Toxicology Brief managing common poisonings in companion animals

PEER-REVIEWED The 10 most common toxicoses in dogs Irina Meadows, DVM, and Sharon Gwaltney-Brant DVM, PhD ogs are usually exposed to potentially toxic house- Chocolate hold products and medications accidentally. But 2 Chocolate contains two types of Dsometimes well-intentioned owners unknowingly methylxanthine, theobromine and caf- give their dogs harmful products and medications. To help feine, with their amounts varying de- prepare you for patients with theses toxicoses, we com- pending on the type of chocolate. For piled this list of the 10 most common hazards to dogs, example, milk chocolate contains about based on the number of calls we have received at the 60 mg/oz methylxanthine, dark chocolate about 150 mg/oz, ASPCA Animal Poison Control Center (APCC) between 2001 and baking chocolate about 450 mg/oz.3 and 2005.1 Clinical signs of chocolate ingestion range from GI upset to cardiovascular effects (e.g. tachycardia, hypertension or hy- Ibuprofen potension, arrhythmias) to CNS signs (e.g. agitation, pacing, hy- 1 Ibuprofen, a nonsteroidal anti- peractivity, tremors, seizures). The toxicity depends on the inflammatory drug with analgesic, anti- type of chocolate, the amount ingested, the size of the animal, inflammatory, and antipyretic effects,2 is and the animal’s sensitivity to methylxanthines. Mild stimula- available in a variety of strengths. The tion such as hyperactivity, agitation, and restlessness may most common over-the-counter occur in dogs ingesting around 20 mg/kg methylxanthine. strength is 200 mg, but the prescription-strength tablets can Cardiotoxicosis may occur in dogs ingesting 40 mg/kg, and contain up to 800 mg ibuprofen. Ibuprofen has a narrow dogs ingesting more than 60 mg/kg may exhibit severe CNS margin of safety in dogs, and acute toxicosis is common. signs, such as tremors and seizures.3 GI signs such as vomiting Dogs are often exposed to ibuprofen accidentally when and diarrhea can occur with any amount because of choco- they chew on a medicine bottle, but sometimes owners late’s high fat and sugar content. give ibuprofen to their dogs intentionally for pain control. Treating chocolate ingestion includes inducing emesis or Ibuprofen overdose can cause GI, renal, and central nerv- performing gastric lavage, administering activated charcoal ous system (CNS) effects. Doses of 25 mg/kg or more often (multiples doses are recommended with large ingestions), lead to gastrointestinal (GI) problems and ulceration, mani- monitoring the patient’s vital signs closely, and providing sup- fested as vomiting, diarrhea, or abdominal pain. Doses ap- portive care. Continuous electrocardiogram (ECG) monitoring proaching 175 mg/kg increase a dog’s risk of developing is advisable in cases in which cardiotoxicosis is expected. Per- acute renal failure,2 but older dogs or those with preexisting forming baseline serum chemistry profiles and monitoring renal compromise may exhibit renal failure at lower doses. electrolytes in symptomatic animals are also recommended. With doses greater than 400 mg/kg, CNS effects such as de- Dogs should be stabilized before you initiate decontamination pression, seizures, and comas may occur. procedures. Administer intravenous fluids to enhance methyl- Treatment for acute ibuprofen toxicosis includes induc- xanthine excretion, beta-blockers (e.g. propranolol, metopro- ing emesis, administering activated charcoal (multiple char- lol) to reduce tachycardia, and diazepam to control agitation coal doses are indicated to reduce enterohepatic recircula- and tremors. Methylxanthines can be reabsorbed from the tion in dogs that have ingested high doses of ibuprofen) bladder, so monitor urine output and consider placing a uri-

