Neurotoxins Flashcards
what is the initial approach to intoxication?
GI decontamination!
- emesis: for recent ingestion and asymptomatic patient
-at home: hydrogen peroxide
-clinic:
–dogs: apomorphine, ropinirole
–cats: dexmedetomidine, xylazine, hydromorphone
-complication: aspiration pneumonia
-contraindications: corrosive agents, volatile agents, symptomatic agents
–patient MUST have a normal mentation!! - gastric lavage
- activated charcoal +/- cathartic: binds to toxins, inhibits systemic absorption
ocular decontamination: flush eye with physiological saline
skin decontamination:
-oil-based toxins: should be bathed off in tepid water and a liquid dish detergent multiple times as soon as possible after exposure
-gentle clipping of the hair may also help remove to toxin
if antidote available, give it
then intravenous lipid emulsions
describe intravenous lipid emulsions
- used for lipophilic toxins (ivermectin, marijuana, lidocaine, ibuprofen, etc.)
- MOA unknown: but create a lipid sink in blood so toxins go to the sink instead of the organs
- generally considered safe and well tolerated but potential adverse effects:
-hyperlipidemia, pancreatitis
-can contaminate with bacteria bc is fat, so use sterile technique!! and don’t use bag for >24 hours
describe extracorporeal blood purification
hemodialysis, hemoperfusion, or therapeutic plasma exchange
-blood is purified outside the body
what are the 2 types of neurotoxins?
- neuroexcitatory: hyperexcitable, seizures, muscle fasciculations
-systemic complications: hyperthermia and heat stroke, rhabdomyolysis, acute kidney injury, DIC - neuroinhibitory: obtundation, stupor and coma, weakness or flaccid paralysis
-systemic complications: respiratory paralysis
describe general treatment of neurotoxins
- start with systemic stabilization:
-airway/breathing
-circulation: HR, BP
-temperature!! - usually supportive care is most important
A. IV fluid therapy: shock bolus, maintenance, dehydration, ongoing losses
B. temperature control:
–neuroexcitatory lead to hyperthermia, control seizures/tremors that caused, cool down with water, fans, IV fluids
–neuroinhibitory: cause hypothermia, active warming
C. oxygen if needed
D. general nursing care: soft padded bedding, turn patient if unable to turn on their own, eye lubricant if can’t blink, bladder mgmt
E. GI supportive care: anti-emetics to prevent aspiration pneumonia - antidotes rarely available:
-pralidoxime is used in organophosphate toxicosis
describe monitoring post neurotoxicity
crucial!
TPR, BP, ECG, urine output, pulse ox, end tidal CO2/venous CO2
describe the tremoring patient
- can be hard to differentiate from seizures (esp for owners)
- usually acute onset
- emergency management:
-triage exam: treat shock with IV fluids
-frequently hyperthermic so active cooling
-stop the tremors!
how do you stop the tremors?
- ideal: IV methocarbamol
-can repeat if necessary
-minimal systemic effects - midazolam/diazepam can also be helpful
- minimize stimulation
- sometimes additional sedating drugs are necessary
-acepromazine: can cause hypotension so ensure patient is systemically stable first
-dexmedetomidine: can cause decreased cardiac output so ensure patient is systemically stable first
describe differentials for tremors
dogs: tremorgenic mycotoxins
cats: permethrin
-cause tremors alone
other excitatory neurotoxins: tea tree oil, organophosphates, chocolate, cocaine
-but usually cause other systemic effects too
also primary neurologic disease can also cause, so getting a history is important!
