Elimination & Detox 2: Hepatotoxins Flashcards
what its he MOST COMMON TYPE of LIVER INJURY in SMALL ANIMALS?
this type of injury is ____-DEPENDENT, ____ reaction to a ____
INTRINSIC LIVER INJURY = DOSE-DEPENDENT, PREDICTABLE, reaction to a TOXICANT
IDIOSYNCRATIC LIVER INJURY tends to be ____, ____ & ___-____ DEPENDENT, potentially ____-____
when do signs appear?
give 3 common clinical signs? they are all…
IDIOSYNCRATIC LIVER INJURY tends to be UNPREDICTABLE, RARE & NON-DOSE DEPENDENT, potentially IMMUNE-MEDIATED
signs can appear WEEKS or MONTHS AFTER EXPOSURE
3 common signs? all EXTRAHEPATIC LESIONS
1. FEVER
2. ERYTHEMA
3. RASH
PERIPORTAL liver damage vs. CENTRILOBULAR liver damage vs. MASSIVE HEPATIC NECROSIS?
PERIPORTAL = toxicants are DIRECTLY INJURIOUS TO CELLS & DAMAGE FIRST HEPATOCYTES THEY ENCOUNTER
CENTRILOBULAR = toxicants that are BIOACTIVATED by CYP450 due to HIGH CONCENTRATION HERE
MASSIVE HEPATIC NECROSIS = injury is SO SEVERE that it EXTENDS ACROSS ENTIRE LIVER LOBULES
ENTEROHEPATIC RECIRCULATION..
= definition w/ biliary system
example of a DRUG that undergoes this
what INTERVENTION (& frequency of dose) can we use to COMBAT THIS if a TOXICANT IS UNDERGOING ENTEROHEPATIC RECIRCULATION?
= compounds that are EXCRETED IN THE BILE might undergo ENTEROHEPATIC RECIRCULATION & have their HALF-LIVES PROLONGED
NSAIDs like NAPROXEN can undergo this in DOGS
ACTIVATED CHARCOAL at REPEATED DOSES can be used to BIND UP SUBSTANCE & DECREASE ITS HALF-LIFE, but only if it’s CAPABLE of binding
give 5 examples of DRUGS that can BE BOUND UP BY ACTIVATED CHARCOAL?
what does this help REDUCE?
5 examples?
1. BROMETHALIN
2. METHYLXANTHINES
3. BARBITURATES
4. IVERMECTIN
5. AMANITINS
helps to reduce HALF LIFE & ENTEROHEPATIC RECIRCULATION
DERMAL PHOTOSENSITIZATION…
= definition
tend to see this in WHAT SPECIES & animals that have WHAT KIND OF LIFESTYLE?
2 etiologies?
likely to occur WHERE on the body?
= when animals have skin that is ULTRA SENSITIVE to UV LIGHT & causes ULCERATION, EROSIONS & NECROSIS
tend to see this in LIVESTOCK ANIMALS that LIVE OUTSIDE
2 etiologies?
- PRIMARY = associated with PHOTODYNAMIC COMPOUNDS in CERTAIN PLANTS
- SECONDARY = due to HEPATOBILIARY INJURY from TOXICANTS that INTERFERE WITH BILE TRANSPORT or UNDERLYING LIVER DZ
tends to occur in regions that are SPARSE WITH HAIR or HAIR IS LIGHT
ACETAMINOPHEN TOXICITY…
pathophysiology? (5)
why is this more toxic in ___ than ___?
pathophysiology?
1. when NORMAL BIOTRANSFORMATION PATHWAYS of GLUCURONIDATION & SULFATION for ACETAMINOPHEN are SATURATED, then CYP450-MEDIATED OXIDATION occurs
- production of TOXIC METABOLUTE N-ACETYL… is PRODUCED INSTEAD
- toxic metabolite then CONJUGATES with GLUTATHIONE to produce NONTOXIC metabolites
- but once GLUTATHIONE DEPLETED, TOXIC METABOLITE binds to SH-CONTAINING PROTEINS in LIVER CELLS
- causes LIVER PEROXIDATION –> LIVER TOXICITY
why is this more toxic in CATS than DOGS?