and GI protectants (H2-blockers, sucralfate, misoprostol), and nary catheter to keep the bladder empty. Signs can last 24 to inducing diuresis with intravenous fluids at twice the main- 72 hours because of the long half-life of theobromine in dogs tenance rate while monitoring renal function. With timely (17.5 hours vs. 4.5 hours for caffeine).3 and appropriate treatment, most dogs are expected to have a positive outcome. Ant and roach baits 3 The product names may vary, and the containers may be referred to as cham- “Toxicology Brief” was contributed by Irina Meadows, DVM, and Sharon Gwaltney-Brant, DVM, PhD, ASPCA Animal Poison Control bers, discs, stations, systems, traps, baits, Center, 1717 S. Philo Road, Suite 36, Urbana, IL 61802. The department or trays, but most ant and roach baits use editor is Petra A. Volmer, DVM, MS, DABVT, DABT, College of Veterinary an attractant (often peanut butter), a Medicine, University of Illinois, Urbana, IL 61802. sweetening agent, and bread. And while these baits once con- tained compounds that are relatively highly toxic to mammals

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(e.g. arsenic trioxide, lead arsenate), the most common insecti- Ingesting a bromethalin-containing rodenticide may cause cides used in ant and roach baits today are boric acid, aver- vacuolization and severe spongiosis of the white matter mectin, fipronil, hydramethylnon, propoxur, and sulfluramid.1 within the CNS and cerebral edema.6 Bromethalin ingestion Because of the low concentration of the insecticide and can cause signs ranging from tremors and seizures (convul- the small size of the bait, serious toxicosis in mammalian sant syndrome) to weakness and paralysis (paralytic syn- pets ingesting the baits is not expected.4 In many instances, drome). Convulsant syndrome usually occurs at doses of 2.3 the risk of foreign body obstruction from the plastic or metal mg/kg and higher. Paralytic syndrome is more likely when a part of the container is of greater concern than the active in- dog ingests a lower dose.6 gredients. Signs of ingestion are usually limited to mild GI Ingesting cholecalciferol-containing rodenticides can in- upset and do not require specific treatment. crease dogs’ serum calcium and phosphorus concentra- tions, potentially leading to acute renal failure and tissue Rodenticides mineralization.7 4 The three main types of rodenticides Perform gastric decontamination procedures (induce emesis are those containing anticoagulants and administer activated charcoal with a cathartic) as soon as (warfarin, brodifacoum, diphacinone possible after any rodenticide ingestion. Do not induce emesis [also called diphenadione]), those con- in symptomatic animals (e.g. bleeding or seizing animals).

taining bromethalin, and those contain- Treat anticoagulant-rodenticide ingestion with vitamin K1 ing cholecalciferol. orally for 14 to 30 days, depending on the specific active in- Anticoagulant rodenticides are probably the most com- gredient. It is recommended to evaluate the one-stage pro- monly used rodenticides in the world. Ingesting an anticoag- thrombin time at 48 hours after the last dose of vitamin K1. ulant rodenticide can block vitamin K-dependent clotting fac- An alternative to treatment is to monitor the prothrombin tor synthesis by inhibiting the 2,3-epoxide reductase enzyme, time at 48 and 72 hours after ingestion, and if elevated, initi- 8 which results in a coagulopathy three to five days after in- ate vitamin K1 therapy. Animals that have developed a coag- gestion (possibly sooner in immature animals).5 ulopathy may require whole blood or plasma transfusion and oxygen. The prognosis for animals that have developed 72 to 96 hours. If hyperphosphatemia or hypercalcemia oc- a coagulopathy is guarded and depends on the bleeding site. curs, perform saline diuresis, and administer corticosteroids, Because no specific treatment for bromethalin toxicosis is furosemide, or phosphate-binding agents. Salmon calcitonin available, aggressive decontamination is critical. If clinical or pamidronate may also be needed. Pamidronate, a