615 lines
30 KiB
Plaintext
615 lines
30 KiB
Plaintext
Topic: TOAD TOXINS
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0.0 OVERVIEW
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0.1 LIFE SUPPORT
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This overview assumes that basic life support measures
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have been instituted.
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0.2 CLINICAL EFFECTS
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0.2.1 SUMMARY
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A. There are several types of toxic substances found in
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toads, including cardioactive agents, catecholamines,
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indolealkylamines and non-cardiac sterols. These toxins
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are located in the skin and parotid glands and may be
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transferred by handling or ingesting a toad's skin.
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0.2.3 HEENT
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A. Secretions of the toad parotid glands will cause pain
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and severe irritation when placed in eyes, nose, and
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throat.
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0.2.4 CARDIOVASCULAR
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A. Dogs who have been poisoned with bufagins develop
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ventricular fibrillation and symptoms resembling
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digitalis poisoning. Vasoconstriction may also be seen.
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0.2.5 RESPIRATORY
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A. Dyspnea and weakened respirations may be seen.
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0.2.6 NEUROLOGIC
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A. Paralysis and seizures have been reported in both humans
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and animals. Many bufagins have local anesthetic
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actions, especially on the oral mucosa.
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0.2.7 GASTROINTESTINAL
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A. Salivation and vomiting were often seen in animals.
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These toxins may cause numbness of the oral mucosa if
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ingested.
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0.2.14 HEMATOLOGIC
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A. Cyanosis has been seen in poisoned dogs.
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0.2.18 PSYCHIATRIC
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A. HALLUCINATIONS: Drug users have been known to smoke the
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chopped skins of toads for their hallucinogenic effect.
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0.3 LABORATORY
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A. No toxic levels have yet been established for any of the
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bufagins. Since many of the other substances are
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metabolized rapidly, laboratory analysis is impractical.
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0.4 TREATMENT OVERVIEW
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0.4.1 SUMMARY
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A. There are three primary areas of toxicity, the first
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involving cardiac glycoside effects, the second, the
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pressor effects, and the third, the hallucinogenic
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effects. Usually the cardiovascular effects are the
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most prominent. Treatment is directed at prevention of
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absorption, and monitoring for EKG effects and
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hyperkalemia. Lidocaine, a transvenous pacemaker, and
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cholestyramine have all been used to treat digitalis-
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like poisonings. FAB fragments have not been reported
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to be of use in toad poisoning.
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B. Hemodialysis has been ineffective in removing cardiac
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glycosides.
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0.5 RANGE OF TOXICITY
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A. The skin of one toad is sufficient to cause significant
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symptoms and even death in both animals and humans.
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Topic: TOAD TOXINS
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B. No toxic serum or blood levels have yet been established.
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1.0 SUBSTANCES INCLUDED
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1.1 THERAPEUTIC/TOXIC CLASS
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A. There are several types of toxic substances found in the
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venom of toads.
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1. CARDIOACTIVE SUBSTANCES: Bufagins (bufandienolides) are
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cardioactive substances found in toad venom. They have
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effects similar to the cardiac glycosides found in
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plants. Bufotoxins are the conjugation products of the
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specific bufagin with one molecule of suberylargine
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(Chen & Kovarikova, 1967). Bufotoxins were originally
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isolated from the parotoid glands of toads, but have
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since been seen in various plants and mushrooms
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(Siperstein et al, 1957; Lincoff & Mitchel, 1977; Kibmer
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& Wichtl, 1986).
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2. CATECHOLAMINES: There are also several catecholamines
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in toad venom. Epinephrine has been found in as high a
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concentration as 5% in the venom of several species.
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Norepinephrine has also been found (Chen & Kovarikova,
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1967).
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3. INDOLEALKYLAMINES: Chemicals found include several
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bufotenines. Bufotenines are organic bases containing
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an indole ring and have primarily oxytocic actions and
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often pressor actions (Palumbo et al, 1975). Specific
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substances include bufothionine, serotonin,
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cinobufotenine, bufotenine, and dehydrobufotenine (Chen
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& Kovarikova, 1967). Bufotenine is the 5-hydroxy
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derivative of N,N,dimethyltryptamine and is a
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hallucinogen (Gilman et al, 1985).
