Toxins Flashcards
(37 cards)
what are the two types of unknown toxin?
The unknown toxin may only present once clinical signs are occurring i.e. the owner has not seen the exposure
Or
Known ingestion/exposure to something with unknown effects. (eg human medication)
what are the principles behine know toxin ingestion?
- Decontamination
- Assessment of effects
- Treatment of symptoms
what are the prinicples and drugs behind decontamination if a toxin is eaten?
- Mucous membrane absorption; rapid, you’ve already missed the boat by presentation.
◦ if has eaten something caustic eg bleach rising the mouth is a good idea - Gastric transit – Induce emesis or gastric decontamination
◦ Window of opportunity; 2-8 hours in dogs, 2-12 hours in cats.
‣ eaten on an empty stomach will stay in stomach longer
emisis:
◦ Apomorphine – licensed in dogs (very effective)
◦ Alpha-2 agonist e.g. xylazine, medetomidine – not licensed but can be used in cats (moderately effective)
gastric decontamination:
◦ Stomach lavage; orogastric tube placed (through the hole in vet wrap) and warmed saline or hartmann’s used to flush the stomach
‣ Always kink the tube on removal to avoid aspiration
Intestinal absorption
* Arguably you could try to reduce intestinal transit time e.g. with laxatives but this will likely cause fluid and electrolyte losses unnecessarily.
* Absorbants – Activated charcoal
in what patients and substances should emisis after toxin ingestion be avoided?
◦ Avoid emesis in neurologically compromised patients e.g. obtunded due to aspiration risk
◦ Avoid enesis in caustic substances “home remedies” e.g. hydrogen peroxide and causing oesophagitis and potential major complications
how is decontamination performed with toxins that are via skin exposure?
- Washing the skin is primarily performed with water
- Can apply activated charcoal topically before washing off – messy!
- Lipid soluble toxins can be removed easily with soap
◦ E.g. fairy liquid - Prolonged washing e.g. several minutes (>5mins), can increase absorption of some chemicals (“wash in effect”)
- Take care when drying – absorption through abrasions
Once toxins are in the blood stream, we still have the opportunity to prevent them being metabolised, what two methods can be used to do this?
- The solution to pollution is dilution
◦ The simplest approach is **fluid therapy **
‣ Increase GFR and promote renal excretion (if renally excreted)
‣ Increased organ perfusion and transit of compounds (so can’t cause as much damage when traveling through) (if not renally excreted)
◦ E.g. 2 x Maintenance in the normally hydrated patient (want fluid overload)
Lipid infusion
* Works well for lipid soluble compounds
◦ fat into body, lipid soluble toxin binds to that fat and then is metabolised in a non-toxic way
◦ Fatty acids are a cardiac energy source (so keeping heart fed while dealing with the consequences of the toxin)
* Minimal side effects – pulmonary lipid embolus,
when assessing a pateint that has een exposed to toxins, what are you looking for?
Neuro – seizures, ataxia, sedation
Cardiovascular – arrythmias, tachycardia, bradycardia, hypotension, hypertension
Gastrointestinal – vomiting and diarrhoea
But some will require investigations;
Renal – azotaemia, inappropriate USG
Hepatic – jaundice, elevations in ALT, ALP, bile acids
Haematological;
* decreased Clotting – prothrombin time, activated partial thromboplastin time, thromboelastography, point-of-care ultrasound
* Anaemia – PCV, HCT.
Cardiovascular arrhythmias – ECG
what are the three lines of treatment for seizures?
- Diazepam IV x 3 (midazolam is a superior drug but it is not licensed for that) (rectal diazepam is not as effective)
◦ wait 10mins, if not worked give another does, repeat 3 times, if not worked need to escalate to more aggressive therapy) - Levetiracetam, phenobarbital IV - 2nd line
- Propofol CRI - 3rd line, induced coma, need to ventilate for the animal
what is the treatment for hepatic damge caused by toxin injestion?
Supportive in nature
* SAMe, Ursodeoxycholic acid, Silybin (milk thistle) (given together)
what is the treatment for acute kidney injury caused by toxin injestion?
