Herp Toxicology Flashcards
1
Q
Describe ivermecting toxicity in reptiles.
What species are affected?
What is the mechanism of action?
What are the clinical signs in affected animals?
How is this diagnosed and treated?
A
- Ivermectin.
- Avermectin family.
- Macrocylic lactone from fermentation broth of the fungus Streptomyces avermitilis.
- Injectable, spray, oral.
- Potentiates the effects of GABA (inhibitory neurotransmitter gamma-aminobutyric acid).
- Stimulate release of GABA by presynaptic sites, increase GABA binding to postysynaptic receptors, leads to NM blockage.
- Also open chloride channels in CNS, depress neuronal function.
- Paralysis and death of parasites.
- Concurrent t with diazepam, also works through GABA potentiation, may heighten deleterious effects.
-
Depression, paralysis, coma, death in chelonians, crocodilians, indigo snakes.
- May have BBB more permeable than other species.
- May be result of p-glycoprotein mutation in membranes of CNS.
- Or may have a specific protein only in brains of ivermectin-sensitive spp.
- Toxic reactions reported in tortoises, skinks, chameleons, nile crocodiles. Mild reaction in ball pythons may occur.
- Has been used with safety for tx of Foleyella in chameleons and internal parasites in monitors and green iguanas, always use with caution.
- Dx – history of exposure, clinical signs.
- Nx samples – frozen brain, liver, fat.
- Can also detect in serum.
- No known antidote.
- Tx supportive – decontamination with soap and water, fluid therapy, nutritional support, monitoring of electrolytes, resp support.
- Recovery may take days to weeks.
- NEVER GIVE TO CHELONIANS, GRAVID ANIMALS, OR NEONATES.
2
Q
Describe fenbendazole toxicity in reptiles.
What species have died following high doses?
What are some of the side effects of its usage?
A
- Fenbendazole.
- Benzimidazole type of antiparasiticide.
- Metabolite, oxfendazole inhibits glucose uptake in parasites.
- High margin of safety, even at 6x recommended dose in reptiles.
- Drug of choice for nematode infections in reptiles, oral, per cloaca, or powdered on food.
-
Four adult Fea’s vipers died after single dosages (very high).
- Nx suggested intestinal changes consistent with fenbendazole toxicity.
- Possibly caused heteropenia, leucopenia, generalized lymphopenia, increased UA, P, TP, decreased glucose in tortoises with high doses.
- Causes agranulocytosis in mammals at high doses, liver toxicity, BM toxicity.
- No antidote, tx supportive.
- Monitor CBC with long term use.
3
Q
Describe metronidazole toxicity in reptiles.
What is its mechanism of action?
What clinical signs are observed in affected reptiles?
A
- Metronidazole.
- Used as an antibacterial, antiprotozoal, appetite stimulant.
- Suspension, injectable, and tablet.
- Specific for Giardia and other protozoal organisms.
- Disrupts DNA in target microbes through reaction with intracellular metbaolites.
- CNS toxicity, dose-related.
- Hepatotoxic, carcinogenic.
- Ataxia, inability to walk, nystagmus, opisthotonos.
- Most patients recovery with fluids, thermal and resp support.
- May need ventilator. Recovery make take several days.
- Used as an antibacterial, antiprotozoal, appetite stimulant.
4
Q
Describe antifungal toxicities in reptiles.
What type of drug is amphotericin B? How does it work? How does it cause toxicity?
What is the mechanism of griseofulvin? What adverse effects does it cause?
How do the azoles work? What type of toxicity do they cause?
A
- Antifungal toxicity.
- Amphotericin B.
- Macrolide, inhibits ergosterol synthesis.
- Potent nephrotoxin.
- Renal vasoconstriction, reduces glomerular filtration rate, direct toxic effects on membranes of renal tubule cells.
- Acute tubular necrosis.
- CS – acute renal failure, anorexia, lethargy, weight loss, etc.
- Elevated BUN, Cr, decreased K and Na in mammals.
- Monitor UA, BUN, electrolytes in reptiles.
- GFR determination by iohexol excretion should be considered.
- Tx – discontinue drug, aggressive fluid therapy (sodium chloride-containing fluids).
- Tx with mannitol may help increase elimination of amphotericin B.
