Toxicology

Question 0

How is hydration and metabolic derangements assessed in poisoned patients?

Answer 0

As poisons have the potential to cause severe acid base and electrolyte abnormalities, in addition to organ specific toxicities it is important to obtain a full serum biochemical profile and blood gas analysis. Derangements should be identified and addressed.

Question 1

How should seizures and tremors be controlled in a poisoned patient?

Answer 1

Anticonvulsant therapy should be administered to seizuring animals or to animals with uncontrolled muscle tremorscontractions. Diazepam is given IV for both seizures and muscle tremors although as its effect may be short lived it may need to be combined with a barbiturate e.g phenobarbitone.

Question 2

Describe gastrointestinal decontamination of poisoned patients?

Answer 2

GI decontamination should begin as soon as the animal is stable. Induction of emesis should be considered only if the patient is alert and responsive. Emetics include apomorphine, ipechacuana syrup. Do not induce emesis if the poison is corrosive. Gastric lavage hshould be carried out with warm saline in animals with impaired consciousness - light anaesthesia may be necessary. Reduce further absorption of toxin by administration of activated charcoal which adsorbs toxins. 2-8g/kg initially. Repeat doses of AC should be given especially if there is known enterohepatic circulation of toxins e.g ibuprofen. Purgatives may be of benefit in addition to intetinal adsorbents e.g sorbitol, sodium sulphate or magnesium sulphate.. Bathe animal.

Question 3

How is elimination of the toxin enhanced ?

Answer 3

IVFT maintains renal perfusion and may aid elimination of toxns. Forced diuresis may be applicable to some toxicities eg aspirin, whereby diuretics are combined with IVFT. Frusemide or mannitol. Ion trapping may reduce renal re absorption of toxins - alkalinisation of urine reduces aspirin and barbiturate resorption, acidification of urine (ammonium chloride administration) facilitates excretion of strychnine.

Question 4

What is intravenous fat emulsion?

Answer 4

May be considered when treating life threatning arrythmias caused by lipid soluble drugs e.g acute local anaesthetic toxicity, verapamil toxicity, propranolol induced hypotension, TCA toxicity, Ca channel blocker toxicity. the mechanism of actio: 1) a lipid sink: the ILE forms a conduit to redistribution. 2) effects on sodium and calcium ion channels. 3) it has metabolotropic effects through secondary messengers (gproteins) 4)alkaline pH. 5) energy substrate for cardiac muscle.

Question 5

What supportive care should be used in poisoning?

Answer 5

Supportive care may be required for several days until normal homeostatic mechanisms have been restored and toxin eliminated. Attention should be paid to maintaining adequate tissue oxygenation, which may involve oxygen supplementation, appropriate hydration, maintenance of normal body temperature, correction and maintenance of normal electrolyte status, physical therapy including frequent turning to prevent musculoskeletal complications of recumbency and nutrition.

Question 6

Describe paracetamol toxicity

Answer 6

Toxicity as a result of administration by an uninformed owner - dose dependent. 200-600mg/kg in dogs, 50-10mg/kg in cats. Elimination of paracetamol is primary via conjugation with glucuronide and sulphates in the liver followed by extrection of these in the bile and urine. In the cat the red blood cell is most susceptible to oxidative injury, haemoglobin is oxidised to methaemoglobin resulting in cyanosis. toxic effects are secondary to high levels of toxic metabolites - damage teo cell membranes via lipid peroxidation and to glutathione depletion which renders cells susceptible to oxidative injury. In the dog liver is most suceptible, hepatocellular necrosis leads to typical clinical signs of liver failure.

Question 7

What is the treatment for paracetamol toxicity?

Answer 7

reduce further absorption; induction of emesis or gastric lavage within 1-2 hours of ingestion, activated charcoal, supportive care, oxygen, IVFT, blood transfusion, glutathione precursors administered to replenish cellular glutathione stores, vitamin C and methylene blue.

Question 8

Describe NSAID ibuprofen toxicity

Answer 8

Reduce production of prostaglandins and thromboxane by direct inhibition of cyclooxygenase enzymes. The analgesic, antpyretic and anti inflammatory actions of nsaids are mediated by inhibition of cox-2. cox 1 leads to reduction of gastric prostaglandins and bicarbonate secretion - gastric ulceration, renal toxicity in dehydration due to inhibition of renal prostaglandin production. Vomiting, depression, anorexia, diarrhoea, melaenia and pupd. Delayed clearance in young and old animals.

Question 9

What is the treatment for ibuprofen toxicity?

Answer 9

Reduce further absorption - induce emesis or perform gastric lavage, activated charcoal,, continued every 6 hours for 72 hours due to enteroheatic circulation of ibuprofen, IVFT to maintain renal perfusion, misoprostol, h2 antagonists, proton pump inhibitors omeprazole and sucralfate.

