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Hepatotoxicants
Justine A. Lee, DVM, DACVECC, DABT CEO, VetGirl [email protected] @VetGirlOnTheRun @drjustinelee
Introduc1on
Garret Pach1nger, VMD, DACVECC
COO, VetGirl
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Introduc1on
Jus1ne A. Lee, DVM, DACVECC, DABT CEO, VetGirl
Financial disclosure
Hepatotoxicants
ā¢āÆ Xylitol ā¢āÆ NSAIDs ā¢āÆ Veterinary drugs ā¢āÆ Oral diazepam (cats) ā¢āÆ Metaldehyde ā¢āÆ Mushrooms ā¢āÆ Blue-Āāgreen algae ā¢āÆ Sago palm ā¢āÆ Acetaminophen
Why do we see hepatotoxicity? ā¢āÆ Liver common site Ć receives 25-Āā30% of cardiac output
ā¢āÆ Site of first-Āāpass clearance for most oral drugs
ā¢āÆ P450 and other biotransforma1on enzymes can generate reac1ve metabolites
ā¢āÆ 2 types of drug-Āāinduced hepatoxicity: āāÆ Cytotoxic (Ć hepatocyte necrosis) āāÆ Cholesta1c (Ć due to inhibi1on of biliary transporters)
ā¢āÆ Sugar-free, natural sweetener
ā¢āÆ Found in everything! āāÆ Sugar-free gums, candies, mints āāÆ Chewable multivitamins āāÆ Baked goods āāÆ Mouthwashes āāÆ Toothpastes āāÆ Anything āsugar-freeā
Xylitol
Xylitol ā¢āÆ Variable amounts in everything
āāÆ2 mg -1 gm/piece of gum is average
ā¢āÆ How toxic is it? āāÆ> 0.1 g/kg Ć hypoglycemia āāÆ> 0.5 g/kg Ć acute hepatic necrosis
ā¢āÆ Clinical signs: āāÆSigns of hypoglycemia: weakness, collapse, vomiting,
ataxia (< 1 hour) āāÆLiver injury (days later)
Xylitol toxicity for a 30 kg dog ā¢āÆ Trident and Orbit gums (2 mg to 0.2 g/piece):
āāÆ 15 pieces Ć hypoglycemia āāÆ 75 pieces Ć liver failure
ā¢āÆ Ice Breakers gum (1 g/piece): āāÆ 3 pieces Ć hypoglycemia āāÆ 15 pieces Ć liver failure
How do we treat xylitol toxicosis?
ā¢āÆ STAT blood glucose (BG) + chemistry āāÆTreat hypoglycemia STAT
ā¢āÆ 1 mg/kg 50% dextrose IV diluted
ā¢āÆ Decontamination āāÆDelayed emesis induction if asymptomatic! āāÆDo not give activated charcoal!
What doesnāt bind to AC: āolsā
ā¢āÆ Alcohols āāÆ Ethylene glycol āāÆMethanol
ā¢āÆ Xylitol
ā¢āÆ Heavy metals āāÆ Zinc āāÆ Iron
Xylitol treatment
ā¢āÆ If hypoglycemic or toxic dose Ć BG monitoring with 2.5-5% dextrose CRI in IVF
ā¢āÆ Recheck BG q. 4 hours Ć slowly wean off
ā¢āÆ Maintain BG for several hours OFF any dextrose
ā¢āÆ If hepatotoxic dose: āāÆ SAM-e āāÆ Chemistry q. 24 hours X 2 days
Veterinary NSAIDs ā¢āÆ NSAIDs inhibit conversion of arachadonic acid to
prostaglandins by inhibition of COX enzymes
ā¢āÆ General wide margin of safety in dogs
ā¢āÆ Adverse effects (AE): āāÆGI: vomiting, diarrhea
ā¢āÆ Less common AE: āāÆGI ulcer āāÆHepatotoxicity (1.4 cases out of every 10,000 dogs)
Veterinary NSAIDS: DOGS ā¢āÆ General rule with veterinary NSAIDs:
āāÆ 5X therapeu1c dose = GI āāÆ 10X therapeu1c dose = AKI
ā¢āÆ Carprofen: āāÆ 20 mg/kg: GI ulcers āāÆ 40 mg/kg: AKI
ā¢āÆ Deracoxib: āāÆ 10-15 mg/kg: GI ulcers āāÆ 30 mg/kg: AKI
REFERENCES: ā¢āÆ Peterson. Veterinary NSAIDS. In Five-ĀāMinute Veterinary Consult Clinical Companion Small Animal Toxicology Wiley-ĀāBlackwell 2011,pp 354-Āā361. ā¢āÆ Talcon PA, Gwaltney-ĀāBrant SM. Nonsteroidal An1inflammatories. Small Animal Toxicology Elsevier 2013, pp. 687-Āā708.
