Poisons and toxins 1 & 2 Flashcards
Hx important for toxicology
- what?
- signalment
- how much and toxic dose
- when (decontaminate, should they be showing CS?)
- CS
- vomiting?
- other hx (meds, chronic illness)
Common presenting problems with toxicology
- neuro (seizure, tremor)
- renal azotaemia
- haematologic (anaemia, coagulopathy)
- CV (tachycardia, arrhythmia)
- hepatic/ GIT
- metabolic (hypoglycaemia, acidaemia)
Classic signs indicating toxin ingestion
- known toxin ingestion
- acute onset
- scavenger (walk off lead, children, parties)
- excluded other cause
Natural toxin groups
plants, animals, fungi, inorganic matter
Chemical toxin groups
- drugs/ meds
- pesticides (domestic, agricultural)
- household chemicals
- industrial chemicals
Aspects of toxicokinetics
= between administered dose and compound at site of action
- uptake, transport, metabolism and transformation, sequestration, excretion (i.e absorption, distribution, metabolism and excretion)
Aspects of toxicodynamics
= between compound at site of action and adverse or toxic effect
- binding
- interaction
- induction of toxic effects
- depends on protein binding and cellular changes and cytoprotection
What are important things to know relating to toxin toxicokinetics and toxicodynamics?
- time to peak
- T (1/2)
- route of elimination / site of metabolism
- GI recirculation
- Target receptors
- antidotes
- whether lipophilic
How can the cardiovascular system be affected? Tx?
- arrhythmia - ECG, anti-arrhythmics
- shock - IV bolus
How can the respiratory system be affected? Tx?
- oxygen
How can the neurological system be affected?
- SEIZURES - diazepam, propofol and phenobarbital (this order, diazepam better for idiopathic epilepsy so often need propofol, phenobarbital takes 20-30 minutes to work
- TREMORS - methocarbamol and diazepam (methocarbamol is a mm relaxant)
If hyperthermic, what should you do?
Cool to 39.3 degrees (don’t cool below this or the temperature will rapidly drop), running water, fan, IVF
After addressing the MBS with acute toxicity, what are your considerations?
- temperature
- blood glucose
- PCV/ TP and smear
- coagulation (PT, APTT)
- biochemistry (renal, hepatic)
- haematology
- UA
What needs to be considered when tx a toxicity?
- what? caustic? (acid, alkali, bleach)
- when?
- amount? toxic dose/ LD50? volume?
- CS
- recumbent/ seizure/ gag reflex present?
- pharmacokinetics (enterohepatic metabolism? renal excretion? binds charcoal? antidote?)
- risk of tx?
List tx options for toxicity
- emesis
- milk
- gastric lavage
- enema
- activated charcoal
- sorbitol (cathartic)
- IVF
- dermal decontamination
- antidotes
- lipids (Intralipid)
- dialysis
What is a cathartic drug?
one that accelerates defaecation, opposite of a laxative, example is sorbitol
Indications - emesis
Recent ingestion (
Contraindications - emesis
- recumbent, unconscious, no gag, seizure
- caustic (acid, alkali, bleach)
- petroleum
- detergents
Method to induce emesis - 4
- Apopmorphine: give one dose, second if not working, don’t give a third time
- Xylazine (cats)
- Medetomidine (cats)
- Hydrogen peroxide (USA)
Gastric/colonic lavage - indications
- ingestion
CI - gastric/colonic lavage
caustic
Complications gastric lavage
- aspiration pneumonia (cuff ETT)
- hypothermia
Complications - emesis
aspiration pneumonia
Method - gastric lavage
GA –> ETT –> pass stomach tube (length muzzle to last rib, wide bore, lubricate) –> lavage stomach (instil 10-20ml/kg of water into stomach, slosh around abdomen, place end of stomach tube below animal to empty, repeat until no more contents retrieved) –> 3 sided lavage (R/L lateral and sternal recumbency) –> remove stomach tube (kink so no leakage into oesophagus)
Activated charcoal (AC) - indications
- toxins which bind to AC
- enterohepatic metabolism
CI - activated charcoal
- recumbent, unconscious, no gag, seziure
- toxins which DON’T bind AC (ethylene glycol, alcohol, alkali, petroleum, heavy metals, xylitol)
What is xylitol?