signs develop, they are difficult to treat, and the patient’s bisphosphonate used in people to treat hypercalcemia of prognosis is guarded. Therapy is directed at resolving cere- malignancy, is a preferred agent in treating cholecalciferol bral edema and addressing seizures, usually by administering toxicosis.7 Although expensive, a single dose of pamidronate corticosteroids, furosemide, mannitol, and diazepam. Since is often sufficient to lower calcium concentrations enough the cerebral edema from bromethalin toxicosis is intra- that the animal can be returned home with minimal addi- myelinic,6 it does not respond well to standard therapy. Man- tional treatment. nitol, corticosteroids, and furosemide may temporarily lower cerebrospinal fluid pressure, but signs often progress once Acetaminophen these treatments are discontinued. 5 Acetaminophen is available as tablets, In rats, an extract of Ginkgo biloba was shown to reduce capsules, or liquids, either alone or com- the development of cerebral edema and brain lipid peroxi- bined with other compounds such as dation when administered orally immediately after gavage opioids, aspirin, caffeine, and antihista- with a lethal dose of bromethalin.6 Whether G. biloba or its mines. Acetaminophen toxicosis can re- extracts would influence the development of clinical signs in sult in hepatotoxicosis, methemoglobinemia, and facial and dogs with bromethalin toxicosis is unknown, but you may paw edema.9 Some dogs have developed transient kerato- wish to consider it in patients in which other options have conjunctivitis sicca after ingesting acetaminophen doses well been unsuccessful. below the amounts previously considered to be of concern.1 Treating cholecalciferol-containing rodenticide ingestion Hepatotoxicosis can occur with doses of 50 to 100 mg/kg, requires close monitoring of the serum calcium and phos- and methemoglobinemia may occur in up to 75% of dogs in- phorus concentrations and the renal function parameters for gesting 200 mg/kg.10 ➤

See brief summary on page 146. ■ Circle 109 on Reply Card Toxicology Brief continued

To treat acetaminophen toxicosis, ini- and cyclosporine if needed.9 The facial Dogs can maintain a remarkably tiate gastric decontamination procedures, and paw edema will resolve on its own, normal physiologic state in the face of a and then administer a 5% N-acetylcys- so corticosteroids and antihistamines are massive L-thyroxine overdosage. Such teine (NAC) solution. Administer 140 not indicated. resistance to developing thyrotoxicosis mg/kg NAC orally as a loading dose, fol- can be explained in part by pharmaco- lowed by 70 mg/kg every six hours for Pseudoephedrine- kinetics, such as poor GI absorption, 9 at least seven doses. Although NAC is 6 containing serum tri-iodothyronine (T3) and thyrox- not labeled for intravenous administra- cold medications ine (T4) being highly protein bound, al- tion, it can be given intravenously in life- Many cold medica- ternative metabolic pathways, and threatening situations by using a bacte- tions contain pseu- greater potential for biliary excretion riostatic filter (0.2 µm). Administer fluid doephedrine, a and fecal loss. In addition, certain or- therapy to maintain hydration; diuresis sympathomimetic drug structurally simi- gans (particularly the liver and kidneys) does not enhance acetaminophen elimi- lar to amphetamines. Pseudoephedrine can concentrate thyroid hormones intra- nation. Adjunctive therapies include ad- ingestion can lead to dose-dependent cellularly, thereby rendering these hor- ministering ascorbic acid, which helps stimulation of the cardiovascular system mones unavailable to bind to tissue re- reduce methemoglobin to hemoglobin; and the CNS. The most common clinical ceptors and induce a physiologic effect. cimetidine, which inhibits cytochrome P- signs include agitation, hyperactivity, Thus, the liver and kidneys can act as 450 oxidation in the liver and