Veterinary NSAIDS: DOGS ā¢āÆ Chronic dosing: Hepatotoxicity
āāÆ Associated with carprofen Ć no known dose āāÆ Develops 5-Āā30 days; median 19 days āāÆ Ć±Ć±Ć±ALT āāÆ If ALT normal, itās not from carprofen
āāÆ Associated with Labrador retrievers? ā¢āÆ Are these the breeds that get osteoarthri1s? ā¢āÆ Over-Āārepresented breed
MacPhail et al, 1998
Veterinary NSAIDS: DOGS ā¢āÆ Discuss rare risks with pet owner!
ā¢āÆ Baseline blood work ā¢āÆ Recheck in 2 weeks; q. 3-Āā6 months thereaser
āāÆ Rare with acute toxicity āāÆ Treatment:
ā¢āÆ Immediate discon1nua1on ā¢āÆ Treatment for hepa1c failure ā¢āÆ Hepatoprotecants (e.g., SAMe)
How do we treat NSAID toxicosis? ā¢āÆ Decontaminate! (e.g., emesis, activated charcoal)
āāÆ Recent ingestion? āāÆ Type of pill?
ā¢āÆ Gel cap vs. chewable āāÆ Does it undergo enterohepatic recirculation? āāÆ Activated charcoal + cathartic
NSAIDS that undergo enterohepa2c recircula2on (Give me mul2ple doses of charcoal, please!)
NSAIDs that DO NOT undergo enterohepa2c recircula2on (NO mul2ple dose charcoal, please!)
NSAIDs we donāt know about
Meloxicam (significant) Carprofen (limited) Ketoprofen (suspected)
Deracoxib Tepoxalin (unknown)
NSAIDs: Treatment ā¢āÆ Clinicopathologic monitoring
āāÆ Baseline CBC, chemistry, UA, USG āāÆ If nephrotoxic dose:
ā¢āÆ PCV/TS, renal panel q. 24 hours X 2-3 days ā¢āÆ Recheck 1-2 days later
āāÆ If hepatotoxicity: ā¢āÆ PCV/TS, chemistry q. 24 hours while hospitalized ā¢āÆ PT/PTT Ć Vitamin K dependent factors ā¢āÆ If neurologic Ć NH3 or bile acids
NSAIDs: Treatment ā¢āÆ Aggressive IVF
āāÆ Does not aid in elimination āāÆ Vasodilate renal vessels Ć prevent AKI āāÆ 2.5-3.5X maintenance āāÆ Goal of fluid therapy:
ā¢āÆ Hemodilution: PCV/TS 35%/5 mg/dL
ā¢āÆ Anti-emetic therapy āāÆ Especially if MD A/C
ā¢āÆ Gastric protectants āāÆ Sucralfate āāÆ H2 blocker vs. misoprostol vs. omeprazole
ā¢āÆ Treatment for liver failure
Veterinary drugs: Dose-Āādependent hepatotoxicity
ā¢āÆ Azathioprine (NAC?) ā¢āÆ Ketoconazole
āāÆ 10 vs. 5 mg/kg/day
ā¢āÆ Amiodarone (an1-Āāarrhythmic) āāÆ 45% of dogs affected
ā¢āÆ Lomus1ne (CCNU) āāÆ 6% hepatotoxicity āāÆ 29% ƱLES by 5 fold āāÆ Boxers?
