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Clinical Toxicology Sharon Gwaltney-Brant DVM, PhD, DABVT, DABT ASPCA Animal Poison Control Center, Urbana, IL Decontamination INTRODUCTION Although the basics of decontamination are similar amongst species, the specific method of decontamination that is chosen in each case must be guided by the exposure circumstances and the species exposed. Most toxin exposures can be broken down into ocular, dermal and oral exposures. Following are methods of decontamination for each of these exposure types. OCULAR EXPOSURE Ocular exposures may cause irritation to corrosion of the ocular tissues depending on the substance, the concentration, the exposure time and the sensitivity of the patient. With any ocular exposure, the eyes should be flushed repeatedly with tepid water or saline solution for a minimum of 20-30 minutes. An eyedropper can be used for smaller patients like birds or reptiles. With a larger patient, fill a plastic cup and slowly pour over the ocular area. Patients can be given a mild sedative prior to flushing if needed and if the health of the patient will allow. If not sedated, the patient should be allowed to rest at regular intervals during the flushing to minimize stress. Fluorescein staining should be performed after flushing and repeated at 12 - 24 hours post-exposure to check for corneal ulceration. Treatment with lubricant ointments should follow staining. DERMAL EXPOSURE Dermal exposures may occur to a large variety of substances including petroleum products, pesticides and insecticides, corrosive or irritating materials and substances that are sticky (tar, asphalt, sap and glue). Removal of dermal substances may be less stressful if the patient is sedated. Sedatives should only be used if the health of the patient will allow. If not sedated, the patient should be allowed to rest at regular intervals during the bathing to minimize stress. For mammals, bathing in a mild liquid dishwashing detergent (Dawn) and warm water is recommended. Baths may need to be repeated to completely remove the toxicant. Afterwards, the animal should be rinsed well with warm water and towel dried to prevent chilling. These patients should be kept in a warm environment away from drafts until completely dry. For smaller patients that resent being sprayed with water, the bucket technique may be helpful. Fill a bucket with soapy warm water. Hold the patient, supporting the hind legs and dunk into the bucket up to the neck. Remove the patient and continue bathing. Use a fresh bucket with plain warm water to rinse well. Dermal substances can be removed from birds by misting with room temperature water in a warm environment. The bird should be misted until you can no longer smell or feel the product on the bird's feathers. If just misting does not remove the product and soap is needed, a liquid dishwashing detergent (Dawn) should be diluted in the misting bottle and applied. After removal of the substance, the bird should be rinsed via misting with plain water until all soap is removed. With heavy exposures, birds may be bathed with liquid dishwashing detergent and rinsed well. After misting or bathing, the bird should be wiped with a dry towel and kept in a warm environment away from drafts until completely dry. The procedure for reptiles is similar. When working with sticky substances, do not use solvents for removal. The solvents may be irritating or corrosive to the patient. To remove sticky substances from mammals, trim the fur to remove as much of the substance as possible. Then work a small amount of vegetable oil, mineral oil, mayonnaise or peanut butter through the rest of the substance until it breaks down into "gummy balls". Afterwards, wash with liquid dishwashing detergent as described above. For birds, do not trim the feathers, just utilize vegetable oil, mineral oil mayonnaise or peanut butter and then mist as described above. ORAL EXPOSURE Dilution Dilution with milk or water is recommended in cases of corrosive ingestion. A suggested dose is 1-3ml/lb. For mammals, milk or water is recommended. For birds and reptiles, juicy fruits and vegetables can be fed to accomplish dilution. Emesis Emesis is most productive if performed within 2-3 hours post-ingestion. Feeding the animal a small moist meal before inducing vomiting can increase chances of an adequate emesis. Emetics generally empty 40-60% of the stomach contents and are assumed to be more beneficial than gastric lavage. Dogs, cats, ferrets, and potbelly pigs are examples of house pets that can vomit. Emetics should not be used in rodents, rabbits, birds, horses, and ruminants. Induction of emesis is contraindicated with ingestion of alkalis, acids, corrosive agents, or hydrocarbons. Pre-existing conditions of the patient may also cause use of an emetic to be contraindicated. Emesis should not be attempted if the animal has already vomited or is exhibiting clinical signs. 3 % hydrogen peroxide is a useful emetic. The dosage is 1 teaspoon/5 lbs body weight, not to exceed 3 tablespoons. Vomiting usually occurs within minutes and the dose can be repeated once if not initially successful. Apomorphine hydrochloride can also be utilized, but its use is controversial in some species including cats. The dosage is 0.04 mg/kg IV or conjunctivally. The eye should be rinsed well after conjunctival usage. Other emetics have been recommended including salt, liquid dishwashing liquid, xylazine, syrup of ipecac and powdered mustard. I would not recommend any of these as they are not as effective as hydrogen peroxide or apomorphine and certain of these, including salt, xylazine and syrup of ipecac, may cause significant adverse effects. Adsorbents Activated charcoal adsorbs a chemical or toxicant and facilitates its excretion via the feces. The recommended dose of activated charcoal for all species of animals is 1-3 gms/kg (or 1 - 3 mg/g) body weight. Repeated doses of activated charcoal every 4-8 hours at half the original dose may be indicated when enterohepatic recirculation is known to occur. Many birds will regurgitate a portion of the activated charcoal dose given and it is not uncommon for dogs and cats to vomit after activated charcoal administration. Activated charcoal can be given orally with a large syringe or with a stomach tube. In symptomatic or uncooperative animals, anesthesia may be needed. A cuffed endotracheal tube should be used in the sedated or clinically depressed animal to prevent aspiration. Activated charcoal should not be given to animals that have ingested caustic materials. Other chemicals that are not effectively absorbed by activated charcoal include ethanol, methanol, fertilizer, fluoride, petroleum distillates, most heavy metals, iodides, nitrates, nitrites, sodium chloride, and chlorate. Kaolin-Pectin (Kaopectate) has also been recommended as an adsorbent in some instances. Kaolin is a form of clay (hydrated aluminum silicate) and pectin is a purified carbohydrate derived from fruits. Another clay, bentonite (colloidal hydrated silica) is recommended in some literature. In most instances, except for paraquat exposures, activated charcoal is a superior absorbent to the clays. Burnt toast had been discussed in the past but is no longer considered to be an effective adsorbent. Cathartics Cathartics enhance elimination of substances, including activated charcoal, by moving them through the gastrointestinal tract. Without cathartics, the toxicant bound by activated charcoal can eventually be released and reabsorbed. Cathartics are not to be used if the animal has diarrhea or is dehydrated. There are saline, osmotic and bulk cathartics. Bulk cathartics can be utilized in mammals and birds. One such cathartic is psyllium (Metamucil ). The dose for dogs and cats is 1 teaspoonful mixed with food every 12 - 24 hours. Psyllium is dosed in birds as follows: mix ½ teaspoon with 60 ml of baby food and give via a dosing syringe or eyedropper. Unspiced, canned pumpkin can also be used in cats and dogs. Dilute peanut butter, fruit or vegetables can be utilized in birds and reptiles. Timothy hay can be utilized in rabbits. Osmotic cathartics, like sorbitol, pull electrolyte-free water into the gastrointestinal tract. Sorbitol is commonly combined with activated charcoal in prepared products. The dose is 3ml/kg. Osmotic cathartics can be utilized in mammals, birds and reptiles. Saline cathartics include sodium sulfate (Glauber's salts) and magnesium sulfate (Epsom salts). Saline cathartics act by stimulating gastrointestinal motility. The dose is 250 mg/kg mixed in water or activated charcoal. Saline cathartics should not be used in birds or reptiles. Enemas Enemas are helpful when elimination of toxicants from the lower gastrointestinal tract is desired. General technique is to use plain warm water or soapy warm water. Enemas are not recommended for birds. In reptiles, enemas may be useful since ingested materials often lag for prolonged periods in the colon. Lavage Gastric lavage is used in mammals to remove recently ingested toxicants. General anesthesia must be maintained when performing gastric lavage. An endotracheal tube should be in place to prevent aspiration. Body temperature water should be instilled via gastric tube at 10 ml/kg BWT. Use only gravity to instill and to drain the liquid, repeat until lavage fluid runs clear. Use of large bore tubes and multiple flushes will yield better success. Gastric lavage should not be used to remove caustic substances or hydrocarbons. Rabbits have a very thin stomach wall so use great caution when performing gastric lavage. For patients with cheek pouches, the cheek pouches should be emptied in cases of oral exposure to a toxicant. Crop lavage is used in birds to remove recently ingested toxicants. Frightened and fractious birds should be anesthetized prior to crop lavage. An endotracheal tube should be placed to prevent aspiration. The crop should be flushed gently with warm saline and aspirated. This should be repeated 3 - 4 times. Crop lavage should not be performed in cases of caustic or petroleum distillate ingestion. Further Reading
