Acetaminophen is rapidly and almost completely absorbed from the GI tract. The half-life of APAP in the cat is 5 hours, compared to 1.1 hours in the dog, and 2.6 hours in humans.4 Glucuronidation and sulfation are the two major conjugation pathways used by most species to metabolize APAP. Unfortunately, cats are deficient in glycuronyl transferase and are poor sulfators so cats cannot metabolize APAP to its nontoxic metabolites. Acetaminophen is metabolized through the P450 system resulting in the oxidative metabolite N-acetyl-para-benzoquinoneimine (NAPQI). NAPQI binds to sulfhydryl groups on hepatic cell membranes and damages the lipid bilayer. When present, glutathione conjugates and neutralizes the effects of NAPQI. When glutathione stores are depleted, NAPQI causes liver damage. While liver necrosis is rare in cats, elevated liver enzymes may be seen. Alanine transferase (ALT), aspartate transferase (AST), and bilirubin may rise within 24 hours of ingestion and peak within 48 to 72 hours.

In cats, the major adverse effects of APAP toxicosis are related to methemoglobin and hemolysis. Secondary clinical signs are vomiting, lethargy, facial and paw edema, brown to blue colored mucous membranes, dyspnea, and death. Acetaminophen is deacetylated to p-aminophenol by carboxylesterases, then reacetylated back to APAP by NAT isoform 2. P-aminophenol is a reactive compound that can co-oxidate with hemoglobin to form methemoglobin. Para-aminophenol accumulates in RBCs and appears to be the metabolite responsible for methemoglobinemia and Heinz body formation.⁵ Cats are deficient in arylamine NAT activity which contributes to this species-dependent methemoglobinemia. Cats also have a relative deficiency of methemoglobin reductase in their RBCs which makes it more difficult for them to reverse the hemoglobin damage.

There is no safe dose of APAP for cats. Doses as low as 10 mg/kg have produced signs of poisoning in cats.⁶ Cats should be monitored for methemoglobinemia for 6 to 8 hours after ingestion. Methemoglobin values will begin to increase within 2 to 4 hours of ingestion and methemoglobinemia (Fig. 34.1) should be grossly visible by 6 to 8 hours. Heinz body formation follows. While human hospitals may have the ability to check a qualitative APAP plasma level, this this test is not sensitive enough for cats. Cats with negative results have still developed clinical signs.

Symptomatic patients need initial stabilization and potentially oxygen supplementation. If methemoglobinemia is present or expected, N-acetylcysteine (Mucomyst, NAC) therapy should be started.7 N-acetylcysteine provides a precursor in the synthesis of glutathione, can be oxidized to organic sulfate for the sulfation pathway, and provides an alternative substrate for conjugation of NAPQI. N-acetylcysteine is available as 10% and 20% solutions. Both solutions must be diluted to a 5% concentration with dextrose or sterile water before administration. An initial oral loading dose of 140 mg/kg is given, followed by 70 mg/kg every 6 hours for 7 treatments, or longer if the patient is still symptomatic. If the cat already has methemoglobinemia, an oral loading dose of 280 mg/kg should be given. N-acetylcysteine should be given before activated charcoal if possible. If not, a 2-to-3-hour wait is needed after activated charcoal before oral administration of NAC. The IV route can be used to administer NAC without a waiting period after activated charcoal. Fluid therapy should be used to correct dehydration and supply maintenance needs.

Ascorbic acid is thought to provide a reserve system in the reduction of methemoglobin back to hemoglobin. However, efficacy is questionable, and vomiting is common after oral administration. Cimetidine, an inhibitor of cytochrome P450, was historically recommended to prevent metabolism of APAP to NAPQI. It is now contraindicated in cats as cimetidine blocks one of the only pathways cats have to convert methemoglobin back to hemoglobin. There is also some evidence that silymarin and s-adenosylmethionine may protect the liver in cats with acetaminophen toxicity.^7,8 A whole blood transfusion will increase oxygen carrying capacity, but the cat must be monitored for volume overload and the new hemoglobin can also be affected if there is still circulating free APAP.

Prognosis for recovery from APAP toxicosis can be good with early recognition and intervention. Clinical signs of methemoglobinemia may last 3–4 days, but hepatic injury may not resolve for several weeks. In a study of canine and feline toxin exposures reported to a national animal poison control center from 2009 to 2014, 54 feline exposure incidents to APAP were recorded with a 28% case fatality ratio.¹

The therapeutic oral dose in cats (10 to 20 mg/kg) is administered every 48 hours. Poor glycine conjugation rather than poor glucuronidation appears to be the cause of slow ASA clearance in cats. The half-life of ASA in cats is 22 hours compared with 4.5 hours in dogs, and 2.3 hours in humans.9 As the glycine enzyme system becomes saturated, the half-life of ASA increases. For example, an oral dose of 25 mg/kg has an elimination half-life of almost 45 hours in cats.