ā¢āÆ Acetaminophen ā¢āÆ Phenobarbital
Phenobarbital ā¢āÆ Can result in subclinical Ʊin bile acids to clinical hepatopathy Ć
fulminant liver failure
ā¢āÆ Signs typically develop > 1 year of treatment
ā¢āÆ Higher phenobarbital serum concentra1ons have not be correlated with development of Ʊbile acids!
ā¢āÆ CATS: doesnāt cause enzyme induc1on (ƱLES) or hepatotoxicity
Reference: Trepanier LA. Drug-Āāassociated liver disease. Kirk CVT XV
Veterinary drugs: Idiosyncra1c hepatotoxicity
ā¢āÆ Poten1ated sulfonamides (NAC?) āāÆ Black or tan with white feet!
ā¢āÆ Zonisamide āāÆ 2 dogs; 1 euthanized due to severe liver failure āāÆ CS developed in 10-Āā21 days
ā¢āÆ Felbamate (with phenobarbital)
ā¢āÆ Methimazole āāÆ 1-Āā2% of cats āāÆ Different from ƱALT, ALP from ƱT4
Veterinary drugs: Idiosyncra1c hepatotoxicity
ā¢āÆ Primidone ā¢āÆ Valproate (Depakote) ā¢āÆ Anabolic steroids ā¢āÆ Doxycycline ā¢āÆ Metronidazole ā¢āÆ Phenytoin ā¢āÆ Arsenical an1helminthics (sodium thiacetarsamide) ā¢āÆ Diazepam (cats)
Veterinary drugs ā¢āÆ Acute toxicosis is rare, but can be seen with massive inges1on
ā¢āÆ Chronic inges1on Ć hepatotoxic
ā¢āÆ Monitor pa1ent carefully āāÆMonitoring blood work āāÆ Discon1nua1on of meds PRN āāÆ Hepatoprotectants
Benzodiazepines (BZO)
ā¢āÆ Common brand names: Valium, Clonazepam, Alprazolam
ā¢āÆ Parenteral routes: very safe
ā¢āÆ Dog: oral route OK
ā¢āÆ Cat: oral route Ć acute hepa1c necrosis
Benzodiazepines: Cats ā¢āÆ Not recommended for behavioral reasons, appe1te s1mulant, FUO,
etc. in cats due to repe11ve dosing
ā¢āÆ Likely idiosyncra1c āāÆ CS develop > 5011 days of oral treatment āāÆ Seda1on, malaise, ataxia, jaundice
ā¢āÆ Ć±Ć±Ć±ALT, AST, TBILI, PT/PTT
ā¢āÆ Center SA et al 1996: 91% died
ā¢āÆ NO ORAL generic or brand BZO for cats!
Metaldehyde
ā¢āÆ Snail and slug bait
ā¢āÆ āShake and bakeā
ā¢āÆ Clinical signs: tremors, seizures, hyperthermia
ā¢āÆ Rare reports of possible hepatotoxicity āāÆ No biopsy? āāÆ Overhyped?
ā¢āÆ Slowly being replaced off the market by iron sulfate (less toxic)
Metaldehyde: Treatment ā¢āÆ Decontamina1on
āāÆNot if symptoma1c! āāÆETT + gastric lavage instead! āāÆOne dose of ACC
ā¢āÆ Radiographs?
ā¢āÆ Temperature regula1on
ā¢āÆ IVF
ā¢āÆ An1-Āāconvulsants and muscle relaxants!
MUSHROOMS
Mushrooms
ā¢āÆ Several thousand species in North America
ā¢āÆ < 100 toxic āāÆMost are Amanita
ā¢āÆ No simple test, hard to ID āāÆ North American Mycology Associa1on āāÆ hnp://www.namyco.org/toxicology/iden1fiers.html
Mushrooms
ā¢āÆ Unless youāre a mycologist or experienced mushroom hunterā¦ āāÆNever trust a mushroom unless itās from the grocery store!