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4. NONCARDIAC STEROLS: The sterols found in toad venom
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include cholesterol, provitamin D, gamma sitosteral, and
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ergosterol. They do not appear to have a significant
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role in toxicity (Chen & Kovarikova, 1967; Palumbo et
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al, 1975).
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1.3 DESCRIPTION
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A. Toads known to contain toxins include:
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1. Bufo alvarius
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2. Bufo americanus
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3. Bufo arenarum
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4. Bufo asper
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5. Bufo blombergi
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6. Bufo bufo
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7. Bufo bufo gargarizans
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8. Bufo formosus
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9. Bufo fowerii
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10. Bufo marinus
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11. Bufo melanostictus
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12. Bufo peltocephalus
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13. Bufo quercicus
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14. Bufo regularis
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15. Bufo valliceps
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16. Bufo viridis
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1.4 GEOGRAPHICAL LOCATION
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A. Toads are found throughout the world, Bufo marinus having
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one of the widest distributions.
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Topic: TOAD TOXINS
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2.0 CLINICAL EFFECTS
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2.1 SUMMARY
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A. Poisoning by toad toxins is primarily a problem with
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animals and may be fatal (Perry & Bracegirdle, 1973).
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There have been fatalities in Hawaii, Phillipines, and
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Fiji occurring after eating the toads as food (Tyler,
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1976; Palumbo et al, 1975). The toxins are located in
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the skin and parotid glands and may be transferred by
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handling a toad. A toad that sits in a dog's watering
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dish for some time may leave enough toxin to make the pet
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ill (Smith, 1982). The toxicity varies considerably by
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the toad species and its geographic location. The death
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rate for untreated animals exposed to Bufo marinus is
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nearly 100% in Florida, is low in Texas, and only about
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5% in Hawaii (Palumbo et al, 1975).
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2.3 HEENT
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2.3.2 EYES
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A. IRRITATION: If the secretions of the toad parotid
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glands come in contact with human eyes, pain and severe
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irritation will result (Tyler, 1976; Smith, 1982).
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2.3.4 NOSE
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A. IRRITATION: Exposure of the nasal mucous membranes to
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the toad toxins may produce severe irritation (Chen &
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Kovarikova, 1967).
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2.3.5 THROAT
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A. The mouth and throat may become anesthetized if
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bufotoxins have been ingested (Chen & Kovarikova, 1967).
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2.4 CARDIOVASCULAR
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A. VENTRICULAR FIBRILLATION: Dogs intentionally poisoned
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with bufagins orally develop ventricular fibrillation and
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if untreated - death (Palumbo et al, 1975). The symptoms
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resemble digitalis poisoning.
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B. VASOCONSTRICTION: Bufagins constrict arterial blood
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vessels (Chen & Kovarikova, 1967). Bufotenine itself is
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not hallucinogenic, but acts as a pressor rather than a
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hallucinogen in humans (Kantoretal, 1980).
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2.5 RESPIRATORY
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A. DYSPNEA: Weakened respirations may be seen if toad
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toxins have been ingested (Smith, 1982).
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2.6 NEUROLOGIC
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A. PARALYSIS: Paraplegia has been noted in toad poisonings
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of dogs and cats. Incoordination and progressive
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paralysis may be earlier symptoms (Perry & Bracegirdle,
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1973; Smith, 1982).
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B. SEIZURES: Have been reported in poisoned dogs and a few
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cats (Palumbo et al, 1975; Chen & Kovarikova, 1967), as
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well as a 5-year-old boy (Hitt & Ettinger, 1986). Onset
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was within 5 minutes. The seizures continued unabated
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for 60 minutes.
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C. LOCAL ANESTHESIA: Many bufagins have local anesthetic
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actions, especially on the oral mucosa (Chen &
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Kovarikova, 1967).