- Do not use in animals with preexisting renal disease.
- Griseofulvin.
- Inhibits fungal spindle activity, leads to distorted weakened fungal hyphae.
- BM suppression in mammals, mech unknown.
- Anorexia, lethargy, diarrhea, anemia with intoxication.
- Teratogenic in pregnant animals.
- Tx – discontinue drug, symptomatic support. No antidote.
- Wash with gentle soap and water for topical tx.
- Inhibits fungal spindle activity, leads to distorted weakened fungal hyphae.
- Imidazoles (ketoconazole) and triazoles (itra, flu).
- Interfere with ergosterol synthesis.
- Ketoconazole also directly effects fungal membranes.
- Metabolized by liver.
- CS – anorexia, lethargy, wet loss, diarrhea, elevated liver enzymes.
- No antidote.
- Tx – stop drug, decontaminate topicals, supportive care.
- Counter hepatotoxicity.
- Amphotericin B.
5
Q
Describe antibiotic toxicities in reptiles.
How do the aminoglycosides work? What adverse effects can occur?
How does chloramphenicol work? What is the major toxicity?
What is the main adverse effect associated with enrofloxacin administration?
A
- Antibiotic toxicity.
- Gentamicin – aminoglycoside.
- Bacteriocidal, broad spectrum except strep and anaerobes.
- Inhibits protein synthesis by binding 30S ribosomes.
- Nephrotoxicity and ototoxicity well documented in reptiles.
- Amikacin – aminoglycoside.
- Nephrotoxicity primary effect.
- Must remain hydrated during therapy.
- Ototoxicity also reported.
- Chloramphenicol.
- Inhibits protein synthesis by binding with ribosomes.
- Major toxicity is hemorrhage.
- All vertebrates.
- Dose-dependent BM suppression, reduction in RBC, WBC, platelets in mammals.
- Tx supportive, blood transfusions.
- May suppress appetite.
- Enrofloxacin.
- FQ.
- Bacteriocidal, broad spectrum.
- Inhibits DNA gyrase (DNA and RNA synthesis).
- Can cause severe muscle and skin necrosis if SC or IM.
- Only a single IM injection is recommended, followed by oral therapy.
- High pH, dilution is ineffective for practical applications.
- At a pH of 10 it would be necessary to dilute 1 mL enro with 1000 mL to get close to a pH of 7.
- Gentamicin – aminoglycoside.
6
Q
Chlorhexidine and iodine can both be toxic to reptiles. Under what conditions?
Bleach can produce what types of lesions in reptiles?
Diosctyl Sodium Sulfosuccinate (DSS) is a commonly used stool softener - what lesions has it caused in reptiles when administered orally?
A
- Misc drugs and products.
- Chlorhexidine vs iodine toxicity.
- Povidone iodine inactivated by presence of organic material, little residual activity.
- Both are cytotoxic in higher concentrations, may slow granulation tissue formation, impair or delay wound healing.
- Soaking can be life threatening.
- Intoxication in turtles soaked in chlorhexidine scrub for 1 hour.
- Tx – remove from soak, rinse, and support with warmth and fluids.
- Never leave unattended in a bath.
- Bleach.
- Moderately irritating.
- Necer apply to live animals.
- Alkali-type burns in eyes.
- Immediate copious irrigation minimizes damage.
- Was with mild soap and lukewarm water.
- Keep out of recently bleached cages for 24h minimum.
- Dioctyl Sodium Sulfosuccinate (DSS).
- Anionic surfactant substance, traditionally recommended as a laxative and stool softener for variety of verts.
- Fatalities in reptiles after oral use have been reported.
- Changes in gastric and esophageal mucosa in gopher snakes.
- Specific dose not established in reptiles.
- May result in aspiration pneumonia.
- Chlorhexidine vs iodine toxicity.
7
Q
What are the signs of vitamin A toxicity?
What about vitamin D toxicity? How can it be managed?
A
- Vitamin toxicity.
- For water-soluble vitamins, excreted into urine, margin of safety is large.
- Vit A.
- Inappetance, full-thickness skin sloughing, secondary bacterial infection, discoloration of skin, lethargy.
- Tx – stop administration, give fluids, nutritional support.
- Can completely recover with time.
- Vit D.