āāÆDeadly mushrooms exist everywhere! ā¢āÆ Amanitas
āāÆWorst case scenario! ā¢āÆ Not all deadly mushrooms look deadly
āāÆWhite bunon cap
Types of mushrooms
ā¢āÆ Amani1ns ā liver failure: āāÆ Develop GI signs (6-Āā24 hours) āāÆ āFalse recoveryā period āāÆ Fulminant liver failure (36-Āā48 hours) āāÆ Possible AKI too āāÆ Tx: decontamina1on, IVF, hepatoprotectants, symptoma1c suppor1ve care, monitoring
ā¢āÆ Types: Amanita, Galerina, Lepiota, A. phalloids (death cap, death angel), A. ocreata
Types of mushrooms ā¢āÆ Muscarine
āāÆ CS: SLUDGE signs āāÆ Tx: Decontamina1on, atropine, suppor1ve care āāÆ Types of mushroom: Inocybe, Clitocybe dealbata āāÆ āSwea1ng mushroomā
ā¢āÆ Muscimol and ibotenic acid āāÆ CS: ataxia, seda1on, muscle spasms, seizures āāÆ Types: Amanita muscaria, A.pantherina
Types of mushrooms ā¢āÆ False morel
āāÆ CS: vomi1ng, diarrhea, seizures (rare) āāÆ Tx: Decontamina1on, symptoma1c suppor1ve care āāÆ Types of mushroom: Gyromitra spp.
ā¢āÆ Gastrointes1nal irrita1on āāÆ CS: vomi1ng, diarrhea āāÆ Tx: Decontamina1on, symptoma1c suppor1ve care, an1-Āāeme1cs, IVF āāÆ Seen in 1-Āā6 hours; last 1-Āā2 days āāÆ Types: Agaricus, Boletus, Entoloma
Types of mushrooms ā¢āÆ Hallucinogenic mushrooms
āāÆ CS: ataxia, howling, aggression, nystagmus, hyperthermia āāÆ Treatment not generally necessary āāÆ Type: Psilocybe, Conocybe, Gymnopilus spp.
Cyanobacteria: Blue-Āāgreen algae ā¢āÆ Algae blooms
āāÆ Most non-Āātoxic, but hard to iden1fy with naked eye āāÆ Toxic to everything!
ā¢āÆ Stagnant, hot, humid condi1ons āāÆ Brackish water āāÆ Freshwater
ā¢āÆ Wind blows the algae to one side of the lake ā¢āÆ MOA:
āāÆ Neurotoxins: Anabeana, Aphanizomenon,etc. āāÆ Hepatotoxins: MicrocysAs, Nodularia
Cyanobacteria: Blue-Āāgreen algae ā¢āÆ Microcys1ns inhibit protein phosphatases 1 and 2A Ć sevre liver
damage and acute centrilobular necrosis
ā¢āÆ Anatoxin-Āāa Ć potent cholingeric agonist at nico1nic acetylcholine receptors Ć con1nuous electrical s1mula1on at NMJ
ā¢āÆ Anatoxin-Āāas Ć irreversible acetylcholinesterase inhibitor (OP like); doesnāt cross BBB
ā¢āÆ Toxic dose? 50-Āā11,000 mcg/kg
Blue-Āāgreen algae ā¢āÆ Can see very acute clinical signs
ā¢āÆ Death can occur within minutes to hours (neurotoxin) or hours to days (hepatotoxin)
ā¢āÆ Dermal irrita1on
ā¢āÆ Grave prognosis
Blue-Āāgreen algae: Clinical signs
ā¢āÆ Microcys1ns: āāÆ GI: vomi1ng, diarrhea āāÆ Weakness, collapse āāÆ CARDIAC: pallor, tachycardia, shock
ā¢āÆ Anatoxin-Āāa: āāÆ CNS: paralysis, cyanosis, death
ā¢āÆ Anatoxin-Āāas: s = saliva1on āāÆ SLUDGE like signs āāÆ Tremors, ataxia, seizures, respiratory arrest
Blue-Āāgreen algae: Treatment
ā¢āÆ Decontamina1on: osen too late āāÆEmesis? āāÆGastric lavage + ac1vated charcoal āāÆBathe (using protec1ve gear)
ā¢āÆ Clinicopathologic tes1ng: āāÆPCV/TS/BG āāÆBaseline CBC, chemistry, PT/PTT
Sago Palm Cycas Revoluta
ā¢āÆ Highly poisonous to both pets and humans
ā¢āÆ Plant thrives in hot, humid climates (tropical/subtropical) āāÆSouthern states āāÆHawaii
ā¢āÆ Found as Bonsai plants, outside, houseplants
ā¢āÆ Used to be a toxicant of the SE SW USA āāÆ Now everywhere!
