Toxicities Flashcards
What can neuroexcitatory toxins cause in:
A) CNS?
B) PNS?
A) CNS: hyperexcitability, seizures, ataxia
B) PNS: muscles tremors and fasciculation
What can neuroinhibitory toxins cause in:
A) CNS?
B) PNS?
A) CNS: obtundation, stupour, coma
B) PNS: weakness, flaccid paralysis
How can you decontaminate gastrointestinally absorbed toxins?
–Emesis (within 2 hrs from ingestion) in alert patients
–Gastric lavage (within 2 hrs from ingestion) in subdue/comatose animals. Has to be done under GA and extreme care taken to protect airways
–Activated charcoal 1-5g/kg every 6-8 hrs for up to 24 hrs. In alert patients!
–Colonic lavage and cathartics
How can you decontaminate a cutaneous toxin?
–Bath, in stable patients
How can you decontaminate an inhaled toxin?
–Ventilation (mechanical in severe cases)
How can you decontaminate if an animal was exposed to a lipophilic substance?
Lipid infusion (Intralipid®), if exposure to lipophilic substances, acts as lipid sink. Bolus of 2mg/kg, followed by CRI of 4mg/kg/hr for 4 hrs
Name 6 neuroexcitatory toxins (8)
- Ivermectin and macrolide parasiticides
- Metaldehyde
- Methylxanthines
- Organophosphate and carbamates
- Permethrin
- Mycotoxines
- Strychnine
- Lead
How can Ivermectin, moxidectin, selamectin, milbemycin cause toxicity after ingestion? (3)
–Large-animals deworming products or contaminated faeces
–Iatrogenic by overdosing or wrong route or administration (ie per os instead of topic)
–Care with collie breeds (MDR1 mutation)
How does Ivermectin and macrolide parasiticides cause toxicity?
- Mechanism of action –> agonist at the GABAA-gated chloride channels in the CNS
- Initial neuroexcitation, followed at high doses by flaccid paralysis and coma
What is the toxicity of Ivermectin and macrolide parasiticides in:
A) Susceptible breeds?
B) Other breeds?
C) Cats?
A) 0.1mg/kg
B) 2.5mg/kg
C) 0.3-1.3mg/kg sc
What is the half life of Ivermectin and macrolide parasiticides?
2-19 days
How is Ivermectin and macrolide parasiticides toxicity diagnosed?
History
What is the clinical presentation of Ivermectin and macrolide parasiticides toxicity?
–Ataxia
–Lethargy
–Tremors
–Mydriasis
–Blindness
–Hypersalivation
–Disorientation
–Seizures
–Weakness
–Stupor
–Coma
–Respiratory failure
How can we manage Ivermectin and macrolide parasiticides toxicity?
–Emesis
–Activated charcoal
–Lipid infusion
–Phenobarbital for seizure control or propofol CRI if not responding
What is the prognosis of Ivermectin and macrolide parasiticides toxicity?
Dose related - can be guarded. Long recovery.
What is found in slug and snail baits which causes toxicity?
Metaldehyde
What is the mechanism of toxicity for metaldehyde?
•Mechanism of action
–Reduces levels of GABA (reduced inhibition à means excitation)
–Reduces levels of noradrenaline and serotonin
=Pro-convulsive effect
What are the clinical signs of metaldehyde?
–Anxiety
–Muscle tremors
–Fasciculations
–Ataxia
–Seizures
–Tachypnoea
–Tachycardia
–Hyperthermia
= HEAT STROKE
How do you diagnose metaldehyde toxicity?
History
How do you manage metaldehye toxicity?
–Emesis or gastric lavage
–Activated charcoal
–Benzodiazepine/phenobarbital (muscle tremors and seizures)
–Propofol infusion (severe cases of refractory seizures)
–Monitor body temperature!!!
What is the prognosis of metaldehyde toxicity?
Good if prompt intervention
What are caffeine, thoebromine (chocolate), theophylline?
Methylxanthines
What is the mechanism of action of Methylxanthines toxicity?
–Causes elevation of intracellular cyclic AMP, this results in increase in intracellular CA++ = neuromuscular excitability and inoptropic effect
–Competitive inhibition of adenosine receptors = CNS stimulation
With caffeine and theobromine:
A) When do you have clinical signs?