Toxicology of Common Household Hazards ACIDS AND ALKALIS Acids Products containing acids include cleaning agents (e.g. toilet bowl cleaners), anti-rust compounds, etching compounds, automotive batteries, and pool sanitizers. The relative toxicity of an acid is related to its concentration and decreases with dilution. Acids produce localized coagulation necrosis of tissue and generally produce immediate pain upon exposure, which helps to limit ingestion. In most cases, clinical signs occur almost immediately upon exposure. Oral exposure results in oral pain, vocalization, dysphagia, vomiting (+/- blood), abdominal pain, and irritation or ulceration of oral and/or esophageal mucosa. Lesions often appear milky white to gray initially, then gradually turn black. Esophageal lesions are less common than with alkaline products. With high levels of exposure, gastric ulceration is also possible. Dermal exposure results in dermal irritation or ulceration, accompanied by intense local pain. Inhalation of acid fumes may result in dyspnea, pulmonary edema, tracheobronchitis or pneumonitis. Ocular exposure may result in corneal erosion or ulceration. Attempts to chemically neutralize with a weak alkali are contraindicated, as this may stimulate an exothermic reaction that will exacerbate tissue injury. Treatment of oral exposure includes immediate dilution with water or milk. Gastric lavage and induction of emesis are contraindicated due to the risk of increasing corrosive injury. Activated charcoal is ineffective for caustic agents and should not be used. Treatment of oral lesions is symptomatic, and should include antibiotics to prevent infection; pain management (butorphanol), sucralfate slurries to treat oral, esophageal or gastric ulcers; intravenous fluids to maintain hydration; and provision for nutritional support (e.g. gastrostomy tube). The use of corticosteroids to decrease inflammation and esophageal stricture formation is controversial, as steroids will delay wound healing and may increase susceptibility to infection. Dermal exposures should be treated with copious flushing with clear water for 15 minutes. For ocular exposures, eyes should be flushed with room temperature water or sterile saline solution for 15 minutes. Fluorescein staining of the eyes should be performed, and corneal erosion or ulceration should be treated as needed. Animals with significant respiratory signs (coughing, dyspnea, etc.) should be monitored for a minimum of 24 hours for the development of pulmonary edema. Supplemental oxygen or other respiratory supportive care should be used as needed. Alkalis Alkaline products include sodium or potassium hydroxide, ammonium hydroxide, sodium or potassium hydroxide, and potassium permanganate. Common sources of alkaline products include drain openers, automatic dishwasher detergents, alkaline batteries, toilet bowl cleaners, swimming pool products and radiator cleaning agents. Agents with pH greater than 11 should be considered to be capable of causing significant corrosive injury. Alkaline agents penetrate local tissue rapidly and deeply, causing liquefactive necrosis. Unlike acidic products, very little pain may be evident upon initial contact with an alkaline product, which may encourage further contact and ultimately result in more extensive exposures. Clinical signs may not develop immediately, and it may require up to 12 hours for the full extent of tissue damage to become apparent. Acute signs include depression, hypersalivation, anorexia, oral inflammation or ulceration, smacking of lips, tongue flicking, dysphagia, vomiting (+/- blood), abdominal pain, and melena. Significant hyperthermia (>104 F) may accompany oral inflammation. Esophageal and/or pharyngeal ulceration may occur. Inhalation of corrosive material may result in coughing, dyspnea, and moist lung sounds. Sequelae can include esophageal perforations or strictures and pleuritis or peritonitis from leakage of ingesta through perforated mucosa. As with oral acid exposures, emesis should NOT be induced and activated charcoal should not be given. Complete evaluation of the oral cavity and pharynx for ulceration or irritation should be performed upon presentation of the animal to the veterinarian, although with very recent exposures the oral cavity may appear normal. Evidence of oral discomfort and inflammation generally develop within 2 to 4 hours, although the full extent of injury may not be evident until 12 hours post exposure. It is important to remember that the absence of oral burns does not preclude the development of esophageal burns. Endoscopy may be elected for cases in which esophageal damage is a concern, although delaying endoscopy for 12 hours will allow the full extent of the burns to develop. Should mucosal burns develop, treatment should include antibiotics, pain medication as needed, gastrointestinal protectants (e.g. sucralfate), anti-inflammatories (corticosteroid use is controversial) and general supportive care. In cases with severe oral burns or esophageal burns, placement of a gastrostomy tube will facilitate nutritional support while allowing for mucosal healing. Esophageal lesions may take weeks to heal and there is risk of stricture formation, leading to impairment of esophageal function. BATTERIES Flashlights, remote controls, battery-operated toys, watches, calculators, hearing aids, etc. all provide the opportunity for pets, especially dogs, to be exposed to alkaline or disc batteries. Most alkaline dry cell batteries use potassium hydroxide or sodium hydroxide to generate current, and disc, nickel-cadmium, and silver batteries are generally of the alkaline type. The alkaline gel within a battery cause liquefactive necrosis of tissue, resulting in burns that can penetrate deeply into the local tissue. Lithium disc batteries tend to lodge in the esophagus, increasing the risk of esophageal ulceration. In addition, batteries casings may result in respiratory or gastrointestinal obstruction if inhaled or swallowed. When batteries are chewed and the contents released, alkaline burns result (see Alkali section). Signs of foreign body obstruction (vomiting, anorexia, tenesmus, etc) may occur when casings are swallowed; disc batteries may be inhaled, resulting in acute dyspnea and cyanosis. Treatment of battery exposures is as for exposure to any alkaline product (see Alkali section). In the case of lithium batteries, administration of tap water in 20 ml boluses every 15 minutes has been shown to decrease the severity and delay the development of current-induced tissue injury in dogs. Radiography to determine the location of the battery casing should be performed in cases where the casing is missing. The decision to remove a battery present in the stomach depends on the size of the animal, battery size, and evidence of battery puncture. Batteries that are small relative to the size of the animal will often pass uneventfully through the GI tract and into the stools. Bulky diets may assist in the passage of the battery. If the battery is not seen in the stools within 3 days of ingestion, radiography is recommended to verify the location of the battery. Batteries that have not passed thorough the pylorus within 48 hours are unlikely to do so and may require endoscopic or surgical removal, although endoscopic removal is not recommended in cases where there is suspicion that the battery has been punctured. DETERGENTS Non-ionic and Anionic Detergents Non-ionic and anionic detergents are found in a wide variety of household products, including body soaps, shampoos, dishwashing detergents, various household cleaners, etc. These products are gastrointestinal and ocular irritants with few to no systemic effects. Clinical signs consist of hypersalivation, vomiting, and diarrhea, and are generally mild and self limiting, although ingestion of large quantities may result in more severe vomiting (+/- blood) requiring veterinary intervention. Protracted vomiting may also cause dehydration and electrolyte abnormalities necessitating parenteral fluid therapy. Management includes symptomatic treatment for gastric upset and parenteral fluid therapy, if indicated. Treat ocular exposures by flushing eyes with room temperature water or sterile saline solution for 5 minutes. While corneal injury is unlikely, if persistent photophobia, blepharospasm, or lacrimation should occur, the eye should be fluorescein stain to rule out corneal erosions or ulcers. Cationic Detergents Cationic detergents are contained in fabric softeners, some potpourri oils, hair mousse, algaecides, germicides and sanitizers. Cationic detergents are more toxic than non-ionic/anionic detergents and can cause extensive systemic and local effects at levels as low as 2% or less. Local tissue injury caused by cationic detergents resembles that seen with exposure to alkaline products (see Alkali section). In addition, cationic detergents can cause systemic toxicity including CNS depression, coma, seizures, hypotension, muscular weakness and fasciculations, collapse, pulmonary edema, and metabolic acidosis; the mechanism of these signs is not known. Treatment of local exposure is similar to that for alkaline products (see Alkali section). Systemic signs should be treated symptomatically (i.e. fluids for hypotension, diazepam for seizures, etc.). POTPOURRI Liquid potpourri may contain essential oils and cationic detergents; because product labels may not list