Sago Palm
ā¢āÆ Not a true palm ā¢āÆ Of the Cycadacae order
ā¢āÆ Genera Cycads, Macrozamia, and Zamias
ā¢āÆ Common names: āāÆ Cycad āāÆ Cardboard palm āāÆ Japanese cycad āāÆ Coon1e plant
Cycas revoluta
Sago Palm Cycas Revoluta
ā¢āÆ All parts of plant poisonous
ā¢āÆ Seeds contain the largest amount of toxin
ā¢āÆ Inges1on of as linle as 1-Āā2 seeds Ć severe clinical signs: āāÆVomi1ng āāÆDiarrhea āāÆDepression/lethargy āāÆSeizures āāÆLiver failure
Toxicity
ā¢āÆ Hepatotoxicity āāÆ Centrolobular and mid-Āāzonal coagula1ve hepa1c necrosis
ā¢āÆ Gastrointes1nal
ā¢āÆ Central nervous system (CNS)
ā¢āÆ Cardiotoxicity?
Cycad: Three Primary Toxins
ā¢āÆ Cycasin, an azoglycoside āāÆ In GIT Ć converted to methylazoyxmethanol (MAM) by a B-Āāglucosidase
āāÆHepatotoxic
ā¢āÆ B-Āāmethylamino-ĀāL-Āālanine (BMAA) āāÆNeurotoxic amino acid
ā¢āÆ High molecular weight substance āāÆS1ll uniden1fied
Sago Palm: GIT Clinical Signs
ā¢āÆ Gastrointes1nal: ā¢āÆ Anorexia ā¢āÆ Protracted vomi1ng ā¢āÆ Hematemesis ā¢āÆ Plant contents seen in emesis? ā¢āÆ Diarrhea (melena, hematochezia) ā¢āÆ Abdominal pain ā¢āÆ Dehydra1on
ā¢āÆ Seen within 15 minutes to several hours
Sago Palm: Hepa1c Clinical Signs
ā¢āÆ Hepatotoxicity: ā¢āÆ Lethargy ā¢āÆ Icterus ā¢āÆ Increased LFT ā¢āÆ Melena ā¢āÆ Petechhia/ecchymoses ā¢āÆ Coagulopathic ā¢āÆ Ascites
ā¢āÆ Seen within 24-Āā72 hours post-Āāinges1on
Sago Palm: CNS Clinical Signs
ā¢āÆ CNS: āāÆ Lethargy āāÆMentally obtunded āāÆ Hepa1c encephalopathy āāÆ Ataxia āāÆ Tremors āāÆ Seizures āāÆ Coma āāÆ Death
ā¢āÆ Seen within 48-Āā72 post-Āāinges1on
Sago Palm: Cardiac?
ā¢āÆ Long-Āāterm cardiotoxicity? ā¢āÆ Anecdotally reported 18 months out ā¢āÆ Cardiomyopathy?