may help panting, hyperthermia, hypertension, buffers by releasing small or large reduce acetaminophen metabolism; and tachycardia, head bobbing, or mydriasis. amounts of hormones, depending on S-adenosylmethionine in patients in Ingesting as little as 10 to 12 mg/kg what the body needs, back into the which long-term treatment of hepatic in- pseudoephedrine can cause life-threat- plasma. In an overdose situation, these jury is needed. Monitor serum chemistry ening signs.11 buffer organs can concentrate the extra profile parameters, and evaluate tear Treatment includes gastric deconta- hormone and not release the already production and administer artificial tears mination in asymptomatic animals, pa- stored hormone.12 tient monitoring, and symptomatic Dogs ingesting 0.2 mg/kg levothy- care. Agitation and hyperactivity are roxine may develop mild signs, and best controlled with acepromazine; dogs ingesting 1 mg/kg or more may avoid diazepam because it may exacer- need treatment. Hyperactivity and bate the agitation. Administer pheno- tachycardia are the most common signs barbital or pentobarbital to control se- of thyrotoxicosis.13 vere tremors and seizures, and give Initiate gastric decontamination pro- isoflurane in refractory cases. Fluid cedures in patients that ingest a large therapy enhances pseudoephedrine ex- dose, and monitor the patients’ ECGs,

cretion and protects the kidneys from blood pressures, and serum T4 concen- myoglobinuria, which can result from trations. Treatment is symptomatic and excessive shaking. Because of likely supportive. Diazepam can be given to hypertension, do not exceed fluid rates control hyperactivity, and beta-blockers of one and a half to two times the can be given to control tachycardia.12 maintenance rate unless the dog is in shock or dehydrated. Closely monitor Bleach the heart rate and rhythm, and use 8 Regular household beta-blockers, such as propranolol, if bleaches contain tachycardia is severe. Signs can persist 3% to 6% sodium for up to 72 hours.11 hypochlorite; com- mercial bleaches Thyroid hormones are typically much more concentrated. 7 Natural (desiccated Color-safe bleaches contain sodium thyroid) and syn- peroxide, sodium perborates, or enzy- thetic (levothyrox- matic detergents. Most household ine) derivatives of bleaches are mild to moderate irritants thyroid hormones and are not associated with a marked are used to treat hypothyroidism in ani- degree of tissue destruction. Household mals and people. bleaches can cause skin or eye irrita-

146 MARCH 2006 Veterinary Medicine tion, mild oral or esophageal burns, or GI irritation.14 Com- line, naphtha, mineral oil). GI signs such as vomiting and mercial bleaches can be corrosive and lead to severe stom- diarrhea are common in dogs ingesting hydrocarbons. Mild atitis, pharyngitis, esophagitis, or esophageal ulcerations. In- to moderate eye irritation and reversible ocular injury may halation exposure to bleach can cause respiratory irritation, occur after contact with most hydrocarbons.16 Acute but coughing, and bronchospasm. More serious damage can prolonged skin exposure to some hydrocarbons can result occur when bleach is mixed with ammonia-containing in dermal burns and, occasionally, systemic effects. Low- agents, forming chloramine and chlorine gases. Inhaling viscosity, highly volatile hydrocarbons (e.g. those found in these gases can lead to a chemical pneumonitis. kerosene, gasoline, liquid furniture polish) are aspiration To treat dermal exposure, bathe the dog with mild dish- hazards. Pulmonary damage, transient CNS depression or washing detergent. The preferred initial treatment with excitement, hypoxia, inflammation, and, potentially, sec- bleach ingestion is oral dilution with milk or water. Dilution ondary infection (pneumonia) can occur.16 Hepatic and is most effective if it is performed early. Emesis is contraindi- renal damage have been reported from a percentage of cated