ingredients, it is wise to assume that a given liquid potpourri contains both ingredients. Essential oils can cause mucous membrane and gastrointestinal irritation, central nervous system depression, and dermal hypersensitivity and irritation. Severe clinical signs can be seen with potpourri products that contain cationic detergents. Dermal exposure to cationic detergents can result in erythema, edema, intense pain, and ulceration. Ingestion of cationic detergents may lead to tissue necrosis and inflammation of the mouth, esophagus, and stomach. Treatment is symptomatic and supportive (see Cationic Detergent section). GLOW-IN-THE-DARK STICKS AND JEWELRY Glow-in-the-dark items are popular novelty items that are sold at fairs, carnivals, novelty stores and skating arenas. These items include glo-sticks and glow-in-the-dark jewelry (necklaces, bracelets, etc). The primary luminescent agent in these types of products is dibutyl phthalate (n-butyl phthalate), an oily liquid that is also used as a plasticizer and insect repellent. Dibutyl phthalate is of relatively low toxicity (LD50 >8000 mg/kg in rats). Pet exposures to glow-in-the-dark items are unlikely to cause serious problems due to the low toxicity, extremely unpleasant taste and small amounts of dibutyl phthalate in these types of items. Between 1998 and mid 2001, ASPCA Animal Poison Control Center has consulted on 209 exposures to glow items in pets. Of these, 153 involved cats, 54 involved dogs, and 2 involved pet birds. Exposures generally occurred when the pets bit into glo-sticks or jewelry. The extremely unpleasant taste of dibutyl phthalate is thought to be responsible for the clinical signs seen and to limit exposure to these items. Signs generally occur within seconds of the pet biting into the item. Compared to dogs, cats tend to have a much more exaggerated reaction to the taste of dibutyl phthalate. Cats may display profuse salivation and foaming, with occasional retching and/or vomiting. More dramatic are the behavioral effects in cats from exposure to glow items, with neurological signs such as hyperactivity, aggression, head shaking, hiding, and agitation being reported. Rarely, transient panting, dyspnea, tremors and urinary incontinence have been reported in cats. In contrast, dogs may show no reaction or may have mild salivation or retching, with behavioral effects being rarely reported. In all cases, signs are generally self-limiting and should resolve once the pet gets the taste of the product out of its mouth, so the goal of managing an exposure to glow items is to dilute the taste using milk or highly palatable food (e.g. canned tuna). Any chemical that has gotten on skin or fur should be bathed off to prevent re-exposure should the animal groom itself; taking the pet into a darkened room will aid in identifying the luminescent chemical on the skin or coat. For ocular exposure, copious flushing of the eyes is recommended. In most cases, once the disagreeable taste is dealt with, the animals will return to normal with no further treatment needed. BREAD DOUGH Raw bread dough made with yeast poses mechanical and biochemical threats to animals ingesting it. The warm, moist gastric environment stimulates yeast growth, resulting in expansion of the dough mass, resulting in gastric distention, which if severe, can result in respiratory and vascular compromise. Perhaps more significant is the release of alcohol from yeast fermentation, resulting in profound metabolic acidosis, CNS depression and death. Early clinical signs may include unproductive attempts at emesis, abdominal distention, and depression. As alcohol intoxication develops, the animal becomes ataxic and disoriented. Eventually, profound CNS depression, weakness, recumbency, coma, hypothermia may occur. Management of exposure includes decontamination and treatment for alcohol toxicosis. Because emesis is often unsuccessful, gastric lavage is initially recommended. The veterinarian should be prepared to perform gastrotomy should the lavage fail to remove the bulk of the dough mass due to the glutinous nature of the dough. Treatment for alcohol intoxication should proceed as previously described. CHOCOLATE There are a wide variety of chocolate and cocoa products to which pets may be exposed, including candies, cakes, cookies, brownies, and cocoa bean mulches. Not surprisingly, the incidence of accidental chocolate exposures in pets occurs around holidays, especially Easter, Halloween and Christmas. The active (toxic) agents in chocolate are methylxanthines, specifically theobromine and caffeine. Methylxanthines stimulate the CNS, act on the kidney to stimulate diuresis, and increase the contractility of cardiac and skeletal muscle. The relative amounts of theobromine and caffeine will vary with the form of the chocolate (see table).
Cocoa beans may contain up to 255 mg theobromine per ounce of beans, although the exact amount will vary due to natural variation of the cocoa beans. The LD50's of theobromine and caffeine are 100-300 mg/kg, but severe and life threatening clinical signs may be seen at levels far below these doses. Based on NAPCC experience, mild signs have been seen with theobromine levels of 20 mg/kg, severe signs have been seen at 40-50 mg/kg, and seizures have occurred at 60 mg/kg. Accordingly, less than 2 ounces of milk chocolate per kg is potentially lethal to dogs. Clinical signs occur within 6-12 hours of ingestion. Initial signs include polydipsia, bloating, vomiting, diarrhea, and restlessness. Signs progress to hyperactivity, polyuria, ataxia, tremors, seizures, tachycardia, PVC's, tachypnea, cyanosis, hypertension, hyperthermia, and coma. Death is generally due to cardiac arrhythmias or respiratory failure. Hypokalemia may occur later in the course of the toxicosis. Because of the high fat content of many chocolate products, pancreatitis is a potential sequela. Management of chocolate ingestion includes decontamination via emesis followed by gastric lavage. Because methylxanthines undergo enterohepatic recirculation, repeated doses of activated charcoal are usually of benefit in symptomatic animals (vomiting may need to be controlled with metoclopramide). Intravenous fluids at twice maintenance levels will help maintain diuresis and enhance urinary excretion. Because caffeine can be reabsorbed from the bladder, placement of a urinary catheter is recommended. Cardiac status should be monitored via EKG and arrhythmias treated as needed; propranolol reportedly delays renal excretion of methylxanthines, so metoprolol is the beta-blocker of choice. Seizures may be controlled with diazepam or a barbiturate. In severe cases, clinical signs may persist up to 72 hours. MACADAMIA NUTS Macadamia nuts are cultivated from Macadamia integrifolia trees commonly found in Hawaii and Australia. Macadamias are a popular nut for snacking, and used in baking as well. Clinical signs are reported at ingestions as low as 2.4 g/kg body weight. No deaths have been reported at this time. Doses of 1 g/kg, or higher, require decontamination. Clinical signs include weakness, depression, vomiting, ataxia, tremors, transient paresis, and hyperthermia. Mild elevations in serum triglycerides, lipase and alkaline phosphatase may be seen, and should return to normal in 48 hours. Treatment of clinical signs includes fluids and thermorgulation. A cold water enema can speed recovery. Prognosis of macadamia nut ingestion is good. GRAPES & RAISINS Between 1989 and 2001, ASPCA Animal Poison Control Center received over 25 calls regarding dogs that had developed renal failure subsequent to ingestion of grapes and raisins. The quantities of grapes/raisins has ranged from 0.1 oz/kg to 8 oz/kg. Grapes included those purchased from stores, home-grown grapes fresh off of the vine, and grape pressings left over from wine making. Raisins included a variety of brands of commercial raisins. To date the toxic principle is unknown. Analysis of grapes or raisins involved in some of these cases has been negative for heavy metals, pesticides, and known mycotoxins. In most cases, dogs started vomiting within 6 hours of ingestion, with grapes/raisins often seen in the vomitus. Other signs reported in the first 24-36 hours were diarrhea (+/- blood), anorexia, lethargy, and abdominal pain. Ninety five percent of dogs had elevated serum creatinine upon presentation to the veterinarian; ninety percent had elevated blood urea nitrogen on presentation. Some dogs also had elevations in serum calcium, phosphorus, glucose, liver enzymes, amylase or lipase. Half of the dogs developed anuric or oliguric renal failure within 36-72 hours of ingestion of grapes or raisins, and one third of the dogs died or were euthanized due to poor response to treatment for renal failure. One dog with anuric renal failure recovered following peritoneal dialysis. Until more information is available, ASPCA Animal Poison Control Center is recommending that dogs ingesting grapes or raisins, especially in large quantities, be managed aggressively. Early decontamination via emesis or lavage followed by activated charcoal is recommended. Fluid diuresis (two times maintenance) for 48 hours should be instituted, and serial serum chemistries should monitored for at least 72 hours post ingestion. Use of diuretics to maintain adequate urine flow is essential in cases of oliguria or anuria. If available, peritoneal dialysis or hemodialysis may be considered in cases of refractory anuria/oliguria. Symptomatic care for vomiting, diarrhea, or other signs may be required. Animals developing severe oliguria or anuria have a poor prognosis. MOLDY FOOD (TREMORGENIC MYCOTOXINS) Tremorgenic mycotoxins produced by molds on foods are a relatively common, and possibly under-diagnosed, cause of tremors and seizures