- Discourage commercial oral D3 supplements to avoid expense of UVB.
- Toxicity related to hypercalcemia.
- Dystrophic calcification of GIT, renal, pulmonary, cardiovascular, and synovial tissues.
- Definitive and accurate dx possible by submission of blood for 25OHD3 levels measured by high-performance liquid chromatography or liquid chromatography-mass spec.
- Tx – complete removal of vit D supplements, diuresis, cortisone may help with hypercalcemia.
- Resolution of soft-tissue calcification may not be successful.
- Calcitonin historically recommended, safety not known.
- Pamidronate disodium (bisphosphonate) has been recommended in dogs for hypercalcemia.
8
Q
Describe organophosphate toxicity in reptiles.
WHat is their mechanism of action?
What are the clincial signs of affected animals?
How are they treated?
A
- Organophosphates and carbamates.
- Most commonly used insecticides worldwide.
- Dips, sprays, topical medications, systemic antiparasitic agents, flea collars.
- i.e. chlorpyrifos, dichlorvos, diazinon, cythionate, fenthion, malathion, ronnel, parathion, trichlorfon, vaponna.
- Related to carbaryl, bendiocarb, methiocarb, propoxur, cabofuran.
- Toxicity in reptiles is well known.
- Used intentionally to control some populations of iguanas, snakes, geckos.
- Ophthalmic and otic pathologies in box turtles.
- Interfere with metabolism and breakdown of acetylcholine at synaptic junctions.
- Ache breaks down acetylcholine, inhibited by OP and carbamates.
- Acetylcholine accumulates at synapses.
- Excites, then paralyzes transmission, give characteristic nerve gas signs.
- Inhibition of synapse irreversible with OP, reversible with carbamates.
- Excites, then paralyzes transmission, give characteristic nerve gas signs.
- Readily absorbed – dermal, resp, GI, conjunctival.
- May happen more readily when given with imidothiazoles i.e. levamisole.
- Acetylcholine accumulates at synapses.
- Ache breaks down acetylcholine, inhibited by OP and carbamates.
- Dips, sprays, topical medications, systemic antiparasitic agents, flea collars.
- CS – salivation, ataxia, muscle fasciculations, inability to right themselves, coma, resp arrest.
- Death from massive resp secretions, bronchiolar constriction, effects on resp centers in medulla leading to cessation of breathing.
- Blood levels variable, poorly diagnostic unless paired.
- Brain acetylcholinesterase considered definitive.
- Wash animals with dermal exposure, dry after rinsing.
- Fluid therapy.
- Specific antidote – muscarinic antagonist atropine.
- More modern poisons tend to bind irreversibly.
- Atropine may help with salivation, bronchospasm, dyspnea.
- Diazepam may be given as needed for seizure.
- Antihistamines controversial, most likely not effective.
- Px depends on dose, duration of exposure, size of animal.
- To promote slow absorption and avoid direct contact with reptile skin, some insecticides can be applied to a piece of tape and then adhered to scales for 2-3 days.
- There are safer options.
- Most commonly used insecticides worldwide.
9
Q
Describe pyrethrin toxicity in herps.
What is the mechanism of toxicity?
What are the clinical signs of affected animals?
How are they treated?
A
- Pyrethrins and pyrethroids.
- Made from dried and ground Chrysanthemum cineriifoliu.
- Pyrethroids are synthetic derivatives of pyrethrin.
- Only one product licensed for use in reptile parasites is Provent-a mite (Permethrin).
- Pyrethroids are synthetic derivatives of pyrethrin.
- Alter activity of Na ion channels of nerves.
- Prolong period of Na conductance and increase length of depolarizing action potential.
- Results in repetitive nerve firing and death.
- Can intoxicate host animals.
- Potential for transcutaneous absorption, use with caution.
- Never give concurrently with other antiparasiticides.
- Prolong period of Na conductance and increase length of depolarizing action potential.
- CS – within 15 min of application, salivation, ataxia, inability to right themselves, muscle fasiculations.
- Idiosyncratic reactions at lower doses than expected.
- Small percentage of animals appear highly sensitive.
- No known antidote.
- Dermal decontamination, isotonic fluids, atropine, diazepam.
- No good antemortem test.
- No identifiable lesions postmortem.
