Each year, the ASPCA Animal Poison Control Center (APCC) (United States) and Veterinary Poisons Information Service (VPIS) (United Kingdom) manage hundreds of thousands of poisoning calls. At the ASPCA APCC, an estimated 50% of pet poisonings comprise human over the counter (OTC) and prescription medications. In this lecture, we will review the mechanism of toxicosis, clinical signs, and overall treatment of the top 20 most common poisons affecting dogs and cats. In the veterinary poisoned patient, the goal of decontamination is to “inhibit or minimize further toxicant absorption and to promote excretion or elimination of the toxicant from the body.” When treating the poisoned patient, the clinician should have an understanding of the toxic dose (if available), the pharmacokinetics (including absorption, distribution, metabolism, and excretion), the underlying mechanism of action, and the potential clinical signs that can be observed with the toxicant. This will help determine appropriate decontamination and therapy for the patient. If this information is not readily available, the reader is advised to contact VPIS or an Animal Poison Control for life saving, 24/7 advice as needed. For further review on decontamination and specific treatment, attendees are referred to a veterinary toxicology book for more detailed review.

Calcium Channel Blockers, Beta-Blockers, ACE-Inhibitors, Statins, and Diuretics

Certain cardiac medications include broad categories such as calcium channel blockers (CCB), beta-blockers (BB), and angiotensin-converting enzyme (or “ACE”) inhibitors. These medications are commonly used in both human and veterinary medicine to treat underlying cardiac disease or hypertension. Each category of cardiac medication has different margins of safety. CCB and BB toxicosis should be treated aggressively, as these two categories of medications have a narrow margin of safety. Toxicosis of these agents can result in myocardial failure, severe bradycardia, and hypotension; untreated, cardiac output becomes reduced, and secondary severe hypoperfusion and acute kidney injury (AKI) can potentially develop. With ACE-inhibitors, severe overdoses can cause hypotension, dizziness, weakness, and hypotension. In general, there is a wider margin of safety with ACE-inhibitors, which are typically considered much safer. Pets ingesting small amounts of ACE-inhibitors can potentially be monitored at home, unless they have underlying disease (e.g., kidney failure, cardiac disease, etc.). With ACE-inhibitors, ingestions >10–20× a therapeutic dose are generally considered toxic, and can result in severe clinical symptoms (e.g., hypotension). Treatment for any cardiac medication includes decontamination (e.g., emesis induction, gastric lavage, activated charcoal (AC) administration), blood pressure monitoring, aggressive IV fluid therapy if hypotension is detected, and blood work monitoring. With severe toxicosis, the use of high-dose insulin therapy or intravenous lipid emulsion may be warranted as a potential antidote for calcium channel blocker toxicosis.

Selective Serotonin Re-Uptake (SSRI)

Selective serotonin re-uptake inhibitors (SSRIs) are a class of medications that are commonly used in human medicine for depression. Common examples include the following drugs:

• Fluoxetine (Prozac^® in human beings; Reconcile™ in veterinary medicine)
• Citalopram (Celexa^®)
• Paroxetine (Paxil^®)
• Sertraline (Zoloft^®)

Other similar drugs include selective norepinephrine re-uptake inhibitors (SNRIs), which include common drugs like duloxetine (Cymbalta^®), nefazodone (Serzone^®), and venlafaxine (Effexor^®). SNRI and SSRI drugs result in similar clinical signs of toxicosis, and therefore, are treated the same. In veterinary medicine, SSRIs are used for a wide array of behavioral problems, including feline urine spraying, canine separation anxiety, lick granulomas, etc. These SSRI drugs work by blocking the reuptake of serotonin in the pre-synapse, thereby increasing the levels of serotonin in the pre-synaptic membrane. In small animal patients, common clinical signs from SSRIs include sedation or central nervous system (CNS) stimulation, anorexia, lethargy, and serotonin syndrome. Clinical signs of serotonin syndrome include gastrointestinal (GI) signs (e.g., hypersalivation, vomiting, diarrhea, abdominal pain) and CNS signs (e.g., stimulation, mydriasis, tremors, seizures, hyperthermia secondary to tremoring and seizuring). Treatment for antidepressants includes decontamination (ideally done at a veterinarian, due to the rapid onset of clinical signs), sedation (e.g., with acepromazine or chlorpromazine), intravenous (IV) fluid therapy, blood pressure and electrocardiogram (ECG) monitoring, thermoregulation, muscle relaxants (for tremors; methocarbamol 22–55 mg/kg, IV, PRN), anticonvulsants (e.g., phenobarbital 4–16 mg/kg, IV, PRN; diazepam 0.25–0.5 mg/kg, IV, PRN), serotonin antagonists (e.g., cyproheptadine [1.1 mg/kg for dogs or 2–4 mg total per cat] PO or rectally q 6–8), and supportive and symptomatic care. In general, the prognosis for antidepressant toxicosis is excellent.

