Toad Toxins

 Topic: TOAD TOXINS

0.0  OVERVIEW

 0.1  LIFE SUPPORT

This overview assumes that basic life support measures

have been instituted.

 0.2  CLINICAL EFFECTS

  0.2.1  SUMMARY

    A. There are several types of toxic substances found in

toads, including cardioactive agents, catecholamines,

indolealkylamines and non-cardiac sterols.  These toxins

are located in the skin and parotid glands and may be

transferred by handling or ingesting a toad's skin.

  0.2.3  HEENT

    A. Secretions of the toad parotid glands will cause pain

and severe irritation when placed in eyes, nose, and

throat.

  0.2.4  CARDIOVASCULAR

    A. Dogs who have been poisoned with bufagins develop

ventricular fibrillation and symptoms resembling

digitalis poisoning.  Vasoconstriction may also be seen.

  0.2.5  RESPIRATORY

    A. Dyspnea and weakened respirations may be seen.

  0.2.6  NEUROLOGIC

    A. Paralysis and seizures have been reported in both humans

and animals.  Many bufagins have local anesthetic

actions, especially on the oral mucosa.

  0.2.7  GASTROINTESTINAL

    A. Salivation and vomiting were often seen in animals.

These toxins may cause numbness of the oral mucosa if

ingested.

  0.2.14  HEMATOLOGIC

    A. Cyanosis has been seen in poisoned dogs.

  0.2.18  PSYCHIATRIC

    A. HALLUCINATIONS:  Drug users have been known to smoke the

chopped skins of toads for their hallucinogenic effect.

 0.3  LABORATORY

   A. No toxic levels have yet been established for any of the

bufagins.  Since many of the other substances are

metabolized rapidly, laboratory analysis is impractical.

 0.4  TREATMENT OVERVIEW

  0.4.1  SUMMARY

    A. There are three primary areas of toxicity, the first

involving cardiac glycoside effects, the second, the

pressor effects, and the third, the hallucinogenic

effects.  Usually the cardiovascular effects are the

most prominent.  Treatment is directed at prevention of

absorption, and monitoring for EKG effects and

hyperkalemia.  Lidocaine, a transvenous pacemaker, and

cholestyramine have all been used to treat digitalis-

like poisonings.  FAB fragments have not been reported

to be of use in toad poisoning.

    B. Hemodialysis has been ineffective in removing cardiac

glycosides.

 0.5  RANGE OF TOXICITY

   A. The skin of one toad is sufficient to cause significant

symptoms and even death in both animals and humans.

Topic: TOAD TOXINS

   B. No toxic serum or blood levels have yet been established.

1.0  SUBSTANCES INCLUDED

 1.1  THERAPEUTIC/TOXIC CLASS

   A. There are several types of toxic substances found in the

venom of toads.

    1. CARDIOACTIVE SUBSTANCES:  Bufagins (bufandienolides) are

cardioactive substances found in toad venom.  They have

effects similar to the cardiac glycosides found in

plants.  Bufotoxins are the conjugation products of the

specific bufagin with one molecule of suberylargine

(Chen & Kovarikova, 1967).  Bufotoxins were originally

isolated from the parotoid glands of toads, but have

since been seen in various plants and mushrooms

(Siperstein et al, 1957; Lincoff & Mitchel, 1977; Kibmer

& Wichtl, 1986).

    2. CATECHOLAMINES:  There are also several catecholamines

in toad venom.  Epinephrine has been found in as high a

concentration as 5% in the venom of several species.

Norepinephrine has also been found (Chen & Kovarikova,

1967).

    3. INDOLEALKYLAMINES:  Chemicals found include several

bufotenines.  Bufotenines are organic bases containing

an indole ring and have primarily oxytocic actions and

often pressor actions (Palumbo et al, 1975).  Specific

substances include bufothionine, serotonin,

cinobufotenine, bufotenine, and dehydrobufotenine (Chen

& Kovarikova, 1967).  Bufotenine is the 5-hydroxy

derivative of N,N,dimethyltryptamine and is a

hallucinogen (Gilman et al, 1985).