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2.7 GASTROINTESTINAL
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A. SALIVATION: Intense salivation is usually seen in
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poisoned cats and dogs (Perry & Bracegirdle, 1973), and
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Topic: TOAD TOXINS
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was seen in one 5-year-old boy (Hitt & Ettinger, 1986).
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B. VOMITING: Is often present in animals (Perry &
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Bracegirdle, 1973).
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C. NUMBNESS: If ingested, the toxins cause numbness of the
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oral mucosa (Smith, 1982; Chen & Kovarikova, 1967).
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2.12 FLUID-ELECTROLYTE
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A. HYPERKALEMIA: Similar to that seen with digitalis
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poisoning, may be seen.
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2.13 TEMPERATURE REGULATION
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A. FEVER: Is a symptom common to ingestion of toads by cats
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and dogs (Perry & Bracegirdle, 1973).
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2.14 HEMATOLOGIC
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A. CYANOSIS: Has been seen in dogs (Hitt & Ettinger, 1986).
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2.15 DERMATOLOGIC
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A. PERSPIRATION: Although handling toads is generally not
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considered seriously injurious to humans, it is thought
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to dramatically reduce perspiration (Smith, 1982).
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2.18 PSYCHIATRIC
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A. HALLUCINATIONS: In 1971, drug users in Queensland were
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smoking the chopped skins of Bufo marinus for its
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hallucinogenic effect (Tyler 1976). Toad skin has been
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used for its hallucinogenic properties throughout the
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world (Emboden, 1979), but Bufo alvarins is the only Bufo
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species known to contain a hallucinogenic tryptamine
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(McKenna & Towers, 1984).
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3.0 LABORATORY
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3.2 MONITORING PARAMETERS/LEVELS
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3.2.1 SERUM/BLOOD
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A. No toxic levels have yet been established for any of the
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bufagins. Many of the other substances are metabolized
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rapidly, and laboratory analysis would be impractical.
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3.2.3 OTHER
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A. EKG: Patients who have had significant exposures should
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have a baseline EKG to observe for abnormalities.
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Symptomatic patients should continue to have EKGs
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performed.
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B. A serum potassium level should be drawn to test for
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hyperkalemia (Chen & Kovarikova, 1967).
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4.0 CASE REPORTS
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A. A typical animal case report involves a dog that finds a
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slow hopping toad and mouths the animal playfully. The
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animal usually experiences immediate salivation, and
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irritation of the mucus membranes of the mouth and
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throat. If the dog eats the toad, vomiting and paralysis
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may lead to seizures and death. Animals who recover
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usually do not have significant sequelae.
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B. Although human deaths have been reported in the lay
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literature, we were able to find only one case report of
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a human death or serious intoxication in the medical
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literature. This was a 5-year-old who had mouthed a Bufo
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alvarius (Colorado River Toad) and developed status
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epilepticus successfully treated with diazepam and
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phenobarbital (Hitt & Ettinger, 1986).
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5.0 TREATMENT
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5.1 LIFE SUPPORT
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Topic: TOAD TOXINS
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Support respiratory and cardiovascular function.
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5.2 SUMMARY
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A. There are 3 primary areas of toxicity. The first
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involves the cardiac glycoside-like effects of the
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bufagins; the second is the pressor effects of the
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catecholamines; and the third is the hallucinogenic
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effect of the indolealkylamines. After a toad had been
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ingested, it is difficult to evaluate which of these
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effects will predominate. Usually, the cardiovascular
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effects are the most prominent. The patient should be
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observed for arrhythmias and for hallucinations. There
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have been minimal human exposures, so clinical
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presentation and course are difficult to predict.
