Newer antidotal therapies (Proceedings)
Antidotes can be divided into three broad catagories: chemical antidotes, pharmacologic antidotes, and functional antidotes. Chemical antidotes act directly on the toxicant to make it less toxic and/or more readily excreted. Pharmacologic antidotes antagonize toxic agents at their receptor sites or through other macromolecules. Functional antidotes are agents that act on the symptoms of poisoning. In many cases, these antidotes have no real effect on the toxicant itself, but they lessen the severity of the clinical picture of the intoxicated patient.
Chemical antidotes: Chelators
DeferoxamineDeferoxamine (Desferal®, Ciba) is a chelating agent approved for use in humans for the treatment of acute iron poisoning, chronic iron overload and treatment of chronic aluminum overload in patients on chronic dialysis. It has been used off label to treat iron toxicosis in animals. Deferoxamine forms a chelate complex with free iron, which is then excreted in the urine and bile. Deferoxamine is most effective within the first 24 hours, before the iron has been distributed to the tissues. The extrapolated animal dose for iron toxicosis is 40 mg/kg, IM, every 4-8 hours. The IM route is preferred, as too rapid IV administration can cause hypotension and pulmonary edema. The efficacy of deferoxamine can be increased by giving ascorbic acid after the gut has been cleared of iron. The deferoxamine-iron complex gives a salmon pink color to the urine ("vin rose"). Continue to chelate until urine clears or until serum iron levels return to normal.
DMSA (2,3-dimercaptosucinic acid, succimer)
Succimer (Chemet®, McNeil Consumer Products) is approved for the treatment of childhood lead poisoning. It has also been used to treat arsenic and mercury poisoning and does not bind iron, calcium or magnesium. Succimer is available as 100 milligram capsules. It is a structural analog to BAL (British Anti-Lewisite, dimercaprol) but has less potential to cause nephrotoxicity. Succimer is preferred over Ca-EDTA and penicillamine, as succimer can be given while lead is still in the GI tract (the other 2 increase lead absorption), it comes in an oral form, it has a lower incidence of causing GI upset and it is also less likely than the others to induce Zn deficiency. Succimer, however, is more expensive than the other options (capsules are approximately $4 apiece). Succimer can impart a 'sulfur' odor to patients while it is being administered; while this is an issue in human patients as it often results in poor compliance, the effect of this on compliance in veterinary patients is not known.
Although not approved for animal use, there are published doses for treating lead toxicosis. The dose for dogs and cats is 10 mg/kg PO TID for 10 days (administer on empty stomach; per rectum if animal is vomiting). Dosing for caged birds is 25-35 mg/kg PO BID 5 days a week for 3-5 weeks. Higher doses (80 mg/kg) have caused death in cockatiels. It is not uncommon for there to be a post-chelation rebound (or elevation) of blood lead levels. Most of the time, this is due to redistribution of the lead from bone and tissue stores in animals chronically exposed to lead. If lead levels are still increased and the animal is still symptomatic, a repeated round of therapy can be pursued. If the animal is asymptomatic, there is no need to retreat, even if lead levels are outside the normal ranges. Persistent elevations may suggest continued exposure to lead, so evaluation of the animal's environment may be indicated.