in pet animals. Because of their relatively indiscriminate appetites, dogs tend to be most commonly exposed to tremorgens. These toxins are produced from a variety of fungi, however tremorgens produced by Penicillium spp. are the most commonly encountered. These molds grow on practically any food, including dairy products, grains, nuts, and legumes; compost piles may also provide a source of tremorgens. Tremorgens have a several different mechanisms of actions: some alter nerve action potentials, some alter neurotransmitter action, and while others alter neurotransmitter levels. The overall affect is the development of muscle tremors and seizures. Clinical signs include fine muscle tremors that may rapidly progress to more severe tremors and seizures. Death generally occurs in the first 2 to 4 hours and is usually secondary to respiratory compromise, metabolic acidosis or hyperthermia. Other signs that may be seen include vomiting (common) hyperactivity, depression, coma, behavior alterations, tachycardia, and pulmonary edema. Asymptomatic animals exposed to moldy foods should be decontaminated via emesis or lavage followed by activated charcoal and cathartic. In symptomatic animals, control of severe tremors or seizures has priority over decontamination. Seizures may respond to diazepam, however others have had better success with methocarbamol (Robaxin ; 55-220 mg/kg IV to effect), especially in seizuring animals. Barbiturates may be used in animals that are unresponsive to other anticonvulsants. Supportive care should include intravenous fluids, thermoregulation, and correction of electrolyte and acid-base abnormalities. In severe cases, signs may persist for several days, and residual fine muscle tremors may take a week or more to fully resolve. Testing of stomach content, suspect foods, or vomitus for tremorgens is available through the Animal Health Diagnostic Laboratory, Michigan State University (517-355-0281). MOTHBALLS Mothballs may be composed of either 100% naphthalene or 99% paradichlorobenzene. Naphthalene-based mothballs are approximately twice as toxic as paradichlorobenzene, and cats are especially sensitive to naphthalene. Naphthalene causes Heinz bodies, hemolysis, and, occasionally, methemoglobinemia in dogs with doses of 411 mg/kg or more (one 2.7 g mothball contains 2700 mg of naphthalene). Paradichlorobenzene primarily affects the liver and CNS, although methemoglobinemia and hemolysis have been reported in humans. Signs of ingestion of naphthalene mothballs include emesis (early), weakness, icterus, lethargy, icterus, brown-colored mucous membranes, and collapse. Rarely, hepatitis has been reported 3-5 days post-ingestion. Paradichlorobenzene mothballs may cause GI upset, ataxia, disorientation, and depression. Elevations in liver serum biochemical values may occur within 72 hours of ingestion. Treatment of mothball ingestion includes early emesis, activated charcoal, and cathartic. Treatment for hemolysis or methemoglobinemia (blood replacement therapy, methylene blue, etc) may be necessary. Intravenous fluid diuresis should be maintained in cases with hemolysis in order to minimize the risk of hemoglobin-induced renal nephrosis. Evidence of hepatic damage, based on biochemical values, would indicate that symptomatic therapy for general liver failure (oral antibiotics, lactulose, dietary management, etc) should be instituted. PENNIES Ingestion of coins by pets, especially dogs, is not uncommon. Of the existing US coins currently in circulation, only pennies pose a significant toxicity hazard. Pennies minted since 1983 contain 99.2% zinc and 0.8% copper, making ingested pennies a rich source of zinc. Other potential sources of zinc include hardware such as screws, bolts, nuts, etc., all of which may contain varying amounts of zinc. In the stomach, gastric acids leach the zinc from its source, and the ionized zinc is readily absorbed into the circulation, where it causes intravascular hemolysis. The most common clinical signs of penny ingestion are vomiting, depression, anorexia, hemoglobinuria, diarrhea, weakness, collapse and icterus. Secondarily, acute renal failure may develop. Clinical laboratory abnormalities will be suggestive of hemolysis (elevated bilirubin, hemoglobinemia, hemoglobinuria, regenerative anemia) and may also indicate the development of kidney failure. Serum zinc levels may be obtained-blood should be collected in all plastic syringes (no rubber grommets) and shipped in Royal blue top vaccutainers to minimize contamination with exogenous zinc. Radiography of the abdomen may reveal the presence of coins or other "hardware" within the stomach. Treatment for recently ingested pennies would include induction of vomiting. Activated charcoal is not indicated, as it is of little benefit in binding metals. Removal of zinc-containing foreign bodies via endoscopy or gastrotomy/enterotomy may be required. Treatment for symptomatic animals should include blood replacement therapy as needed, intravenous fluids, and other supportive care. The use of chelators may not be necessary in cases where prompt removal of the zinc source is accomplished. If chelation therapy is instituted, careful monitoring of renal parameters is important for the duration of therapy. DESICCANTS Desiccants are included as moisture absorbents. They are found in shoeboxes, new sweaters, computers, leather products like brief cases, computer equipment, medications and food. Occasionally, desiccants might be used as an insecticide, particularly for slugs. Silica gel is one of the most common desiccants. Silica gel is a white powder, or a lustrous granule. Silica gel comes in paper packets or plastic cylinders. Packages of silica gel are attractive to pets because of a rustling noise, and the packages are easy to bat around. Most ingestions will not cause clinical signs, although a mild gastrointestinal upset may occur. Treatment is symptomatic and supportive. If a large amount is ingested, a potential for a foreign body or osmotic diarrhea exists. Food products often contain desiccants which contain iron. Deli meats, pepperoni, etc are likely to have this type of desiccant. The iron content can range from 30-60%. Once the iron has oxidized, the resulting compound (iron oxide) is inert and non-toxic. However, if enough iron has been ingested prior to oxidation, iron toxicosis is potentially possible. Doses of iron greater than 20 mg/kg can cause gastrointestinal signs, and doses of greater than 60 mg/kg can cause systemic effects, including hepatotoxicity. Clinical signs usually develop from 1-6 hours post ingestion. Simple GI upset at lower doses usually resolve within 6-24 hours. Activated charcoal is not an effective adsorbent, but milk of magnesia can complex with iron, and decrease absorption. In large doses, monitor the serum iron (SI) and total iron binding capacity (TIBC). These tests are usually available in a timely manner at human hospitals. If the SI is greater than the TIBC, chelation may be required. Desferoxamine is a specific iron chelator. Dosed at 40 mg/kg IM every 4-8 hours, desferoxamine is most effective in the first 24 hours. The desferoxamine-iron complex turns urine a salmon pink color. Chelation continues until the urine color is normal. Once chelation begins, TIBC will be artificially elevated, and can not be used as a marker. Fluids and other supportive care should be administered as needed. FURTHER READING
Selected Herbal Toxicities Herbal preparations are increasing dramatically in usage. A recent telephone survey discovered that 42% of US households had used at least one alternative therapy over the preceding 12 months. In 1997, the herbal medicine industry generated about $3.24 billion in sales. Many people not only use alternative therapies themselves, but also give various therapies to their pets, with or without advice from a veterinarian. The odds are that at least some clients in an average practice will have an interest in, or ask about the use of alternative medicine. The regulation of herbs and other dietary supplements differs from most pharmaceutical drugs. In 1994, the Dietary Supplement and Health Education Act (DSHEA) was created. This act includes vitamins, minerals, neutraceuticals, and herbs. Under the DSHEA, supplement manufacturers are not required to prove efficacy, safety, and there are no mandated quality controls. The FDA can intervene if enough adverse reactions to a specific product occur, but the burden of proof is on the FDA to prove a particular product is harmful. Manufacturers are allowed to state what effect a product is expected to produce (such as the antidepressant effects produced by St. John's Wort) but the manufacturer can not claim a product specifically cures a stated effect. The label must include the statement that the claims have not been evaluated by the FDA. The American Herbal Products Association (AHPA) has developed a safety classification of herbs. Classification is only included for herbs associated with a history of use and only for quantities associated with therapeutic use. The assumption that a consumer will use herbal products in an informed, rational manner is implicit in the classification process. There are four classes. Class 1 includes herbs that can be safely consumed when used appropriately. Class 2 is herbs that have restricted use, unless otherwise prescribed by an expert. Class 2a is for external use only. Class 2b is not to be used during pregnancy. Class 2c is not to be used during nursing and Class 2d includes other specific use restrictions as noted on label information. Class 3 is for herbs for which significant data exists to require the following label "To be used only under the supervision of an expert qualified in the appropriate use of this