    4. NONCARDIAC STEROLS:  The sterols found in toad venom

include cholesterol, provitamin D, gamma sitosteral, and

ergosterol.  They do not appear to have a significant

role in toxicity (Chen & Kovarikova, 1967; Palumbo et

al, 1975).

 1.3  DESCRIPTION

   A. Toads known to contain toxins include:

1.  Bufo alvarius

2.  Bufo americanus

3.  Bufo arenarum

4.  Bufo asper

5.  Bufo blombergi

6.  Bufo bufo

7.  Bufo bufo gargarizans

8.  Bufo formosus

9.  Bufo fowerii

10. Bufo marinus

11. Bufo melanostictus

12. Bufo peltocephalus

13. Bufo quercicus

14. Bufo regularis

15. Bufo valliceps

16. Bufo viridis

 1.4  GEOGRAPHICAL LOCATION

   A. Toads are found throughout the world, Bufo marinus having

one of the widest distributions.

Topic: TOAD TOXINS

2.0  CLINICAL EFFECTS

 2.1  SUMMARY

   A. Poisoning by toad toxins is primarily a problem with

animals and may be fatal (Perry & Bracegirdle, 1973).

There have been fatalities in Hawaii, Phillipines, and

Fiji occurring after eating the toads as food (Tyler,

1976; Palumbo et al, 1975).  The toxins are located in

the skin and parotid glands and may be transferred by

handling a toad.  A toad that sits in a dog's watering

dish for some time may leave enough toxin to make the pet

ill (Smith, 1982).  The toxicity varies considerably by

the toad species and its geographic location.  The death

rate for untreated animals exposed to Bufo marinus is

nearly 100% in Florida, is low in Texas, and only about

5% in Hawaii (Palumbo et al, 1975).

 2.3  HEENT

  2.3.2  EYES

    A. IRRITATION:  If the secretions of the toad parotid

glands come in contact with human eyes, pain and severe

irritation will result (Tyler, 1976; Smith, 1982).

  2.3.4  NOSE

    A. IRRITATION:  Exposure of the nasal mucous membranes to

the toad toxins may produce severe irritation (Chen &

Kovarikova, 1967).

  2.3.5  THROAT

    A. The mouth and throat may become anesthetized if

bufotoxins have been ingested (Chen & Kovarikova, 1967).

 2.4  CARDIOVASCULAR

   A. VENTRICULAR FIBRILLATION:  Dogs intentionally poisoned

with bufagins orally develop ventricular fibrillation and

if untreated - death (Palumbo et al, 1975).  The symptoms

resemble digitalis poisoning.

   B. VASOCONSTRICTION:  Bufagins constrict arterial blood

vessels (Chen & Kovarikova, 1967).  Bufotenine itself is

not hallucinogenic, but acts as a pressor rather than a

hallucinogen in humans (Kantoretal, 1980).

 2.5  RESPIRATORY

   A. DYSPNEA:  Weakened respirations may be seen if toad

toxins have been ingested (Smith, 1982).

 2.6  NEUROLOGIC

   A. PARALYSIS:  Paraplegia has been noted in toad poisonings

of dogs and cats.  Incoordination and progressive

paralysis may be earlier symptoms (Perry & Bracegirdle,

1973; Smith, 1982).

   B. SEIZURES:  Have been reported in poisoned dogs and a few

cats (Palumbo et al, 1975; Chen & Kovarikova, 1967), as

well as a 5-year-old boy (Hitt & Ettinger, 1986).  Onset

was within 5 minutes.  The seizures continued unabated

for 60 minutes.

   C. LOCAL ANESTHESIA:  Many bufagins have local anesthetic

actions, especially on the oral mucosa (Chen &

Kovarikova, 1967).

 2.7  GASTROINTESTINAL

   A. SALIVATION:  Intense salivation is usually seen in

poisoned cats and dogs (Perry & Bracegirdle, 1973), and

Topic: TOAD TOXINS

was seen in one 5-year-old boy (Hitt & Ettinger, 1986).

   B. VOMITING:  Is often present in animals (Perry &

Bracegirdle, 1973).