B) When do you have seizures?
A) 20mg/kg
B) 60mg/kg
What are the clinical signs within 1-2 hours of ingestion of Methylxanthines?
–Restlessness
–Hyperactivity
–V+ve and D+ve
–Tachycardia/tachypnoea
–Polyuria
–Muscles twitching
–Seizures (tonic or tetanic)
–Hyperthermia
How do you diagnose Methylxanthines ingestion?
History
How do you manage Methylxanthines toxicity?
–Emesis/activated charcoal
–Control ventricular arrhythmias (lidocaine, procainamide, Ca channel blockers, B blockers)
–Control muscle tremors and seizures with benzodiazepines (diazepam)
–Control temperature
What is the prognosis if Methylxanthines are ingested?
Good if early treatment
What is the mechanism of toxicity with Organophosphate and carbamates?
•Inhibit the action of the AChE (acetylcholinesterase)
=Ach accumulates in the synaptic space
What are the 3 syndromes of ingesting Organophosphate and carbamates?
- Acute toxicity
- Intermediate
- Delayed (neuropathy)
With organophosphate and carbamate acute toxicity:
A) Muscarnic clinical signs?
B) Nicotinic signs?
C) CNS signs?
A) Hypersalivation, lacrimation, urination, defecation vomiting, miosis, bradycardia, bronchospasm
B)–Muscle fasciculation, twitches and tremors
–(delay NM signs) weakness and paralysis
C)
–Anxiety, ataxia, seizure, obtundation, coma
What are the clinical signs of intermediate syndrome (7-96 hours) with Organophosphate and carbamates?
•Severe NM signs, weakness, neck ventroflexion, forelimbs weakness and hypoventilation
When is delayed neuropathy and what is seen with Organophosphate and carbamates?
•1-4 weeks after exposure
–Anorexia, lethargy, pelvic limbs paresis, hyperaesthesia, neck venroflexion (cat)
How do you diagnose organophosphate and carbamate ingestion?
- Known exposure
- Whole blood (heparin) cholinesterase activity <25-50%
- Gastric content
How do you manage Organophosphate and carbamates ingestion?
- Skin decontamination, emesis, activated charcoal (depending on exposure)
- Atropine 0.02mg/kg iv (muscarinic signs)
- Pralidoxime (2-PAM) 10—20mg/kg sc, im or iv (care, may worsen clinical signs!)
- Supportive care
What is the prognosis of ingesting organophosphate and carbamates?
Good if they survive initial toxicity
Why are cats susceptible to permethrin toxicity?
Deficiency in hepatic glucuronidatin
What is the mechanism of toxcitiy of permethrin?
- Slows both opening and closing of voltage sensitive Na+ channels
- Resulting prolonged depolarisation
What is the clinical presentation of permethrin toxicity?
- Muscle fasciculation
- Ears twitching
- Tremors
- Ataxia
- Seizures
- Hyperthermia
- Hyperaesthesia
When do animals present with permethrin toxicity?
3 hours - 3 days
How do you diagnose permethrin toxicity?
History of exposure
How do you manage permethrin exposure?
- Decontamination of skin if dermal exposure (use washing up liquid!)
- Control temperature hyperthermia but also hypothermia (after bath)
- Drug therapy aimed at controlling tremors and seizures
–Benzodiazepine
–Phenobarbital
•Intravenous lipid administration
What is the prognosis of permethrin expsosure?
- Usually good if treatment/decontamination is promptly started
- Recovery takes between 2 to 7 days
What are penitrem A and roquefortine?
Mycotoxines (tremogenic)
What is the mechanism of action of mycotoxines (tremogenic)
Unknown- –Likely inhibition of glycine function or release (in the CNS)
What are the clinical signs of Mycotoxines (tremogenic)?
- Hyperaesthesia, restlessness, vomiting, salivation, muscle tremors, seizures and status epilepticus (dose dependent)
- Heat stroke!!!
When do clinical sigs present with mycotoxines?
30 minutes to several hours
How do you diagnose Mycotoxines (tremogenic) toxicity?
- History
- Mass spectroscopy
- Chromatography
- Culture of vomitus
How do you manage Mycotoxines (tremogenic) exposure?