describe tremorgenic mycotoxins
- penitrem A and roquefortine
- found in moldy food or decomposing organic matter such as compost
- exact mechanism unknown
- rapid onset of action, can progress to seizures
- dx: history and clinical signs
- tx: stop the tremors!, supportive care, IV LIPID therapy
- prognosis: good if treat appropriately, can result in death if not treated
describe permethrins/pyrethroids
- come in a variety of formulations (topical and environmental insecticides)
- cats can have increased susceptibility bc deficiency in hepatic glucuronidation
-inappropriate topical admin of specific flea products for dogs - management:
-wash pet with warm water and dish soap (avoid hypothermia)
-stop tremors
-IV fluids and supportive care
-IV lipid therapy! - prognosis: good with appropriate therapy
describe seizures due to toxins
- seizures due to intoxications are relatively uncommon
- history and clinical signs, IF seizing due to toxins:
-signs are usually very acute
-usually NOT normal in between seizures: other clinical signs both neuro and non neuro
-neuro exam: signs should be symmetrical!!! - extracranial seizures
-hypoglycemia due to xylitol toxicity
-electrolyte abnormalities
-hepatic encephalopathy
-toxins: bromethalin, etc.
describe bromethalin (rodenticide)
- causes cerebral edema by uncoupling mitochondrial oxidative phosphorylation (no energy = no Na+/K+ ATPase pump = cellular edema)
clinical signs:
1. hours to days after ingestion
2. severity depends on amount ingested (smaller and can have later onset)
-mild: hindlimb ataxia and paresis
-moderate: slow onset of signs and progression over the next days
-severeL generalized seizures, hyperexcitable, hyperthermia, coma, resp failure, death
diagnosis: history and clinical signs
-no pathognomonic
-post-mortem: bromethalin found in fat kidney, liver, and brain
treatment:
-acute ingestion: aggressive decontam
-no antidote, only symptomatic supportive care
–tremors and seizures: bendodiazepines +/- phenobarb
–cerebral edema: mannitol, hypertonic saline, elevate head 30 degrees
–IV fluids and nutritional support
–recumbency care
prognosis: guarded in severe cases; mild signs may recover
describe the obtunded and weak patient
abnormal mentation caused by systemic disease OR neurological disease
rule out systemic disease:
-full physical exam
-CBC/chem
differentials:
-primary metabolic disease
-neuromuscular disease
-toxins: ivermectin, baclofen, high marijuana dose, benzodiazepines, metronidazole, ethylene glycol
describe management of the obtunded/weak patient
- ensure able to protect airway (is gag reflex intact?)
-if not, tube to prevent aspiration pneumonia - are they able to ventilate on own?
-if CO2 >60mmHg = ventilator - if can’t blink: lube eyes
- turn if needed (rotate)
- IV fluids
- if recovery prolonged, may need feeding tube
describe ivermectins and other macrocylic lactones
- agonists at the GABA, A-gated chloride channels in the CNS
- dogs with a mutation in p-glycoprotein (MDR1) are more susceptible
-serves as an efflux pump for lipophilic compounds in the CNS, lead to an accumulation of drug within the CNS and more toxicity
-collies, border collies, shetland sheep dogs, australian shepherds and other herding breeds - may initially result in neuroexcitation, but higher doses can result in flaccid paralysis and coma
describe clinical signs, treatment, and prognosis of ivermectin and macrocyclic lactone toxicity
clinical signs:
-ataxia, LETHARGY, tremors, mydriasis, BLINDNESS, hypersalivation, disorientation, and seizures
-may progress to weakness, stupor, coma, resp failure
treatment:
1. symptomatic:
-seizure control but AVOID benzos bc could potentiate CNS toxicosis due to GABA binding and lead to prolonged recovery
-aggressive supportive care
-IV LIPID therapy
prognosis:
-guarded if ivermectin dose received is >5mg/kg
-recovery may be prolonged, especially in animals exposed to a longer-acting drug such a moxidectin, taking 2-3 weeks for full recovery
describe the “acting funny patient”