Amphetamines

Amphetamines are used for a variety of medical and illicit reasons. Legal forms include prescription medications for attention-deficit disorder/attention deficit-hyperactivity disorder (ADD/ADHD), weight loss, and narcolepsy. Examples of amphetamines include:

• Dextroamphetamine
• Amphetamine (Adderall^®)
• D-amphetamine (Dexedrine^®)
• Methamphetamine (Desoxyn^®)
• Lisdexamfetamine (Vyvanse^®)

Illegal forms of amphetamines include street drugs like methamphetamine, crystal meth, and ecstasy. This class of drugs acts as sympathomimetic agents, meaning they stimulate the sympathetic system. Amphetamines also cause stimulation of α and β-adrenergic receptors and stimulate release of serotonin and norepinephrine; this results in increased catecholamine stimulation in the synapse. Amphetamines also increase release of serotonin from the presynaptic membrane, resulting in serotonin syndrome. With amphetamine toxicosis, secondary stimulation of certain body systems can result in significant clinical signs: GI (e.g., vomiting, diarrhea, hypersalivating), CNS (e.g., agitation, mydriasis, tremors, seizures), cardiovascular (e.g., tachycardia, hypertension), and respiratory (e.g., panting). Both clinical signs and treatment for amphetamine toxicosis are similar to SSRI toxicosis, and include IV fluids, cooling measures, sedation (e.g., with acepromazine or chlorpromazine), muscle relaxants, anticonvulsants, thermoregulation, blood pressure monitoring, and symptomatic/supportive care.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDS)

NSAIDs are competitive inhibitors of prostaglandin synthesis (cyclooxygenase or “COX” inhibitors) and result in decreased prostaglandin, which is important for normal homeostatic function (including maintaining renal blood flow, maintaining mucous production in the stomach, etc.). Common OTC human NSAIDs include active ingredients such as ibuprofen and naproxen sodium. Common prescription veterinary NSAIDs can also result in toxicosis, particularly when available in the chewable, palatable formulation. Examples of veterinary NSAIDs include carprofen, deracoxib, etogesic, previcoxib, etc. With NSAID toxicosis, the GI tract, kidneys, CNS, and platelets can be affected. Cats and certain breeds of dogs (e.g., German shepherds) seem to be more sensitive to NSAIDs and should be treated aggressively. With cats, severe acute kidney injury (AKI) is often more clinically seen with NSAID toxicosis at lower doses (as compared to dogs). With dogs, signs secondary to GI ulceration (e.g., vomiting, diarrhea, melena, hematemesis, etc.) are more commonly seen initially, followed by secondary AKI. With NSAID toxicosis, it is important to keep in mind that each NSAID has a different toxic dose, margin of safety, half-life, and route of excretion, and the ASPCA Animal Poison Control Center should be contacted to identify what specific NSAID, and toxic dose was ingested. For example, in dogs, ibuprofen results in GI signs at doses as low as 16–50 mg/kg, while severe GI signs may be seen at 50–100 mg/kg. Renal compromise may be seen at doses of 100–250 mg/kg (resulting in potential AKI), and fatalities have been reported at doses >300 mg/kg. This differs tremendously from naproxen sodium (dogs), where severe clinical signs can be seen at doses as low as 5 mg/kg. Clinical signs of NSAID toxicosis include anorexia, vomiting, hematemesis, diarrhea, melena, abdominal pain, lethargy, malaise, uremic halitosis, dehydration, etc. Treatment includes decontamination, the use of activated charcoal (often multiple doses due to enterohepatic recirculation, if appropriate), GI protectants (e.g., H₂ blockers, sucralfate), aggressive IV fluid therapy (to help maintain renal blood flow), anti-emetic therapy, and symptomatic and supportive care. With high doses, anticonvulsants may also be necessary if CNS signs develop.

