(A)Articles recognized in the official United States Pharmacopeia, official Homoeopathic Pharmacopoeia of the United States, official National Formulary, or any supplement to any of them; and

(B)Articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals; and

(C)Articles (other than food) intended to affect the structure or any function of the body of man or other animals; and

(D)Articles intended for use as a component of any articles specified in clause (A), (B), or (C). 21 U.S.C. 321(g)(1)

Drugs administered to animals to treat (diagnose, cure, mitigate, treat, or prevent a disease or to affect the structure or any function of the body) a toxicosis are regulated by the FDA under the FFDCA and its implementing regulations, published in Title 21 of the Code of Federal Regulations (available on-line at http://www.gpoaccess. gov/cfr/). Practicing veterinarians often place drugs used in treating an animal toxicosis into three categories—general treatment, supportive treatment, and specific treatment. This chapter does likewise.

General Treatment

General treatment is normally given irrespective of the toxin, unless there is a preexisting contraindication. General treatment is often intended to induce emesis, reduce absorption, or enhance elimination of toxins. Emetics commonly used in dogs or cats include apomorphine, xylazine, salt, syrup of ipecac, and hydrogen peroxide (see references). Activated charcoal is often used orally to reduce further absorption of toxins from the gastrointestinal tract, whereas soap and water are often used dermally to remove a toxin from the skin or reduce toxin absorption through the skin. Mineral oil, sodium sulfate, and other laxatives are often used to enhance elimination of toxins still present in the gastrointestinal tract. Gastric lavage may be used to enhance removal of toxins still present in the stomach.

Supportive Treatment

Myriad drugs are given to animals with toxicoses with the intention of providing supportive treatment. Supportive treatment is also often given irrespective of the specific toxin. These drugs are normally given to correct an abnormal physiologic state. For example, fluids may be given to treat dehydration, bicarbonate may be given to treat acidosis, and furosemide may be given to treat edema or anuria.

Specific Treatment

A few drugs are indicated when a specific toxin is known or suspected. These specific treatment agents are often called antidotes. (The definition of antidote used in this article is not as defined by the FDA but rather as presented in different veterinary texts). An antidote is a substance that can counteract the activity or effect of a known or suspected poison.

Antidotes may be classified according to their mechanism of action: chemical or pharmacologic. Chemical antidotes interact specifically with a toxicant or neutralize a toxicant. For example, chelators combine with elements (especially heavy metals) to form complexes that can then be eliminated (as with molybdenum and sulfate for copper toxicity and calcium ethylenediaminetetraacetic acid [EDTA] for lead toxicity). Pharmacologic antidotes may neutralize or antagonize the metabolic or physiologic effects of a toxicant, for example (1) preventing formation of toxic metabolites as with 4-methylpyrazole for ethylene glycol toxicity; (2) competing with a toxicant’s action at a receptor site as with naloxone for opioid toxicity; (3) facilitating more rapid or complete urinary elimination of a toxicant by alkalizing the urine with sodium bicarbonate (to eliminate salicylate, phenobarbital, and 2,4-D), (4) facilitating elimination by acidifying the urine with ammonium chloride (to eliminate amphetamine, phencyclidine, and strychnine); (5) blocking receptors responsible for the toxic effect as with atropine for organophosphate toxicity; or (6) aiding in the restoration of normal detoxification mechanisms as with N-acetylcysteine for acetaminophen toxicity). In addition, specific antidotes may act directly on the toxin as in the case of antitoxins.

Animal Drugs That Are Biologics

Some drugs used to treat toxicoses are not approved by the FDA under the FFDCA but are licensed by the U.S. Department of Agriculture (USDA) under the Virus-Serum-Toxin Act (VSTA). The VSTA is implemented by the Center for Veterinary Biologics of the USDA Animal and Plant Health Inspection Service. Examples of such products include antivenins and antitoxins. Animal drugs produced and distributed in full conformance with VSTA have a USDA code rather than an FDA-assigned New Animal Drug Application [NADA] or Abbreviated New Animal Drug Application [ANADA] number. Examples include botulinum antitoxin (USDA Code 6400), tetanus antitoxin (USDA Code 6302.00 & 6302.01), and Crotalidae antivenin (USDA Code 6101.00). Antivenins for animals that are licensed as biologics by the USDA are a unique form of legally marketed animal drugs.*^† More information about the USDA Center for Veterinary Biologics and a listing of licensed veterinary biologics are available at http://www.aphis.usda.gov/animal_health/vet_biologics/.

Drugs Approved to Treat Toxicoses

The limited availability of drugs approved to treat toxicoses is a long-standing problem in veterinary medicine. The drugs listed in Web Table 10-1 are approved by the FDA for use in animals for treatment of toxicoses. Use of these drugs, as indicated on labels, does not give rise to the extralabel drug use issues (discussed later in this chapter). Other than the approved uses of the seven drugs listed in Web Table 10-1, any drug used to treat animal toxicoses is likely done so in an extralabel, or an unapproved, manner. Consequently, review of extralabel drug use regulations may be of value to practicing veterinarians (see Web Table 10-1).

Extralabel Drug Use: Definition

ELU is defined in 21 CFR § 530.3 as actual use or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling. This includes, but is not limited to, use in species not listed in the labeling; use for indications (disease or other conditions) not listed in the labeling; use at dosage levels, frequencies, or routes of administration other than those stated in the labeling; and deviation from the labeled withdrawal time based on these different uses. According to 21 CFR § 530.2, extralabel drug use is limited to treatment modalities when the health of an animal is threatened or suffering or death may result from failure to treat.

When considering an ELU of an approved drug, veterinarians are encouraged to keep in mind that ELUs are permitted only for such therapeutic uses. In the authors’ view, treating animals with a toxicosis are cases in which the health of the animals is threatened or suffering or death may result from a failure to treat the animals. Consequently, treatment of animals with a toxicosis often meets the purpose of the regulation implementing the ELU statute. Only veterinarians may authorize or prescribe ELU. Laypersons may administer an approved animal or human drug in an extralabel manner only under the supervision of a licensed veterinarian.