Question 10

Describe aspirin toxicity

Answer 10

Ulcerogenic and nephrotoxic potential, also causes hyperventilation followed by a severe metabolic acidosis, clinical signs include pulmonary oedema, seizures, respiratory depression and coma. in addition to treatment of nsaid toxicity as outlined, elimination of salicylate can be enhanced by forced diuresis with careful attention to fluid balance to avoid overload. administration of bicarbonate is also indicated if severe acidaemia is present.

Question 11

Describe ethylene glycol toxicity

Answer 11

Ethylene glycol is an organic solvent used in anti freeze. high palatability. mortality due to oliguric renal failure. causes vomiting due to Gi irritation and cns depression, toxicity caused by metabolism of EG by alcohol dehydrogenase to glycoaldehyde, glycolic acid and oxalate. Glycoaldehyde results in CNS depression, ataxia, stupor and sseizures. Severe metabolic acidosis occurs as a result of glycolic acid accumulation. most f the metabolites are directly toxic to the renal tubular epithelium and formation of calcium oxalate crystals contributes to anuric/oliguric renal failure.

Question 12

What are the clinical signs of ethylene glycol toxicity?

Answer 12

nausea and vomiting, neurological signs, acute renal failure, anorexia, depression, vomiting, oral ulceration and renal pain, high anion ga, metabolic acidosis, azotaemia, hyperpohsphataemia, hyperkalaemia, hypocalcaemia and hyperglycaemia, isothenuria seen in dogs and reduced USG in cats, calcium oxalate crystalluria, ethylene glycol test kits available. woods lamp may detect sodium fluorescein in antifreeze solutions in the paws, face and vomitus. Renal ultrasonography - increased cortical echogenicity.

Question 13

What is the treatment for ethylene glycol toxicity?

Answer 13

Reduce further absorption; induce emesis or perform gastric lavage if within 1-2 hours of ingestion. Administer activated charcoal. Decontaminate the patient. Aggressive IVFT to maintain renal perfusion. Consider peritoneal dialysis or haemodialysis. bicarbonate therapy for metabolic acidosis. Mannitol to promote diuresis. Administration of drugs which competitively inhibit alcohol dehydrogenase reduce the conversion of EG to toxic metabolites, ethanol or 4-methylpyrazole. Thiamine and pyridoxine enhance metabolism of glycoxylic acid to non toxic metaboiltes.

Question 14

What are other toxic causes of acute renal failure?

Answer 14

Easter lily in cats and raisin/grape sultana toxicity in dogs. the mechanisms not currently understood and toxic doses are variable. management is aimed at reducing exposure if recent ingestion has been observed and managing acute renal failure. Prognosis for renal failure is extremely guarded.

Question 15

What are the effects of neurotoxins?

Answer 15

Categorised into excitatory and inhibitory neurotoxins. Intoxication with an excitatory neurotoxin typically results in muscle twitching,tremors, tonic contractions and seizures. Excitatory neurotoxins include strychnine, metaldehyde, organophosphates/carbamates, certain recreational drugs, blue green algae. Inhibitory neurotoxins tend to result in CNS depression and coma in conjunction with respiratory depression and bradycardia. Inhibitory neurotxins include alphachloralose and the avermectins. Acombination of both excitatory and inhibitory neurological signs may be observed e.g permethrin, marijuana.

Question 16

Describe metaldehyde toxicity?

Answer 16

metaldehyde is a molluscicde which causes its toxicity by inhibiting y-amino-byturic acid (GABA) it may also increase monoamine oxidate actvity resulting in decerased levels of noradrenaline and 5-hydroxytryptamine resulting in decreased seizure threshold. Clinical signs occur within 1-3 hours post ingestion and include abdominal discomfort, salivation, vomiting, diarrhoea, tachycardia and tachypnoea, hyperaesthesia, hyperthermia and muscle tremors. Opisthotonus and convulsions may be seen. Convulsions may give way to CNS depression/narcosis. Livver failure may develop as a late sequel to intoication. Once absorbed it is rapidly metabolised by the liver with only a fraction being excreted unmetabolised in the urine. Confirmation of intoxication is by analysis of stomach contents, serum and urine.

Question 17

What is the treatment for metaldehyde toxicity?

Answer 17

Reduce further absorption by gastric decontamination by gastric lavage preferable to emesis in this toxicity, induction of emesis may induce violent muscle activity and acetaldehyde in gastric contents is caustic. Administer activated charcoal +/- sorbitol purgative. IVFT, general nursing care, cooling if hyperthermic, muscle relaxants, anticonvulsant drugs therapy, diazepam/barbiturates.