Paracetamol

Paracetamol (N-acetyl-p-aminophenol), a cyclooxygenase (COX)-3 inhibitor, is a popular OTC analgesic and antipyretic medication used frequently in humans. It is not considered a true NSAID as it lacks anti-inflammatory properties. Normally, part of this drug is metabolized into non-toxic conjugates via the metabolic pathways (glucuronidation and sulfation); some is metabolized into the toxic metabolite, N-acetyl-para-benzoquinone imine (NAPQI) via the cytochrome P-450 enzyme pathway. Typically, NAPQI is detoxified by conjugation with glutathione in the liver. Toxicosis occurs when glucuronidation and sulfation pathways are depleted; this results in toxic metabolites building up and secondary oxidative injury occurring. While this drug is very safe for human use, it has a narrow margin of safety in dogs and cats; the severity of toxicosis and development of clinical signs is species dependent. Cats have an altered glucuronidation pathway and a decreased ability to metabolize paracetamol, making them much more susceptible to toxicosis. In cats, red blood cell (RBC) injury is more likely to occur in the form of methemoglobinemia (metHb), and toxicity can develop at doses as low as 10 mg/kg. In cats, lethargy, swelling of the face or paws, respiratory distress, brown mucous membranes, cyanosis, vomiting, and anorexia may be seen secondary to metHb. In dogs, hepatic injury is more likely to occur; paracetamol toxicosis can occur at doses >100 mg/kg, while metHb can develop at doses of >200 mg/kg. Dogs may develop clinical signs of keratoconjunctivitis sicca (dry eye), malaise, anorexia, hepatic encephalopathy, vomiting, melena, and icterus secondary to hepatotoxicity. Treatment includes decontamination, administration of activated charcoal (AC), anti-emetic therapy, IV fluid therapy, treatment for hypoxemia (e.g., oxygen, blood transfusion, etc.), antioxidant therapy (e.g., vitamin C), provision of a glutathione source (S-adenosyl-methionine or SAMe), and the antidote N-acetylcysteine (NAC, ideally IV) to limit formation of the toxic metabolite NAPQI by providing additional glutathione substrate. Baseline blood work and follow-up biochemical panels should be performed to monitor for the presence of metHb, Heinz body anemia, or evidence of hepatotoxicity. Generally, prognosis is fair to excellent with therapy. If clinical signs resolve and liver enzymes are within normal limits after 48 hours of NAC therapy, patients can be discharged with SAMe (for 30 days). Those with severe hepatic failure have a poorer prognosis.

Pyrethrins and Pyrethroids

Pyrethrins and their synthetic derivative, pyrethroids, are commonly found in household insect sprays and insecticides (e.g., permethrin, cypermethrin, cyphenothrin, etc.). Due to a cat’s altered liver glucuronidation metabolism, cats are significantly more sensitive to pyrethrins than dogs. While a precise toxic dose for cats is not well established, products containing greater than a 5–10% concentration of pyrethrins may lead to systemic toxicosis. The diluted amount found in household insect sprays and topical flea sprays and shampoos is typically <1%. Toxicosis from exposure to these products is highly unlikely. The application of canine spot-on pyrethrin/pyrethroid based insecticides (typically ~40–50% concentration) to cats is the primary cause of feline pyrethrin toxicosis. Cats that groom dogs following recent spot-on applications are also at high risk for toxicosis; ideally, pets should be separated until the spot-on product has completely dried on the dog to prevent cat exposure. Signs of systemic toxicosis in cats include GI signs (e.g., hypersalivation, vomiting, nausea), neurologic signs (e.g., disorientation, weakness, hyperexcitability, tremors, seizures), and respiratory signs (e.g., tachypnea, dyspnea). Tremors are extremely responsive to methocarbamol (22–220 mg/kg, IV PRN to effect), a centrally acting muscle relaxant, although oral absorption of methocarbamol is often slower in onset of action. In general, tremors are less responsive to benzodiazepines (e.g., diazepam). Seizures may be controlled with phenobarbital (e.g., 4–16 mg/kg, IV PRN to effect) or general gas anesthesia. Dermal decontamination is crucial but should be performed after stabilization. This should be performed with a liquid dish detergent (e.g., Dawn, Palmolive). Supportive care including the monitoring and maintenance of hydration, body temperature, and blood glucose levels are necessary. Signs may persist for 1–4 days, depending on the animal. The prognosis is excellent with aggressive dermal decontamination and treatment.