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5.3 ORAL/PARENTERAL EXPOSURE
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5.3.1 PREVENTION OF ABSORPTION
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A. EMESIS
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1. Emesis may be indicated in substantial recent
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ingestions unless the patient is obtunded, comatose or
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convulsing or is at risk of doing so based on
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ingestant. Emesis is most effective if initiated
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within 30 minutes of ingestion. Dose of ipecac syrup:
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ADULT OR CHILD OVER 90 TO 100 POUNDS (40 to 45
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kilograms): 30 milliliters; CHILD 1 TO 12 YEARS: 15
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milliliters; CHILD 6 TO 12 MONTHS (consider
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administration in a health care facility): 5 to 10
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milliliters. After the dose is given, encourage clear
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fluids, 6 to 8 ounces in adults and 4 to 6 ounces in a
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child. The dose may be repeated once if emesis does
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not occur within 30 minutes.
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2. If emesis is unsuccessful following 2 doses of ipecac,
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the decision to lavage or otherwise attempt to
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decontaminate the gut should be made on an individual
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basis. This amount of ipecac poses little toxicity of
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itself.
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3. Refer to the IPECAC/TREATMENT management for further
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information on administration and adverse reactions.
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B. MULTIPLE DOSE ACTIVATED CHARCOAL/CATHARTIC
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1. Cardiac glycosides and bufandienolides are adsorbed to
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activated charcoal and enterohepatic circulation may be
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decreased by multiple-dose activated charcoal (Balz &
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Bader, 1974).
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2. Repeated oral charcoal dose (every 2 to 6 hours) may
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enhance total body clearance and elimination. A saline
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cathartic or sorbitol may be given with the first
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charcoal dose and repeated until charcoal appears in
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the stools. Do not repeat charcoal if bowel sounds
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absent.
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3. Administer charcoal as slurry. The FDA suggests a
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minimum of 240 milliliters of diluent per 30 grams
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charcoal (Dose: Optimum dose of charcoal is not
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established; usual INITIAL dose is 30 to 100 grams in
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adults and 15 to 30 grams in children; some suggest
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using 1 to 2 grams per kilogram as a rough guideline,
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particularly in infants). REPEAT doses have ranged
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from 20 to 50 grams in adults. Doses in children have
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Topic: TOAD TOXINS
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not been established, but one-half the initial dose is
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recommended.
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4. Administer a saline cathartic or sorbitol, with the
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INITIAL charcoal dose, mixed with charcoal or
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administered separately. Dose:
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a. Magnesium or sodium sulfate (ADULT: 20 to 30 grams
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per dose; CHILD: 250 milligrams per kilogram per
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dose) OR magnesium citrate (ADULT AND CHILD: 4
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milliliters per kilogram per dose up to 300
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milliliters per dose).
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b. Sorbitol (ADULT: 1 to 2 grams per kilogram per dose
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to a maximum of 150 grams per dose; CHILD: (over 1
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year of age): 1 to 1.5 grams per kilogram per dose
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as a 35 percent solution to a maximum of 50 grams
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per dose). Consider administration in a health care
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facility, monitoring fluid-electrolyte status,
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especially in children.
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5. When used with multiple-dose charcoal regimens, the
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safety of repeated cathartics has not been established.
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Hypermagnesemia has been reported after repeated
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administration of magnesium containing cathartics in
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overdose patients with normal renal function. In young
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children, cathartics should be repeated no more than 1
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to 2 times per day. Administration of cathartics
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should be stopped when a charcoal stool appears.
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Cathartics should be used with extreme caution in
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patients who have an ileus or absent bowel sounds.
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Saline cathartics should be used with caution in
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patients with impaired renal function.
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6. Refer to the ACTIVATED CHARCOAL/TREATMENT management
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for further information on administration and adverse
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reactions.
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C. One of the best first aid measures to prevent toxicity
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in animals is to immediately flush the oral mucous
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membranes of dogs, cats, and even people who have had
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mucous membrane exposure to decrease absorption. Do not
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swallow the rinse water.
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5.3.2 TREATMENT
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A. CARDIAC EFFECTS
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1. MONITOR EKG CONTINUOUSLY: For abnormal cardiac rates
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and rhythms. In patients with previously healthy
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hearts, the most common manifestation is bradycardia
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with or without varying degrees of AV block. Peaked T
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waves, depressed ST segments, widened QRS, and
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prolonged PR interval may also be noted.