Question 18

Describe permethrin toxicity

Answer 18

Cats are more sensitive to the effects of permethrin than dogs and toxicity often due to inappropriate use of permethrin spot on for dogs being administered to cats, despite the warnings. permethrins affect sodium channels resulting in repetitive nerve stimulation and result in excitatory neurological signs although ataxia and depression may also be seen. Treatment is supportive.

Question 19

Describe chocolate toxicity

Answer 19

Chocolate contains theobromine, a methylxanthine which antagonises the effects of adenosine. acute intoxication results in restlessness, panting, diuresis, vomiting and diarrhoea and may progress to give rise to cns excitation and cardiac arrhythmias. dogs appear to absorb theobromine slowly giving a slightly longer window of opportunity for preventing toxicity by gastrointestinal decontamination. Treatment of toxicity is supportive with IVFT, muscle relaxants/anticonvulsants for CnS signs and anti arrythmic drugs if cardiac arrhythmias are persistent; beta blockers, may be required for management of supra ventricular tachycardias and lignocaine may be required for the management of life threatening ventricular tachycardia.

Question 20

Describe strychnine toxicity

Answer 20

strychnine is an excitatory neurotoxin which sed to be used for killing moles. Extremely toxic and rapid absorption following ingestion leads to acute onset of clinical signs. strychnine exerts effects by blocking inhibitory effect of glycine at the level of spnal cord, brain and thalamus, which inhibition results in unchecked neuronal activity with highly exaggerated reflex arcs, mild to severe muscle spasm, may progress to a full tetanic convulsion. Death usually associated with respiratory paralysis. Hyperthermia often observed. Onset 10-120 minutes agter ingestion.

Question 21

describe toxicity by organophosphates and carbamates?

Answer 21

Ops and carbamates are insecticides that exert their neurotoxicity by inhibition of acetylcholinesterase which results in prolonged activity of acetylcholine at the neuromuscular junction. Nicotinic signs include muscle tremors, generalised muscle tetany followed by weakness, anxiety, hyperactivity, seizures to severe cns depression, salivation, lacrimation, urination, defaecation, bradycardia, dyspnoea, miosis, can be absorbed through skin, resp tract or GI tract. dermal exposure - 12-24 hours. OPS bind irreversibly to AChE whereas carbamates result in reversible inhibition as ache is released following hydrolysis of carbamate.

Question 22

Describe toxicity with alphachloralose

Answer 22

Used as a rodenticide and bird poison. It has both CNS stimulatory and CNs ddepressive effects. the depressant effects tend to predominate. this results in the clinical signs of hypothermia, bradycardia cns and respiratory depression.

Question 23

Describe toxicity with avermectins?

Answer 23

Used as endo and ecto parasites in large and small animals. avermectins cause CNS depression due to enhanced gaba activity. collie breeds more sensitive to avermectin toxicity due to an inability to expel these compounds from the CSf, clinical signs include bradycardia, resp depression, cns depression and coma. prognosis is dose dependent and supportive care may be required for daysweeks. Reduce further absorption, nutritional support, body temp support, respiratory support.

Question 24

Describe anticoagulant rodenticide toxicity

Answer 24

Relatively common in small animals - usually ingestion in dog, in cat usually of an intoxicated rodent. Anticoagulants include warfarin, bromadiolone and difenacoum. They inhibit vitamin K epoxide reductase, these anticoagulants prevent recycling of vitamin K in the liver. Vitamin K epdent coagulation factors are impaired and become depleted resulting in a clinical coagulopathy. Clinical signs indicative of secondary haemostatic disorder and reflect the site of bleeding, epistaxis, haemoptysis, dyspnoea due to haemorrhage, haematoma formation.

Question 25

what is the treatment for anticoagulant rodenticide toxicity?

Answer 25

Reduce further absorption, induce emesis, gastric lavage, vitamin K1 therapy should be administered by subcutaneous injection followed by oral administration. Synthesis of new coagulation factors is rapid occurring within 6-12 hours. therapy may need to be continued for as l ong as 4 weeks. PT should be measured 36–48 and 72 hour after cessation of therapy. Short half life of factor VII (6hours) the PT is the first parameter to become prolonged if duration of therapy is not sufficient. Treatment should be continued for a further 7 days then coagulation is re assessed.

Question 26

Describe adder bite poisoning

Answer 26

Venom produced by adder contains enzymatic and non enzymatic toxins and clinical signs can range from localised tissue necrosis with vascular permeability, oedema and vasodilation, with concurrent alteration in mentation to death as a consequence of severe distributive shock, Haemolysis and disseminated intravascular coagulation. The majority of bites affect head and face. Mortality is increased when the bite is located on extremity.

Question 27

What is the treatment for european adder bites?

Answer 27

Supportive and symptomatic therapy, ivft, analgesia, use of broad spec antibs and corticosteroids - controversial European adder anti serum is available.