Vomiting is the most common clinical sign followed by fever, hyperpnea, melena, abdominal pain, seizures, and coma. Elevations in liver enzymes, respiratory alkalosis, metabolic acidosis, and increased bleeding time may be seen. Decontamination is rarely performed due to the quick absorption of ASA in the GI tract. Treatment includes antiemetics, GI protectants, IV fluid therapy, and management of acidosis.

Lisdexamphetamine (Vyvanse, Takeda Pharmaceutical) is used to treat attention-deficit/hyperactivity disorder in children. Lisdexamphetamine is a prodrug of dextroamphetamine. Amphetamines cause stimulation of the CNS and cardiovascular system. They increase the concentration of endogenous catecholamines at synapses in both the brain and heart. Cats appear to be attracted to lisdexamphetamine capsules and will readily ingest them. As this is an extended-release medication, signs may be delayed for several hours after ingestion and last for 24 to 72 hours.10 The most common clinical signs in cats include hyperactivity, tachycardia, tremors, tachypnea, and hyperthermia. Vomiting, diarrhea, hypertension, and seizures are less commonly reported. Severe signs can be seen with doses greater than 0.6 mg/kg.

Emesis may be attempted but is usually unrewarding in the cat. Activated charcoal with or without gastric lavage may be administered if severe signs are expected. Intravenous fluid therapy is important to maintain cardiovascular stability. Signs such as agitation and hyperactivity respond best to phenothiazines such as acepromazine (0.05 to 0.1 mg/kg, IV or IM). Diazepam should be avoided as it can worsen dysphoria. Cyproheptadine (2 to 4 mg, PO or per rectum, given once or twice), a nonselective serotonin antagonist, can be used to manage some of the stimulatory CNS effects. Beta blockers such as atenolol (6.25 mg, PO, every 12 hours) or propranolol (0.02 mg/kg, IV, titrate dose upward as needed) can be used to manage tachycardia. The prognosis is good with treatment.

Nonsteroidal anti-inflammatory drugs reduce pain and inflammation by preventing prostaglandin (PG) synthesis through cyclo-oxygenase inhibition. Unfortunately, PG inhibition also blocks the beneficial effects of PGs. Multiple NSAIDs are available including over-the-counter, prescription, and veterinary versions. Cats may be inappropriately given NSAIDs by owners or they may voluntarily eat a veterinary chewable formulation. Cats can also develop problems when given therapeutic doses of NSAIDs during surgery (secondary to anesthesia-induced hypotension).11 Cats are more sensitive than dogs to the adverse effects of NSAIDs because they have a limited glucuronyl-conjugating capacity. However, half-lives can vary from species to species. While cats clear carprofen more slowly (half-life, 18 hours) than dogs (12 hours) and humans (12 hours), they clear piroxicam much more quickly (half-life, 11 hours) than dogs (40 hours) or humans (47 hours).⁹ The pharmacokinetic profile of piroxicam in cats does not show any evidence for enterohepatic recirculation.⁹

Therapeutic doses of NSAIDs can cause vomiting in some cats. With overdoses, decreased secretion of the protective mucus layer of the stomach plus increased gastric acid secretion leads to GI ulcers. Renal adverse effects of NSAIDs are seen with higher doses due to the decreased synthesis of renal PGs leading to afferent renal arteriolar constriction, decreased renal blood flow, decreased GFR, and acute kidney injury. Some NSAIDs, such as ibuprofen, have been associated with CNS signs such as ataxia and seizures, or coma at very high doses.

Vomiting usually begins in the first 2 to 6 hours after ingestion, with GI ulcers forming after 12 hours. Onset of acute kidney injury begins within 12 hours but may be delayed depending on the NSAID.⁶

Decontamination is rarely effective as NSAIDS are quickly absorbed. Activated charcoal should be administered if the amount ingested is likely to cause renal damage (Table 34.2). If the NSAID undergoes enterohepatic recirculation, repeating a half dose of activated charcoal in 6 to 8 hours may be considered. Medications to prevent or decrease GI ulceration should be given. Misoprostol (5 µg/kg, PO, every 8 hours) is a synthetic PG and may be helpful for treating or preventing gastric ulceration caused by NSAIDs. However, due to the small size of cats, it must be compounded to be dosed accurately. Proton pump inhibitors (e.g., omeprazole, 0.7 to 1 mg/kg, PO, every 24 hours) can help suppress gastric acid to allow healing to occur. Sucralfate (250 to 500 mg, PO, up to every 6 hours) binds to erosions and ulcers and helps protect them from exposure to gastric acid, bile acids, and pepsin. Antiemetics should be administered as needed. Gastric protection is recommended for 5 to 14 days depending on the NSAID involved.