- Emesis, gastric lavage, activated charcoal (for 24 hrs to reduce enteroepatice recirculation of the toxin)
- Benzodiazepine/phenobarbital
- General anaesthesia
- Supportive care
What is the prognosis of Mycotoxines (tremogenic) exposure?
•Generally good, improvements in 1 to 5 days
What is Strychnine?
A pesticide
What is the mechanism of action of Strychnine?
- Blocks the action of glycine (inhibitory neurotransmitter)
- Prevents the release of glycine from Renshaw cells in the spinal cord
What is the clinical presentation of Strychnine exposure?
- Quick onset 10-120 minutes from exposure (inhalation, ingestion)
- Progressive and severe muscle spasm and extensor rigidity (saw horse and risus sardonicus), convulsions, heat stroke
- Paralysis of diaphragm, (hypoventilation = death)
How do you diagnose Strychnine exposure?
- History
- Analysis of gastric content
How do you manage exposure to Strychnine?
- Emesis (not recommended if the clinical signs are already present)
- Gastric lavage under GA
- Activated charcoal
- Muscle spasm and convulsions must be controlled by
–Benzodiazepines
–Phenobarbital
–CRI propofol (24-72hrs)
•Mechanical ventilation may be necessary
What is the prognosis of Strychnine exposure?
- Fair to guarded
- One of the most painful toxicities
What is the mechanism of action of lead toxicity?
- Binds to sulfhydryl groups (interferes with haem synthesis, RBC fragility, basophilic stippling)
- Neurotoxicicty likely linked to interference with action of GABA, capillary damage, neuronal necrosis, inhibition of Ca2+, interference with dopamine uptake.
What are the clinical signs of lead ingestion?
•Systemic signs
–Vomiting, anorexia, abd pain, lethargy, PU/PD
•Neuro signs
–Behavioural changes, ataxia, head pressing, blindness, tremors, polyneuropathy, seizures. (signs can be intermittent and depend on duration of exposure and amount ingested)
How do you diagnose exposure to lead?
- History
- Presence of nucleated RBC and basophilic stippling
- Blood and urine lead levels (>0.35ppm in blood and >0.75ppm in urine à acute toxicity)
Radiographs?
How do you decontaminate lead exposure?
–Emesis
–Surgical removal of lead foreign body
–Magnesium sulphate 200-500mg/kg PO, cathartic and reduces absorption
•Chelation therapy
–Succimer 10mg/kg q8 hrs for 10 days
–Calcium EDTA 27mg/kg q6hrs SC injection has to be diluted!!!(can cause renal tubular necrosis)
–D-penicillamine 10-15mg/kg per day for 1 week
- Seizures should be controlled with benzodiazepine
- Mannitol can be used to reduce ICP
What is the prognosis of lead exposure?
•Variable, generally good if undergoing chelating therapy
Name 2 neuroinhibtitory toxins (2)
- Macadamia nuts
- Metronidazole
What is the mechanism of action of Macadamia nuts toxicity?
Unknown
What is the clinical presentaton when Macadamia nuts have been consumed?
- 12-24hrs after ingestion
- Pelvic limb weakness, stifness, paresis and muscle tremors
- Vomiting and hyperthermia
How do you diagnose Macadamia nuts consumption?
History
How do you manage a dog which has consumed macadamia nuts?
- Emesis (within 2-4 hrs)
- Supportive care (fluidotherapy, antiemetics, control temperature)
- Methocarbamol (muscle tremors)
Where will you find Metronidazole?
Commonly used antibacterial and antiprotozoal antibiotic
What is the mechanism of action of metronidazole?
•Mechanism of action as neurotoxin not fully understood.
–Purkinje cell loss
–Axonal degeneration in vestibular tracts
What is the toxic dose of metronidazole?
60mg/kg a day
What is the clinical presentation of a dog exposed to metronidazole?
- Ataxia
- Vestibular signs
- Tremors
- Seizures
- Peripheral neuropathies
How do you diagnose metronidzole toxicity?
History
How do you manage a dog exposed to metronidazole?
- Discontinuing metronidazole
- Supportive care
- Diazepam 0.2-0.5mg/kg PO for 3 days