substance." Class 4 is for herbs for which insufficient data are available to classify. Specific herb discussions follow. MA HUANG, SIDA CORDIFOLIA, and CITRUS AURANTIUM Ma Huang is produced from Ephedra sinica, as well as other Ephedra species and herbs such as Sida cordifolia. Other common names of ma huang include yellow horse and sea grape. S. cordifolia is often known as Indian common mallow. Bitter orange, Citrus aurantium, contains synephrine. Historically, ma huang has been used in China for around 5000 years. This herb was used to treat asthma, colds and flu, fevers, congestion and coughs. Today, ma huang is frequently used as a weight-loss aid because of its stimulant properties and as a decongestant because it is vasoconstrictive. Ma Huang is also abused, like an illicit drug, because of its hallucinogenic and stimulant properties. When used as a weight-loss aid, frequently caffeine-containing plants are included in the formulation, which can increase toxicity. Some formulations will list the quantity of ephedrine per unit of drug. The active components of Ephedra sinica and Sida cordifolia are alkaloids, including ephedrine and pseudoephedrine. Due to many recent reports of adverse effects of Ephedra species, more products are substituting Sida cordifolia and advertising the product as ephedrine free. Bitter orange usage is increasing in frequency as well, because it contains synephrine, instead of ephedrine. The FDA has banned Ephedra containing substances, but did not specifically list the active constituents. Many people stockpiled their favorite products when the ban was announced, so Ephedra cases will continue. Products containing S. cordifolia and bitter orange cause the same clinical syndrome as those containing Ephdedra. Pharmacologically, ephedrine and pseudoephedrine are sympathomimetic alkaloids. The alkaloids stimulate alpha- and beta-adrenergic receptors, causing the release of endogenous catecholamines at synapses in the brain and heart. This stimulation results in peripheral vasoconstriction and cardiac stimulation. This results in increased blood pressure, tachycardia, ataxia, restlessness, tremors, and seizures. The kinetics reported are based on pseudoephedrine. One study has demonstrated comparable pharmacokinetics between botanical ephedrine and synthetic ephedrine hydrochloride. Onset of clinical signs following ingestion of ephedrine or pseudoephedrine may be as early as 30 minutes or delayed several hours post ingestion. Underlying disease may increase an animal's susceptibility to toxicity. Some of these conditions include heart disease, diabetes, and seizure disorders. Once an animal becomes symptomatic, clinical signs may last for thirty-six to forty-eight hours. Pseudoephedrine is excreted in urine as an unchanged drug. In humans, the elimination half-life varies between 2-21 hours, depending on the urine pH. Clinical signs have been seen in dogs at 5-6 mg/kg and deaths have occurred at 10-12 mg/kg. Dogs have a narrow margin of safety compared to other species. Toxicity can be increased if other sympathomimetic substances (such as phenylpropanolomine) are taken at the same time. Other drugs that interact with sympathomimetics include NSAIDS, monoamine oxidase inhibitors, digitalis, and tricyclic antidepressants. Clinical signs of ma huang toxicosis in animals are comparable to those seen with overdoses of over-the-counter and prescription products containing pseudoephedrine. Effects are generally limited to the cardiovascular and central nervous systems. Initial signs usually begin with restlessness, pacing, and agitation. Vocalization may occur. Dogs may exhibit hallucinogenic behavior. On clinical examination, mydriasis, tachycardia, hypertension, muscle tremors, and seizures may be present. Death is usually due to cardiovascular collapse. For a recent ingestion (fifteen minutes or less) in an asymptomatic animal, emesis may be induced. Administer activated charcoal and a cathartic. Tremors, seizures, and nervousness are best controlled by acepromazine maleate (0.05 to 1 mg/kg IV, IM, or SQ), chlorpromazine (0.5 to 1 mg/kg IV or IM), or a barbiturate such as phenobarbital (3 mg/kg IV to effect). For acepromazine and chlorpromazine, start at the low end of the dosage range and increase as needed. Dissociative effects of benzodiazepines are frequently exaggerated in dogs with pseudoephedrine toxicosis; dogs may actually become more agitated after the administration of diazepam. Propranolol (0.02 to 0.06 mg/kg slowly intravenously) or another beta-blocker can be used to control tachycardia. Administer intravenous fluids, and monitor the animal. Hypertension can cause pulmonary edema, although it is rare. Obtain baseline blood tests, including serum potassium and glucose concentrations. GUARANA Guarana is the common name of Paullinia cupana, a plant containing high levels of caffeine. Guarana may contain 3% to 5% caffeine by dry weight compared to coffee beans (1-2 % caffeine) and tea (1-4 % caffeine). Common names include Brazilian cocoa and Zoom. Theobromine and theophylline have also been found in the plant. Historically, guarana was used to provide energy during fasting, as an aphrodisiac, and to prevent malaria and dysentery. Guarana is frequently found in herbal weight loss aids (with or without ma huang) and in products promising increased energy. Because guarana contains methylxanthines, it produces a clinical syndrome similar to chocolate, coffee, or over the counter stimulant products which contain caffeine. Caffeine is a methylated xanthine. It increases cyclic AMP, releases catecholamines, and increases muscular contractility. The net effect is a positive inotropic and chronotropic effect on the heart, cerebral vasoconstriction, renal vasorelaxation, and smooth muscle relaxation in the gastrointestinal tract. Caffeine is well absorbed orally. The plasma half-life in the dog is 4.5 hours. Caffeine is metabolized in the liver and undergoes enterohepatic recirculation. Caffeine is excreted through the urine. As with Ma huang, there are several medical conditions, which may enhance toxicity. These conditions include heart and kidney disease, and ulcers. Caffeine has caused birth defects in animals. The LD50 of caffeine in dogs is reported to be 140 mg/kg. However, serious toxicity and death have been reported at doses much lower than the LD50 . Signs of acute caffeine toxicity in humans appear at 15 to 30 mg/kg and the lethal dose is estimated to be 100 to 200 mg/kg. For combinations of ma huang and guarana, the minimum dose at which clinical signs were reported is 1.3 mg/kg ma huang and 4.4 mg/kg guarana. The minimum dose at which death was reported was 5.8 mg/kg ma huang and 19.1 mg/kg guarana. These doses were obtained from cases reported to the ASPCA Animal Poison Control Center. There are multiple drugs that can interact with caffeine. Besides pseudoephedrine and ma huang, monoamine oxidase inhibitors, aspirin, and cimetidine are commonly used medications that should not be combined with caffeine. The sedative effects of benzodiazepines may be decreased by caffeine. Clinical signs include vomiting, restlessness and hyperactivity, polydipsia and polyuria. Tachycardia and other cardiac arrhythmias such as premature ventricular contractions (PVCs), are possible. Clinical signs progress to muscle tremors and seizures, and finally death. Treatment consists of early decontamination. Induce emesis in an asymptomatic animal or perform gastric lavage. Because enterohepatic recirculation occurs in caffeine toxicosis, repeated doses of activated charcoal are beneficial. Cardiac function should be monitored. Tachycardia can be treated with a beta-blocker such as metoprolol or propranolol. The dose is the same as in ma huang toxicosis. Premature ventricular contractions can be treated with lidocaine. Lidocaine is dosed at an initial bolus of 2-4 mg/kg slowly intravenously, followed by an IV drip of a 0.1% solution at 30-50 mcg/kg/minute. Muscle tremors and seizures are treated with diazepam (0.5-1.0 mg/kg in increments of 5-10 mg, to effect) or a barbiturate can be used (dose as per ma huang). IV fluids potentially enhance excretion. A urinary catheter should be placed because methylxanthines can be absorbed through the bladder wall. GRIFFONIA SIMPLICIFOLIA Griffonia simplicifolia seeds are used as a source of 5-hydroxytryptophan (5-HTP). This extract is generally used to treat depression, headaches, obesity and insomnia in humans. 5-HTP is reported to increase serotonin in the CNS. Label information may list 5-HTP, 5-hydroxytryptophan, or griffonia seed extract as an ingredient. Drug interactions with MAO inhibitors, antidepressants, and herbs such as St. John's Wort can occur. 5-HTP is rapidly and well absorbed from the gastrointestinal tract. 