Hydrocarbons

Hydrocarbons consist of chemicals containing a hydrogen and carbon group as their main constituents. Examples include liquid fuels such as kerosene, engine oil, tiki-torch fuels, gasoline, diesel fuels, paint solvents, wood stains, wood strippers, liquid lighter fluids, asphalt/roofing tar, etc. These are often referred to as “petroleum distillates” based on their viscosity, carbon chain length, and lipid solubility. It is contraindicated to induce emesis with hydrocarbon toxicosis due to the risks of aspiration pneumonia; due to the low viscosity of hydrocarbons, these compounds are more easily aspirated, resulting in respiratory injury and secondary infection. In general, hydrocarbons are GI tract irritants, but can also be irritants to the respiratory system (if inhaled), eyes, and skin. Clinical signs include vomiting, nausea, tachypnea, and dermal or ophthalmic irritation. Typically, GI tract irritation is self-limiting. Patients should be treated with anti-emetic therapy, possible SQ fluid therapy (to assist in hydration), fasting (no food per os), and initiation onto a bland diet. Patients demonstrating any coughing, retching, or tachypnea post-ingestion should have chest radiographs performed to rule out aspiration pneumonia, of which treatment is supportive (e.g., oxygen therapy, IV fluids, antibiotic therapy, nebulization and coupage, etc.).

Asthma Inhalers (e.g., Albuterol)

Asthma inhalers are often used in both human and veterinary medicine. Various types of medications may be used, including steroids (e.g., fluticasone) or beta agonists (e.g., albuterol, salbutamol, etc.). When beta-agonist inhalers are accidentally chewed and punctured by dogs, they can result in a severe, life-threatening, acute toxicosis (inhaled steroids are not a large toxicity issue). Because inhalers often contain approximately 200 metered, concentrated doses, a massive amount of beta-agonist is released with just one puncture. Clinical signs include cardiac (e.g., tachycardiac, a “racing heart rate” per the owner, injected gums, hypotension, hypertension, severe arrhythmias), electrolyte changes (e.g., severe hypokalemia, hyperglycemia), GI (e.g., vomiting), and CNS (e.g., mydriasis, agitation, weakness, collapse, death). Treatment includes stat electrolyte monitoring, IV fluids, potassium supplementation, blood pressure and ECG monitoring, sedation/anxiolytics (if the patient is agitated, hypertensive, and tachycardic), antiarrhythmics such as beta-blockers (e.g., propranolol, esmolol, etc.), and symptomatic supportive care. Treatment for 24–36 hours is typically necessary, until clinical signs resolve.

Household Cleaners

Most surface cleaners are generally benign, and when ingested directly from the bottle, can result in minor GI signs. However, certain concentrated cleaners can be highly toxic or corrosive. Household bleach is a GI irritant, but “ultra” bleach can be corrosive, resulting in severe esophageal or upper GI damage. Concentrated lye products, toilet bowl cleaners, and oven cleaners are also corrosive, and immediate flushing out the mouth for 10–15 minutes should be performed prior to veterinary visit to minimize tissue injury. Appropriate pet-proofing (such as keeping toilet seats down or securing cleaners in a locked or elevated bathroom cabinet) are the easiest way to prevent this specific toxicosis.

