Please scroll down for more information on the following topics:
- Apomorphine to Stimulate Vomiting
- Accidental Poisoning
- N-acetylcysteine as an Antidote for Acetaminophen Toxicosis
- Dimercaptosuccinic Acid for Lead Poisoning in Cats
- Penicillamine for Long-Term Treatment of Lead Poisoning
- 4-Methylpyrazole for Ethylene Glycol (Antifreeze) Poisoning
Apomorphine to Stimulate Vomiting
Emetic drugs are usually administered in emergency situations after ingestion of a toxin. “Apomorphine is an opiate drug that acts as a potent central dopamine agonist to directly stimulate the CTZ. It can be administered PO, IV, or SC; the IM route is not as effective. It can also be applied directly to conjunctival and gingival membranes, using the tablet formulation, which can easily be removed once emesis is initiated. Vomiting usually occurs in 5-10 min. Although apomorphine directly stimulates the CTZ, it has a depressant effect on the emetic center. Therefore, if the first dose does not induce emesis, additional doses are not helpful. Because the vestibular apparatus may also be involved in apomorphine-induced vomiting, animals that are sedate and motionless will not vomit as readily as animals that are active. Because it can cause CNS stimulation, apomorphine is used cautiously in cats. Opiate-induced excitement in cats can be treated with naloxone (an opiate antagonist).”
Apomorphine dosage for dogs: 4 mg/kg PO; 0.02 mg/kg IV; 0.3 mg/kg SC (from Merck Veterinary Manual, 8th edition, p. 1681); 0.25mg/kg (as a tablet) into the conjunctival sac (from Plumb’s Veterinary Drug Handbook, p.51).
Accidental poisoning “is not a rare event; and veterinarians need to have access to antidotes. However, there are relatively few products specifically labeled for use in these instances, so it has not really been legal for veterinarians to have previously prepared antidotes for poisonings on hand in emergency rooms. For example, if a case of lead poisoning is diagnosed and the veterinarian needs some calcium EDTA as an antidote, there is no product available labeled for use in animals… Compounding offers opportunities for facilities to have [items such as calcium EDTA] on hand…for emergency treatment, in anticipation of a legitimate prescription.”
Intl J of Pharm Comp 1997 July/Aug; 1(4): 240
N-acetylcysteine as an Antidote for Acetaminophen Toxicosis
N-acetylcysteine (NAC) is the antidote of choice for the treatment of acetaminophen poisoning, one of the most common types of intoxication in dogs and cats. NAC acts principally by replenishment of intracellular glutathione stores and detoxification of the reactive metabolite (NAPQI). NAC acts as a scavenger of free radicals, blocks the conversion of hemoglobin to methemoglobin, and can reduce the extent of liver injury.
Although NAC is most effective if administered less than 12 hours after ingestion of acetaminophen, the use of NAC as an antidote is still recommended up to 36 to 80 hours after acetaminophen ingestion.
Oral NAC, IV NAC, and IV sodium sulfate were evaluated as treatments for cats who had received toxic sublethal doses of acetaminophen (APAP). At the dosage levels used, oral NAC, IV NAC, and IV sodium sulfate were equally effective antidotes, as measured by decreased methemoglobinemia, increased whole blood reduced glutathione, decreased APAP half-lives, and increased urinary excretion of the APAP-sulfate conjugate. All the antidotal treatments produced results significantly different from those in the control cats.
To determine if rectally administered N-acetylcysteine (NAC) is absorbed into the systemic circulation, NAC was administered into the rectal vault (2.0 g/kg) of swine via a balloon-tipped Foley catheter inserted into the animals’ rectums. NAC administered via the rectal route resulted in systemic absorption as determined by spectrophotometric methods in 5 of the 7 study animals. This study provides important information regarding the development of a potential alternative route for the administration of NAC to dogs.