   C. NUMBNESS:  If ingested, the toxins cause numbness of the

oral mucosa (Smith, 1982; Chen & Kovarikova, 1967).

 2.12  FLUID-ELECTROLYTE

   A. HYPERKALEMIA:  Similar to that seen with digitalis

poisoning, may be seen.

 2.13  TEMPERATURE REGULATION

   A. FEVER:  Is a symptom common to ingestion of toads by cats

and dogs (Perry & Bracegirdle, 1973).

 2.14  HEMATOLOGIC

   A. CYANOSIS:  Has been seen in dogs (Hitt & Ettinger, 1986).

 2.15  DERMATOLOGIC

   A. PERSPIRATION:  Although handling toads is generally not

considered seriously injurious to humans, it is thought

to dramatically reduce perspiration (Smith, 1982).

 2.18  PSYCHIATRIC

   A. HALLUCINATIONS:  In 1971, drug users in Queensland were

smoking the chopped skins of Bufo marinus for its

hallucinogenic effect (Tyler 1976).  Toad skin has been

used for its hallucinogenic properties throughout the

world (Emboden, 1979), but Bufo alvarins is the only Bufo

species known to contain a hallucinogenic tryptamine

(McKenna & Towers, 1984).

3.0  LABORATORY

 3.2  MONITORING PARAMETERS/LEVELS

  3.2.1  SERUM/BLOOD

    A. No toxic levels have yet been established for any of the

bufagins.  Many of the other substances are metabolized

rapidly, and laboratory analysis would be impractical.

  3.2.3  OTHER

    A. EKG:  Patients who have had significant exposures should

have a baseline EKG to observe for abnormalities.

Symptomatic patients should continue to have EKGs

performed.

    B. A serum potassium level should be drawn to test for

hyperkalemia (Chen & Kovarikova, 1967).

4.0  CASE REPORTS

   A. A typical animal case report involves a dog that finds a

slow hopping toad and mouths the animal playfully.  The

animal usually experiences immediate salivation, and

irritation of the mucus membranes of the mouth and

throat.  If the dog eats the toad, vomiting and paralysis

may lead to seizures and death.  Animals who recover

usually do not have significant sequelae.

   B. Although human deaths have been reported in the lay

literature, we were able to find only one case report of

a human death or serious intoxication in the medical

literature.  This was a 5-year-old who had mouthed a Bufo

alvarius (Colorado River Toad) and developed status

epilepticus successfully treated with diazepam and

phenobarbital (Hitt & Ettinger, 1986).

5.0  TREATMENT

 5.1  LIFE SUPPORT

Topic: TOAD TOXINS

      Support respiratory and cardiovascular function.

 5.2  SUMMARY

   A. There are 3 primary areas of toxicity.  The first

involves the cardiac glycoside-like effects of the

bufagins; the second is the pressor effects of the

catecholamines; and the third is the hallucinogenic

effect of the indolealkylamines.  After a toad had been

ingested, it is difficult to evaluate which of these

effects will predominate.  Usually, the cardiovascular

effects are the most prominent.  The patient should be

observed for arrhythmias and for hallucinations.  There

have been minimal human exposures, so clinical

presentation and course are difficult to predict.

 5.3  ORAL/PARENTERAL EXPOSURE

  5.3.1  PREVENTION OF ABSORPTION

    A. EMESIS

    1. Emesis may be indicated in substantial recent

ingestions unless the patient is obtunded, comatose or

convulsing or is at risk of doing so based on

ingestant.  Emesis is most effective if initiated

within 30 minutes of ingestion.  Dose of ipecac syrup:

ADULT OR CHILD OVER 90 TO 100 POUNDS (40 to 45

kilograms):  30 milliliters; CHILD 1 TO 12 YEARS:  15

milliliters; CHILD 6 TO 12 MONTHS (consider

administration in a health care facility): 5 to 10

milliliters.  After the dose is given, encourage clear

fluids, 6 to 8 ounces in adults and 4 to 6 ounces in a

child.  The dose may be repeated once if emesis does

not occur within 30 minutes.