5-HTP readily crossed the blood-brain barrier. Once target cells are reached, 5-HTP is converted to serotonin (5-hydroxytryptamine). Serotonin is important in the regulation of sleep, cognition, behavior, temperature regulation, and other functions. In dogs, the minimum toxic dose reported is 23.6 mg/kg and the minimum lethal dose reported in dogs is 128 mg/kg. There is not necessarily a good correlation between severity of signs and dose ingested. Signs have been reported from 10 minutes up to four hours post ingestion. Signs can last up to 36 hours. Clinical signs resemble serotonin syndrome in humans. Signs include seizures and tremors, depression, ataxia, and hyperesthesia. Gastrointestinal effects including vomiting, diarrhea, and drooling are common. Severe hyperthermia and blindness have been reported. Treatment includes early decontamination. Seizures, tremors, and other neurologic signs usually respond well to diazepam (0.2 to 1 mg/kg, IV to effect) or barbiturates. Fluid therapy should be initiated. Hyperthermia can be managed with cool water baths and fans. Baseline blood and chemistry panels should be obtained. Cyproheptadine is a serotonin antagonist and can be used at 1.1 mg/kg PO or rectally until signs resolved. YOHIMBINE Yohimbine is derived from the bark of Pausinystalia yohimbe. It has long been considered an aphrodisiac, and the bark was smoked as a hallucinogen. In traditional medicine, angina and hypertension were treated with yohimbine. Today, it is mostly used as a sexual stimulant, and is frequently marketed as herbal Viagra. Pharmacologically, yohimbine is classed as an alpha 2-adrenergic blocking agent. A first pass effect can be seen, and the drug is metabolized in the liver. Metabolites are eliminated in the urine. The T1/2 in dogs is 1.5-2 hours. In large doses, severe and life threatening clinical signs can be seen. Clinical effects are related to the alpha 2 blockade and subsequent CNS and cardiovascular stimulation. Clinical signs include hyperactivity, agitation, tremors , seizures, vomiting, diarrhea, abdominal pain, hypertension initially followed by a profound hypotension. Treatment includes early decontamination. Control tremors and seizures with diazepam or a barbiturate. Monitor blood pressure, body temperature, and oxygen saturation. IV fluids should be given. Monitor blood glucose. Do not use epinephrine and dopamine for treatment of hypotension. Dopamine has been associated with fatal cardiac arrest when given in association with other alpha 2-adrenergic blocking agents in people. The FDA has warned that several products listed as containing yohimbine and other drugs actually contain tadalafil, a prescription drug labeled for erectile dysfunction. Clinical signs and treatment may vary if labeling information is incorrect. ECHINACEA PURPUREA Echinacea purpurea is one of the most popular herbal supplements in use today. The common names of Echinacea include purple coneflower, comb flower, scurvy root, and others. Echinacea is indigenous to the United States and cultivated elsewhere. The plant is a perennial herb with narrow leaves and can grow up three feet. It is not unusual to have Echinacea confused with Parthenium integrifolium, a member of the same family, but one that contains no pharmacological activity. Historically, echinacea was used by Native Americans and adopted by settlers. Uses ranged from "blood purifiers" to dizziness to rattlesnake bites. Extracts were widely used as anti-infectives until antibiotics were discovered. Echinacea contains essential oils, as well as glyco-proteins, alkamides, and flavonoids. All parts of the plant are used in various herbal preparations. Echinacea is taken as a tincture, in capsular form, and applied locally to wounds. Echinacea is typically used as an immune stimulant and as supportive therapy for the common cold or coughs, urinary tract infections, and stomatitis. Echinacea is recommended for chronic skin ulcers or poorly healing wounds. Since Echinacea is suspected of being an immunostimulant, it should not be taken for more than 8 consecutive weeks. Echinacea is contraindicated in progressive diseases such as AIDS or multiple sclerosis, and tuberculosis. Echinacea has a wide margin of safety. Arabinogalactan, a purified compound found in E. purpurea, has been dosed at 4 gm/kg IP and IV with no toxic effects. People have reported a variety of adverse effects including hypotension, dizziness, fever, chills, nausea and vomiting, dyspnea and dermatological effects. At least some of the effects are probably due to hypersensitivity and allergic reactions. The ASPCA National Animal Poison Control Center has received 45 calls involving Echinacea since 1992. In many cases, multiple herbal trades were ingested, or the capsules contained multiple ingredients. The most common clinical signs when echinacea was the only trade ingested were vomiting and drooling. In two cases, the animal developed a mild cough, possibly associated with retching. Both hyperactivity and lethargy were reported. Erythema was reported in 1 case. In 25 cases, no clinical signs developed. A small ingestion of Echinacea generally does not require medical intervention. Any gastrointestinal upset is generally self-limiting and the pet owner will be able to treat with supportive care (NPO, kaolin/pectin 1-2 ml/kg QID prn). It is imperative to determine if the animal ingested other herbal products or medications. Large recent ingestions can be treated with gastric decontamination. If an animal develops severe vomiting, symptomatic treatment with IV fluids and other supportive care should be initiated. CHAMOMILE Chamomile refers to both German chamomile (Matricaria recutita) and Roman chamomile (Chamaemelum nobile). Common names for German chamomile include wild chamomile and pin heads. Common names for Roman chamomile include garden chamomile, sweet chamomile, ground apple and whig plant. The plant is indigenous to Europe and northwest Asia and naturalized in America. German chamomile is an annual and Roman chamomile is a slow growing perennial. The plant is erect and grows to about 20-40 cm. Flowers are white with yellow centers. Chamomile has been used since the Roman empire. It was used as an anti-spasmodic and sedative. In folk medicine, chamomile is used for rheumatism and intestinal parasitism. Chamomile has also been used as a hair tint and cigarette flavoring. In veterinary medicine, the most common uses are as a natural wormer, sedative, and as a treatment for aggression. Chamomile contains essential oils, flavanoids, and hydroxycoumarins. Both fresh and dried flower heads are used. Some preparations will use the entire plant. Chamomile is most frequently taken as a tea. Ointments, gels, and bath salts are also available. Chamomile is used as a sedative and gastrointestinal antispasmodic. It may also be taken to treat colds, bronchitis and fevers. In one study, the development of gastrointestinal ulcers caused by indomethacin (a non-steroidal anti-inflammatory) was prevented by chamomile. This study was performed in rats. Topically, chamomile is used to treat wounds and burns. Chamomile is contraindicated in pregnancy (especially early pregnancy). Bisaldolol, which accounts for 50% of the essential oils found in chamomile, has an acute LD50 of 15 ml/kg in rats and mice. In a 4-week subacute toxicity study, 1-2 ml/kg given orally to rats produced no significant effects. Hypersensitivity and anaphylaxis has been reported. Contact dermatitis occurs in people sensitive to other plants in the family, such as ragwort. Ingestion of large quantities of the flower heads produces vomiting. The ASPCA National Animal Poison Control Center has had 6 cases of ingestion in cats. Three cases involved gastrointestinal upset (vomiting and/or diarrhea), 4 cases reported depression and lethargy, and 2 cases reported epistaxis. Of the two cats with epistaxis, one also developed hematomas. Epistaxis and hematoma development is probably due to the hydroxycoumarin content. One cat developed no clinical signs. The majority of dogs developed no clinical signs. Vomiting and hypersalivation were the most commonly reported clinical signs in dogs. Management of recent ingestions includes gastric decontamination. In cases of large ingestions, activated charcoal can be given. Treatment for gastric irritation is symptomatic and supportive (NPO, gastrointestinal protectants, fluid therapy if severe vomiting or dehydration occurs). If anaphylaxis occurs, standard therapy with epinephrine, steroids, and antihistamines should be initiated. For animals with bleeding disorders such as von Willebrand's, or cats, a packed cell volume and activated clotting time or coagulation profile may be required. If necessary, a blood transfusion could be administered. ST. JOHN'S WORT St. John's wort (Hypericum perforatum) is a rapidly rising herbal star. It is also known as goatweed, rosin rose, and Klamath weed. St. John's wort is a perennial native in Europe, Canada, and the United States. This plant can be found throughout much of the United States, but northwestern states have had the greatest livestock economic losses due to Hypericum. There are several Hypericum species, some with overlapping ranges, but the most important is Hypericum perforatum. The plant grows aggressively in roadside areas and ditches, meadows and woods. The height is usually two feet. The yellow flowers bloom from June through September. The plant must be harvested between July and August and dried immediately to retain pharmacological properties. St. John's Wort has been used since the middle ages. Traditionally, this herb is used as an antidepressant, to treat diarrhea and gastritis. It was also used to treat insomnia and cancer. Topically, the herb is mixed with olive oil to create "red oil" and used for inflammation. In veterinary medicine, this plant is well known for causing photosensitization in livestock and horses. St. John's wort has been responsible for devastating economic losses. The major active constituents are anthraquinone derivatives, hypericin and pseudohypericin, as well as flavanoids. The concentration varies considerably depending on harvest time, drying process, and storage. St. John's wort is used primarily as an antidepressant and sedatives. Studies have shown that St. John's wort inhibits serotonin uptake, accounting for the antidepressant effects. It is taken as an infusion or as dried herb. The most common preparation is a standardized 300 mg capsule. St. John's wort can interact with several medications. It decreases the activity of protease inhibitors, antagonizes reserpine, and increased stupor when consumed with alcohol. Monoamine oxidase inhibitors (MAO) such as seligiline (Anipryl ) are potentiated