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2. HYPERKALEMIA: Hyperkalemia following acute overdose
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may be life-threatening. The emergency management of
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life-threatening hyperkalemia (potassium levels greater
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than 6.5 mEq/L) includes the intravenous administration
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of bicarbonate, glucose, and insulin. DOSE:
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Administer 0.2 units/kg of regular insulin with 200 to
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400 mg/kg glucose (IV dextrose 25% in water).
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Concurrent administration of IV sodium bicarbonate
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(approximately 1.0 mEq/kg up to 44 mEq per dose in an
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adult) may be of additive value in rapidly lowering
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Topic: TOAD TOXINS
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serum potassium levels. Monitor the EKG while
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administering the glucose, insulin, and sodium
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bicarbonate. This therapy should lower the serum
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potassium level for up to 12 hours.
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3. ATROPINE: Atropine is useful in the management of
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bradycardia, varying degrees of heart block and other
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cardiac irregularities due to the digitalis-like
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induced effects of enhanced vagal tone on the SA node
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rhythmicity and on conduction through the AV node.
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DOSE: Adult: 0.6 mg per dose IV; Child: 10 to 30
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mcg/kg per dose up to 0.4 mg per dose (may be repeated
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as needed to achieve desired effects). Monitor EKG
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carefully while administering atropine.
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4. PHENYTOIN: Phenytoin is useful in the management of
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digitalis-like induced ventricular dysrhythmias and
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improves conduction through the AV node. Low dose
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phenytoin (Adult: 25 mg per dose IV at 1 to 2 hour
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intervals; Child: 0.5 to 1.0 mg/kg per dose IV at 1 to
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2 hour intervals) appears to improve AV conduction.
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Larger doses are needed for the management of
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ventricular dysrhythmias: Loading Dose for adults and
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children: Administer 15 mg/kg up to 1.0 gram IV not to
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exceed a rate of 0.5 mg/kg per minute. Maintenance
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Dose: Adults - administer 2 mg/kg IV every 12 hours as
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needed; Child - administer 2 mg/kg every 8 hours as
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needed. Monitor serum phenytoin levels just prior to
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initiating and during maintenance therapy to assure
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therapeutic levels of 10 to 20 mcg/ml (39.64 to 79.28
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nmol/L). Monitor EKG carefully.
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5. LIDOCAINE
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a. Lidocaine is useful in the management of ventricular
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tachyarrhythmias, PVC's, and bigeminy. Lidocaine does
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not improve conduction through the AV node.
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b. ADULT: BOLUS: 50 to 100 milligrams (0.70 to 1.4
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milligrams per kilogram) under EKG monitoring. Rate:
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25 to 50 milligrams per minute (0.35 to 0.70
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milligrams per kilogram per minute). A second bolus
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may be injected in 5 minutes if desired response is
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not obtained. No more than 200 to 300 milligrams
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should be administered during a one hour period.
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INFUSION: Following a bolus, an infusion at 1 to 4
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milligrams per minute (0.014 to 0.057 milligram per
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kilogram per minute) may be used. PEDIATRIC: BOLUS:
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1 milligram per kilogram. INFUSION: 3 micrograms per
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kilogram per minute.
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6. TRANSVENOUS PACEMAKER: Insertion of a transvenous
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pacemaker should be considered in those patients with
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severe bradycardia and/or slow ventricular rate due to
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second degree AV block who fail to respond to atropine
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and/or phenytoin drug therapy.
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7. FAB FRAGMENTS: Have not been documented to be of any
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value in the treatment of bufagins. Cross reactivity
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has not been proven.
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8. CHOLESTYRAMINE: Digitoxin (and theoretically bufagins)
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elimination appears to be enhanced by the serial
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Topic: TOAD TOXINS
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|
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administration of cholestyramine, 4 grams orally every
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6 hours. Cholestyramine appears to have minimal effect
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on absorption and excretion of cardiac glycosides in
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man.
