Vitamin K antagonists (google says: inhibit the generation of an active form of vitamin K1 via inhibition of vitamin K1 reductases). And Vitamin K1 is required for clotting factor synth!
vit K1 dependant clotting factors? in what way is K1 needed for these factors?
2,7,9,10!! (their precursors are activated by vit K1)
2 first generation anticoag roenticies? 2 second gen ones? why do we carE?
First: Warfarin, Diphacinone. Second: Brodifacoum, Bromadiolone.... we care because it has to do with DURATION OF ACTION! 2 gen has longer half life (when in doubt, assume 2nd gen, treat for like 3-4 weeks)
clinical bleeding how long after clotting synth stops/after ingestion?
24-72hrs (implication: can induce emesis if just happened, and then can monitor for bleeding after 2 days to see if they need vit K, instead of immediately putting them on it-- save money from owner. or can immediately put them on K. either way, take 2-3 to stop bleeding, so have a window where can just recheck them. and if they arent bleeding after 2-3 days, know decontamination worked and dont HAVE to do K tx for months)
why would a anticoag tox pt present in shock?
hemorrhagic shock bc bleeding- typically cavitary bleeding. Can bleed into pericardium (dont poke it. they will die.)
*remember anticoag dogs can come in just bc theyre coughing....why coughing?
bleeding into dorsal tracheal membrane, Pulmonary parenchymal hemorrhage
what will coag testing be like with anticoag tox?
Prolongation PT, PTT ((pt is external path and only 7 is external and factors are 2,7,9,10 so strong extrnal path inhibition--> strongly prolonged pT. and factor 7 also has the shortest half life)
what is the PIVKA test looking at?
Accumulation of inactivated vit K dependent factor pre-cursors. "Protein Induced by Vitamin K Antagonism" test. without K1 to activate precursor clotting factor forms, they just start building up....can check for these
how do you tx anticoag tox?
first GI decontamination!! Then obv give vit K1-- and need to tx for 3-4 weeks. DO NOT GIVE VITAMIN K IV!!! can cause anaphylaxis. Give SQ. Also, VIT K1 IS FAT SOLUBLE. NEED TO GIVE WITH FATTY MEAL!!! (like A/D) bc needs fat to be absorbed. Just dont give with diet food basically. ALSO, takes like 24-32 hours for the K to start working, so need to provide supportive care in the meanwhile-- fresh frozen plasma**, blood products, IV fluids, O2. Then make sure you follow up: repeat coag panel 48hr after last vit K pill-- need to wait to make sure duration therapy was correct. and last dose active for another 24hrs...and then wait another day. so test 2 days after stop for follow up coag test.
what is bromethalin?
it is a neurotoxic anti rodenticide!
MOA of bromethalin?
interferes with cell membrane pumps. Ion pump dysfunction --> cell swelling, death!
CSs of bromethalin tox? when do you see the CSs? tx?
Neurologic!! convulsions, paralytic. But take 1-4d to see CSs after ingestion-- so often miss GI contamination. Also no antidote, so tx supportive (anticonvulsants,fluids, nutrition). Recovery is possible- need to be aggressive in management tho
what is zinc phosphide? MOA?
This is gopher bait. Grain based and smells like fish. Causes an ACUTE tox. MOA: when zinc phosphide hits acidic pH of stomach(gastric pH must be between 1-3), it starts to produce phosphine gas. induces death via anoxia. asphyxiate on a cellular level.
CSs of zinc phosphide?
(remember anoxia on cellular level) RAPID onset (15min-4hr) anorexia, hyperesthesia, tremors, agitation, vomiting, increased rate and depth of respiration, abdominal pain, bloat or GDV (bc gas being produced in stomach), death due to anoxia, CNS signs.
if you want to know what toxic agent killed them, what can you do to find out?
rapidly freeze stomach contents.
what might you be able to measure that would be elevated with zinc phosphide tox?
what odor might you smell with zinc phosphide?
Acetylene odor (fishy smell)
***so you get your zinc phosphide tox patient in, you know there is no specific antidote but you can do your regular things- what should you know about inducing emesis?
can def do this, but CAUTION, phosphene gas is being produced in acidic stomach, so if induce in closed room, YOU Can inhale it.
what can you give to tx zinc phosphide?
no specific antidote, but can give antacids bc need acidic pH to convert the zinc phosphide to phosphene gas...so change pH
what is metaldehyde?
this is slug and snail bait (metal slugs)
MOA of metaldehyde?
readily crosses the BBB--> decreases in GABA levels--> excitation (hyperexcitable)--> disinhibition of neuronal excitation
when do CSs start for metaldehyde poisoning? what are the CSs you see?
usually start within 3 hours, will see hyperthermia bc convulsing so hard (inc metabolism), also see SLUD(E) signs, neuro signs (agitation, convulsions, tremors, ataxia, and incoordination). Usually die from RESP FAILURE within 4-24 hours.
tx/px for metaldehyde?