Vitis vinifera (Grapes, Raisins, Sultanas, and Some Currants)

Grapes, raisins, and sultanas have been recently associated with development of acute kidney injury (AKI) with ingestion. All types have been implemented with toxicosis, including organic grapes, commercial grapes, homegrown grapes, and seedless or seeded grapes. The mechanism of toxicosis is recently thought to be due to tartaric acid (also found in cream of tartar and tamarind fruit). Common kitchen items also contain grapes, sultanas, raisins, or currants in their active ingredient, including raisin bread, trail mix, chocolate-covered raisins, cereal with raisins, cream of tartar, tamarind fruit, dehydrated tamarind fruit, etc. Currently, grapeseed extract has not been associated with nephrotoxicity. Treatment for grape and raisin ingestion includes aggressive decontamination as the first line of therapy. Grapes and raisins seem to stay in the stomach for a prolonged period of time and are not rapidly broken down or absorbed from the gastrointestinal (GI) tract; hence, delayed emesis induction even several hours post-ingestion can still be initiated to maximize decontamination methods. One dose of activated charcoal can also be administered to prevent absorption of the unknown nephrotoxin. In general, all ingestions should be treated as potentially idiosyncratic and be appropriately decontaminated and treated. Initially, vomiting may be observed within the first 24 hours of ingestion. Within the next 12–24 hours, clinical signs of lethargy, dehydration, vomiting, diarrhea, anorexia, abdominal pain, uremic breath, and diarrhea may be seen. Azotemia may develop within 24 hours, with hypercalcemia and hyperphosphatemia occurring first. Oliguria and anuria may develop 48–72 hours post-ingestion, at which point the prognosis is poorer. Treatment includes decontamination, aggressive intravenous (IV) fluid therapy, antiemetics, blood pressure and urine output monitoring, and serial blood work monitoring (q 12–24 h for several days). In severe cases, hemodialysis or peritoneal dialysis may be necessary. Asymptomatic patients that have been adequately decontaminated and survive to discharge should have a renal panel and electrolytes monitored 48–72 hours post-ingestion. Overall, the prognosis varies from good to poor, depending on time to decontamination, response to therapy, and prevalence of oliguria or anuria. While 50% of dogs that ingest grapes and raisins never develop clinical signs or azotemia, aggressive treatment is still warranted.

Xylitol

Xylitol is a natural sweetener found in small quantities in certain fruit. Xylitol has gained recent popularity because it is sugar-free, and is often found in diabetic snacks, foods, baked foods, mouthwashes, toothpastes, chewing gum, mints, candies, and chewable multivitamins. Sugarless products, particularly those with xylitol listed within the first 3–5 active ingredients (AI), can result in severe toxicosis within 15–30 minutes of ingestion. Ingestion of xylitol results in an insulin spike in non-primate species, resulting in severe hypoglycemia. Many pieces of candy and gum (e.g., Orbit™, Trident™, Ice Breakers™) contain various amounts of xylitol ranging, on average, from 2 mgs to 1.0 grams/piece. Unfortunately, not all sources are disclosed by the company (e.g., how many grams of xylitol may be in each piece of gum) due to a proprietary nature. With xylitol toxicosis, it is imperative to calculate whether a toxic dose has been ingested. Doses >0.1 g/kg are considered toxic and result in profound, sudden hypoglycemia from insulin stimulation. Higher doses (>0.5 g/kg) of xylitol have been associated with acute hepatic necrosis. Clinical signs of xylitol toxicosis include lethargy, weakness, vomiting, collapse, anorexia, generalized malaise, tremors, and seizures (from hypoglycemia). When hepatotoxic doses are ingested, clinical signs and clinicopathologic findings may include melena, icterus, increased liver enzymes, diarrhea, hypoglycemia, hypocholesterolemia, decreased BUN, hypoalbuminemia, etc.

When presented a patient that has ingested a toxic amount of xylitol, a blood glucose should be checked immediately upon presentation; if hypoglycemic, a bolus of 1 ml/kg of 50% dextrose, diluted with an additional amount of 0.9% NaCl (in a 1:3 ratio) should be given IV over 1–2 minutes. Emesis induction should not be performed until the patient is euglycemic. Keep in mind that activated charcoal does not reliably bind to xylitol and is not routinely recommended for xylitol toxicosis. Hypoglycemic patients should be hospitalized for IV fluid therapy (supplemented with dextrose [2.5–5% dextrose, CRI, IV]) for approximately 24 hours, and frequent blood glucose check should be performed every 1–4 hours. For patients ingesting a hepatotoxic amount of xylitol, the use of hepatoprotectants (e.g., SAMe), antiemetics, and supportive care (including frequent liver enzyme monitoring) are warranted.