synthetic sweetener
Complications - activated charcoal
- aspiration pneumonia
- if contains sorbitol –> dehydration (therefore only use this type of AC once/ first time, subsequently just AC)
Method of administration - AC
- 1-2g/kg PO: food, syringe
- q4 hours or until faeces black (warn clients)
Diuresis - indications
- renal excretion of toxins in toxic form (lilies, raisin, EG)
- nephrotoxic
Diuresis - CI
risk of fluid overload (anuric/ oliguric, cardiac dz, pulmonary dz)
Distinguish anuria and oliguria
anuria = no passage of urine oliguria = reduced urine production and excretion
Dermal decontamination - indications
Dermal toxins (permethrin - cats, engine oil, oil on birds)
Dermal decontamination - considerations
- hypothermia
- sedation
Method - dermal decontamination
Clip contaminated area, wash with vegetable oil and washing up liquid (dog shampoo not good for this)
Indications - intralipid
Lipophilic toxins (i.e. Log P >1):
- local anaesthetics
- ivermectin
- permethrin
- baclofen
- marijuana
- mycotoxin
- TCA, beta-blcoked, Ca channel blocker
Adverse effects - intralipid
RARE:
- lipaemia
- pancreatitis
- hypersensitivity
CS - permethrin toxicity in cats
mm fasiculations (mild), although not a seizure, animal can be very hypothermic. Tx with IVF, usually 24 hr hospitalisation
Opioid antidote
naloxone
Alpha-2 agonist antidote
atipamezole
Benzodizepine antidote
flumazenil
Ethylene glycol (EG) antidote
ethanol (or just vodka!), 4- methylpyrazole is hard to get and expensive but also works
Paracetamol antidote
N- acetylcyssteine
NSAID antidote
misoprostol
Anticoagulant rodenticide antidote
vitamin K
Which toxins would you treat with dialysis? (not needed to memorise this)
- ethylene glycol
- baclofen
- paracetamol
- aminoglycosides
- ethanol
- mushroom
Ddx - toxins causing seizures and tremors
- metaldehyde (snail/slug pellets)
- mycotoxin (mouldy bread)
- theobromine (chocolate, caffeine)
- permethrin (topical flea tx, toxic to cats
- recreational drugs
- lead
- OPs/ carbamates
Outline metaldehyde toxicosis
- commonest cause of death in dogs (VPIS cases)
- kills slugs/snails by dehydration and paralysis
- method in mammals unclear
- is a tetramer of acetaldehyde
- is hydrolysed by gastric acid to acetaldehyde but clinical relevance of this is doubtful
- metaldehyde itself or unknown metabolite may be responsible
- disruption of GABAergic system may cause the convulsant activity
- not lipophilic
LD50 - metaldehyde in dgs
- 100-1000mg
- variable individual resonse
- other threshold indicated to be > 2mg/kg
Tx - metaldehyde
- gastric decontamination and observation (if
Toxic dose - metaldehyde
LD50 = 500mg/kg
Source - tremorgenic mycotocins
some mouldy foods, silage and compost
Tx - mycotoxins
- apomorphine
- activated charcoal
- diazepam
- cool IV fluids
What is roquefortine C?
the mould present in blue cheese, humans tolerate this well, dogs don’t
At what levels does theobromine cause toxic effects, severe signs and seizures in dogs?
- TOXIC EFFECTS: >20 mg/kg
- SEVERE SIGNS: 40-50mg/kg
- SEIZURES: 60 mg/kg
What quantities of theobromine do dark, milk and white chocolate cause toxicity?
- DARK: treat for > 3.5g/kg
- MILK: treat for > 14g/kg
- WHITE: by law, can only contain cocoa butter and thus minimal concentrations of theobromine
CS - theobromine toxicity
- vomitting
- diarrhoea
- PD
- salivation
- dehydration
- CNS/ myocardial stimulation: tremor, convulsions, tachycardia, hypertension, arrhythmias
- Renal failure
- fatal cases - severe convulsions/ circulatory failure
Tx - theobromine toxicity
- emesis
- activated charcoal
- adequate hydration
- benzodiazepines for CNS stimulation
- lidocaine or beta-blocker for rapid tachycardia/ arrhythmia
Mechanism - permethrin toxicity - cats
alteration of voltage- dependent sodium channels in nerve membranes causes repetitive discharges or membrane depolarisation. Some may also inhibit GABA-R. Loss of this inhibition can lead to hyperexcitability of nervous tissue.
Timings of effect of permethrin toxicity in cats
- onset at 1-3 hours (up to 36 hours)
- duration of effects 1-3 days, rarely up to 7 d
3 main CS of permethrin toxicity in cats
- hypersalivation
- tremor
- fasciculations
- many others too
Tx - feline permethrin toxicity
- Intravenous lipid infusion *
- diazepam,
- pentobarbital
- propofol
- methocarbamol (a centrally acting skeletal mm relaxant, has been effective where benzodiazepines have failed)
Toxins which can cause coagulopathy
- anticoagulant rodenticide
- coagulopathy secondary to hepatopathy (xylitol)
Toxins –> haemolysis - 2
- paracetamol (cats)
- onion/ garlic
What is the toxin in anticoagulant rodenticide?
- most are second generation
- commonest are bromodioloe and difenacoum
- others: brodifacoum, flocoumafen
- commonly at 0.005% strength baits, some professional compounds may be more concentrated (0.1%)
How do anticoagulant rodenticides cause toxicity?
inhibit vitamin K expoxide reductase which converts vitamin K epoxide to vitamin K –> depletion of vitamin K which converts precursor coagulation proteins to their activated forms.
Outline pharmacodynamics/kinetics of anticoagulant rodenticide
- peak plasma levels vary (mins to hours)
- plasma elimination half life is 14 hr (warfarin) and 6 days (brodifacoum)
CS - anticoagulant rodenticide
- CS relatively uncommon as clotting facotrs have a long half life so there is a delay between exposure and CS>
- onset of CS at 27 - 72 hours: increased clotting or PT time, main effect is haemorrhage with bruising, bleeding, gums, nose, GIT, wounds
- other CS: dyspnoea, lethargy, weakness…
Difenacoum - treatment threshold for acute exposure
100g bait/ kg at 0.005%
Flucoumafen - treatment threshold for acute exposure
Potentially toxic dose - bodifacoum
0.04 mg/kg
Potentially toxic dose - bromadiolone
0.35 mg/kg
Potentially toxic dose - difenacoum
5 mg/kg
Potentially toxic dose - flocoumafen
0.0075 mg/kg
Tx - anticoagulant rodenticide with CS or elevations in clotting/ PT
Vitamin K1 therapy (until PT normalises and then orally in divided doses for about 3 weeks, before finally discontinuing tx, check PT 1-3 days after). Whole blood/ plasma transfusions may be required. Monitor PCV and TS q 12 hours.
Tx - anticoagulant rodenticide without CS and normal PT for 3 days
Tx not required
Advice to client if pet has ingested anticoagulant rodenticide
- no off-lead walks
- care when playing with other animals
- no bones
In which species does paracetamol toxicity cause the most porblems?
dogs
Other terms for paracetamol
acetaminophen or APAP
Mechanism of paracetamol toxicity
- saturation of metabolic pathways
- toxic metabolite conjugated by glutathione
- glutathione promptly depleted
- cats lack metabolic capacity to detoxify paracetamol
Paracetamol - early cs (
- progressive cyanosis (fails to respond to O2 tx)
- brown/blue MM
- weak and lethargic
Mid CS - paracetamol (2-24 hours)
- facial/ paw oedema
- vomiting
- depression
- dark brown blood (methaemoglobinaemia) and remains dark on aeration
Longer CS - paracetamol (> 24 hours)
- severe methaemoglobinaemia
- hepatic necrosis
Toxic dose - paracetamol - dogs and cats
DOG: 150 mg/kg
CAT: 20 mg/kg
Tx - paracetamol toxicity
- emesis (within 2 hours)
- activated charcol
- ANTIDOTE: acetylcysteine (precursor of glutathione)
What UA sign is typically seen with acute kidney injury?
Casts (a type of sediment)
Toxins causing renal damage
- ethylene glycol (EG) - occasionally
- NSAIDs - one of commonest
- aminoglycosides (gentamicin)
- lilly (cats)
- grapes/ raisins (dogs)
Which NSAID is most commonly ingested by pets?
ibuprofen and meloxicam
n.b. in veterinary, COX-2 specific inhibitors are commonly used
What is NSAID toxicity largely due to?
COX-1 inhibition
NSAID toxicity - early CS - 3
- GIT erosion, ulcer, perforation
- V/D - both may be bloody
- CNS (rarely, ataxia, lethargy, drowsiness), large doses
NSAID toxicity - late CS - 2
- renal failure
- hepatic damage
Toxic dose - ibuprogen
10 mg/kg
Toxic dose - carprofen (commonest veterinary NSAID)
40 mg/kg
Toxic dose - meloxicam
- Oral > 1mg/kg
- SC 0.2 mg/kg
Tx - NSAID toxicity
DECONTAMINATION: - emesis (optimal within 2 hrs ingestion) - activated charcoal (repeat dose) MAINTAIN RENAL FUNCTION - oral fluid therapy - IVF - maintenance for 24-48 hours * be guided by renal function tests*
How can gastric ulceration be prevention with NSAID toxicity?
