Here are the top tips from each of the 5 toxins discussed!
5-Fluorouracil
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Tip #1
Metabolites of 5-fluorouracil/5-FU inhibit the TCA (Krebbs/Citric acid) cycle, which leads to a decrease in the amount of GABA in the brain. This causes seizure activity, one of the severe consequences of 5-FU toxicosis.
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Tip #2
Seizure activity can occur within an hour, or be delayed for up to 26 hours, but even so the seizures seen can still be very severe in nature.
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Tip #3
Any exposure to 5-FU should result in hospitalisation and continuous monitoring for 26 hours for this reason.
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Tip #4
Also note benzodiazepines are not effective for managing these seizures, as they work as a competitive agonist of GABA-A receptors in the brain. Barbiturates, propofol, Keppra or inhalational GA can all be used depending on severity and response. Keppra seems to produce good results in author’s experience
1. In addition, metronidazole is contraindicated, as it increases 5-FU plasma levels.
2. There is an antidote – vistonuridine. Can only be given before ANY neurologic signs seen, and cost is $75K a dose!! (And I assume that is USD)
Bromethalin
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Tip #1
Bromethalin uncouples oxidative phosphorylation – whenever you read this about any toxin, you know it is BAD! (think cyanide as an example)
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Tip #2
Causes a lack of ATP generation in the mitochondria of neuronal cells and this lack of ATP impairs ATP-ase pumps, including Ca2+ membrane pumps. Fluid accumulation occurs within the myelin sheath of nerve cells, and nerve conduction is interrupted.
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Tip #3
There may be high dose/rapid onset stimulatory signs or low dose/slower onset depressive signs, but can also have both syndromes at once.
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Tip #4
Once severe signs are seen the prognosis is grave and any treatment is likely to only provide transient improvement
5-hydroxytryptophan
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Tip#1
5-HTP is a human supplement that stands for 5-hydroxytryptophan. It is often combined with vitamins, calcium, magnesium, and melatonin, and xylitol can be listed as an “inert” ingredient. It is sold OTC for depression, anxiety and insomnia.
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Tip #2
Ingestion of 5-HTP in even small amounts (3 mg/kg) in dogs can cause serotonin syndrome – this is because 5-HTP is a normal metabolite of tryptophan that is rapidly converted to serotonin. The normal rate-limiting step in the production of serotonin via this pathway is the conversion of tryptophan to 5-HTP, which is why ingesting tryptophan in veterinary “calming” diets is not considered dangerous but a small amount of 5-HTP can rapidly lead to clinical signs of intoxication.
Strychnine
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Tip #1
Strychnine toxicity results in a very rapid onset of clinical signs – within 10 minutes to 2 hours. Glycine is an inhibitory neurotransmitter to interneurons in the spinal cord and motor neurons. Strychnine antagonises glycine at the glycine receptor, leading to uncontrolled reflex activity and extensor rigidity and violent seizure activity.
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Tip #2
Note that when treating, anticonvulsant therapy may need to be provided in the form of GA for 24-48 hours, and a muscle relaxant – e.g., methocarbamol - should generally also be administered to these patients. Repeated doses may be required.
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Tip #3
The use of intralipids may be beneficial for these patients, but take care that this can also bind any therapeutic agent you have given, such as anticonvulsants. NB Keppra is less affected by intralipids than other antiepileptic agents.
Cycads/Sago Palms
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Tip #1
Cycads, or Sago Palms, can be very toxic, with 1 or 2 seeds being enough to kill a medium to large sized dog (such as a Labrador).
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Tip #2
As well as the well-known cycasin hepatotoxin which also causes GI signs there are two neurotoxins, BMAA and an unidentified toxin. These can cause weakness, ataxia, tremors and seizures.
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Tip #3
Treatment involves standard decontamination (ensure the use of an antiemetic prior to charcoal to prevent aspiration) and the administration of cholestyramine to prevent enterohepatic circulation of the toxin, which is excreted in the bile and is then available to be reabsorbed into the circulation
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Tip #4
The prognosis is guarded once the patient is symptomatic, and gut decontamination needs to be initiated as early as possible. With aggressive early therapy the prognosis is good.