Chocolate (Theobromine/Caffeine)

Chocolate is one of the most well-known toxic foods that pet owners are aware of. Chocolate contains methylxanthines such as theobromine and caffeine. Methylxanthines antagonize adenosine receptors and inhibits cellular phosphodiesterases, causing an increase in cAMP. Methylxanthines also stimulate release of catecholamines (e.g., norepinephrine) and cause an increase of calcium entry into cardiac and skeletal muscle, resulting in central nervous system (CNS) stimulation, diuresis, and myocardial contraction. When ingested in toxic doses, clinical signs may include agitation, vomiting, diarrhea, panting, tachycardia, polyuria, hyperthermia, muscle tremors, and seizures. Clinical signs of theobromine toxicosis can be seen at within a few hours, up to 10–12 hours out (as the absorption time is slow). As theobromine has a very long half-life (e.g., 17 hours), treatment may be necessary for 72–96 hours. Toxic doses of theobromine can be seen at:

• >20 mg/kg: mild signs of agitation and gastrointestinal distress (e.g., vomiting, diarrhea, abdominal pain)
• >40 mg/kg: moderate signs of cardiotoxicosis can be seen in addition to aforementioned signs (e.g., tachycardia, hypertension)
• >60 mg/kg: severe signs of neurotoxicosis can be seen in addition to aforementioned signs (e.g., tremors, seizures)
• 250–500 mg/kg: LD₅₀ (for dogs)
• 200 mg/kg: LD₅₀ (for cats)

Rarer secondary complications may also be seen from chocolate toxicosis, including pancreatitis and secondary aspiration pneumonia. In general, the darker and more bitter the chocolate, the higher the concentration of methylxanthines in the product. For example, a 20 kg dog would need to ingest approximately 14 oz of milk chocolate, or 4.5 oz of semi-sweet, or 2 oz of unsweetened chocolate to cause moderate signs of toxicity (e.g., agitation, tachycardia). As chocolate tends to stay in the stomach for a prolonged period of time, delayed emesis induction (e.g., even several hours after ingestion)—provided the patient is asymptomatic—may help decontaminate the patient, as chocolate tends to remain in the stomach for quite some time. Further decontamination includes the administration of multiple doses of activated charcoal (1–2 g/kg q 4–6 h × 4 doses), as methylxanthines undergo enterohepatic recirculation. Treatment includes gastrointestinal support (e.g., antiemetics), supportive care, IV fluid therapy, frequent walks (to prevent reabsorption of methylxanthines from the urine across the bladder wall), sedatives for agitation (e.g., acepromazine, butorphanol), beta-blockers for persistent tachycardia or hypertension (e.g., propranolol), methocarbamol for tremors, and anticonvulsants for seizures, as needed.

Insoluble Calcium Oxalates (Dieffenbachia/Philodendron)

According to the ASPCA Animal Poison Control Center, the most common plant exposure is to the Araceae plant family. These plants contain insoluble calcium oxalate crystals and include the Dieffenbachia family of plants. These are common houseplants, as they require little water or light, and can survive in office conditions. Other types of insoluble oxalate containing plants include:

• Arrowhead vine
• Calla lily
• Devil’s ivy
• Dumbcane
• Elephant’s ear
• Mother-in-law’s tongue
• Peace lily
• Philodendron
• Pothos
• Sweetheart vine
• Umbrella plant

The plants contain needle sharp crystals, which are often arranged in bundles called raphides. When dogs or cats bite or chew into the plant, it releases the crystals, resulting in acute, profuse pain to the oropharynx. Clinical signs of insoluble calcium oxalate plant toxicosis includes: hypersalivation, pawing at the mouth or muzzle, anorexia, vomiting, and edema of the lips, tongue, and oropharynx may be seen. Very rarely, dyspnea and upper airway swelling can be seen secondary to severe inflammation and swelling of the laryngeal area. If ocular exposure occurs (rare), severe photophobia, pain, and conjunctival swelling can occur. While clinical signs may appear to be dramatic to the pet owner, signs are primarily localized to the oropharynx and generally are self-limiting. Treatment can potentially be done at home by the pet owner, and includes removal of the plant, flushing of the mouth (if possible), and offering small amounts of palatable fluid (e.g., canned tuna water, milk, yogurt, chicken broth, etc.) to flush the crystals from the mouth. For more severe clinical signs that present to the veterinarian, the use of antiemetics, fluid therapy (e.g., subcutaneous [SQ] or intravenous [IV]), or analgesics may be necessary. Atropine is not recommended for the hypersalivation.