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9. One 5-year-old boy did well on high-dose hydrocortisone
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sodium succinate and phenobarbital (Hitt & Ettinger,
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1986).
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B. ANIMALS (ESPECIALLY DOGS) (Palumbo et al, 1975):
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1. ATROPINE: May be used to decrease secretions and block
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vagal effects. It is not a specific antidote.
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2. ANTIHISTAMINES OR CORTICOSTEROIDS: May reduce the
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effects of bufotoxins on the mucous membranes of the
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mouth and other organs, but have little direct action.
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3. PENTOBARBITAL-INDUCED ANESTHESIA: Does increase canine
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tolerance to toad venom intoxication.
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4. PROPRANOLOL: Has been tried on canines, with some
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success. The dose used was high: 5 mg/kg.
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5.3.3 ENHANCED ELIMINATION
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A. MULTIPLE DOSE ACTIVATED CHARCOAL: May be of some use.
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It has been used after IV administration of methyl
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proscillaridin (Belz & Bader, 1974).
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B. HEMODIALYSIS: Has been ineffective in removing cardiac
|
||
glycosides but may assist in restoring potassium to
|
||
normal levels. It has yet to be tried on bufagins.
|
||
5.6 DERMAL EXPOSURE
|
||
5.6.1 DECONTAMINATION
|
||
A. Wash exposed area extremely thoroughly with soap and
|
||
water. A physician may need to examine the area if
|
||
irritation or pain persists after washing.
|
||
5.6.2 TREATMENT
|
||
A. Effects may be seen after dermal exposure. Treatment
|
||
should be as appropriate under the oral treatment
|
||
section.
|
||
6.0 RANGE OF TOXICITY
|
||
6.2 MINIMUM LETHAL EXPOSURE
|
||
A. The skin of one toad is sufficient to cause significant
|
||
symptoms and even death in both animals and humans.
|
||
6.4 TOXIC SERUM/BLOOD CONCENTRATIONS
|
||
A. No toxic serum or blood levels have yet been established.
|
||
6.6 LD50/LC50
|
||
A. TABLE I - BUFAGIN LETHAL DOSES IN CATS
|
||
NAME Mean (Geo.)
|
||
LD,, mg/kg
|
||
Arenobufagin 0.08
|
||
Bufotalin 0.13
|
||
Desacetylbufotalin 0.26
|
||
Cinobufagin 0.20
|
||
Acetylcinobufagin 0.59
|
||
Desacetylcinobufagin inactive
|
||
Cinobufotalin 0.20
|
||
Acetylcinobufotalin 0.18
|
||
Desactylcinobufotalin inactive
|
||
Marinobufagin 1.49
|
||
Acetylmarinobufagin 0.95
|
||
12Beta-Hydroxymarinobufagin 3.00
|
||
Topic: TOAD TOXINS
|
||
|
||
Bufotalidin (hellebrigenin) 0.08
|
||
Acetylbufotalidin 0.06
|
||
Resibufogenin inactive
|
||
Acetylresibufogenin inactive
|
||
12Beta-Hydroxyresibufogenin 4.16
|
||
Bufalin 0.14
|
||
Telocinobufagin 0.10
|
||
Bufotalinin 0.62
|
||
Artebufogenin inactive
|
||
Gamabufotalin 0.10
|
||
Vallicepobufagin 0.20
|
||
Quercicobufagin 0.10
|
||
Viridobufagin 0.11
|
||
Regularobufagin 0.15
|
||
Fowlerobufagin 0.22
|
||
B. TABLE II BUFOTOXIN LETHAL DOSES IN CATS
|
||
NAME Mean (Geo.)