- IVFT +/- diuretics depending on urine output (need to make sure they don’t go into a negative fluid balance as this will reduce perfusion to the kidney and compound the damage to the kidneys with hypoxic damage due to reduced renal blood flow)
- Dialysis
what is the treatment for the cardiovascular and respiratory effects caused by toxin ingestion?
what is the treatment for ventricular tachycardia, supraventricular tachycardia, bradycardia?
- Anti-arrythmics (e.g. lidocaine, amiodarone), beta-blockers (e.g. propranolol), parasympatholytics (e.g. atropine)
◦ ventricular tachycardia - lidocaine
◦ supraventricular tachycardia - beta blocker
◦ bradycardia - atropine - Blood pressure management – Fluid therapy, vasopressor (e.g. nor-adrenaline) or anti-hypertensives (e.g. amlodipine)
- Oxygen therapy
what is the treatement for vomiting caused by toxin injestion?
omiting – may not want to stop in the acute phase
* Irretractable vomiting – anti-emetic (e.g. maropitant, metoclopramide, ondansetron) and fluid therapy
* Diarrhoea – fluid therapy, gastro-intestinal diet
what is the treaatment for decreased clotting and anaemia caused by toxin injestion?
- Clotting – Vitamin K1 (esp warfarin toxin), Plasma (if just clotting issue)
◦ if animal has low platelets then needs platelets - Anaemia – Packed Red Blood Cells/Whole Blood.
what is the effect of ibruprofen/NSAID ingestion?
what compound in the body do they have an effect on and what is the role of this compound?
what are the clinical signs?
what dose do they need to be ingested at to cause toxic effects?
what is the specific treatment?
COX inhibitors – reducing prostaglandin production.
PGE2 and PGI2 play important roles in:
* Maintaining afferent renal blood flow
* Maintaining GI mucous production, mucosal blood flow and cell turnover
Clinical signs – Haemorrhagic vomiting/diarrhoea, AKI.
Ibuprofen – 10mg/kg GI signs, 100mg/kg renal signs
Specific treatments:
* H2 blockers – ranitidine/cimetidine (reduce gastric acid secretion, NSAID damages mucosa, hydrochloric acid with further damage mucosa)
* Proton pump inhibitor – omeprazole
* Prostaglandin analogue – misoprostol (not in the pregnant patient) - direct counteraction
* Intralipid infusion
what is the effect of aspirin toxicity? what is the role of the compound this affects?
what are the clinicla signs?
what is the treatment?
Very similar to other NSAIDs but may have greater inhibition of Thromboxane in addition to prostaglandin inhibition.
Thromboxane (TXA2) is important for platelet function
Clinical signs
* Thrombocytopathy – bleeding e.g. prolonged BMBT
* Haemorrhagic vomiting/diarrhoea, AKI.
- H2 blockers – ranitidine/cimetidine (reduce gastric acid secretion, NSAID damages mucosa, hydrochloric acid with further damage mucosa)
- Proton pump inhibitor – omeprazole
- Prostaglandin analogue – misoprostol (not in the pregnant patient) - direct counteraction
- Intralipid infusion
Bleeding is unlikely to be significantly associated with death before other damage.
just use peripheral vein for blood sample (not jugular) and will bleed a lot
how is paracetamol metabolised? what is the issue with this?
- Metabolised by the liver, primarily by glucuronidation then sulphate conjugation.
- Those pathways can become saturated, cytochrome P450 oxidises the excess into N-acetyl-p-benzoquinone (NAPQI) – which is really horrible!!
- NAPQI is de-toxified by glutathione – but glutathione stores can be exhausted.
- Another potential metabolite produced is para-aminophenol (PAP) also not nice!
NAPQI causes
* Hepatic cell necrosis
* Nephrotoxicity
PAP causes
* Methemoglobinemia
* Prevents haemoglobin releasing oxygen
what are the clinical signs of paracetemol toxicity? what are the diagnostic clues?
Clinical signs:
* Brown mucous membranes (methemoglobin)
* Jaundice, abdominal pain, lethargy, vomiting (direct hepatic damage)
* AKI
* Signs of hypoxia to tissues – brady or tachy arrythmias, peripheral oedema (especially the neck in dogs), respiratory distress.