Lilies

The common “true” Lily (from the Lilium spp. and Hemerocallis spp.) is often found in gardens, floral arrangements, or as fresh cuttings. These beautiful, fragrant flowers are known as the common Easter, tiger, Japanese show, stargazer, rubrum, and day lily. All parts of the plant, including the pollen and water in the vase, are toxic to cats, and result in severe AKI. As little as 2–3 leaves or petals (even the pollen or water from the vase) can result in AKI, and clinical symptoms are typically seen within hours. Clinical signs include early onset vomiting, depression, and anorexia, which progresses to anuric AKI in 1–3 days. Clinicopathologic testing reveals severe azotemia, epithelial casts (12–18 hours post-ingestion) on urinalysis, proteinuria, and glucosuria. Treatment includes aggressive decontamination (e.g., emesis induction, administration of one dose of activated charcoal), GI support (e.g., antiemetics, H₂ blockers, etc.), and IV fluid therapy for approximately 48–72 hours (or until resolution of azotemia). The use of SQ fluid therapy is generally not sufficient for the treatment of lily toxicosis. While rarely performed in veterinary medicine, the use of peritoneal or hemodialysis has been successful in anuric AKI cases. With treatment, the prognosis is good if treatment is initiated early and aggressively. Adequate decontamination is of the utmost importance. If aggressive IV fluid therapy is initiated within 18 hours, the overall response to therapy is good. However, if treatment is delayed beyond 18–24 hours, or anuria has already developed, the prognosis is grave.

Marijuana

With the legalization of marijuana in several states, there has been an increased prevalence of accidental exposure to dogs, cats, and children within the past few years. As a result, veterinarians need to be aware of this growing toxicant. Judicious history taking, along with rapid recognition of clinical signs, is imperative, as pet owners are often unwilling to admit to this illicit drug toxicosis in their pets. Thankfully, with appropriate decontamination and treatment, the prognosis is excellent with symptomatic and supportive care. Marijuana, found in the Cannabis sativa plant, contains the toxic ingredient tetrahydrocannabinol (THC). Marijuana is also commonly known under the nicknames Mary Jane, pot, hemp, hashish, pot, grass, weed, devil weed/week, etc. Synthetic marijuana, commonly found in stores, causes similar clinical signs (see treatment). THC directly affects cannabinoid (CB1) receptors in the brain, affecting neurotransmitters (e.g., dopamine, serotonin, gamma-aminobutyric acid [GABA]). This can result in either stimulatory or inhibitory signs. Marijuana is rapidly absorbed either orally or when smoked (e.g., via inhalation), and is eliminated via the liver, bile (55%), feces (45%), and urine (17%). Some enterohepatic recycling occurs. Duration of signs typically occur within 30 minutes and can last up to 3 days (with an average duration of clinical signs of 18–24 hours). Important to note is that clinical signs can be seen at very low doses of marijuana exposure; that said, the LD₅₀ in dogs is extremely high (considered to be >3 g/kg). Animals may exhibit mild to moderate signs after inhalational exposure (e.g., smoke), but are more likely to become symptomatic after ingestion (which is the more common route of accidental animal exposure). Clinical signs include central nervous system signs (e.g., ataxia, disorientation, hyperesthesia, agitation, hyperactivity, dysphoria, mydriasis, behavioral changes, tremors, seizures, coma), gastrointestinal signs (e.g., hypersalivation, vomiting), cardiopulmonary signs (e.g., bradycardia, tachycardia, hypoventilation), and miscellaneous other signs (e.g., urinary incontinence, temperature changes [e.g., hypo- or hyperthermia], death). Clinical signs of marijuana toxicosis can quickly progress to obtundation, coma, bradycardia, hypotension, tremors, seizures, and rarely, death. Signs can develop quickly (within 5 minutes) or be delayed up to 12 hours; most often, occur with 1–3 hours of exposure. Treatment for marijuana poisoning includes appropriate decontamination, symptomatic supportive care, antiemetic therapy, and treatment for life-threatening clinical signs (e.g., atropine, intubation mechanical ventilation, etc.). One potential “antidote” that can be in severe, potentially life-threatening cases is the use of intravenous lipid emulsion (ILE). Dosing for ILE in veterinary medicine is extrapolated from human medicine at:

• 20% solution: 1.5–4 ml/kg IV over 1 minute, followed by 0.25 mg/kg/min, over 30–60 minutes.
• Re-dosing of aliquots of 1.5 ml/kg q 4–6 h can also be continued for 24 h if needed or follow-up CRI doses of 0.5 ml/kg/h can be continued until clinical signs improve (not to exceed 24 h).

Anticoagulant Rodenticides (ACR)

First and second generation ACR anticoagulants result in inhibition of vitamin K epoxide reductase, resulting in inactivation of clotting factors II, VII, IX, and X. First generation rodenticides (e.g., warfarin, pindone) had been largely replaced by more potent second-generation anticoagulants (e.g., brodifacoum, bromadiolone, diphacinone, chlorophacinone, etc.); however, recent EPA mandates have eliminated many second generation ACRs due to relay toxicosis. Each individual ACR varies in the margin of safety and LD₅₀. Some have very narrow margins of safety (e.g., brodifacoum), while some have very wide margins of safety (e.g., bromadiolone). When in doubt, the toxic dose should be calculated, or the ASPCA APCC contacted to determine if a toxic dose has been ingested. Finally, keep in mind that species differences exist; cats are much more resistant to the effects of ACR as compared to dogs.

When a toxic ingestion of ACR has occurred, prolongation in coagulation factors (prothrombin [PT] or activated partial thromboplastin time [aPTT]) is not seen for 36–48 hours, as based on the half-life of factor VII. Clinical signs typically do not develop for 3–5 days. Clinical signs are due to clotting factor depletion, resulting in generalized hemorrhage. The most common clinical signs include lethargy, exercise intolerance, inappetence, pallor, dyspnea, coughing, hemoptysis, etc. Hemoabdomen, hemothorax, pericardial effusion may also occur. Rarer clinical signs include gingival bleeding, epistaxis, ecchymosis, petechiae, hematuria, bleeding into the subcutaneous space or joint space, and melena.

Errors are often made by veterinary professionals when it comes to the medical management of ACR rodenticides. While it is often appropriate to decontaminate a patient with emesis induction and activated charcoal administration, with non-toxic ingestions (based on the LD₁₀), this is often unnecessary (unless the patient is neonatal, geriatric, has an underlying hepatopathy, or has previously ingested a ACR before). Next, the administration of a “one time,” parenteral injection of vitamin K₁ at the time of decontamination is unnecessary and potentially detrimental. First, vitamin K₁ is faster absorbed orally than parenterally (particularly with a fatty meal). Another reason why the “one-time shot” should be avoided is because it will skew point-of-care, accurate blood results of the PT test. As factor VII has the shortest half-life, PT will be the first blood test to be prolonged with ACR ingestion; however, this prolongation of the PT will not normally occur until approximately 36–48 hours post-ACR ingestion. Testing prior to this time is unnecessary (unless the patient has been chronically ingesting a ACR over several days), as the PT will be normal prior to 36–48 hours. By administering a “one-time shot” of vitamin K₁ therapy, the patient’s PT will be falsely normal at 48 hours, and instead, the patient will be coagulopathic days later (3–5 days, instead of 2 days). Normally, clinical signs of acute, ACR toxicosis typically occur at 3–5 days post-ingestion. With a “one-time shot,” the patient will bleed out at 5–7 days instead of 3–5 days!

Conclusion

Pet owners should be appropriately educated on how to pet-proof the house and be trained on what common human medications can be toxic to pets. Pet owners should also be appropriately educated on crate training to help minimize toxin exposure. When in doubt, an animal poison control center or toxicology reference should be consulted for toxic ingestions that veterinarians are unaware of.

Note: when in doubt, all drug dosages should be confirmed and cross-referenced with a reference guide such as Plumb’s Veterinary Drug Handbook.

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