Baseline Blood Work
ā¢āÆ CBC ā¢āÆ Biochemistry ā¢āÆ PCV/TS/BG/liver panel q. 24 hours X 3 day ā¢āÆ PT/PTT ā¢āÆ Bile acids vs NH3
+ ā¢āÆ Repeat blood work once discharged
āāÆMay see Ć©LFT at 24-Āā48 hrs; can last from 2-Āā9 days long
Clinicopathologic Changes:
ā¢āÆ Anemia vs. hemoconcentra1on ā¢āÆ Hypoalbuminemia ā¢āÆ Hypocholesterolemia ā¢āÆ Ć© bilirubin ā¢āÆ Ć© or ĆŖ glucose ā¢āÆ Ć© lactate ā¢āÆ Ć© WBC ā¢āÆ Thrombocytopenia/coagulopathy ā¢āÆ Ć© or ĆŖ BUN
Histopathologic Lesions
ā¢āÆ Cirrhosis
ā¢āÆ Focal centrolobular and midzonal coagula1on necrosis
ā¢āÆ Secondary changes due to hepa1c encephalopathy āāÆBrain and spinal cord demyelina1on and axonal degenera1on
Ferguson et al. JVIM 2011
Ferguson et al. JVIM 2011
ā¢āÆ 34 dogs exposed to sago palm
ā¢āÆ Overall outcome: ā¢āÆ 50% died/euthanized
ā¢āÆ Results: ā¢āÆ Non-Āāsurvivors : ā ALT, TBILI on presenta1on, ā albumin compared to survivors
ā¢āÆ NS: ā coagula1on 1mes ā¢āÆ A/C correlated with longer survival ā¢āÆ Nega1ve prognos1c factor: āAST
Sago Palm: Treatment
ā¢āÆ Decontamina1on āāÆEmesis induc1on? āāÆAc1vated charcoal: mul1ple doses āāÆAn1-Āāeme1c
GENERAL TREATMENT FOR ANY HEPATOTOXICANT!
General Treatment for Hepatotoxicants
ā¢āÆ Fluid therapy āāÆBalanced crystalloid āāÆFluid closest to pa1entās sodium āāÆAvoid LRS
ā¢āÆ Colloidal support? āāÆ If TS < 5 mg/dL, consider Hetastarch āāÆ1 ml/kg/hour
Treatment: Gastrointes1nal support
ā¢āÆ An1-Āāeme1cs āāÆMaropitant? (1/2 dose) āāÆOndansetron, dolasetron
ā¢āÆ Gastric protectants āāÆ High gastrin levels
ā¢āÆ Sucralfate ā¢āÆ H2 blocker vs. misoprostol vs. omeprazole
Hepatoprotectants
ā¢āÆ SAMe āāÆ Increases glutathione āāÆ Improves membrane stability āāÆCytokine modula1on āāÆAn1-Āāapop1c āāÆDose: 20 mg/kg PO X 30 days
Hepatoprotectants
ā¢āÆ Milk thistle (Silbyin) āāÆReac1ve oxygen species scavenger
āāÆAn1-Āāinflammatory āāÆAn1-Āāfibro1c āāÆ Increases protein synthesis āāÆCholere1c āāÆDose: 20 ā 50 mg/kg q. 6-Āā24 hrs PO
āāÆFOR HOW LONG?
Hepatoprotectants
ā¢āÆ N-Āāacetylcysteine (NAC) āāÆ Increases glutathione āāÆAn1-Āāinflammatory āāÆ Improved microcircula1on āāÆ Improved oxygen delivery? āāÆDose: 280 mg/kg IV, then 70 mg/kg q 6 hrs X 2 days
Treatment for Coagulopathy
ā¢āÆ If coagulopathic Ć āāÆ Vitamin K SQ or PO
ā¢āÆ 1 mg/kg PO, SQ q 12 hours
āāÆ Fresh frozen plasma or frozen plasma ā¢āÆ 6-Āā20 ml/kg IV
Treatment
ā¢āÆ An1convulsants āāÆDiazapem or injectable Keppra: lowest effec1ve dose!