GI decontamination! (emetics, gastric lavage, enemas can help bc rapid), resp and CV support, CNS support (Diazepam, pentobarbital, phenobarbital, methocarbamol), help control hyperthermia (fluids, control convulsions, evaporative cooling). If survive 24hr, prog is good. Full recovery 2-3 days
why are we always worried about kidneys with toxins in the blood?
kidneys get 25% CO (one of highest %s seen by one organ system. So anything in blood is going to see kidneys quickly in large volume over time. circulating toxins a high risk. )
what are 3 major metabolic functions of the kidney, and how do they all play a role in screwing over the kidney with toxins?
(1) Biotransformation: happen in the renal tubular epithelium, can create toxic intermediates (2) Endocytosis/pinocytosis: uptake of small proteins in proximal tubules--> concentrates toxicants in tubular epithelial cells (3) Tubular secretion/reabsorption: concentrates toxicants in renal proximal tubular cells, can be passive or active
what weird thing has ethylene glycol in it?
what should you know about species differences with ethylene glycol?
LD50 differs between dogs and cats!!! CATS WAY MORE SENSITIVE. which means tests might not even be good for cats bc toxic dose can be below tests threshold.
peak levels of antifreeze in...
MOA of ethylene glycol?
EG itself is not toxic. the prob is liver metabolizes it to toxic intermediates: glycoaldehyde, glycolic acid* (most toxic!!), glyoxylic acid. (via alcohol dehydrogenase). and then MAKE toxic components. ergo, BLOCK ENZYME is tx.
What is stage one of ethylene glycol tox like- when does it occur?
Stage 1: 30min-12hrs after ingestion. They are PU/PD, and progress to signs of intoxication: depression, incoordination, ataxia, paresis, seizures, and coma. So stage one is mostly characterized by NEURO SIGNS and it is the golden period- hopefully see them in 1-3 hours because past that antidote doesn't really work.
what is stage two of ethylene glycol tox like- when does it occur?
12-24 hours after ingestion. see resp(tachypnea, pulmonary edema, congestion) and cardio signs (tachycardia). Also there will be a severe metabolic acidosis.
what is stage three of ethylene glycol tox like? when does it occur?
24-72 hours after ingestion, this is when you start seeing kidney signs. Unfortunately usually see them during this stage. This is the point where there is a buildup of uremic toxins and you will see GI/oral ulcers, melena, hematemesis (or emesis,anorexia), neuro (depression, seizures 2* to uremia)-- onset of OLIGURIA/renal failure/azotemia/uremia. decreased urine output with low specific gravity or anuria
So main signs of stage 1, 2, and 3 of ethylene glycol tox?
(1) neuro (2) resp (3) renal
what should you know about using commercial kits to test for ethylene glycol tox?
kits cannot detect under 50mg/dL, but CATS can get toxic signs before this threshold is reached, so might be a false neg on a cat. Hence, the vet EGT kit is only labeled for dogs. Can detect for up to 12 hours.
what other substance, if consumed, can cause a false positive on a ethylene glycol tox test?
what will urine look like/have with ethylene glycol tox?
Ca Oxalate mono OR dihydrate crystalluria (w/in 3hrs for cats, 4-6hrs in dogs), isosthenuria, Glucosuria, hematuria, proteinuria, pyuria (glom and prox tubular injury), tubular casts (sig tubular insult), and sometimes the urine will fluoresce under woods lamp (not very accurate but fun)
in what ways will chemistry be different with ethylene glycol?
(1) Increased Osmolal Gap (2) High Anion Gap (AG) metabolic acidosis (DUELS!!) (AG= (Na + K) – (Cl + HCO3) ) (3) Azotemia (elevated phosphorus, hyperkalemia) (4) Decreased iCa (bc Ca being bound to the acids in the EG to make the CaOx crystals) (5) Hyperglycemia: aldehyde-induced inhibition of glucose metabolism
2 drugs to treat EG tox?
(1) Fomepizole (TOC), Inhibits alcohol dehydrogenase directly so the EG is not converted into its toxic metabolites. (2) Ethanol-- competes with EG for alcohol dehydrogenase.
how useful is dialysis for EG tox?
prog of EG tox?
if <8hrs since consumption, good. Poor if more.
what is really weird and crazy about raisin/grape tox?
severity is VARIABLE and there is no dose-dependant relationship! also dont know what the actual toxin in it is
what is the major problem grapes cause?
RENAL FAILURE-- generally AKI not CRF
CSs of grape tox?
(causes renal failure!!) Vague, GI (vomiting, anorexia, lethargy) PU/PD. Abd painful, can be dehydrated/shocky. will haev azotemia, metabolic acidosis, hyperkalemia (H and K stay bc kidney not filtering right)
tx for grape tox like?
well we dont know the toxin, so basically support: Fluid therapy, Correct acid-base imbalance, Promote diuresis (furosemide, mannitol), Treat electrolyte imbalances, monitor Ins/Outs/Urine output. May require AGGRESSIVE support. ((she said grapes and lepto are basically the worst)
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