Fluid diuresis for 24 to 48 hours is recommended when the amount of NSAID ingested is likely to cause renal damage. Intravenous fluid therapy at two times the maintenance requirement is needed to maintain adequate renal blood flow and GFR. Fluid therapy should be adjusted based on hydration status and urine output. Hemodialysis may be necessary if unresponsive oliguric or anuric kidney injury develops. Serum blood urea nitrogen (BUN) and creatinine should be measured at baseline, 24 hours, 48 hours, and potentially 72 hours depending on the NSAID. Prognosis for recovery from NSAID ingestion is good with early, aggressive management. More information on precautions and appropriate use of NSAIDs is found in Chapter 6: Assessment and Management of Pain.

In a study of 33 cats that ingested selective serotonin reuptake inhibitors (SSRIs), the most commonly ingested drugs were venlafaxine (Effexor) and fluoxetine (Prozac).12 In a review of companion animal exposures reported to a national poison control center, venlafaxine was one of the top five drug exposures for cats.¹ Venlafaxine is now classified as a subtype of antidepressant called serotonin–norepinephrine reuptake inhibitors. It inhibits reuptake of serotonin and norepinephrine and is also a weak dopamine reuptake inhibitor. While it is rare for cats to willingly ingest most medications, for some reason they will readily eat venlafaxine capsules. As venlafaxine is available as both an immediate-release and extended-release formulation, signs can occur quickly or may be delayed for several hours after ingestion. It is important to note that venlafaxine will give a false positive reaction for phencyclidine (phenylcyclohexyl piperidine or PCP) on many over the counter urine drug tests.

Cats ingesting doses of venlafaxine as low as 2 to 3 mg/kg can develop serotonin syndrome. The most common clinical signs include mydriasis, vomiting, tachypnea, tachycardia, ataxia, and agitation. Owners may report vocalization and “staring off into space.” In the study of 33 cats that ingested SSRIs, 12 had ingested venlafaxine.¹³ Six cats developed clinical signs; some cats developed multiple signs. The most common signs were CNS stimulation (83%), CNS depression (50%), and GI signs (50%). Cardiovascular signs were seen in one of the six cats. All cats that developed GI signs also had CNS depression. Cats can be symptomatic for up to 72 hours with ingestion of the extended-release formulation.

Emesis can be attempted in asymptomatic individuals. With high doses, activated charcoal can be administered with a second dose in 4 to 6 hours if the extended-release formulation of venlafaxine was ingested. Supportive care such as IV fluid therapy should be instituted. Acepromazine (0.05 to 0.1 mg/kg, IV or IM) may be used for agitation, and cyproheptadine (2 to 4 mg per cat, PO or rectally [crushed in water]) may aid in antagonizing the serotonin effects. Heart rate and blood pressure should be monitored; treatment with beta blockers or pressor agents should be used as needed. Venlafaxine is lipid soluble, and ILE has been used in humans to decrease clinical signs and treatment time. With appropriate treatment, the prognosis is good for full recovery.

Cannabinoids act on various cellular pathways though cannabinoid receptors. In humans, cannabinoids have been investigated as therapeutic drugs for treatment of cancer, nausea and vomiting, pain, and other problems. Unfortunately, there is little published evidence on the veterinary medical use of cannabinoids; most reports are on toxic effects in dogs. Products for pets are usually derived from hemp (a variety of C. sativa) which has a lower concentration of THC than marijuana. Hemp-based CBD products may be available in some countries as oils, tinctures, or powders. These pet products are marketed as aids for itching, anxiety, nausea, poor appetite, seizures, cancer, and many other problems but the health claims are largely anecdotal. As of this writing, no CBD products have been licensed for use in cats or dogs in most countries. Although CBD is thought to have limited toxicity, in dog studies, liver enzyme elevations have been noted.12,14 The safe dose in cats is not known. Veterinarians in many countries are allowed to discuss the medical use of cannabis but are not allowed to recommend or prescribe a product.

In areas where cannabis has been legalized for medical or recreational use in humans, reports of toxicosis in pets, primarily dogs, have increased.¹⁵ However, toxicosis in cats has also been reported.¹⁶ The most common signs of toxicosis in cats include ataxia, lethargy, mydriasis, hypersalivation, vomiting, hyperesthesia, hypothermia, tachypnea, and bradycardia. Pets are also at risk of respiratory tract irritation from secondhand smoke. The clinical signs are not pathognomonic for cannabinoid toxicosis, and some owners will be reluctant to provide information on the exposure, whether it was accidental or intended. Urine strip tests or referral laboratory blood tests for illicit substances in humans are often used in pets with suspected intoxication but have not been validated for use in dogs or cats.