ā¢āÆ Blood work monitoring:
āāÆRecheck chemistry/PT/PTT q 24 hours while hospitalized
āāÆRecheck 2-Āā3 days aser discharge āāÆWeekly thereaser un1l LES WNL
ACETAMINOPHEN & PARACETAMOL
Bud, 30 kg, 5 yo, MC, Labrador
ā¢āÆ Ate 2 tablets of Tylenol Cold & Flu
ā¢āÆ Owner just came home from work
ā¢āÆ Dog is asymptoma1c at home ā¢āÆ Plan?
67
Bud, 30 kg, 5 yo, MC, Labrador
ā¢āÆ Induce emesis
ā¢āÆ Find out whatās actually in Tylenol Cold & Flu and calculate if itās toxic or not
ā¢āÆ Refer away to someone else
68
Bud, 30 kg, 5 yo, MC, Labrador
ā¢āÆ Induce emesis
ā¢āÆ Find out whatās actually in Tylenol Cold & Flu and calculate if itās toxic or not
ā¢āÆ Refer away to someone else
69
Whatās in Tylenol Cold & Flu, anyway?
WTF?
Whatās The Formula1on (WTF)? ā¢āÆ Availability ā lots of forms!
Tablets: 500 mg, 1000 mg Caplets: 500 mg Capsules: 500 mg Soluble Tablets: 120 mg, 500 mg Suspension: 120 mg/5 mL, 250 mg/5 mL Solu1on for infusion: 10 mg/mL (50 mL, 100 mL vials) Suppositories: 60 mg, 125 mg, 250 mg, 500 mg
ā¢āÆ Common pain medica1on
ā¢āÆ COX3 inhibitor
Whatās in Tylenol Cold & Flu, anyway?
ā¢āÆ Per tablet: āāÆAcetaminophen ā 650 mg āāÆ Pseudoephedrine ā 60 mg āāÆDextromethorphan ā 30 mg
ā¢āÆ Toxicity: āāÆAcetaminophen ā 650 X 2/30 kgs = 43 mg/kg āāÆ Pseudoephedrine ā 60 X 2/30 kgs = 4 mg/kg āāÆDextromethorphan ā 30 X 2/30 kgs = 2 mg/kg
Acetaminophen
ā¢āÆ Range of toxicity: āāÆCat/ferret: 10-Āā60 mg/kg (some say 50-Āā100 mg/kg) āāÆDog: 100-Āā150 mg/kg
ā¢āÆ MetHb seen at > 200 mg/kg
Cats
āāÆ Methemoglobinemia (metHb) vs. liver failure āāÆ Clinical signs:
ā¢āÆ Within 1-Āā2 hours: anorexia, hypersaliva1on, facial/paw edema ā¢āÆ Progresses to lethargy, methemoglobinemia (metHb),
cyanosis, Heinz body anemia, hemoglobinuria ā¢āÆ Death, hepa1c failure
Dogs
ā¢āÆ KCS (dry eye) ā¢āÆ Liver failure ā¢āÆ Clinical signs:
āāÆWithin 4-Āā12 hours: cyanosis, hemoglobinuria, anemia, metHb
āāÆ Progresses to: depression, anorexia, vomi1ng, colic, liver failure
āāÆ Takes several days before signs of liver failure seen: icterus, increased LFT (24-Āā72 hours)
ā¢āÆ ā ALT, AST, Tbili ā¢āÆ ā albumin, BUN, cholesterol, glucose
Treatment ā¢āÆ Decontamina1on? Rapid absorp1on!
āāÆ + emesis induc1on āāÆAc1vated charcoal X1 (if recent inges1on) āāÆ Some enterohepa1c recircula1on?
ā¢āÆ Baseline blood work:
āāÆHematology āāÆ PCV tube (chocolate-Āācolored blood) + smear (Heinz bodies)
āāÆ Chemistry āāÆ Venous blood gas?