    2. If emesis is unsuccessful following 2 doses of ipecac,

the decision to lavage or otherwise attempt to

decontaminate the gut should be made on an individual

basis.  This amount of ipecac poses little toxicity of

itself.

    3. Refer to the IPECAC/TREATMENT management for further

information on administration and adverse reactions.

    B. MULTIPLE DOSE ACTIVATED CHARCOAL/CATHARTIC

    1. Cardiac glycosides and bufandienolides are adsorbed to

activated charcoal and enterohepatic circulation may be

decreased by multiple-dose activated charcoal (Balz &

Bader, 1974).

    2. Repeated oral charcoal dose (every 2 to 6 hours) may

enhance total body clearance and elimination.  A saline

cathartic or sorbitol may be given with the first

charcoal dose and repeated until charcoal appears in

the stools.  Do not repeat charcoal if bowel sounds

absent.

    3. Administer charcoal as slurry.  The FDA suggests a

minimum of 240 milliliters of diluent per 30 grams

charcoal (Dose: Optimum dose of charcoal is not

established; usual INITIAL dose is 30 to 100 grams in

adults and 15 to 30 grams in children; some suggest

using 1 to 2 grams per kilogram as a rough guideline,

particularly in infants).  REPEAT doses have ranged

from 20 to 50 grams in adults.  Doses in children have

Topic: TOAD TOXINS

not been established, but one-half the initial dose is

recommended.

    4. Administer a saline cathartic or sorbitol, with the

INITIAL charcoal dose, mixed with charcoal or

administered separately.  Dose:

a.  Magnesium or sodium sulfate (ADULT:  20 to 30 grams

    per dose; CHILD: 250 milligrams per kilogram per

    dose) OR magnesium citrate (ADULT AND CHILD:  4

    milliliters per kilogram per dose up to 300

    milliliters per dose).

b.  Sorbitol (ADULT: 1 to 2 grams per kilogram per dose

    to a maximum of 150 grams per dose; CHILD: (over 1

    year of age):  1 to 1.5 grams per kilogram per dose

    as a 35 percent solution to a maximum of 50 grams

    per dose).  Consider administration in a health care

    facility, monitoring fluid-electrolyte status,

    especially in children.

    5. When used with multiple-dose charcoal regimens, the

safety of repeated cathartics has not been established.

Hypermagnesemia has been reported after repeated

administration of magnesium containing cathartics in

overdose patients with normal renal function.  In young

children, cathartics should be repeated no more than 1

to 2 times per day.  Administration of cathartics

should be stopped when a charcoal stool appears.

Cathartics should be used with extreme caution in

patients who have an ileus or absent bowel sounds.

Saline cathartics should be used with caution in

patients with impaired renal function.

    6. Refer to the ACTIVATED CHARCOAL/TREATMENT management

for further information on administration and adverse

reactions.

    C. One of the best first aid measures to prevent toxicity

in animals is to immediately flush the oral mucous

membranes of dogs, cats, and even people who have had

mucous membrane exposure to decrease absorption.  Do not

swallow the rinse water.

  5.3.2  TREATMENT

    A. CARDIAC EFFECTS

    1. MONITOR EKG CONTINUOUSLY:  For abnormal cardiac rates

and rhythms.  In patients with previously healthy

hearts, the most common manifestation is bradycardia

with or without varying degrees of AV block.  Peaked T

waves, depressed ST segments, widened QRS, and

prolonged PR interval may also be noted.

    2. HYPERKALEMIA:  Hyperkalemia following acute overdose

may be life-threatening.  The emergency management of

life-threatening hyperkalemia (potassium levels greater

than 6.5 mEq/L) includes the intravenous administration

of bicarbonate, glucose, and insulin.  DOSE:

Administer 0.2 units/kg of regular insulin with 200 to

400 mg/kg glucose (IV dextrose 25% in water).

Concurrent administration of IV sodium bicarbonate

(approximately 1.0 mEq/kg up to 44 mEq per dose in an

adult) may be of additive value in rapidly lowering

Topic: TOAD TOXINS

serum potassium levels.  Monitor the EKG while

administering the glucose, insulin, and sodium

bicarbonate.  This therapy should lower the serum

potassium level for up to 12 hours.