- Keep sprays away from eyes and mouth.
- Made from dried and ground Chrysanthemum cineriifoliu.
10
Q
Describe rodenticide toxicity in reptiles.
What is the mechanism of anticoagulant rodenticide? What clotting factors are affected? How do reptiles get exposed? How are they treated?
What is the mechanism of bromethalin? What are the typical clinical signs? What treatments are recommended?
What is the mechanism of cholecalciferol toxicity?
A
- Rodenticides.
- Long-acting anticoagulants 80% cases.
- Same action as warfarin but more potent, longer half-life.
- Decrease activity of vit K dependent blood-clotting factors.
- 2, 7, 9, 10.
- Decrease activity of vit K dependent blood-clotting factors.
- Taken off market in US.
- CS – hemorrhage. Most common CS is dyspnea.
- Anorexia, weakness, lethargy.
- Molasses-soaked grain laced with the anticoagulant attract reptiles.
- May not show evidence of hemorrhage.
- Can influence thermoregulation and cause overheating.
- Reptiles appear to have variable response to the effects.
- PT can be a helpful baseline.
- Antidote is vit K1 if PT is increased.
- Use mammal doses.
- May need to tx 3-4 weeks.
- PT test again 48h after stopping Vit K1. If normal, discontinue.
- Vit K1 tx can be given SQ or orally.
- IV high incidence of anaphylaxis in mammals.
- Tx with vit K1 and possible O2, plasma transfusion.
- Same action as warfarin but more potent, longer half-life.
- Bromethalin.
- Not reported but possible.
- Neurotoxin.
- Uncouples oxidative phosphorylation.
- Brain primary target.
- Causes brain electrolyte disturbances, development of cerebral edema.
- CS – hind limb paralysis, abnormal postures, fine muscle tremors, seizures. Coma.
- CS usually within 24h of ingestion.
- Nonselective vertebrate poison.
- Antemortem dx based on exposure history, CS.
- Postmortem detection in frozen fat, liver, kidney, brain.
- No antidote, tx directed at reducing GI absorption and providing supportive care.
- Tx of cerebral edema in severe cases.
- Dexamethasone and mannitol has been recommended to control cerebral edema in mammals. Rarely successful.
- Seizures, paralysis, or coma – grave prognosis.
- Cholecalciferol.
- Vit D3.
- Causes hypercalcemia through mobilization of body stores of Ca found in bone.
- Dystrophic hypercalcemia results in calcification of blood vessels, organs, soft tissues.
- Leads to nerve and muscle dysfunction and cardiac arrhythmias.
- Dx by submission of 25OHD3 levels measured by chromatography.
- Pred and furosemide used in mammals.
- Fluids essential.
- Calcitonin recommended, efficacy questionable.
- Pamidronate disodium in dogs.
- Prognosis poor with dystrophic mineralization.
- Long-acting anticoagulants 80% cases.
11
Q
Describe the toxicities associated with insecticides and repticides in reptiles.
What is the mechanism of metaldehyde? What is the target organism? What are the clinical signs in affected reptiles?
What is the mechanism of toxicity of alpha-chloralose?
What is teh mechanism of toxicity of acetaminophen?
A
- Metaldehyde.
- Slug and snail baits.
- Metaldehyde may be agent affecting CNS, degradation to acetaldehyde once thought to be action of poisoning.
- GABA levels decreased.
- Depression, seizures, coma.
- CS – ataxia, incoordination, locomotor signs, muscle spasms, abnormal postures, convusions.
- CS within few hours of ingestion.
- Antemortem analysis of stomach contents, serum, and urine, postmortem frozen liver samples.
- No specific antidote.
- Supportive care.
- Oxygen to counter respiratory depression.
- Mammals – shake and bake syndrome, tx with diazepam.
- Counter hyperthermia.
- Prognosis better if survive first 36 h.
- Repticides – used in some parts of the world exclusively to control reptile pests.
- Alpha-chloralose.
- Produces hypnotic effect by interfering with body temp control mechanism in reptile.
- Chloralose – avicide and rodenticide use to kill mice at temps below 15 deg C, also demonstrated in reptiles.
- Toxic component mixed with strawberries and dyed pink to attract geckos.
- Stunned within minutes, do not move more than 2 m away from initial feeding point.
