Neurotoxins

Question 1

what is the initial approach to intoxication?

Answer 1

GI decontamination!

1. 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!!
2. gastric lavage
3. 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

Question 2

describe intravenous lipid emulsions

Answer 2

1. used for lipophilic toxins (ivermectin, marijuana, lidocaine, ibuprofen, etc.)
2. MOA unknown: but create a lipid sink in blood so toxins go to the sink instead of the organs
3. 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

Question 3

describe extracorporeal blood purification

Answer 3

hemodialysis, hemoperfusion, or therapeutic plasma exchange

-blood is purified outside the body

Question 4

what are the 2 types of neurotoxins?

Answer 4

1. neuroexcitatory: hyperexcitable, seizures, muscle fasciculations
   -systemic complications: hyperthermia and heat stroke, rhabdomyolysis, acute kidney injury, DIC
2. neuroinhibitory: obtundation, stupor and coma, weakness or flaccid paralysis
   -systemic complications: respiratory paralysis

Question 5

describe general treatment of neurotoxins

Answer 5

1. start with systemic stabilization:
   -airway/breathing
   -circulation: HR, BP
   -temperature!!
2. 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
3. antidotes rarely available:
   -pralidoxime is used in organophosphate toxicosis

Question 6

describe monitoring post neurotoxicity

Answer 6

crucial!

TPR, BP, ECG, urine output, pulse ox, end tidal CO2/venous CO2

Question 7

describe the tremoring patient

Answer 7

1. can be hard to differentiate from seizures (esp for owners)
2. usually acute onset
3. emergency management:
   -triage exam: treat shock with IV fluids
   -frequently hyperthermic so active cooling
   -stop the tremors!

Question 8

how do you stop the tremors?

Answer 8

1. ideal: IV methocarbamol
   -can repeat if necessary
   -minimal systemic effects
2. midazolam/diazepam can also be helpful
3. minimize stimulation
4. 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

Question 9

describe differentials for tremors

Answer 9

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!

Question 10

describe tremorgenic mycotoxins

Answer 10

1. penitrem A and roquefortine
2. found in moldy food or decomposing organic matter such as compost
3. exact mechanism unknown
4. rapid onset of action, can progress to seizures
5. dx: history and clinical signs
6. tx: stop the tremors!, supportive care, IV LIPID therapy
7. prognosis: good if treat appropriately, can result in death if not treated

Question 11

describe permethrins/pyrethroids

Answer 11

1. come in a variety of formulations (topical and environmental insecticides)
2. cats can have increased susceptibility bc deficiency in hepatic glucuronidation
   -inappropriate topical admin of specific flea products for dogs
3. management:
   -wash pet with warm water and dish soap (avoid hypothermia)
   -stop tremors
   -IV fluids and supportive care
   -IV lipid therapy!
4. prognosis: good with appropriate therapy

Question 12

describe seizures due to toxins

Answer 12

1. seizures due to intoxications are relatively uncommon
2. 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!!!
3. extracranial seizures
   -hypoglycemia due to xylitol toxicity
   -electrolyte abnormalities
   -hepatic encephalopathy
   -toxins: bromethalin, etc.

Question 13

describe bromethalin (rodenticide)

Answer 13

1. 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

Question 14

describe the obtunded and weak patient

Answer 14

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

Question 15

describe management of the obtunded/weak patient

Answer 15

1. ensure able to protect airway (is gag reflex intact?)
   -if not, tube to prevent aspiration pneumonia
2. are they able to ventilate on own?
   -if CO2 >60mmHg = ventilator
3. if can’t blink: lube eyes
4. turn if needed (rotate)
5. IV fluids
6. if recovery prolonged, may need feeding tube

Question 16

describe ivermectins and other macrocylic lactones

Answer 16

1. agonists at the GABA, A-gated chloride channels in the CNS
2. 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
3. may initially result in neuroexcitation, but higher doses can result in flaccid paralysis and coma

Question 17

describe clinical signs, treatment, and prognosis of ivermectin and macrocyclic lactone toxicity

Answer 17

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

Question 18

describe the “acting funny patient”

Answer 18

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

Question 19

describe marijuana/THC/Delta 8

Answer 19

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

Question 20

describe methamphetamines

Answer 20

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

Question 21

describe organophosphate insecticides

Answer 21

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

Question 22

describe metaldehyde

Answer 22

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

Question 23

describe lead toxicity

Answer 23

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