Toxicology Module 1 Flashcards
What are the types of decontamination?
- Ocular - irrigate for 20-30mins using tepid water or saline
- Dermal - clip/clean/lavage/lipophilic substances
- GIT - Emesis, gastric lavage, whole bowel irrigation, MDAC
Use of emesis for decontamination?
Not always complete evacuation
Less effective if 2-3 hours post ingestion
Not to be done if caustic toxin ingested (petroleum)
Use of gastric lavage for decontamination?
Can delay absorption if emesis contraindicated - Needs GA
May not be worth it - 15-20min post ingestion, yields 33% of poison load
complications: hypothermia, hypoxaemia, dysrhythmias, laryngospasm, GI perf, electrolyte imbalances
Whole bowel irrigation for decontamination?
May be more effective at removal but no studies to show better than MDAC
Good for slow release capsules/toxins
Similar complications to gastric lavage
Nasogastric tube placed and polyethyleen glycol solution administered till rectal effluent is clear
enemas can be used
MDAC for decontamination?
- Carbon granules with large surface area allowing lots of area to bind and create a intraluminal sink
Not good for ethylene glycol (alcohols), iron compounds, strong alkali - Administered orally or via nasogastric tube
- Complication: vomitting/aspiration
- Similar effects to emesis - 70-90% if <30mins post ingestion
- can have cathartics such as sorbitol that enhance expulsion from GIT
What are principles when dealing with a toxin?
Can it be decontaminated?
Can elimination be enhanced?
Is there an antidote?
Methods to enhance elimination?
Encourages removal of the agent form the plasma by enhancing normal means of excretion (urine/feces) or using medical means
1. Forced diuresis - Increase filtration through kidneys - phenobarbs, bromides, lithium, - not for lipophilic meds
2. Ion-trapping - altering pH of urine to trap highly charged molecules in urine and increase excretion
3. Cholorectics - lipophilic toxins undergo entero-hepatic circulation where certain molecules/metabolites after initial conversion by liver in to bile into the bowel and then resorbed in to small intestines - DESTOLIT : increase bile flow use with MDAC
4. Intralipid - lipophilic LogP >2 - lipid sink
5. Peritoneal/haemodialysis - useful for cardiac/real causes, ibuprofen, NSAID, ethylene glycol
6. Plasma exchange - good for IMHA, ehrlichia, hyperbilirubinaemia- NSAIDs
What are the toxic metabolites of ethylene glycol?
Glycoaldehyde (resp depression/hyperglycaemia) and glyoxalate (acute tubular necrosis) per weight and glycolic acid has the most cumulative toxic effects
Rapidly absorbed from GIT w/n 30mins, peak w/n 3 hours
Metabolism in liver with small amount in kidneys, stomach and excreted in urine
What are the clinical signs of ethylene glycol toxicity?
Stage 1: 30mins of ingestion
- GI signs v+/d+
- neuro: seizures, muscle fasciculations, ataxia
- PUPD
Stage 2: related to metabolites
- cardiopulmonary: increased RR, HR, pulm edema
- renal effects - 12hrs in cats - azotaemia, anuric renal failure
Treatment for glycolic acid toxicosis?
Rapid treatment needed
Emesis w/n 1-2 hrs
Fluid therapy
Antidose: ethanol - ideally given within 6-8hrs, fomipezole (competitive inhibitor of alcohol dehydrogenase)
haemodialysis
Diagnosis of ethylene glycol?
History
Metabolic acidosis (glycolic acid)
Woods lamp for fluorescence in urine around face
calcium oxalate crytalluria (w/n 3-6hrs) - marked azotaemia 6-12hrs, isosthenuric urine
RIM sign in kidney (corticomedullary sign)
Point of care kit
What is the mechanism of paracetamol toxicity?
NAPQI: normally binds with sulphdryl groups of endogenous glutathione - if glutathione depletes then NAPQI accumulates
- causes hepatocellular death with centrolobular necrosis, direct acute tubular necrosis in proximal tubules in kidneys
- oxidative damage to cell membranes and binding to Hb = methhaemoglobin, heinz body anaemia and haemolysis
- Lack of n-acetyltransferase in canine and feline erythrocytes leading to build up of para-aminophenol rather than NAPQI- metHb
Clinical signs of paracetamol toxicity?