- Acetaminophen.
- Very toxic to reptiles.
- Registered for use to control brown tree snakes in Guam.
- Lethality for monitors, pythons, tree snakes.
- Mice injected with acetaminophen provided to wild snakes, death within 48h.
- Mech unknown, suspected liver and kidney toxicity.
- Glutathione depletion can lead to hepatic necrosis.
- Methemoglobinemia has been observed in cats.
- Severe methemoglobinemia in brown tree snakes.
- Emesis in monitor lizards and brown tree snakes.
- Alpha-chloralose.
12
Q
Describe heavy metal toxicity in reptiles.
What are some potential exposures of zinc to reptiles? What organs are affected by zinc toxicity? What are the typical clinical signs?
What is the mechanism of lead toxicity? Which taxa is most suceptible? Why?
A
- Heavy metal toxicosis.
- Zinc.
- May result from excessive zinc intake/supplementation, ingestion of metal objects, Zn oxide ointment, pennies after 1982.
- Mechanism unknown.
- RBC, kidneys, pancreas, liver affected.
- Intravascular hemolysis consistently seen.
- Zn may cause oxidative lysis of RBC membrane and anemia.
- CS delayed with coins.
- Anorexia, lethargy, may mimic enteritis.
- Followed by IV hemolysis, hemoglobinemia, yellow discoloration of skin and MM, wt loss.
- Rads helpful.
- Elevted Zn on serum/plasma sample.
- Nx – liver, kidney, pancreas.
- Tx – remove Zn-containing foreign objects by endoscopy or surgery.
- Fluid therapy, possible blood transfusion for anemia.
- Zn chelators.
- But may be of questionable value once source of exposure is removed.
- Lead toxicosis.
- Lead competes with Ca ions, substitutes for Ca in bone.
- Mimics and inhibits many cellular actions of Ca, Ca flux across membranes.
- Increases levels of cytoplasmic Ca in many cell types.
- Leads to cell mediated death, chronic impairment of neuronal function, diminished energy metabolism by mitochondria, all resulting in apoptosis.
- 90+% bound in RBCs.
- Antemortem detection in blood, post in liver and kidney.
- Blood levels do not always correlate with clinical signs.
- Crocodilians are more susceptible to lead poisoning due to presence of stones in the stomach.
- Help wear down and dissolve ingested metallic pieces, liberate lead can enter blood.
- Tx – chelation with CaEDTA 30 mk/kg IM a24h for 5 days, rest 4 days, repeated 5 days.
- Prokinetics shown to have little effect.
- Removal of metal objects when possible.
- Zinc.
13
Q
Describe the mechanisms of snake envenomations.
What is the mechanism of hyaluronidase?
What is the mechanism of phospholipase A2?
What about collagenase?
A
- Snake envenomations.
- Venom from modified salivary glands.
- Hyaluronidase – catalyzes cleavage of internal glycosides bonds and mucopolysaccharides.
- Potentiates activity of other toxic agents.
- Phospholipase A2 – causes hydrolytic breakdown of membrane phospholipids.
- Cytotoxic, anticoagulant, neurotoxic activities.
- Collagenase – digestion and breakdown of connective tissue.
- Snake venom 90% water, enzymatic an dnonenzymatic proteins, lipids, carbohydrates, biogenic amines.
- Toxins in “killing fraction” aka venins.
- Entire mixture is venom.
- Venomous snakes appear more resistant to their own venom.
- Deaths may still occur.
- Depends on location of bite, volume, size of recipient.
- Some nonvenomous snakes prey on venomous snakes, have some more resistance.
- Sometimes when bitten they still die.
- Male king cobras may bite females during mating.
- Most cases nonlethal.
14
Q
Describe the mechanisms of lizard envenomations.
How is helodermatid venom delivered?
What enzymes are present in their venom?
What is the mechanism of arginine hydrolase?
What is the mechanism of Kallikrein-like enzymes?
What are teh mechanisms of gilatoxin and helothermine?
A
- Lizard envenomations.
- Two known poisonous spp.
- Gila monster – Heloderma suspectum.
- Mexian beaded lizard – Heloderma horridum.
- Venom only used in defense. Sets apart from snakes and spiders that use venom to apprehend prey.