–> CATS CANNOT UNDERGO GLUCURONIDATION, so MORE QUICKLY CREATES TOXIC METABOLITE when ingesting acetaminophen
ID LIKELY DZ
what ETIOLOGY is more common?
DZ = DERMAL PHOTOSENSITIZATION
MORE likely to be SECONDARY to HEPATOBILIARY INJURY (toxicant ingestion) or UNDERLYING HEPATIC DZ
ACETAMINOPHEN TOXICITY in CATS…
what 2 kinds of INJURY to a PARTICULAR ORGAN can occur?
if a CAT presents with PUFFY FACE & FEET, what OTHER clinics finding is likely present/why?
LIVER INJURY can be either…
1. CENTRILOBULAR
2. MASSIVE HEPATIC NECROSIS
PUFFY FACE & FEET in CAT = METHEMOGLOBINEMIA from OXIDATIVE RBC INJURY
ACETAMINOPHEN TOXICITY in DOGS…
in SMALL BREED DOGS, what disease can develop SECONDARILY?
in SMALL BREED DOGS, can develop KCS secondary to ACETAMINOPHEN TOXICITY
N-ACETYLCYSTEINE…
what is the “brand name?”
2 functions? (& overall)
2 routes of administration?
treatment is MOST EFFECTIVE when…
“MUCOMIST”
2 functions? = for ACETAMINOPHEN TOXICITY
- source of -SH to BIND UP TOXIC METABOLITES
- GLUTATHIONE PRECURSOR to help RESTORE glutathione to change TOXIC METABOLITE –> NONTOXIC
2 routes?
1. IV
2. PO
treatment is MOST EFFECTIVE when GIVEN WITHIN 8 HOURS OF INGESTION
ASCORBIC ACID…
also called?
= main function?
how is this drug administered? why can that be an issue? (2)
–> how can we TRY TO SOLVE this issue?
also called “VITAMIN C”
= acts as an ANTIOXIDANT to REDUCE METHEMOGLOBIN back to HEMOGLOBIN that’s secondary to ACETOMINOPHEN TOXICITY
drug given PO, but…
1. MIGHT NOT BE WELL-TOLERATED
2. MIGHT NOT BE ABLE TO REACH HIGH PLASMA CONCENTRATIONS
–> we can try SPIKING THE FLUID BAG W/ VITAMIN C to GIVE IT IV (faster plasma concentration)
SILYMARIN…
aka?
= what is it?
3 functions?
method of action?
this is an ACTIVE INGREDIENT in WHAT COMMON VET MEDICATION?
AKA MILK THISTLE
= NUTRACEUTICAL for LIVER
3 functions?
1. ACUTE & CHRONIC LIVER DZ
2. CIRRHOSIS
3. HEPATOPROTECTIVE AGENT
method of action? = REDUCE HEPATIC COLLAGEN FORMATION & INCREASE HEPATIC GLUTATHIONE CONTENT
SILYMARIN is an ACTIVE INGREDIENT in DENAMARIN
SAMe (S-ADENOSYL-METHIONINE)…
in what common vet medication?
this is an ____ ____ SYNTHESIZED & used PRIMARILY for ___ INJURY
essential for 3 BIOCHEMICAL PATHWAYS in the ___, such as…
in DENOSYL
this is an ENDOGENOUS MOLECULE SYNTHESIZED & used PRIMARILY for LIVER INJURY
essential for 3 BIOCHEMICAL PATHWAYS in the LIVER, such as…
- AMINOPROPYLATION = which helps with LIVER RECOVERY
- TRANSMETHYLATION = CELL MEMBRANE STRUCTURE, FLUIDITY & FUNCTION
- TRANSSULFURATION = allows ALTERNATE SUBSTRATE for TOXIC METABOLITE & PRECURSOR to GLUTATHIONE
4 examples of TOXICANTS that can cause HEPATIC TOXICITY?