both excitatory and inhibitory
differentials: marijuana, methamphetamines, cocaine, antidepressants, chocolate, caffeine, bromethalin, ivermectin, metronidazole, ethylene glycol
management:
1. ensure cardiovascularly stable
2. rule out systemic disease with full physical exam and bloodwork
3. supportive care: quiet environment, IV fluids, nursing care
4. monitoring: TPR, BP. ECG
describe marijuana/THC/Delta 8
clinical signs: usually significantly improved within 24 hours, but can take up to 3 days
CNS: ataxia, hyperesthesia, disorientation, depression, coma (severe)
urinary: incontinence
cardiovascular: either brady or tachycardia
endocrine/metabolic: hypothermia or hyperthermia
GI: primarily vomiting
diagnosis:
1. clinical signs
2. history: acutely neurologic after going outside/to public place
3. most owners deny possibility of exposure
4. urine drug tests: not sensitive, lots of false negatives
treatment:
1. mild cases: no treatment necessary
2. supportive care
3. IV LIPID therapy for severe cases
describe methamphetamines
adderall or illicit drug use
MOA:
-increased catecholamine release (dopamine and norepi)
-inhibition of monoamine oxidase (MAO) causes increases serotonin
clinical signs:
-ataxia, agitation, hyperthermia, tremors, mydriasis, arrythmias, hypertension
-in large doses: seizures, death
-can cause myoglobinuria due to rhabdomyolysis
diagnostics:
1. clinical signs and history
2. urine drug test: unsure about Sp or Se
3. minimum database
treatment: supportive care, no antidote
1. IV fluids
2. hyperthermia: active cooling, IV fluids
3. seizure/tremor control
4. monitor tacharrythmias with continuous ECG and treat if indicated
5. agitation: sedation with acepromazine
6. IV LIPID therapy
describe organophosphate insecticides
uncommon because use is now banned
MOA:
-competitive inhibitors of cholinesterase enzymes causes accumulation of acetylcholine
3 syndromes of toxicity:
1. acute
2. intermediate syndrome
3. OP-induced delayed neuropathy: toxin-induced degeneration of the long motor nerves
clinical signs:
1. muscarinic signs: SLUD, diarrhea, vomiting, miosis, bradycardia, bronchospasm
2. nicotinic signs: muscle fasciculations and tremors
3. CNS signs: anxiety, ataxia, seizures, coma
diagnosis:
1. clinical signs and history
2. whole blood cholinesterase activity (short half life)
3. atropine response test if SLUD signs are present
treatment:
1. atropine is antidote for muscarinic signs, but no effect on nicotinic or CNS signs
-only used for life threatening bradycardia and bronchospasms
2. pralidoxime (2-PAM): acts to reactivate phosphorylated cholinesterase and is indicated for severe nicotinic signs
3. supportive care
describe metaldehyde
slug and snail bait banned in USA
MOA:
-decreases GABA, resulting in excitation
-decreases serotonin and norepinephrine, lowering the threshold for seizures
clinical signs: develop rapidly after ingestion
-anxiety, muscle tremors, ataxia, and then seizures
-tachypnea, hyperthermia, and tachycardia are also common
diagnosis: clinical signs and history
treatment:
1. none specific
2. aggressive symptomatic treatment: control tremors ad seizures
prognosis: generally good if aggressive and rapid supportive care and GI decontam are instituted early and heat stroke has not developed
describe lead toxicity
from lead based paint, batteries, plumbing materials, bullets or pellets, golf balls
acute or chronic intoxications
clinical signs:
1. initially: vomiting, anorexia, abdominal pain, diarrhea
2. lethargy, PU/PD, weight loss, pica or aggression
3. neuro: behavior changes, ataxia, head pressing, blindness, tremors, polyneuropathy and seizures
-signs can be intermittent with periods of normal behavior
diagnosis:
-clinical signs, history (can be hard if chronic exposure)
-blood smear: high numbers of nucleated RBCs and basophilic stippling
-whole blood lead levels
treatment:
1. remove the source
2. chelation therapy: removes lead from blood and soft tissues
-succimer, calcium EDTA, D-penicillamine