|
||
LD, mg/kg
|
||
Viridobufotoxin 0.27
|
||
Vulgarobufotoxin 0.29
|
||
Cinobufotoxin 0.36
|
||
Gamabufotoxin 0.37
|
||
Arenobufotoxin 0.41
|
||
Marinobufotoxin 0.42
|
||
Regularobufotoxin 0.48
|
||
Alvarobufotoxin 0.76
|
||
Fowlerobufotoxin 0.79
|
||
C. REFERENCE: (Chen & Kovarikova, 1967).
|
||
6.8 OTHER
|
||
A. The structure of the cardioactive bufadienolides leads to
|
||
greater potency than the corresponding plant glycosides
|
||
thus the cardenolides of plants - digitoxigenin,
|
||
periplogenin, oleandrigenin, sarmentogenin, and
|
||
strophanthidin, corresponding to bufalin,
|
||
telocinobufagin, bufotalin, gamabufotalin, and
|
||
bufotalidin - have lower toxicities.
|
||
B. The toxicity of the cardioactive bufotoxins is lower than
|
||
those of the corresponding bufagins (bufadienolides)
|
||
(Chen & Kovarikova, 1967).
|
||
C. The skin of Bufo alvarius contains 5-methoxy-N,N-
|
||
dimethyltryptamine (5-MeO-DMT) at a concentration of 50
|
||
to 160 mg/g of skin (Daly & Witkop, 1971).
|
||
7.0 AVAILABLE FORMS/SOURCES
|
||
A. BUFOTOXINS: Is the name of a collection of compounds
|
||
found in the toad venom which may be secreted into toad
|
||
skin or found in 2 glands behind the eyes, called parotid
|
||
glands (Tyler, 1976). Bufotoxins may also be
|
||
specificially applied to the conjugates of a bufagin with
|
||
suberylargine.
|
||
B. Before digitalis was extracted from Digitalis purpura,
|
||
dried and powdered toad skins were used as a cardiac
|
||
medication (Burton, 1977). Other "folk" uses include
|
||
expectorant, diuretic, and remedy for toothaches,
|
||
sinusitis, and hemorrhage of the gums.
|
||
C. Toad skins have also been used for their hallucinogenic
|
||
Topic: TOAD TOXINS
|
||
|
||
effect (Emboden, 1979).
|
||
8.0 KINETICS
|
||
8.1 ABSORPTION
|
||
A. The oral absorption of the bufagins and bufotoxins is
|
||
generally poor. Less than 15% of cinobufagin is absorbed
|
||
orally in rats.
|
||
B. Other components of toad venom are rapidly absorbed via
|
||
mucous membranes and cause immediate symptoms in animals
|
||
(Smith, 1982).
|
||
8.4 EXCRETION
|
||
8.4.3 BILE
|
||
A. Little could be found concerning the excretion of these
|
||
compounds; similar cardenolides and substances such as
|
||
proscillaridin are excreted largely in the bile (Belz &
|
||
Bader, 1974).
|
||
9.0 PHARMACOLOGY/TOXICOLOGY
|
||
9.1 PHARMACOLOGIC MECHANISM
|
||
A. Most bufandienolides are cardiotonic sterols synthesized
|
||
by toads from cholesterol (Siperstein, 1957). The
|
||
lactone ring is 6-membered of an alpha pyrone type
|
||
attached to C17. They have a secondary hydroxy group at
|
||
C3 and are called bufagins - which corresponds to the
|
||
aglycones found in the cardiac glycosides in plants.
|
||
None of these bufandienolides conjugates with a
|
||
carbohydrate (as do the plants) to form glycosides, but
|
||
some do form bufotoxins by combining with suberylargine
|
||
(Chen & Kovarikova, 1967).
|
||
B. In the toad, some of these compounds (eg, resibufogenin)
|
||
are ouabain-like and increase the force of contraction of
|
||
heart muscle (Lichtstein et al, 1986).
|
||
C. The pharmacology of the catecholamines found in toad
|
||
venom is well known and need not be discussed here.
|
||
D. INDOLEALKYLAMINES: Pharmacology is also known. Besides
|
||
having some hallucinogenic effects, these compounds may
|
||
stimulate uterine and intestinal muscle (Chen &
|
||
Kovarikova, 1961).
|
||
9.2 TOXICOLOGIC MECHANISM
|
||
A. Bufagins and bufotoxins have been shown to inhibit
|
||
sodium, potassium, ATPase activity (Lichtstein et al,
|
||
1986). Their action is almost the same as that of the
|
||
digitalis glycosides (Palumbo et al, 1975).