Diagnostic clue – brown blood! In cats, Heinz body anaemia is suggestive.
what does a dog with brown mm and blood and odaema of the neck suggest?
paracetemol toxicity
what is the treatment of paracetemol toxicity?
- N-acetyl cysteine – glutathione precursor (so becomes gluthatione and will) bind the toxic metabolites (NAPQI) - ‘antidote’
- H2 receptor antagonists (e.g. ranitidine) may reduce CP450 oxidation - (but not good evidence)
- Ascorbic acid (Vit C) may reduce methaemoglobin to haemoglobin - (not good evidence but theoretically makes sense so can be given)
- Liver support – SAMe, UDA, Silybin
- AKI support – IVFT
- GI support
what is the pathogenesis of chocolate toxicity, what are the compounds in chocolate that cause this?
what are the clinical signs?
what is the treatment?
Theobromine and caffeine - Both examples of Methyl-Xanthines:
* Increase catecholamine release
* Increases cAMP -> increased intracellular calcium in cardiac and skeletal muscle
* Inhibits adenosine receptors
Primarily affects the cardiac rhythm and CNS. - tachyarrhythmias, with ineffective output as a result
Clinical signs:
1. Hyperactivity – important to ask owners about this!
2. Vomiting/diarrhoea
3. Arrythmias (usually tachy) with VPCs, tachypnoea
4. Seizures
5. Coma
6. Death
Treatment – as per other toxins with some specifics:
* Entero-hepatic recycling – so charcoal every 4-6 hours.
* Severe cases may need intubation, and urinary catheterisation.
what is the pathogenisis of xylitol toxicity?
wwhat are the clinical signs? and diagnostic clues?
what is the specific treatment?
Stimulates insulin release and hepatotoxic
* Prolonged hypoglycaemia - 12-48 hours
* Liver failure – within 72 hours (as metabolised by the liver, and toxic)
* Weakness, collapse, seizures, coma, death
* Jaundice
Diagnostic clues:
* Hypoglycaemia
* Elevated ALT
Specific treatment:
* Hepato-protectants – SAMe, Ursodeoxycholic acid, Silybin
* Glucose supplementation - need to monitor glucose level every hour for 24-48hours (if stable can drop to every 2 hours)
◦ Oral vs IV
◦ Bolus (insulin spikes) vs CRI (hard to maintain at 5%, as will often need more than 5% so can give CRI and boluses)
◦ Try to avoid causing further insulin spikes (best to give constant small meals)
why are cats particularly susceptible to pyrethroids (eg permethrin)? where are pyrethroids found?
Cats are particularly susceptible as they lack the enzyme glucuronyl transferase required for the glucuronidation pathway. (longer and more potent effect). Dogs can also be affected
Found in insecticides such as “Raid” and ant powders, as well as some “old school” flea products.
what is the pathogenesis of pyrethroid toxicity?
what is the diagnosis ?
what is the treatement?
Primarily act on neural axons (sodium channels):
* Ataxia, tremors, disorientation and seizures
* Dyspnoea and respiratory arrest
* Hypersalivation and vomiting
* Uncontrolled seizuring can cause rhabdomyolysis and subsequent AKI (as the breakdown of muscle releases compounds that the kidney then has to deal with)
Diagnosis is usually based on known exposure and clinical signs.
Treatment – general principles, but decontamination may involve the skin (fairy liquid) e.g. flea products.
Intralipid is excellent – permethrin is highly lipophilic!
what problems are caused by the ingestion of cleaning products?
what are the clinical signs?
what is the treatment for toxicity due to cleaning products?
what are the delayed effects of cleaning product injestion?
Many household cleaning products contain either strong acids or alkalis, as a result they are all toxic.
Damage is primarily due to surface contact, in the case of ingestion this will the mucosa, particularly oral, oesophageal and gastric (lesser degree).
Clinical signs – oral pain, dysphagia, regurgitation, vomiting, etc.
Gastric decontamination is dangerous – risk of worsening oesophagitis (vomit will cause damage on the way back up)
Dilution is the solution to pollution – oral water, or washing exposed surfaces with water
Severe oesophagitis can develop post exposure (1-2 weeks later) including strictures (inflammation causes fibrosis that causes strictures)
