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Toxicology: Student Summary

  • Describe the factors that affect toxicity
  • Explore the drugs/chemicals that impact the toxicity in canine and feline species
  • Explore the food sources that cause the toxicity in canine and feline species

What are the factors that should be considered?

  • Factors related to exposure
    • Dose
    • Duration & Frequency of exposure
    • Route of exposure
    • Environmental factors
      • ex., mycotoxins and poisonous plants are correlated with seasonal changes
      • ex., ischemic effects of ergot toxicosis (Winter)
      • ex., plant nitrate levels are affected by amount of rainfall
  • Biological factors
    • Species-specific
    • Age & size
    • Nutritional & dietary factors
  • Clinical factors → affect solubility, ADME
    • Chemical nature of toxic agents
    • Vehicle or carrier
    • Adjuvants
    • Binding agents
    • Flavoring agents

Canine patients (LACK of ACETYLATION)

Drug

Toxic Effects
Isoniazid ● Deficient in enzyme that facilitates xenobiotic acetylation

● Isoniazid requires acetylation to be eliminated

● Eventually toxic metabolites that build up cause adverse effects/toxicity
Sulfonamides ● Cause keratoconjunctivitis sicca (dry eye syndrome) due to direct toxicity to acinar lacrimal glands

*GOOD COUNSELING POINT
Estrogens ● Cause DOSE-RELATED myelosuppression

● Clients who are on estrogen therapy should keep those medications out of dogs’ reach and warn exposure is a potentially fatal emergency

*GOOD COUNSELING POINT
NSAIDs ● Either NSAIDs for humans and other species can cause toxicity to canine patients (MOST COMMON TOXICITY)

● Clients should secure NSAIDs from dogs to reach

*GOOD COUNSELING POINT

 

Just as active ingredients, excipients can cause toxicity in canine friends!1

Excipients

Uses

Toxic Effect
Aromatic amines Flavors and colors Substance dependent
Ethanol Solvent, preservative Ataxia, coma, respiratory paralysis
Ethoxyquin Preservative Nephrotoxicity, hepatotoxicity, thyrotoxicity, alopecia, allergic reactions
Polyethoxylated castor oil Surfactant Anaphylaxis
Polysorbate 20 (Tween) Surfactant Anaphylaxis
Polysorbate 80 (Tween) Surfactant Anaphylaxis
Thimerosal Preservative Cutaneous reactions, anaphylaxis
Xylitol Sweetener Hypoglycemia, hepatocellular necrosis

 

Especially, it requires extra precaution with xylitol!

  • Toxic at low doses (100-500mg/kg)
  • Provokes insulin release that can lead to severe/fatal hypoglycemia and hepatotoxicity
  • Contained in many foods and drugs

What can pharmacists do?

  • do NOT use xylitol containing ingredients in compounding
  • notify veterinarian if a prescribed product contains xylitol

 

What are the foods that we need to consider?

 

Food

Toxic Effects
Caffeine, Chocolate Tachycardia, CNS stimulation, seizures, coma
Garlic, onions, leeks, chives Depression, weakness, hemoglobinemia, hemolysis
Grapes, raisin, currants Acute renal failure
Hops Malignant hyperthermia
Macadamia nuts Lethargy, ataxia, tremors, hyperthermia, seizures
Peanut butter (sweetened with xylitol) Hypoglycemia, hepatoxicity
Salt and salty snack foods Seizures, cerebral edema
Yeast dough Painful bloating, raw dough can make dogs drunk

 

Feline patients (LACK of GLUCURONIDATION, METHYLATION)

  • normally caused by intentional administration, plant ingestions, ingestions from grooming

 

Drug

Toxic Effects

Toxic Mechanism
Acetaminophen Reduction of hemoglobin, methemoglobinemia, failure of oxygen transport Lack of glucuronidation → toxic NAPQI metabolite
Alpha lipoic acid Hepatotoxicity, neurotoxicity unknown
Chloramphenicol Myelosuppression Lack of glucuronidation, hydroxylation, and demethylation → accumulation
Diazepam (oral routes) Fulminant hepatic necrosis Lack of demethylation, hydroxylation → toxic metabolite
Enrofloxacin Retinal toxicity, blindness Failure of ABCG2 ocular barrier → photoactivation to reactive species
Griseofulvin (ultramicrosize) Myelosuppression Myelosuppression
Local anaesthetics (benzocaine) Methemoglobinemia, hemolysis, failure of oxygen transport Oxidative injury to hemoglobin
NSAIDs and salicylates Gastric ulceration, perforation, renal papillary necrosis Accumulation of parent drug and toxic metabolites
Permethrins Tremors and muscle fasciculation, hyperesthesias, hyperthermia, seizures Lack of glucuronidation → accumulation of parent drug and toxic metabolites
Phenazopyridine (azo dye) Heinz body anemia, hemolysis, failure of oxygen transport Oxidative injury to hemoglobin
Propylthiouracil Lethargy, weakness, hemolytic anemia, thrombocytopenia Immune-mediated antinuclear antibody formation
Venlafaxine Sedation, tremors, serotonin syndrome, arrhythmias Non-selective serotonin reuptake blockade

 

 

 

Just as active ingredients, excipients can cause toxicity in feline friends!1

Excipients

Uses

Toxic Effect
Azo dyes Coloring methemoglobinemia
Benzoic acid derivatives

(benzoic acid, benzyl alcohol, sodium benzoate)

 Preservative methemoglobinemia
Essential oils Flea repellent, aromatherapy Oral and lingual ulceration, lethargy, depression, ataxia, tremors, seizures
Ethanol Solvent, preservative Ataxia, coma, respiratory paralysis
Propylene glycol Solvent, moistening agent for semi-soft foods Heinz body hemolytic anemia

 

These are not exhaustive lists of drugs and foods that are likely to cause toxicities to canine and feline. Information is gathered from a variety of sources:

Veterinary toxicology information resources .

Organizations

Principles of Toxicology in Non-Human Species. Accessed August 31, 2021. https://www.powerpak.com/course/content/118899