- ACETAMINOPHEN
- NSAIDs
- XYLITOL
- AMANITA MUSHROOMS
3 SALICYLATES that can be POTENTIALLY TOXIC to SMALL ANIMALS?
dogs vs. cats?
- BISMUTH SUBSALICYLATE (Pepto-Bismol)
- SALICYLATE OINTMENTS (for arthritis & psoriasis)
- OIL OF WINTERGREEN
CATS MORE LIKELY TO EXPERIENCE TOXICITY BECAUSE OF INABILITY TO GLUCURONIDATE
4 CLINICAL SIGNS of ASPIRIN & SALICYLATE TOXICITY?
treatment OVERALL? give 4 SPECIFIC examples
4 clinical signs?
1. METABOLIC ACIDOSIS w/ RESPIRATORY ALKALOSIS
2. GI ULCERATION
3. LIVER NECROSIS
4. COAGULOPATHY
treatment OVERALL = SYMPTOMATIC & SUPPORTIVE!
1. CORRECTION of ACID-BASE abnormalities
2. GI PROTECTANTS
3. WHOLE BLOOD TRANSFUSIONS for HEMORRHAGE/HYPOTENSION
4. HEPATOPROTECTANTS
AFLATOXINS..
= what is it/where is it found?
what STRAIN is the MOST TOXIC & found in HIGHEST CONCENTRATION?
why can this be dangerous for HUMANS?
= common MYCOTOXIN contaminant of LIVESTOCK FEEDS & PET FOODS, including in MEAT, MILK, & EGGS
the AFLATOXIN B1 (AFB1) is MOST TOXIC & FOUND IN HIGHEST CONCENTRATION
can be dangerous for HUMANS because if they EAT ANIMALS THAT HAD AFLATOXINS = can cause TOXICITY IN HUMANS
AFLATOXINS…
5 CLINICAL SIGNS? OVERALL are…
treatment/prevention?
5 CLINICAL SIGNS? = overall NON-SPECIFIC
1. FEED REFUSAL can be the FIRST or ONLY SIGN
2. V+
3. D+
4. ICTERUS
5. COAGULOPATHIES/GI HEMORRHAGES
treatment is SYMPTOMATIC & SUPPORTIVE, AVOID MOLDY FOOD
4 POSTMORTEM changes with AFLATOXIN toxicity?
- CENTRILOBULAR HEPATOCELLUAR NECROSIS
- CANALICULAR CHOLESTASIS
- BRIDGING PORTAL FIBROSIS
- PROLIFERATION of BILE DUCTS
BESIDES AFLATOXIN B1, what are some OTHER kinds of AFLATOXINS & what do they do? (5)
- DON/VOMITOXIN = causes FEED REFUSAL & GI disturbances
- ZEARALENONE = causes ESTROGENIC effects
- FUMONISINS = causes LEUKOENCEPHALOMALACIA in HORSES
- OCHRATOXIN A = causes RENAL TUBULAR NECROSIS
- ROQUEFORTINE & PENITREM A = acts as TREMORGENS
MICROCYSTINS…
= what are they? how do they cause INTOXICATION in host?
in HORSES, they can cause… + 1 “descriptor”
pathophysiology? (3)
= TOXINS that are PRODUCED BY ALGAE when ALGAE ARE INGESTED via ACIDIC ENVIRONMENT OF STOMACH
in HORSES, they can cause LIVER FAILURE; “dishrag,” FLOPPY LIVER
pathophysiology?