because of the irritating properties of household both experimental and field cases of hydrocarbon poison- bleach and the potential corrosive effects of commercial ing. Some hydrocarbons are also apparently capable of bleaches. GI protectants such as sucralfate or H2-blockers can sensitizing the myocardium to endogenous cate- also be used to symptomatically treat bleach ingestion. Treat- cholamines, resulting in arrhythmias and even complete ing corrosive damage may also require pain medications, an- cardiovascular collapse.16 tibiotics, and nutritional support. Oxygen and bronchodila- Because of the risk of aspiration, emesis is contraindi- tors may be needed to treat respiratory signs in cases of cated in patients ingesting products containing hydrocar- inhalation exposure. bons. Dilution can be recommended. To treat topical expo- sure, bathe the dog with a liquid dishwashing detergent. Fertilizer Flush the eyes copiously with saline in cases of ocular expo- 9 Fertilizer products generally contain sure. Closely monitor patients for aspiration pneumonia, par- varying amounts of nitrogen (N), phos- ticularly in vomiting dogs.16 Treatment is supportive and phorus (P), and potassium (K) com- symptomatic. pounds. Product ingredients are often listed as N-P-K 10-8-8, where each Editors’ note: “The 10 most common toxicoses in cats” will ap- number is the corresponding ingredient’s concentration pear in next month’s issue. percentage. Fertilizer formulations include liquid, granular, and solid (e.g. stakes), and fertilizer additives may include REFERENCES 1. Antox [database]. Urbana, Ill: American Society for the Prevention of herbicides, insecticides, fungicides, iron, copper, or zinc. Cruelty to Animals National Animal Poison Control Center. Accessed 2005. Because fertilizers are usually a combination of ingredients, 2. Dunayer E. Ibuprofen toxicosis in dogs, cats, and ferrets. Vet Med 2004;99:580-586. several toxic principles are possible. In general, the ingredi- 3. Gwaltney-Brant S. Chocolate intoxication. Vet Med 2001;96:108-111. ents are poorly absorbed, and most of the signs are related 4. Wismer T. Novel Insecticides. In: Plumlee KH, ed. Clinical veterinary GI toxicology. St. Louis, Mo: Mosby, 2003;183-186. to irritation. 5. Dorman DC. Toxicology of selected pesticides, drugs, and chemicals. Fertilizers have a wide margin of safety.15 GI signs such as Anticoagulant, cholecalciferol, and bromethalin-based rodenticides. Vet Clin North Am Small Anim Pract 1990;20:339-352. vomiting, hypersalivation, diarrhea, or lethargy are common 6. Dorman DC, Cote LM, Buck WB. Effects of an extract of Gingko biloba in dogs after ingesting fertilizers, especially ones with high on bromethalin-induced cerebral lipid peroxidation and edema in rats. Am J Vet Res 1992;53:138-142. percentages of phosphorus and potassium compounds. In 7. Morrow C. Cholecalciferol poisoning. Vet Med 2001;96:905-911. most cases these signs are self-limiting and resolve within 12 8. Merola V. Anticoagulant rodenticides: deadly for pests, dangerous for 15 pets. Vet Med 2002;97:716-727. to 24 hours. 9. Sellon RK. Acetaminophen. In: Peterson ME, Talcott PA, eds. Small an- Treat animals with GI signs supportively with antiemetics, imal toxicology. Philadelphia, Pa: WB Saunders Co, 2001;388-395. GI 10. Beasley VR, Dorman DC, Fikes JD, et al. A systems affected approach fluids, and protectants. Address added insecticides or her- to veterinary toxicology. Urbana, Ill: University of Illinois Press, 1997;178- bicides separately. Heavy metals, such as iron, are generally 180. 11. Means C. Decongestants. In: Plumlee KH, ed. Clinical veterinary toxi- not bioavailable but can pose a hazard when dogs ingest cology. St. Louis, Mo: Mosby, 2003;309-311. large amounts. 12. DeClementi Safrit C. Acute thyroid hormone supplement overdosage. Vet Med 2001;96:424-430. 13. Hansen SR, Timmons SP, Dorman DC. Acute overdose of levothyrox- Hydrocarbons ine in a dog. J Am Vet Med Assoc 1992;200:1512-1514. 