when taken concomitantly. Serotonin syndrome is possible if St. John's wort is taken with selective serotonin reuptake inhibitors (SSRIs) due to synergistic activity. Common SSRIs include fluoxetine (Prozac) and sertraline (Zoloft). Serotonin syndrome has also been noted when St. John's wort is taken with dextrometorphan and meperidine. Sympathomimetics combined with St. John's wort may lead to a hypertensive crisis. Adverse effects occur commonly. In humans, the most frequently reported signs include gastrointestinal upset, allergic reactions, and agitation. Photosensitization has occurred, generally after large doses or long term usage. Prior to 1994, the only cases in the ASPCA National Animal Poison Control Center databanks involved livestock and photosensitization. Almost all cases involving herbal products involve dogs (35 out of 38 cases). In almost half the cases, no signs were reported. The most commonly reported clinical signs were depression, vomiting, and diarrhea. Tremors, and/or seizure were reported in three cases. Two cases developed increased liver enzymes. Recent ingestions are best treated by decontamination. Gastrointestinal disorders are generally easily managed with symptomatic and supportive care. In large ingestions, or unknown quantities, especially if early decontamination is not possible, baseline liver enzymes should be obtained. If evidence of serotonin syndrome develops (tremors, seizures, hyperthermia, vomiting and diarrhea), initiate standard therapy as discussed under griffonia seed extract. If evidence of photosensitization occurs, keep the animal out of sunlight, and provide supportive care for hepatic damage. VALERIAN ROOT Valerian root (Valeriana officianalis) is one of the most popular herbs on the market. Common names include all-heal, heliotrope, Vandal root, and Capon's tale. It is an herbaceous perennial found widely over the United States. The dried rhizome contains a volatile oil with an odor many find offensive. The fresh drug does not have an odor. The plant grows to about 50 to 100 cm high and is erect without a branching stem. Flowers are bright pink to white. The fruit is yellow with a tuft of white hair. Valerian is sometimes confused with Veratrum album, which is a toxic plant. There are over 200 species of valerian, with various degrees of pharmacologic activity. Valeriana officianalis is considered the standard genus and species used in herbal medicine. The primary active ingredients are volatile oils, alkaloids, and most importantly, valepotriates. The root is the only part of the plant that is used. Valerian is classed as generally recognized as safe (GRAS) for food use. The volatile oils are used as flavoring in some food products. Valerian is used primarily as a sedative, and as a sleeping aid. It has also been used in epilepsy, headaches, colic, and numerous other minor ailments. Valerian is frequently taken as a tea, or as an extract. Valerian increases the length of sedation induced by pentobarbital and length of anesthesia produced by thiopental. Valerian has helped ease the effects of withdrawal from benzodiazepines due to similar receptor sites but increases the effects of sedatives if taken concomitantly. Most reports of adverse effects of valerian in human literature occur after chronic use. These effects include headache, cardiac arrhthymias, and agitation. In one case report, 200 mg in a human caused fatigue, tremors, abdominal pain, and mydriasis. Animal studies included injections of 50 mg/kg intravenous in cats which caused a drop in heart rate and blood pressure. Another study found no pharmacological effect in cats at 250 mg/kg. Mice given up to 4600 mg/kg orally produced mild clinical effects. Signs of toxicity included ataxia, hypothermia, and muscle relaxation. The ASPCA Animal Poison Control Center has had only a few calls on valerian ingestion. Most produced no clinical effects, although lethargy and sedation was seen in a cat. Generally, significant treatment would be unnecessary. The sedative effects are generally short-lived and can be managed by an owner at home. Large ingestions in an asymptomatic animal could be treated by decontamination. GARLIC Garlic (Allium sativum) is most often used in cooking. Other common names include stinking rose, treacle, nectar of the gods, and camphor of the poor. Garlic is a perennial bulb with an erect stem. It can grow up to two or three feet. Purple blooms appear from July to September. The bulb has a characteristic odor. The fresh bulb, dried bulb, and liquid extract of the bulb are all used. Historically, garlic has been used to treat diseases ranging from leprosy to clotting disorders in horses. Garlic powder used to be a standard tuberculosis treatment. The volatile oils in garlic contain the active ingredients, a sulfur containing compound and allicin. The majority of pharmaceutical activity is believed to be found in these substances. However, these are also the compounds that produce the characteristic garlic odor. The effectiveness of "de-odorized" garlic is debatable. Garlic has been used to treat high cholesterol, hypertension, as well as the common cold and diabetes. Garlic is contraindicated if gastrointestinal ulcers or inflammation is present. Patients with hypothyroidism should also avoid garlic. It is theorized that consumption of high levels of purified active constituents may cause reduced iodine uptake by the thyroid. Due to increased clotting times, garlic should be avoided prior to surgery. Since garlic can have a hypoglycemic effect, insulin dosages should be monitored carefully. Anticoagulant effects of warfarin may be enhanced by garlic use and clotting times require additional monitoring. Garlic is in the same family as onions and a similar toxic effect would be expected. Onion toxicity results in weakness, tachypnea and tachycardia. Hematological changes including hemolysis, Heinz bodies, and possibly methemoglobinemia may occur. At the ASPCA National Animal Poison Control Center, most calls reported no clinical signs. In cases with clinical signs , the most common effects were vomiting and diarrhea. Tachypnea and tachycardia were also reported in about a third of the cases with clinical signs. A recent paper reported the results of dogs dosed with 1.25 ml of garlic extract/kg body weight (equivalent to 5 g whole garlic/kg) for seven days. These dogs developed oxidative injury to erythrocytes, including Heinz bodies and eccentrocytes. Recent ingestions can be managed with decontamination. Mild gastrointestinal signs can be managed with symptomatic and supportive care. Tachypnea and tachycardia should be monitored and treated if necessary. A complete blood count and coagulation panel should be obtained for baseline purposes if clinical signs progress. ESSENTIAL OILS Essential oils are produced by a large number of plants. The oils are a mixture of terpenes and other chemicals. Essential oils are used from food flavorings to perfumes to medications. The most commonly used essential oils in veterinary medicine include Melaleuca or tea tree oil (Melaleuca alternifolia), pennyroyal oil (Mentha pulegium), D-limonene and linalool (Citrus spp.), Citronella (Cymbopgum nardus), Thuja (Thuja occidentalis), and wormwood or absinthe (Artemisia absinthium). In veterinary medicine, essential oils are most commonly used to treat flea infestations, hot spots or other dermatological conditions, or as wormers. Oils may be found in shampoos, dips, liniments, teas, tinctures, syrups, or other formulations. Essential oils are rapidly absorbed both orally and dermally. They are metabolized by the liver to glucuronide and glycine conjugates. Repeated exposure can cause inductions of the hepatic enzyme systems cytochrome P-450 and UPD-glycuronyl transferase systems. Thus, pre-existing liver disease can increase the risk of toxicity. Cats appear to be more sensitive to essential oils than dogs. The acute LD50 varies significantly between various essential oils. Formulations mixed with an organic solvent, such as alcohol, can allow increased absorption and toxicity. Generally, a greater volume of fresh product is required to produce the same effects as a concentrated essence. The basic mechanism of action is unknown. The most common clinical signs after dermal exposures include ataxia, muscle weakness, depression, and behavioral abnormalities. Severe hypothermia and collapse have occurred in cats. A transient paresis can occur in small breed dogs when melaleuca oil is applied down the spine as a topical flea treatment. Cats have developed scrotal dermatitis after exposure to D-limonene or linalool. Liver failure is associated with essential oils, especially pennyroyal and melaleuca. Oral ingestions cause vomiting and diarrhea. Central nervous system depression may occur, and seizures are possible with large doses. Aspiration pneumonia can occur when essential oils are inhaled. Death can occur with sufficient doses. Signs usually develop from almost immediately up to eight hours post exposure. Recent dermal exposures should be treated by bathing. Activated charcoal is effective in oral exposures. Do not induce emesis because of the potential for aspiration pneumonia. Regulate body temperature. IV fluids help correct hypotension and aids in renal elimination. Monitor electrolytes, cardiac, and respiratory function. Seizures and tremors usually respond to diazepam. Aspiration pneumonia may require oxygen and broad-spectrum antibiotics. Hepatic damage usually responds to good supportive care, although N-acetylcysteine has been used experimentally in humans diagnosed with pennyroyal toxicosis. N-acetylcysteine has a loading dose of 140mg/kg and a maintenance dose of 70 mg/kg QID. Signs usually resolve over a few hours up to a few days. Most animals do have a good prognosis with appropriate treatment. Many mild cases require only mild home treatment and observation. SUMMARY: When a decision has been made to use an alternative therapy, quality assurance is critical. Herbal medications should be treated as medications, with appropriate precautions. Veterinarians should encourage clients to discuss alternative therapies with them. Choice of therapies, diagnoses, and clients expectations should be discussed. Encourage clients to learn the facts behind CAM (complementary and alternative medicine) therapies. When discussing information obtained from web sites, suggest clients use the C.R.E.D.I.B.L.E. evaluation criteria developed by Dr. Gunther Eysenbach.: Current and frequent updates References cited Explicit purpose and intentions of the site Disclosure of sponsors Interests declared and not influencing objectivity (eg financial interests) Balanced content listing advantages and disadvantages Labeled with metadata Evidence level indicated. If a decision is made to refer a pet to a veterinarian practicing CAM, use the same criteria as you would in choosing any specialist: education, training, and professionalism. FURTHER READING