Few reports have detailed treatment of cannabinoid toxicosis in pets and most are in dogs. Many patients require only minimal treatment and may be managed on an outpatient basis. However, ingestion of products containing high levels of natural or synthetic THC can cause life-threatening neurologic, cardiovascular, and respiratory effects. Severe intoxications will require supportive care with IV fluids, management of seizures, and mechanical ventilation. Case reports in dogs have also included the use of ILE and hemodialysis.^17,18

Alpha lipoic acid is frequently sold as 100 or 300 mg capsules and is given orally. It has high bioavailability and is readily absorbed from the GI tract. Plasma levels peak within 2 to 4 hours. The published therapeutic dose for cats is 1–5 mg/kg, with a maximum dose of 25 mg/day.19 In veterinary medicine, ALA has been promoted to treat diabetic polyneuropathy, cataracts, glaucoma, and ischemia–reperfusion injury. It is thought to be 10 times more toxic to cats than humans, dogs, or rats.²⁰ At 30 mg/kg, hypoglycemia and seizures with hepatocellular damage can occur.

Signs of ALA toxicosis can occur 30 minutes to several hours postingestion and include vomiting, ataxia, hypersalivation, tremors, and hypoglycemia. As absorption occurs quickly, decontamination is rarely possible. Inducing emesis and administering activated charcoal with a cathartic can be utilized when possible. Baseline laboratory values for blood glucose, liver enzymes, and electrolytes should be obtained at admission and monitored periodically. Treatment is directed at controlling vomiting, tremors, seizures, and hypoglycemia, supporting liver function, and correcting dehydration if present.

Ant and roach baits (hotels, traps, stations) are commonly found in households. They consist of an insecticide mixed with a bait attractant inside a plastic or metal container. The insecticides most commonly used are present in small amounts and include sulfluramid, fipronil, avermectin, boric acid, and hydramethylnon ( e-Table 34.1). The baits usually contain inert ingredients such as peanut butter, breadcrumbs, sugars, and fats, which can be attractive to pets.

Cats enjoy playing with these baits as they will slide easily across the floor. Exposure usually does not require decontamination or treatment. If clinical signs are seen, they are restricted to mild GI upset.

Although atropine is considered the antidote for the muscarinic signs, it blocks the effects of excess acetylcholine at the neuromuscular junction and should be used with caution. If muscarinic signs are present, a test dose (0.02 mg/kg, IV) can be given to determine if the signs are due to organophosphate or carbamate toxicity versus other causes. If the heart rate increases and the pupils dilate in response to the test dose, the clinical signs are probably not due to organophosphate or carbamate toxicity. This is because the atropine dose required to resolve clinical signs caused by insecticide toxicity is about 10 times the preanesthetic dose of the drug. If insecticide toxicosis is confirmed, atropine can be administered to control muscarinic signs (Table 34.1). The dose is adjusted by monitoring response, especially heart rate and secretion production.

Activated charcoal may be used to bind insecticide in the GI tract, and bathing with soap and water can be used for cats with dermal exposure to prevent further absorption. Additional treatments may include methocarbamol, diazepam, or phenobarbital to control seizures and muscle tremors. Good supportive and nursing care, including IV fluid therapy and nutritional management, is essential.

Severe problems arise when a concentrated dog product is applied to cats. Spot-on products are more concentrated (45%–65% or higher) compared to sprays or shampoos (0.045%–0.15%).21 Cats may also be exposed by contact with dogs treated in the previous 48 hours.

One of the most problematic concentrated synthetic pyrethrins is permethrin. Cats are highly sensitive to the effects of permethrin, likely due to glucuronidase transferase deficiency. Clinical signs of permethrin toxicosis include tremors, muscle fasciculations, ear and facial twitching, hyperesthesia, ataxia, ptyalism, pyrexia, mydriasis, seizures, and, rarely, death.²² Clinical signs may occur within 2 to 4 hours of exposure but can be delayed up to 24 hours. Signs may last 24 to 72 hours, and the severity of clinical signs varies among individuals.

Pyrethrins are quickly metabolized and are not stored in the body. Activated charcoal does not need to be given. Treatment of pyrethrin toxicosis centers around removal of the products from the hair coat and tremor/seizure control (Box 34.2). The entire cat should be bathed completely using lukewarm water and liquid dishwashing detergent.