- Venom glands in lower jaw, delivered to gums at base of teeth, dependent on intense chewing action.
- Multiple enzymatic proteins – hyaluronidase, phospholipase, arginine hydrolase, kallikrein-like enzymes, gilatoxin, helothermine.
- Hyaluronidase acts to decrease viscosity of connective tissue, catalyze cleavage of acid mucoglycosides.
- Arginine hydrolase causes hydrolysis of peptide linkages.
- Kallikrein-like enzymes cause vasodilation, increase capillary permeability, lead to edema, contraction or relaxation of extravascular smooth muscle.
- Gilatoxin – neurotoxic protein.
- Helothermine – depresses body temp in mice.
- Very painful in humans.
- No specific antivenom.
- Bites between tank mates common either due to territoriality or breeding, but no deaths reported.
- Conspecific immunity may be due to osteoderms in skin as protection.
- Two known poisonous spp.
15
Q
What are the mechanisms of toad poisonings?
What is the mechanism of bufotenine?
What about bufagenin?
Bufotoxins?
Indolealkylamines?
A
- Amphibian toxins.
- Genus Bufo source of most toad poisonings.
- Bufo (rhinella) marinus – cane or marine toad.
- Colorado River toad (Bufo alvarius).
- Parotid glands release toxins when threatened.
- Dopamine, NE, E, serotonin, bufotenine, bufagenin, bufotoxins, and indolealkylamines.
- Severe toxicosis in small animals.
- Rapid absorption of toxins through MM of predators, enter systemic circulation.
- PNS, CNS, heart effects.
- Bufotenine – pressor effects on blood vessels, hallucinogenic.
- Bufagenin – digitalis-like effects, alterations in HR and rhythm.
- Bufotoxins – vasoconstrictors, add to pressor effects.
- Indolealkylamines – hallucinogenic.
- Dopamine, NE, E, serotonin, bufotenine, bufagenin, bufotoxins, and indolealkylamines.
- Predator reptiles may encounter poisonous toads in diet.
- No specific antidote, tx supportive.
- Flushing oral cavity, stabilize HR and rhythm, seizure control.
- Genus Bufo source of most toad poisonings.
18
Q
Describe the intraoral approach for complete removal of the venom gland.
A
MARMS – 95. Venomoid Sx
Venomoid surgery - technique developed to alter venom production and delivery systems, rendering reptile nonvenomous
- Mutilation in some countries (illegal)
- Imperfect surgery results in envenomation
- Indication - reduce risk for less experienced keepers
- Performed on reptiles in sting operations to reduce risk to handlers/poachers
- Not recommended for private hobbyists
Snakes
- 1937 used rubber bands for 10-48 h after surgery
- Lateral approach (1970s): leaves scar and elapids develop granulomatous response at surgical site; recent study involving venom duct ligation and resection
- Intraoral approach (1980s): complete removal of venom gland and venom duct (maxillary)
- Prep oral mucosa
- Incision between palatine-fang axis and lip margin
- Careful dissection (ophthalmic instruments) to expose venom gland and duct
- Elapids have thick venom duct - may be difficult to handle
- Largest associated vessel dorsomedial - cautery, ligation in larger snakes
- Venom duct transected at entrance into the base of the maxillary bone
- Dissect and remove as one unit - carefully discard
- Silicone prosthesis - no complications noted
- Closure (simple continuous, monofilament absorbable)
- Perioperative antibiotics
- Do not feed for 2-3 weeks and clean water daily
- Unpublished - 3 snakes underwent surgery - re explored surgical site a year later (no evidence of regeneration) and test prey envenomation negative
19
Q
Describe the venemoid surgery of helodermatids.
Where are their venom glands located?
Describe the approach to remove these glands.
A
Gila monsters and beaded lizards
- Venom glands in ventrolateral regions of mandible
- Prominent swelling along anterior and middle region of lateral lower jaw
- Ventrolateral incision
- Have many tiny ducts from lobulated gland to bases of several teeth
- Lightly pink venom gland elevated from mandible with sharp/blunt dissection
- Hemorrhage minimal; no prosthesis
- Skin closed nonabsorbable - simple interrupted (non everting)
- Feed in 7-10 days
- Remove sutures in 5-6 wks