    3. ATROPINE:  Atropine is useful in the management of

bradycardia, varying degrees of heart block and other

cardiac irregularities due to the digitalis-like

induced effects of enhanced vagal tone on the SA node

rhythmicity and on conduction through the AV node.

DOSE:  Adult:  0.6 mg per dose IV; Child:  10 to 30

mcg/kg per dose up to 0.4 mg per dose (may be repeated

as needed to achieve desired effects).  Monitor EKG

carefully while administering atropine.

    4. PHENYTOIN:  Phenytoin is useful in the management of

digitalis-like induced ventricular dysrhythmias and

improves conduction through the AV node.  Low dose

phenytoin (Adult:  25 mg per dose IV at 1 to 2 hour

intervals; Child:  0.5 to 1.0 mg/kg per dose IV at 1 to

2 hour intervals) appears to improve AV conduction.

Larger doses are needed for the management of

ventricular dysrhythmias:  Loading Dose for adults and

children:  Administer 15 mg/kg up to 1.0 gram IV not to

exceed a rate of 0.5 mg/kg per minute.  Maintenance

Dose:  Adults - administer 2 mg/kg IV every 12 hours as

needed; Child - administer 2 mg/kg every 8 hours as

needed.  Monitor serum phenytoin levels just prior to

initiating and during maintenance therapy to assure

therapeutic levels of 10 to 20 mcg/ml (39.64 to 79.28

nmol/L).  Monitor EKG carefully.

    5. LIDOCAINE

      a.  Lidocaine is useful in the management of ventricular

  tachyarrhythmias, PVC's, and bigeminy.  Lidocaine does

  not improve conduction through the AV node.

      b.  ADULT:  BOLUS: 50 to 100 milligrams (0.70 to 1.4

  milligrams per kilogram) under EKG monitoring.  Rate:

  25 to 50 milligrams per minute (0.35 to 0.70

  milligrams per kilogram per minute).  A second bolus

  may be injected in 5 minutes if desired response is

  not obtained.  No more than 200 to 300 milligrams

  should be administered during a one hour period.

  INFUSION: Following a bolus, an infusion at 1 to 4

  milligrams per minute (0.014 to 0.057 milligram per

  kilogram per minute) may be used.  PEDIATRIC:  BOLUS:

  1 milligram per kilogram.  INFUSION:  3 micrograms per

  kilogram per minute.

    6. TRANSVENOUS PACEMAKER:  Insertion of a transvenous

pacemaker should be considered in those patients with

severe bradycardia and/or slow ventricular rate due to

second degree AV block who fail to respond to atropine

and/or phenytoin drug therapy.

    7. FAB FRAGMENTS:  Have not been documented to be of any

value in the treatment of bufagins.  Cross reactivity

has not been proven.

    8. CHOLESTYRAMINE:  Digitoxin (and theoretically bufagins)

elimination appears to be enhanced by the serial

Topic: TOAD TOXINS

administration of cholestyramine, 4 grams orally every

6 hours.  Cholestyramine appears to have minimal effect

on absorption and excretion of cardiac glycosides in

man.

    9. One 5-year-old boy did well on high-dose hydrocortisone

sodium succinate and phenobarbital (Hitt & Ettinger,

1986).

    B. ANIMALS (ESPECIALLY DOGS) (Palumbo et al, 1975):

    1. ATROPINE:  May be used to decrease secretions and block

vagal effects.  It is not a specific antidote.

    2. ANTIHISTAMINES OR CORTICOSTEROIDS:  May reduce the

effects of bufotoxins on the mucous membranes of the

mouth and other organs, but have little direct action.

    3. PENTOBARBITAL-INDUCED ANESTHESIA:  Does increase canine

tolerance to toad venom intoxication.

    4. PROPRANOLOL:  Has been tried on canines, with some

success.  The dose used was high:  5 mg/kg.

  5.3.3  ENHANCED ELIMINATION

    A. MULTIPLE DOSE ACTIVATED CHARCOAL:  May be of some use.

It has been used after IV administration of methyl

proscillaridin (Belz & Bader, 1974).

    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

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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.