Treatment ā¢āÆ IV fluid therapy Ć perfusion
ā¢āÆ Treatment for hypoxemia: āāÆ Blood transfusions āāÆ Oxygen therapy if dyspneic, cyano1c
ā¢āÆ An1-Āāeme1cs āāÆ Impera1ve with oral an1dote tx
ā¢āÆ H2-Āāblockers? āāÆ No clear benefit! āāÆ Contraindicated with cats
Acetaminophen: āAn1dotesā
ā¢āÆ N-Āāacetylcysteine āāÆ Glutathione source āāÆ Hepatoprotectant
ā¢āÆ Dosing: āāÆ 280 mg/kg loading dose for metHb āāÆ 70 mg/kg q. 6 hours X 7-Āā17 doses āāÆ If normal at 48 hours, D/C
Acetaminophen: āAn1dotesā
ā¢āÆ SAMe (liver protectant) or Silymarin X 30 days
Bud, 30 kg, 5 yo, MC, Labrador ā¢āÆ Non-Āātoxic:
āāÆAcetaminophen < 100 mg/kg āāÆDextromethorphan < 5 mg/kg
ā¢āÆ Treat for pseudoephedrine (4 mg/kg) āāÆModerate to Severe clinical signs: 5-Āā6 mg/kg āāÆDeath: 10-Āā12 mg/kg
ā¢āÆ Consider monitor for dry eye?
80
Summary
ā¢āÆ Treat hepatotoxicants aggressively!
ā¢āÆ The answer to all of toxicology: symptoma1c suppor1ve care and the BIG 4 treatments
Want more? Check out these VetGirl toxicology podcasts!
ā¢āÆ Toxicology mistakes to avoid in your poisoned pa1ents! ā¢āÆ Sleep aid poisoning in dogs and cats ā¢āÆ Intravenous lipid emulsion (ILE) with ivermec1n toxicity in dogs :
Geļæ½ng the skinny on using fat! ā¢āÆ Inducing vomi1ng in dogs and cats: Picking the right eme1c agent ā¢āÆ Ac1vated Charcoal: To Give or Not To Giveā¦ ā¢āÆ Which eme1c should you pick in dogs: Hydrogen peroxide or
apomorphine? ā¢āÆ Fluorouracil (5-ĀāFU) poisoning in dogs: A deadly topical toxin
Want more? Check out these VetGirl toxicology podcasts!
ā¢āÆ Fer1lizer poisoning: Commonly implicated, rarely toxic ā¢āÆ Your pa1ent ate what? Intravenous Lipid Emulsion with Lidocaine
Toxicity in Cats ā¢āÆ Baclofen Toxicity ā Why NOT to relax with this muscle relaxant! ā¢āÆ Cathar1cs: What you need to know about accelera1ng defeca1on! ā¢āÆ How to induce vomi1ng in veterinary medicine ā¢āÆ Xylitol poisoning in dogs ā¢āÆ Veterinary NSAIDS: Friend vs. foe?
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Dr. Jus2ne Lee ā¢āÆ June 19, 2014: Minnesota Veterinary Medical
Associa1on, Saint Paul, MN ā¢āÆ July 26, 2014: AVMA, Denver, CO ā¢āÆ August 12, 2014: Merck, Chicago, IL ā¢āÆ August 13, 2014: Omaha, NE ā¢āÆ August 15-Āā16, 2014: IVS, Seanle, WA ā¢āÆ September 11-Āā12, 2014: IVECCS, Indianapolis, IN Dr. Garret Pach2nger ā¢āÆ August 16-Āā18, 2014: Pennsylvania Veterinary
Medical Associa1on Keystone Veterinary Conference in Hershey, PA
ā¢āÆ September 5, 2014: Leon Veterinary Conference, Guadalajara, Mexico
ā¢āÆ September 24-Āā28, 2014: Southwest Veterinary Symposium, Ft. Worth, Texas
Where is VetGirl going to be? Check out our upcoming 2014 lectures here: