Toxicology Flashcards
What info should be ascertained from the hx?
- what toxin?
- how much
- species/breed/BW (signalment stuff)
- when (can you decontaminate? when should they show clinical sings?)
- clinical sings
- V+
- other eg. medications, chronic illness
What presenting problems may be linked to toxin ingestion?
- neuro (seizure, tremor)
- renal azotaemia
- haemotologic (anaemia, coagulopathy)
- CV (tachycardia, arrhythmia)
- hepatic/GIT
- metabolic (hypoglycaemia, acidaemia)
Give an acronym for DDx
VITAMIN D
- vascular
- inflame/infection/immune mediated
- toxin/trauma
- anomalies
- metabolic
- idiopathic/iatrogenic
- neoplasia/nutritional
- degenerative
What categoried of toxin are possible and what must be remembered about these?
- plants
- animals
- fungi
- inorganic material
- drugs/medicines (human/vet)
- pesticides (domestic/agricultural)
- household chemicals/industrial chemicals
> classifcations are artificial (drugs are chemmicals, food can be plants etc.)
Egs of low toxicity? (assuming acute exposure, and will still be risk of mechanical damage etc. so not harmless)
- baby wipes/nappies
- nappy rash cream
- folic acid
- HRT tablets
- oral contraceptives
- zinc oxide cream
- coal
- cut flower food
- expanded polystyrene
- icepacks
- lipstick
- matches
- silica gel
- emulsion paint
- rubbers
- PVA or super glue
- blue tack
- chalk
- crayons/pencils/paper
What is involved in toxicoKINETICS and toxicoDYNAMICs?
> kinetics (getting to site of action) - uptake - transport - metabolism and transformation - sequestration - excretion > dynamics (once at site of action, protein binding/cellular changes/cytoprotection) - binding - interaction - induction of toxic effects
How may normal drugs kinetics be altered?
- if overdosed, kinetics are different to at therapeutic doses
What should tx of a patient with potential toxin ingestion be based on?
Tx the patient not the toxin eg.
- Arrythmia - ECG, antiarrythmics
- shock - IVF bolus
- Resp problems - O2
- neuro seizures - Diazepam, propofol, phenobarbital
- neuro tremors - methocarbamol, diazepam
- hyperthermic - cool to 39.3
- check blood (glucose, PCV/TP and smear, coagulation PT and APTT, biochem and haem)
- urinalysis
What are PT and APTT?
coagulation parameters
- prothrombin time
- activated partial thromboplastin time
What should be considered before treating a toxin patient?
- what is it (caustic? acid alkali bleach)
- when?
- how much? (toxic dose LD50)
- recumbent/seizuring/gag reflex?
- pharmacokinetics (enterohepatic metabolism/renal excretiong/charcoal binding/antidote?)
- risks of Tx
Potential tx for toxin ingestion
- emesis
- milk
- gastric lavage
- enema
- activate charcoal
- sorbitol (cathartic)
- IVF
- fermal decontamination
- antidotes
- lipids (intralipid)
- dialysis
Indications for emesis?
- ingestion RECENT
potential complications of emesis
aspiration pneumonia
contraindications for emesis
- recumbent/unconscious/no gag/seizure
- caustic (acid/alkali/bleach)
- petroleum
- detergents
How can emesis be induced?
- apomorphine (0.02-0.04mg/kg IV/SC)
- xylazine CATS (0.44 mg/kg IM/SC)
- medetomidine CATS (5-20mcg/kg)
- 3% hydrogen peroxide (1-5ml/kg dog, 10ml/kg cat)
INdications for gastric/colonic lavage?
- ingestion
contraindications for gastric/colonic lavage?
caustic
complications of gastric/colonic lavage?
- aspiration pneumonia (cuff ET tube!)
- hypothermia
Outline how to perform a gastric lavage
- GA (ET tube)
- pass stomach tube (muzzle -> last rib)
- lavage 10-20ml/kg water, slosh around, empty
- repeat until no more contents retrieved
- 3 sided lavage (left, right and sternal)
- remove tube while kinking to prevent leakage into oesophagus
Indications for activate charcoal?
- toxins that will bind to it!
- enterohepatic metabolism
Contraindications for activated charcoal/
- recumbent/unconscious/no gag/seizure
- toxins that don’t bind to AC
- ethylene glycol
- alcohol
- alkali
- petroleum
- heavy metals
- xylitol
complicatiosn of activate charcoal (AC)
- aspiration pneumonia
- if containing sorbitol -> dehydration, only use once
how is activated charcoal administered?
- 1-2g/kg PO
- food.syruinge
- q4hrs for 4 doses or until feaces black
Indications for diuresis?
- renal excretion of toxins
- nephrotoxic
contraindications for diuresis?
- risk of fluid overload
- anuric/oligouric
- cardiac disease
- pulmonary disease
How is diuresis carried out?
- 2-3x maintainance rate IVF
- 48-72hours
> If anuric/oligouric - furosemide (0.5-2mg//kg q2-8hours IV, 2-5mcg/kg/min)
Indications for dermal decontamination?
- dermal toxins (permethrin, engine oil, oil on birds)
contraindications for dermal decontamination?
- hypothermia
- sedation
How can dermal decontamination be carried out?
- clip
- wash with vegetable oil and washing up liquid
Indications for intralipid?
- lipophilic toxins (Log P >1)
- local anesthetics, ivermectin, permethrin, baclofen, marijuana, mycotoxin, TCA, B-blockers, Ca channel blockers
Adverse effects of intralipid use?
- lipaemia
- pancreatitis
- hypersensitivity
How is intralipid given?
- 1.5ml/kg over 5 mins
- CRI 0.25ml/kg/min
- repeat q1-4hours
- check serum for lipaemia
Antidote of opioids
Naloxone
Antidote of a2 ags
Atimpamezole
Antidote of benzos
Flumazenil
Antidote of ethylene glycol
Ethanol / 4-methylpyrazole
Antidote of paracetamol
N-acetylcysteine
Antidote of NSAIDs
misoprostol (Sythetic PGs)
Antidote of anticoagulant rodetnacide
Vitamin K
What is dialysis indicated for?
- ethylene glycol
- baclofen
- paracetamol
- aminoglycosides
- ethanol
- mushrooms
Outline emergency tx protocol for seizures
- neuro (seizure control)
- Diazepam, propofol - CV (shock)
- 20ml/kg bolus IVF - respiratory
- flow by O2/intubate - temperature (if high)
- cool to 39.3
- running water. fan, cold surface
Ddx for seizures and tremor
- metaldehyde (snail pellets)
- mycotoxin
- theobromine (chocolate, caffeine)
- permethrin (topical flea tx, only tox to cats)
- recreational drugs
- lead
- OPs/carbamates
What is the commonest cause of death by toxins in dogs?
- metaldehyde toxicosis (slug pellets)
- LD50 100-1000mg/kg variable
Tx for metaldehyde toxicosis specifically?
- if moderate signs, + activated charcoal left in stomach after
- oral activated charcoal avoided in conscious animals d/t risk of rapid onset convulsions
> control of convulsions and hyperthermia - diazepam, barbituates, propofol +- midazolam, methocarbamol
[metaldehyde NOT lipophilic, log P = 0.12] - haemodialysis been shown to remove metaldehyde from canine plasma IN VITRO
Tx protocol for metaldehyde induced seizures (CAse 1)?
- gastric lavage and enema
- phenobarbitone + propofol CRI
- repeat enema as passing blue feaces
- IVF: maintainance and ongoing losses
- 12hrs later weaned off propofol
- ambulatory with tremors- activated charcoal q4hrs until feaces black
What are mycotoxins?
- fungal metabolites -> toxicity in humans and animals
- tremorgenic mycotoxins present in some mouldy foods, silage and compost
Potential signs of mycotoxicity?
- V+
- ataxia
- hyperaesthesia
- mild hypersalivation
- generalised tremors
Tx mycotoxin
- apomorphine
- activated charcoal
- diazepam
- cool IV fluids
- more diazepam as tremors recurred
- resolved ~18 hours, 8hrs after last dose of diazepam
What is the toxic component of chocolate?
- theobromine
What levels of chocolate ingestion are toxic to dogs?
- toxic > 20mg/kg
- severe signs @ 40-50mg/kg
- seizures @ 60 mg/kg
> dark chocolate tx for >3.5g/kg
> milk chocolate tx for > 14g/kg
> white chocolate contains ONLY COCO BUTTER so not toxic (but ^ sugar so still bad!)
Clinical signs of theobromine ingestion
- VD+
- PD
- salivation and dehydration
- CNS/myocardial stimulation - trmor, convulsions, tachycardia, hypertension and arrhythmias
- renal failure
- fatal cases d/t severe convulsions/circulatory failure
Tx theobromine ingestion?
- emesis
- activate charcoal
- hydration
- benzos for CNS stimulation
- lidocaine/b blocker for tachycardia/arrhythmia
Caue of permethrin toxicity?
Use of dog products on cats
- alters kinetics of nerve membranes -> repetitive discharge of membrane potentials +- inhibition of GABA receptors -> hyperexcitability of nervous tissues
How long does permethrin toxicity take to occour? CLinical signs?
- 1-3hrs, sometimes up to 36 hours after application
- duration of effects 1-3d (
Tx permethrin in cats
- diazepam
- pentobarbital
- propofol
- mathocarbamol (centrally acting skeletal mm relaxant, can be effective if benzos fail)
- intravenous lipd infusion
Clues that indicate collapse d/t anaemia and initial emergency tx.
- CV: 2-ml/kg IVF bolus
- PCV/TS - 25%, 40g/L - anaemic
- blood smear - non-regenerative anaemia, no haemolysis, platelets ok
- AFAST ultrasound - peritoneal effusion
- Abdominocentesis - PCV 30%, TS35g/L
- PT >45s (normal
Ddx for anaemia 2* to toxins
> coagulopathy - anticoagulant rodenticide - coagulopathy 2* to hepatopathy (xylitol) > haemolysis - paracetamol (cats) - onion/garlic
Egs of rodenticide anticoagulants
- bromadiolone, brodifacoum, difenacoum, flocoumafen (2nd gen)
- stronger strength available for professional use, normally ~0.005% strength
What is the pathogenesis of anticoagulatns?
Prevents production of active vitamin K
- active vit K needed for clotting factors
When are peak plasma levels of anticoagulant rodenticide seen?
- vary mins-hrs
- plasma elimination T1/2 = 14hrs for warfarin, = 6d for brodifacoum
Are clinical effects of anticoagulant rodenticide common? What are they?
No uncommon
- clotting factors t1/2 = 6-16 hours so delay between exposure and onset of clinical signs (~27-72hrs)
> clinical signs:
- ^ PT time
- haemorrhage
- bruising
- bleeding gums, nose, GI tract and wounds
- may present as dyspnoea, weakness and lethargy
What does tx threshold for anticoagulant rodenticide ingestion depdend on? Eg doses?
- active ingredient
> difenacoum 0.005% 100g/kg ingestion threshold
> brodifacoum 8g/kg
> Bromadialone 7g/kg
> flucoumafen 0.005% 0.15g/kg ingestion threshold!
If tx is required for anticoagulant rodenticide toxicosis, what is it?
- decontamination
Tx regime for vit K?
- until PT normalises 2-5mg/kg IV/SC/IM daily
- once PT normalised orally for ~3 weeks (2-5mg/kg divded doses)
- check PT 1-3d after discontinuing tx
> whole blood/plasma transfusions may be required
Other names for paracetamol?
- acetaminophen
- APAP
Why does paracetamol toxicity occour? Which species especially?
- saturation of metabolic pathways, toxic metabolite conjugated by glutathione (promptly depleted)
- CATS lack metabolic capacity to detoxify paracetamol
Clinical signs of paracetamol tox?
> early 4-24hrs - facial and paw oedema - V+ - depression - dark brown blood (methaemoglobinaemia) > 24hrs + - severe methaemoglobinaemia - hepatic necrosis > cyanosis and methaemoglobinaemia do not respond to oxygen therapy
Threshold for tx paracetamol tox in cats and dogs. Tx?
Dogs 150mg/kg
Cats 20mg/kg
- emesis (optimal
Ddx for renal signs with toxin ingestion?
- ethylene glycol
- NSAIDs
- aminoglycosides
- Lily (cats)
- Grapes/raisins (dogs)
Potential renal signs seen with toxicosis?
- PCV/TS 45% 67g/l
- biochem urea 22mml/l (3-10 norm), creatinine 550umol/l (
Most common NSAIDs causing renal toxicosis? How do vet and human NSAIDs differ?
- ibuprofen
- naproxen, diclofenac, cerprofen, meloxicam, others
- CoX-2 specific inhibitors used in vet medicine so human drugs potentially dangerous
Pathogenesis of NSAID toxicosis?
- inhibition of COX enzymes
- COX 2 inflammatory response
- sustained reduction of inflammatory response
- toxicity likely d/t COX-1 inhibition
Early signs of NSAID toxicity?
- GI eroisuin, ulceration and perforation possible
- VD+ with blood
- rarely CNS signs (ataxia, lethargy, drowsiness) w/ large doses >400mg/kg ibuprofen
Late signs of NSAID toxicity
- renal failure
- hepatic damage
Which flowers are potentially nephrotoxic?
Lilies - true lily (liliaceae) and day lily (hemerocallidaceae)
- renal failure in cats
Which parts of the lily are toxic? Signs?
All parts (v smalll amount needed for clinical signs) - signs: - GI Iirritation - PU - dehydraion - renal failure \+- seizures if severe
Tx and prognosis of lily toxicity?
Aims > reduce absorption - emesis and/or activated charcoal > enhance renal perfusion - IVF min 48hours > once renal failure has occurred txl limited > prognosis good if tx started before onset of renal impariment > prognosis guarded if renal failure
What cuases chewing gum to be toxic? Pathogensis?
> Xylitol
- naturally occourring sugar alcohol in fruit and veg
- rapid and potent stimulator of INSULIN in dogs dose-dependent)
- liver damage (unknown mechanism)
Where else is xylitol found other than chewing gum?
- highest in gum other than protein bars (higher)
- mints
- protein bars massive amounts
- strepsils
- nurofen
- nicorette gum
- other things
Tx xylitol toxicosis? Monitoring?
- aggressive
- tx for >0.05g/kg (50mg/kg)
- gastric decontamination
> monitoring - baseline glucose, K, Ph, bilirubin, LFTs and clotting tests
- glucose conc q1-2hrs min 12 hrs
- recheck other tests q24hrs min 72hrs
> hypoglycaemia tx - frequent small meals and oral sugar for 8-10hrs
- glucose/dextrose severe cases
- ECG monitoring d/t risk of hypokalaemia induced arrythmias
> hepatotoxicity tx - immediate dextrose tx
- Hepatoprotectants: S-adenosyl L-methione (“Denosyl”) or acetylcystene
Ddx for hepatotoxcity?
- xylitol
- mushroom
- paracetamol
Clinical signs of bendiocarb Ficam W fumigation toxicity?
- mod ataxia
- abnormal lung sounds
- tachycardia
- pupils ____
- bowel sounds____
Tx bendiocarb potential tox
- diazepam and attropine
Toxic doses of Ibuprofen (most common toxicosis)
10mg/kg
Toxic doses of Carprofen (most common vet NSAID)
40mg/kg
Toxic doses meloxicam?
oral >1mg/kg, sc 0.2mg/kg
How can NSAID decontamination be performed?
- emesis optimal
How can gastric ulceration associated with NSAID use be minimised?
> 10mg/kg+ ibuprofen, >150mg/kg carprofen, >2mg/kg oral or >0.2mg/kg SC meloxicam > H2 -R antagonists - Cimetidine (Tagamet) - Ranitidine (Zantac) - Famotidine (Pepcid) > Proton pump inhibitors - Omeprazole > Ulcer healing/coating agent - Sucralfate (Antepsin) > PG supplements - Misoprostol (Cytotec)
Maintaining renal function when using NSAIDs?
- fluid therapy
> oral
> IVF maintainance for 24-48hrs - guided by renal function tests
Tx and monitoring of renal toxicosis with NSAIDs
Tx > Diuresis - IVF 2-3x maintainance - furosemide if anuric despite IVF > Gastroprotection - omeprazole 1mg/kg IV > antiemetic - Maropitant 1mg/kg SC Monitoring - urine output - body weight - urea/creat - potassium - ECG
Mechanism of toxicity of ethylene glycol?
- rapid absorption (cats peka plasma conc eg. glycoaldehyde, glycolic acid (rate limiting step, acidosis and ^ levels in urine indicative) glyoxilic aid, oxalic acid
Diagnostics results with ethylene glycol toxicity?
- azotaemia and hyperglycaemia (inhibition of glucose metabolism)
- ^ osmolality (normal 280-310mOsm/kg, ^ 60mOSm/kg)???
- ^ anion gap (normal 10-12mEg/L ^ to 40mEg/L)
- acidosis (blood
How can ethylene glycol tox be confirmed? Does a negative result r/o?
- urine and other contaminated tissue fluoresces under woods lamp within 6 hrs
- negative does not r/o tox
Tx of ethylene glycol toxicosis?
> early Dx and aggressive tx!!
- gastric decontamination
- confirm dx with urinalysis
- tx to block action of alcohol dehydrogenase
ethanol therapy [most common] or fomepizole EARLY
- IV ethanol (pharmaceutical grade) or vodka
- 5% solution CRI 5ml/kg/hr for 48hrs +
OR - 5ml/kg 20% ethanol in saline IV q6hrs for 5 doses then q8hrs for 4 doses
- oral loading dose 2.4ml/kg 40% solution vodka/whisky [equated to 750mg/kg] 1st hr
- then 0.5ml/kg/hr [equates to 150mg/kg/hr]
Side effects of alcohol tx of ethylene glycol tox?
- significant CNS depression and hypothermia +- hypoglycaemia
Which toxins can cause seizure/tremor?
- metaldehyde
- mycotoxin
- theobromine
- permethrin
- lead
- organophosphate
- recreational drugs
Which toxins can cause anaemia? By what mechanisms?
> coagulation - rodenticide - hepatotxins > haemolysis - paracetamol (cats) - onion/garlic - heavy metals
Which toxins affect the renal system
- ethylene glycol
- NSAIDs
- aminoglycosides
- lilies (cats)
- raisins/grapes (dogs)
Which toxins affect hepatic function?
- xylitol (also -> hypoglycaemia)
- cycad
- mushroom
- paracetamol
Most important point of tx in toxicology?
tx the patient - heart, lung, brain
- also many toxins cause GI signs
