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