14. Kore AM. Common indoor toxicants: bleaches. In: Peterson ME, Talcott 10 Hydrocarbons are in numerous prod- PA, eds. Small animal toxicology. Philadelphia, Pa: WB Saunders Co, ucts, including paints, varnishes, engine 2001;161-162. 15. Albretsen JC. Fertilizers. In: Plumlee KH, ed. Clinical veterinary toxi- cleaners, furniture polish, lighter fluid, cology. St. Louis, Mo: Mosby, 2003;154-155. lamp oils, paint removers, and fuel oil 16. Raisbeck MF. Petroleum hydrocarbons. In: Peterson ME, Talcott PA, eds. Small animal toxicology. Philadelphia, Pa: WB Saunders Co, 2001;666- (e.g. acetone, xylene, kerosene, gaso- 676. ➤

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6. Which statement is true regarding CE QUESTIONS 2 CE hours pseudoephedrine toxicosis? a. Diazepam is recommended to reduce You can earn two hours of Continu- signs of agitation and hyperactivity. ing Education credit from Kansas b. As little as 1 to 2 mg/kg pseudo- State University by answering the fol- ephedrine can cause life-threatening lowing questions on common toxicoses tachyarrhythmias. in dogs. Circle only the best answer for c. Signs of pseudoephedrine toxicosis each question, and transfer your an- include lethargy, hypotension, and swers to the form on page 177. miosis. d. All of the above Article #1 e. None of the above 1. Ibuprofen toxicosis can result in clinical signs involving which organ systems? 7. Even massive overdoses of thyroid a. GI and renal hormones in dogs can be relatively non- b. GI, central nervous, and toxic because of: musculoskeletal a. Poor intestinal absorption c. GI, cardiovascular, and renal b. Alternate metabolic pathways d. GI, renal, and central nervous c. Protein-binding e. GI, central nervous, and cardiovascular d. All of the above e. None of the above 2. Which statement is false regarding chocolate toxicosis? 8. Which statement is true regarding a. Diazepam can be used to manage ag- bleach exposure? itation and tremors. a. GI protectants (e.g. sucralfate, cimeti- b. Dark chocolate has a lower methylxan- dine) are contraindicated because they thine content than baking chocolate. bind with chlorine and increase entero- c. Beta-blockers can be used to manage hepatic recirculation. tachycardias. b. Inhalation exposure to bleach can d. Cardiotoxicosis can occur with inges- cause bronchospasm and coughing. tions of as low as 10 mg/kg c. Dermal exposures should not be methylxanthine. treated by bathing with a mild dish- e. Vomiting and diarrhea are common washing detergent. because of the high fat and sugar d. Color-safe bleaches can cause marked content in chocolate. tissue destruction because they con- tain large amounts of ammonia. 3. Which is not a common insecticide e. After oral ingestion of bleach, dilution used in ant and roach baits? with water is not recommended be- a. Fipronil cause of the increased risk of b. Boric acid aspiration. c. Bromethalin d. Avermectin 9. Most fertilizers tend to have a wide e. Propoxur margin of safety, generally causing which clinical signs after ingestion? 4. In mature animals ingesting anticoagu- a. GI signs lant rodenticides, clotting abnormalities b. Mild ataxia usually occur how long after ingestion? c. Salivation, lacrimation, urination, and a. Four to six hours defecation b. Eight to 12 hours d. Hyperthermia and panting c. 12 to 24 hours e. A self-limiting anisocoria d. Three to five days e. Seven to 10 days 10. Exposure to hydrocarbons, such as those in paints, varnishes, furniture pol- 5. Therapy for acetaminophen toxicosis ish, kerosene, and gasoline, can cause includes all of the following except: which of the following signs? a. Pamidronate a. CNS depression or excitement b. N-acetylcysteine b. Vomiting and diarrhea c. S-adenosylmethionine c. Ocular irritation d. Ascorbic acid d. Pulmonary damage e. Cimetidine e. All of the above

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