1. enter HEPATOCYTES via BILE ACID TRANSPORTER mechanism
- INHIBITS PROTEIN PHOSPHATASES –> HYPERPHOSPHORYLATION
- hyperphosphorylation DISRUPTS CYTOSKELETAL STRUCTURE of HEPATOCYTES
MICROCYSTINS…
often causes RAPID ___
what MAIN DISEASE & associated CLINICAL SIGNS (4) can be seen?
animals that ___ might develop ____ _____
2 ADDITIONAL diseases that can be associated with microcystins?
RAPID LETHALITY
DZ = ACUTE HEPATOTOXICOSIS
1. D+
2. V+
3. PALE MMs
4. SHOCK
animals that SURVIVE might develop HEPTATOGENOUS PHOTOSENSITIZATION
2 additional dz…
1. NEPHROTOXICITY
2. PRIMARY LIVER & COLORECTAL CANCER
HEPATOTOXIC MUSHROOMS…
3 species? they ALL contain ___
most FREQUENTLY reported with ingestions of WHAT GENUS & SPECIES?
what’s an IMPORTANT QUESTION to ASK OWNER when determining if the mushroom is HEPATOTOXIC?
3 species? they ALL contain AMANITINS
1. AMANITA (classic)
2. GALERINA
3. LEPIOTA
most FREQUENTLY reported with ingestions of AMANITA PHALLOIDES
should ask owner WHERE THE MUSHROOM WAS GROWING –> what KIND of soil/tree, etc.
PATHOPHYSIOLOGY of HEPATOTOXIC MUSHROOMS? (2)
what 2 KINDS of cells are MOST AFFECTED? both have HIGH ___ ____
pathophysiology?
1. AMANITINS INHIBIT NUCLEAR RNA POLYMERASE II & interfere with DNA & RNA TRANSCRIPTION
- results in INHIBITION of RIBOSOMAL PROTEIN SYNTHESIS
cells with HIGH METABOLIC RATES most affected…
1. INTESTINAL CRYPT CELLS
2. HEPATOCYTES
PHASES of AMANITA PHALLOIDES TOXICOSIS? (4, one is +/-)
- initial 6-12 HOUR LATENT PERIOD followed by PHASE I GI SIGNS
- PHASE II GI SIGNS develop MORE SEVERELY w/ BLOODY D+
- +/- ANOTHER LATENT PERIOD
- PHASE III = HEMORRHAGES, SEIZURES, LIVER/KIDNEY FAILURE & DEATH usually within 4-7 DAYS
general TREATMENT for MUSHROOM TOXICOSIS…
start with INITIAL Tx, 4 MONITORING parameters, 5 SUPPORTIVE tx
- INITIAL DECONTAMINATION with REPEATED DOSES of ACTIVATED CHARCOAL (ONLY IF PATIENT IS STABLE)
- MONITOR..
–> GLUCOSE
–> LIVER ENZYMES
–> RENAL VALUES
–> COAGULATION PARAMETERS - TREATMENT w/ SUPPORTIVE CARE
–> GI PROTECTANTS
–> VITAMIN K1
–> BLOOD REPLACEMENT
–> SEIZURE CONTROL
–> NUTRITIONAL SUPPORT
XYLITOL..
= what is it? is it ALWAYS toxic?
how does TOXICITY manifest in dogs?
can we induce emesis?
5 MONITORING parameters?
= a SUGAR SUBSTITUTE for DIABETICS that CAN BE TOXIC for DOGS/CATS, but SAFE if UNDER TOXIC LEVELS
how does TOXICITY manifest in dogs?
1. QUICKLY ABSORBED in CANINE GI TRACT
2. causes DOSE-RELATED INSULIN RELEASE & subsequent HYPOGLYCEMIA
3. leads to LIVER DAMAGE/FAILURE
EMESIS only effective if WITHIN 30 MINUTES OF INGESTION
MONITOR?
1. ELECTROLYTES
2. BLOOD GLUCOSE
3. LIVER ENZYMES
4. CBC
5. SERUM PHOSPHORUS
XYLITOL..
1 medical treatment option? can we use CHARCOAL?
how long should DOGS BE HOSPITALIZED? why?
treatment?
–> CHARCOAL DOESN’T BIND
–> IV DEXTROSE to help PREVENT HYPOGLYCEMIA & HEPATOPROTECTIVE
dogs should be HOSPITALIZED FOR AT LEAST 12-24 HOURS due to RISK OF DELAYED-ONSET HYPOGLYCEMIA, especially when GUM INGESTED