- H2 receptor antangonists - Cimetidine, Ranitidine, Famotidine
- Proton pump inhibitors - Omeprazole
- Ulcer healing / coating - sucralfate
- Prostaglandin supplementation - Misoprostol
Tx - renal toxicity
- DIURESIS: IVF at 2-3x maintenance, furosemide if anurix despite IVF
- GASTROPROTECTION: omeprazole (easier to give in dogs than cats)
- ANTI-EMETIC: maropitant (1mg/kg)
Monitoring - renal toxicity
- urine output
- BWt
- urea:creatinine
- K+
- ECG
Outline Ethylene glycol (EG) absorption
- rapid - peak plasma concentrations
Mechanism of EG toxicity
- metabolism catalysed by alcohol dehydrogenase
- various intermediate metabolites with toxic actions (glycoaldehyde; glycolic acid = rate limiting step, acidosis and high urine levels indicative; glyoxylic acid; oxalic acid)
Blood results - EG toxicity
- azotaemia
- hyperglycaemia
- increased osmolaality
- increased anion gap
- increased urea: creatinine
- decreased USG
- URINALYSIS: proteinuria, glucosuria, haematuria, albuminuria, calcium oxaluria
Diagnosis - EG toxicity
stains can lend fluorescence to urine and other contaminated tissue examined under Wood’s lamp within 6 hours BUT negative results don’t rule it out
Tx - EG toxicity
- early dx and aggressive intervention (
T/F: true lily (Liliaceae) and day lily (Hemerocallis) cause renal toxicity in cats
True
Outline lilly toxicity
- all parts of plant are toxic
- small amount of plant can have serious consequences
- mechanism of toxicity unknown
- rapid development of CS: GIT irritation, PU, dehydration, renal failure, seizures (severe cases)
Tx - lilly toxicity
- REDUCE ABSORPTION: emesis +/- AC
- PREVENT RENAL SHUTDOWN AND ENHANCE RENAL PERFUSION: IVF diuresis for at least 48 hours
Prognosis - lilly toxicity
- tx options limited once renal failure occurred so guarded.
- good if tx before onset of renal impairment.
What is xylitol?
- natural 5-C sugar alcohol
- in fruits/ vegetables
- not denatured or modified in baking/ cooking
- rapid and potent stimulator of insulin release (dogs, dose-dependent)
- -> liver damage (unknown mechanism)
- e.g. smint pastilles, wrigleys gum
Tx - xylitol toxicity
- aggressive
- treat for > 0.05g/kg (50 mg/kg)
- gastric decontamination
Monitoring - xylitol toxicity
- baseline glucose, K+, phosphorous, total bilirubin, LFTs and clotting tests
- monitor glucose concentrations every 1- 2 hours for at least 12 hours.
- re-check the other tests every 24 hours, for at least 72 hours.
Xylitol effects and tx - 2
- HYPOGLYCAEMIA (tx with frequent small meals, oral sugar for 8-12 hours), glucose/dextrose (severe cases), ECG (risk of hypokalaemia-induced arrhythmias)
- HEPATOTOXICITY: consider immediate dextrose therapy, s-adenosyl-l-methionine or acetylcystein as hepatoprotectants
Overall tx - xylitol
- EMESIS - apomorphine
- Glucose correction
- Monitor: blood glucose (BG), biochem, PCV?TS, coagulation (since liver failure can cause problems with this)
Hepatoxicity - ddx
- xylitol
- mushroom
- paracetamol
What is bendiocarb? CS? Tx?
a widely-used insecticide –> moderate ataxia, abnormal lung sounds, tachycardia, small pupil and increased bowel sounds.
- Tx: single dose of diazepam and atropine
Toxins causing seizure/ tremor (LEARN!!!) - 7
- metaldehyde
- mycotoxin
- theobromine
- permethrin
- lead
- OP
- recreational drugs
Toxins causing anaemia (LEARN!!!) - 6
- COAGULATION:
- rodenticide
- hepatotoxin
- HAEMOLYSIS:
- paracetamol (cats)
- onion/ garlic
- heavy metals
Toxins causing renal problems (LEARN!!!) - 7
- EG
- NSAIDs
- aminoglycosides
- lillies (cats)
- raisin/grapes (dogs)
Toxins causing hepatic problems (LEARN!!!) - 4
- xylitol (also hypoglycaemia)
- cycad (plant that looks like pineapple growing out of ground)
- mushroom
- paracetamol
General methods to treat toxin
- emesis
- milk
- gastric lavage
- enema
- AC
- sorbitol (cathartic)
- IVF
- dermal decontamination
- antidotes
- intralipid
- dialysis
What are the most important systems to treat?
MBS (also toxins often affect GIT)