In dogs and cats, NAC can be administered intravenously or orally, but has a pungent odor. Oral administration of NAC typically causes nausea and vomiting. The oral solution can be compounded as a chicken-flavored preparation to improve palatability. Rapid intravenous administration of NAC can cause hypotension, bronchospasm, and flushing. Reactions can be minimized by slowing the rate of infusion. Activated charcoal may absorb NAC and reduce its effectiveness, so NAC should not be administered within two hours of giving activated charcoal. “Administration of activated charcoal may exacerbate vomiting and lead to aspiration. A strong antiemetic agent (metoclopramide 0.4 mg/kg IV) may be necessary to prevent emesis.”
NAC is currently not approved by the FDA for use in dogs and cats, but is available in human formulations, and upon a prescription order, can be compounded to meet specific veterinary needs.
Dimercaptosuccinic Acid for Lead Poisoning in Cats
The owners of two nine-year-old cats moved to a new house. One week after moving, both cats were vomiting and losing weight so the owners brought the cats to the veterinary clinic. The veterinarian began intravenous hydration. Blood work showed a very high level of nucleated RBC’s. The CBC revealed platelet clumps on feathered edge, few macrocytes, moderate anisocytosis, and occasional acanthocytes (54% and 45.1% NRBC). One cat had two seizures on the first day of hospitalization. Based on the initial signs and nucleated red cells, lead poisoning was suspected, although there was no radiographic evidence of lead ingestion. We tested for lead and began treatment with dimercaptosuccinic acid (DMSA) 40mg/cc.
The cats improved clinically within 24 hours. There were no more seizures and the cats began to eat. The blood lead levels were 164.8 and 210 (normal is 0-25). The cats were treated with 40mg (1cc) of DMSA given orally three times per day for a total of 10 days. DMSA is not commercially available in an injectable or liquid form. Therefore, we worked together with our compounding pharmacist to prepare a sterile formulation that would be suitable for intravenous or oral use.
The second day after therapy had begun, the owners informed us that they had been sanding the painted floors in their new house. The cats probably walked through the dust and in grooming themselves licked the lead paint off their paws. There have been no further problems with the cats to our knowledge. The owner declined to come in for a lead level recheck.
Wright Veterinary Medical Center, Bethlehem, PA
Penicillamine for Long-Term Treatment of Lead Poisoning
Penicillamine chelates a variety of metals, including copper, lead, iron and mercury, forming stable water-soluble complexes that are excreted by the kidneys. Used primarily for its chelating ability in veterinary medicine, it is the drug of choice for copper storage-associated hepatopathies in dogs at a dose of 15mg/kg PO twice daily. Penicillamine may also be used in cystine urolithiasis (penicillamine combines chemically with cystine to form a stable soluble complex that can be readily excreted) and in a different dose for the long-term oral treatment of lead poisoning.
This drug should preferably be given on an empty stomach, at least 30 minutes before feeding. If the animal develops problems with vomiting or anorexia, three remedies have been suggested.
- Give the same total daily dose, but divide into smaller individual doses and give more frequently.
- Temporarily reduce the daily dose and gradually increase to recommended dosage.
- Give with meals (will probably reduce amount of drug absorbed).
Veterinary Drug Handbook, 2nd edition, Donald C. Plumb, Ed.
4-Methylpyrazole for Ethylene Glycol (Antifreeze) Poisoning
Therapy for ethylene glycol poisoning is aimed at preventing absorption, increasing excretion, and preventing metabolism of ethylene glycol to its toxic metabolites. Inhibition of liver alcohol dehydrogenase (ADH), the enzyme responsible for the initial reaction in the metabolic pathway, can be accomplished by giving a compound that combines with the enzyme and renders it inactive. The most effective ADH inhibitor in the dog is 4-methylpyrazole (4-MP), which unlike most competitive inhibitors (ethanol, propylene glycol, and 1,3-butanediol) does not contribute to CNS depression and increased serum osmolality. The recommended dose of 5% (50mg/ml) 4-methylpyrazole is 20 mg/kg body weight IV initially, followed by 15 mg/kg IV at 12 and 24 hr, and 5 mg/kg at 36 hr. While 4-MP is the recommended therapy in dogs, it is not appropriate for use in cats. Although it is non-toxic, it does not effectively inhibit EG metabolism unless administered to a cat at the same time as consumption of EG.
Am J Vet Res 1995;56:825