ABCD's of Rodenticides Introduction There are several different classes of products that may be used as rodenticides, including strychnine, zinc phosphide, and aluminum phosphide. This presentation will focus on the "big three" rodenticides that are most commonly encountered: anticoagulants, bromethalin, and cholecalciferol. Unfortunately, the term "D-con" is used often collectively for all rodenticides regardless of brand name, so whenever possible it is always best to have owners bring in packages to verify products. Similarly, anticoagulants are not color-coded, so the color of the rodenticide provides no insight into which product it is. Baits may be formulated as pellets, bars, grains, or meals. Anticoagulants: Substances Short acting anticoagulants include warfarin and pindone. These agents have short half-lives (<24 hours) compared to the long acting products which have half-lives up to 6-7 days. Long acting anticoagulants include diphacinone, difethialone, chlorophacinone, brodifacoum, and bromadiolone. "Second generation" anticoagulants are those that are effective against warfarin-resistant rats. These agents may be longer acting or more potent (or both) than the first generation anticoagulants. First generation anticoagulants include warfarin, diphacinone, chlorphacinone, pindone and valone. As a general guideline, minimum toxic doses of warfarin are >0.5 mg/kg and other anticoagulants are >0.02 mg/kg. Mechanism of action The anticoagulant rodenticides competitively inhibit vitamin K1 epoxide reductase, preventing the regeneration of inactive Vitamin K1 to its active quinone form. Vitamin K1 deficiency results in depletion of clotting factors II, VII, IX and X (vitamin K-dependent factors) and elevations in precursors to these clotting factors, collectively termed PIVKA or proteins induced by vitamin K antagonists. Because it has the shortest half-life of the vitamin K dependent factors, factor VII it is the first parameter affected. Depletion of factor VII leads to elevation of the prothrombin time (PT). In early cases of toxicoses, the PT may be elevated within 36-72 hours, but the animal is usually still clinically normal. Beyond 72 hours, as other factors become depleted, severe hemorrhage may occur, accompanied by elevations in activated partial thromboplastin time (APTT) and activated clotting time (ACT). In rare instances (e.g. animals with pre-existing bleeding disorders or hepatic disease, etc.) depletion of coagulation factors may occur sooner, resulting in clinical evidence of hemorrhage as early as 24-48 hours following exposure. Clinical signs Often, affected animals are not presented to the veterinarian until signs are severe. Animals may present with frank external hemorrhage from surgical or traumatic wounds, gastrointestinal tract, or other body orifices (e.g. epistaxis, vulvar bleeding). Alternatively, animals may present with vague signs of weakness and anemia without any overt external hemorrhage. Hemorrhage into body cavities such as joints, peritoneal cavity or pleural cavity may an animal that presents with weakness, pallor, abdominal distention, lameness, swollen joints, dermal bruising, muscular hematomas, dyspnea, labored breathing, or muffled heart sounds. Bleeding into the brain or spinal cord may result in severe CNS disturbances, paresis or paralysis. Tracheal constriction due to thymic, peritracheal or laryngeal bleeding may result in severe dyspnea. Clinical pathologic abnormalities may include anemia, thrombocytopenia, hypoproteinemia. Decreases in CO2 and pO2 may be identified. Diagnosis Diagnosis is based on history, compatible clinical signs and laboratory confirmation of coagulopathy. Differential diagnoses would include congenital and acquired coagulopathies, and other causes of anemia (trauma, etc.). Coagulation panels may aid in the differentiation of anticoagulant rodenticide from other coagulopathies (e.g. disseminated intravascular coagulation, von Willebrand's disease, Hemophilia A, etc.). Serum chemistry profiles to detect hepatic or other systemic disease that might affect blood clotting are usually indicated. Anticoagulant toxicosis may be worsened in cases of significant hepatic disease due to impaired ability to synthesize coagulation factors and decreased metabolism of ingested rodenticide. Because PT is the first coagulation factor affected in anticoagulant rodenticide toxicosis, it is the test of choice for early detection. Elevations in PIVKA may also be used early in anticoagulant rodenticide toxicosis, as normal animals should not have PIVKA present in the circulation. Unfortunately, PIVKA proteins have been shown to be elevated in number of other acquired and congenital coagulopathies Treatment Tips
Bromethalin Mechanism of Action and Toxicity Bromethalin uncouples oxidative phosphorylation, resulting in depletion of ATP and loss of energy for sodium-potassium trans-membrane pumps. Intramyelinic edema ensues, characterized by the presence of fluid-filled vacuoles between myelin sheaths. This results in decrease nerve impulse conduction. Baits generally contain 0.01% bromethalin and come in 1.5-ounce packs. Although the literature reports a minimum toxic dose in dogs of 1.67 mg/kg, our experience has indicated that some dogs may show signs at doses as low as 0.9 m/kg. Because of this discrepancy and because treatment once signs have developed is usually unsuccessful, we recommend that decontamination be initiated at doses > 0.1 mg/kg. Cats are considered to be three times more sensitive than dogs, and we recommend decontamination for any cat exposure. Clinical Signs Clinical signs may begin within 24 hours or as long as 2 weeks following ingestion. Earlier onset of signs suggests higher ingested dose and poorer prognosis. High doses (>2 mg/kg) result in a convulsant syndrome characterized by acute onset of severe tremors, hyperexcitability, seizures, rigidity, opisthotonos, decerebrate posturing, hyperthermia and death within 36 hours of ingestion. Lower doses cause a paralytic syndrome that begins as depression, +/- hyperthermia, progressive paresis originating in the rear and moving cranially, progressive CNS signs. In sub-lethal exposures, signs may arrest at some level of paresis, and the animal may recover gradually over weeks to months or may retain permanent motor impairment. Post Mortem Lesions Bromethalin causes spongy degeneration in the white matter of spinal tracts, brainstem, cerebellum, and cerebrum. Electron microscopy demonstrates vacoulation myelin sheaths. Treatment Tips
Cholecalciferol Mechanism of Action and Toxicity Cholecalciferol (Vitamin D3) is metabolized in the liver to calcifediol (25-hydroxycholecalciferol). Calcifediol is then metabolized by the kidney to calcitriol (1,25 - dihydroxycholecalciferol). Cholecalciferol increases intestinal absorption of calcium, stimulates bone resorption, and enhances renal tubular reabsorption of calcium. This results in a serum calcium increase. Prolonged elevation of serum calcium can lead to acute renal failure, cardiovascular abnormalities, and tissue mineralization. The minimum toxic dose of cholecalciferol ranges from 0.5 mg/kg to 3.0 mg/kg. APCC decontaminates at 0.1 mg/kg. One ounce of 0.075% cholecalciferol bait contains 21.28 mg cholecalciferol. Clinical signs: Clinical signs may be delayed in onset and typically occur 18 - 36 hours post ingestion. The most common clincial signs seen with cholecalciferol toxicosis include vomiting, diarrhea, inappetence, depression, polyuria, polydipsia, bradycardia, and cardiac arrhythmia. An initial hyperphosphatemia is often seen within the first 12 hours, followed by a hypercalcemia within 24 hours. Hypercalcemic nephropathy develops, resulting in increases in BUN and creatinine. Differential diagnoses for hypercalcemia include juvenile hypercalcemia, hypercalcemia of malignancy, hypoadrenocorticism, hypoadrenocorticism, primary hyperparathyroidism, and calcipotriene toxicosis. Post Mortem Lesions Post mortem lesions seen with cholecalciferol toxicoses include diffuse hemorrhages of the gastrointestinal tract and possible streaking of the renal cortex. Upon cutting, soft tissues of gastrointestinal tract, heart and kidney lend have a "gritty" feel to the knife. Mineralization and necrosis of gastrointestinal, cardiac, and renal tissues may be seen histologically. Elevated total kidney calcium concentrations may be detected toxicologically. Treatment Tips
What Happens If I Don't Know What Rodenticide This Green Stuff Is? Recommendations
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