|
||
12.0 REFERENCES
|
||
12.1 GENERAL REFERENCES
|
||
1. Belz GG & Bader H: Effect of oral charcoal on plasma
|
||
levels of intravenous methyl proscillaridin. Klin
|
||
Wochenschr 1974; 52:1134-1135.
|
||
2. Burton R: Venomous Animals: Colour Library International
|
||
Ltd. London, 1977.
|
||
3. Chen KK & Kovarikova A: Pharmacology and toxicology of
|
||
toad venom. J Pharm Sci 1967; 56:1535-1541.
|
||
4. Daly JW & Witkop B: Chemistry and pharmacology of frog
|
||
venoms. In: Bucherl W & Buckly EE (eds). Venomous
|
||
Animals and Their Venoms, vol 2, Academic Press, New York,
|
||
1971.
|
||
5. Emboden W: Narcotic Plants. MacMillan Publishing Company,
|
||
Topic: TOAD TOXINS
|
||
|
||
Inc, 1979.
|
||
6. Gilman AG, Goodman LS, Rall TW et al: The Pharmacological
|
||
Basis of Therapeutics, 7th ed. MacMillan Publishing
|
||
Company, 1985.
|
||
7. Gould L, Solomon F, Cherbakoff A et al: Clinical studies
|
||
on proscillaridin, a new squill glycoside. J Clin
|
||
Pharmacol 1971; 11:135-145.
|
||
8. Hitt M & Ettinger DD: Toad toxicity. N Engl J Med 1986;
|
||
314:1517.
|
||
9. Kantor RE, Dudlettes SD & Shulgin AT: 5-Methoxy-a-methyl-
|
||
tryptamine (a, O-dimethylserotonin), a hallucinogenic
|
||
homolog of serotonin. Biological Psychiatry 1980;
|
||
15:349-352.
|
||
10. Kibmer B & Wichtl M: Bufadienolide aus samen von
|
||
helleborus odorus. Planta Med 1986; 2:77-162.
|
||
11. Lichtstein P, Kachalsky S & Deutsch J: Identification of
|
||
a ouabain-like compound in toad skin and plasma as a
|
||
bufodienolide derivative. Life Sci 1986; 38:1261-1270.
|
||
12. Lincoff G & Mitchel DH: Toxic and Hallucinogenic Mushroom
|
||
Poisoning. Van Nostrand Reinhold Company, Dallas, 1977.
|
||
13. McKenna DJ & Towers GH: Biochemistry and pharmacology of
|
||
tryptamines and beta-carbolines, a minireview. J
|
||
Psychoactive Drugs 1984; 16:347-358.
|
||
14. Palumbo NE, Perri S & Read G: Experimental induction and
|
||
treatment of toad poisoning in the dog. J Am Vet Med
|
||
Assoc 1975; 167:1000-1005.
|
||
15. Perry BD & Bracegirdle JR: Toad poisoning in small
|
||
animals. Vet Rec 1973; 92:589-590.
|
||
16. Siperstein MD, Murray AW & Titus E: Biosynthesis of
|
||
cardiotonic sterols from cholesterol in the toad Bufo
|
||
marinus. Arch Biochem Biophys 1957; 67:154-160.
|
||
17. Smith RL: Venomous Animals of Arizona. Cooperative
|
||
Extension Service, College of Agriculture, Univ AZ,
|
||
Tucson, 1982.
|
||
18. Tyler MJ: Frogs. William Collins Ltd, Sydney, 1976.
|
||
13.0 AUTHOR INFORMATION
|
||
A. Written by: David G. Spoerke, M.S., RPh., 06/86
|
||
B. Reviewed by: Ken Kulig, M.D., 06/86
|
||
C. Specialty Board: Biologicals
|
||
D. In addition to standard revisions of this management
|
||
certain portions were updated with recent literature:
|
||
11/86.
|
||
|