Depression, vomitting, lethargy, anorexia, muddy mm, tachycardia, facial/paw edema
Treatment of paracetamol toxicity
- Emesis
- Activated charcoal
- O2 therapy
- pRBC transfusion (methHb)
- Supportive care with fluids
- Frozen plasma +/- vit K
- N-acetylcysteine - glutathione precursor - oral or IV
Coumarin Rodenticides MOA, CS, Dx, Tx
MOA: inhibit vit K epoxide reductase (inhibits recycling in the liver), decrease levels of vit K which is needed to activate coag factors
- 1st and 2nd generation anticoags have the same effect and second generation has a longer period of action
CS: after 3-5 days CS of bleeding become evident
Dx: check clotting factors 48hrs-72hrs post ingestion can check clotting factors - factor 7 (shortest halflife) so PT will be prolonged before aPTT
Tx:
-Emesis and MDAC very effective if instituted within 4hrs of ingestion
- no value to giving vit K prior to 48-72hrs
- Vit. K s/c or blood products if bleeding
- check clotting 48-72hrs post stopping tx
Bromethelin: MOA, CS, Dx, Tx
MOA: neurotoxin - act to decouple oxidative phosphorylation thus reducing ATP levels and increase Na = cellular edema rapidly absorbed and CS develop rapidly - excreted in bile
CS: hindlimb ataxia, lethargy, seizures, resp paralysis, wkness, depression, coma, death
Tx: guarded prognosis if poor CS develop
- Emesis if <1.5-2hrs
- MDAC
- Tx of cerebral edema
- Intralipid
Cholecalciferol: MOA, CS, Dx, Tx
MOA: Cholecalciferol –> calcifediol –> calcitrol –> increased absorption of Ca & P in GIT, kidney and bone
CS: V+/D+, PUPD, muscle tremors, seizures 4-36hrs post ingestion - initially PUPD, lethargy and anorexi and vomitting and then dysrhythmias and renal failure to follow
Tx:
1. Induce emesis
2. MDAC
3. Mx Ca - calciuresis using saline and frusemide together with corticosteroid admin, calcitonin administration, bisphosphates - 24-72hr period before works
4. Mx Ph (oral binders)
Pyrethrins: MOA, CS, Dx, Tx
MOA: contained in flea/tick products can be classified into Type 1 & 2 (with alpha cyano group more toxic) - disrupt voltage sensitive Na channels - affecting the threshold potentials and causing earlier depol
-glucoronide and sulphadryl pathways - cats worse as no sulph
CS: hyperexcitability of cerebellum, cerebrum, peripheral, also blocks GABA receptors and may effect Cl and Ca channels
- hypersalivation, paw flicking, seizures, depression, ataxia
- rapid metabolism - fat soluble usually within 1-3hrs can be delayed up to 36hrs
Tx:
Intralipid - antidote
Dermal decontamination/oral emesis
MDAC, fluid therapy, BZP to decrease C/S
Methocarbamol to decrease tremors
Methylxanthines: MOA, CS, Dx, Tx
MOA: contained in theobromine, metabolised in the liver - enterohepatic cycling
- inhibit cyclic nucleotide phosphodiesterase and antagonises receptor mediated actions of adenosine - diuresis and tachycardia
- increased Ca by increased uptake into cells and decreased sequestration into sarcoplasmic reticulum= increased strength of muscle contractions
CS:
w/n 6hrs: restlessness, panting, vomiting –> tachyarrhythmias, hypertension seizures coma
Tx:
GI contamination
MDAC
IV fluids
methylxanthine output in urine - can be resorbed
b-blocker for tachyarrhythmias
Cannibus: MOA, CS, Dx, Tx
MOA: THC antagonises cannabinoid receptor 1 - affects neurotranmitters: gaba, dopamine, serotonin
Rapidly absorbed and metabolised in the liver
CS: 1-3 hrs of onset
CNS: ataxia, disorientation, hyperaesthesia, agitation, mydriatic pupils
GIT: hypersalivation, v+
Cardiopulm - brady/tachy
Tx:
1. Emesis
2. MDAC
3. Fluid therapy
4. Intra-lipid
5. Extra-corporeal therapy
How does carbon monoxide cause toxicity?
- Binds strongly to and displaces O2 fro Hb (O2 to tissue reduced as can not unbind)
- Binds weakly to myoglobin + cytochrome a3 in the mitochondrial electron transport chain affects ATP generation
- Indirectly (via enhanced neutriphil resp. bburst and nitric oxide generation) causes the production of reactive oxy.nitrogen species cause lipid peroxidation in the brain
What are the clinical signs of carbon monoxide toxicity?
Narcotisation, cerebral edema, seziures, coma death
cherry red mm
co-oximetry
Treatment of carbon monoxide toxicty?
- Oxygen therapy - competitive displacement
- Hyperbaric O2
- Antioxidants - N-AC, Vit E, SAMe, Silybicin
How does N-acetylcysteine work and what toxicity is in used as an antidote for?
Paracetamol/acetametaphin tox
- Binds directly to NAPQI
- Increases glutathione synthesis
- Provides substrates for sulphation
- Decreased NAPQI going back to acetometaphin
What are 4 additional treatment therapies for paracetmol?
- Ascorbic acid - facilitates methHB - HB
- Methylene Blue - Decreases methHB but can cause oxidative damage
- Cimetidine - decrease NAPQI formation
- SAMe + Silybilin - hepatoprotective + antioxidant
