - toxicokinetics:
-lipophilic: rapidly absorbed and widely distributed
-peak plasma levels within 2 hours
-liver biotransformation, urinary excretion: some active metabolites, some enterohepatic circulation
describe TCA MOA
multiple!
- block reuptake of dopamine, NE, 5-HT
- anticholinergic activity
- antihistaminergic activity
- anti alpha-adrenergic activity
describe clinical presentation and treatment of TCA toxicosis
clinical presentation:
1. rapid onset: 30 min (bc lipophilic)
- lethargy, ataxia
- progress to tachycardia, mydriasis, vomiting, hypotension, cardiac arrhythmias, dyspnea, pulmonary edema, seizures, hyperthermia, coma, death
- death within 1-2 hours
treatment:
1. no antidotes!
- CV: fluid therapy for hypotension, hyperthermia
-arrhythmias will resolve in most cases - CNS: diazepam
- GI decontamination:
-skip emesis, go to gastric lavage
-activated charcoal with sorbitol, repeat AC only
describe amphetamines
sources:
-prescription: CNS stimulant, appetite suppressants, mood enhancers
-illegal drug use
formulation:
-tablets
-alkaline
-derivatives: methamphetamine; ecstasy (MDMA)
toxicity:
-approximate oral LD50: 10-30 mg/kg
describe amphetamines toxicokinetics
- absorption:
-alkaline drugs
-rapid intestinal absorption
-peak levels reached within 2-3 hours - distribution: rapid and wide
- elimination:
-biotransformation: liver
-excretion: urine
describe amphetamines MOA
- potentiates catecholamine release
-CNS: adrenal gland
-NE: dopamine - inhibit monoamine oxidase
- block NE-DA re-uptake
describe amphetamine tox clinical presentation
- rapid onset: 1-2 hr
- hyperexcitability, agitation, mydriasis, tremors, hyperreflexia, rapid breathing
- tachycardia, hypertension, cardiac arryhthmias
- infrequent seizures
describe amphetamine tox treatment
- stabilize:
-control hyperactivity: diazepam, barbiturates
-control cardiac arrhythmias
- decontamination:
-emetics, lavage, activated charcoal, cathartic
