Toxicology

Question 1

Toxicological terms

Answer 1

poison: any substance which when introduced into a living organism destroys life or injures health
toxicity: may be due to high dose or high sensitivity

Lethal dose and effective dose

Therapeutic index (TI) is the ratio between Ld50 and Ed50

v. high value=relatively safe

low value=narrow therapeutic range

LD50: dose at which 50% of animals are killed

ED50: dose at which 50% of animals get alleviation from whatever you’re trying to fix.

Question 2

Five basic routes of intoxication

Answer 2

ingestion: food, water source; vomitus, urine, feces
cutaneous: insecticides, topical applications like ectoparasiticides; blood
inhalation: aerosols
injection: blood

ocular

often seen non-specific signs with intoxication

Question 3

How is a poisoned animal treated?

Answer 3

1st: breathing, HR, temp stabilized

information is gathered from owner

continued absorption of poison is prevented

elimination of absorbed poison is attempted

an antidote may be given

symptomatic and supportive care

Question 4

Prevention of continued absorption of poison

Answer 4

wash- cutaneous i.e. bird covered in oil

gastric evacuation

gastric lavage

adsorbent and chelating agents

elimination

Question 5

Stimulation of gastric evacuation

Answer 5

fourth ventricle: chemotrigger zone

vestibular apparatus

medulla: vomiting centre
stomach: vagal and sympathetic afferents from GI tract stimulate trigger zone

small intestine: serotonin is released from enterochromaffin cells in GI tract

3% hydrogen peroxide

syrup of ipecac- toxic alkaloid that causes GI irriation- only give once

Xylazine: alpha 2 agonist- works on MCTZ

Apomorphine (Dopamine agonist: MCTZ)- opioid, but actions via dopamine receptor (agonist). very useful in dogs, can give in eye, gingival mucosa.

Vomiting gets rid of 40-60% of gastric content- not much use after 6 hours. can put salt or mustard at back of tongue.

Question 6

Contraindications of gastric evacuation

Answer 6

seizures

depression/coma

loss of gag reflex

hypoxia

species unable to vomit

ingestion of corrosives/volatile petroleum products

recent abdominal surgery/hernia

Question 7

Gastric lavage

Answer 7

light anaesthesia/cuffed ET tube

tepid tap water/normal saline (5-10ml/kg)

Gravity flow to aspirate

repeat until clear. Useful to keep 1st lavage for analysis

Question 8

Adsorbents

Answer 8

all adsorbents taken orally (cf. chelating agents)

activated charcoal most commonly used- exposed to O2, makes lots of pores and fissures

fuller’s earth

Fecal elimination

no chemical reaction between toxin and adsorbent

good for large non-polar molecules, bad for hydrocarbons, heavy metals or ethanol

Question 9

Cathartics

Answer 9

ways of getting things out of system fast

sodium (glauber’s salts) or magnesium sulphate (epsom salts)- speed transit through gut

sorbitol (often used in activated charcoal which tends to constipate)- or lactulose–helps move things through gut.

Question 10

Enhancing elimination via urinary tract

Answer 10

Acidify: ammonium chloride

Alkalinization: sodium bicarbonate

Close patient monitoring- acid/base balance

Symptomatic, supportive care and monitoring is often sufficient

Question 11

Chelating agents

Answer 11

useful for diagnosis of heavy metal poisoning- usualy eliminated through urine–> can take urine sample to check for heavy metal

Chemical reaction: agent binds metal ions

bound ions are chemically inert and thus prevent poisoning

examples: EDTA, desferrioxamine (particularly good for iron).

Question 12

Chocolate

Answer 12

theobromine (a methylxanthine) in chocolate products

toxicity: white choc 2.2kg/kg
milk: 9g/kg

dark 1.25g/kg

Clinical signs: vomiting, excitability, ataxia, tachycardia

Treatment: decontamination (adsorbent) and symptomatic

Question 13

Ethylene glycol

Answer 13

source: main component of antifreeze

attractive taste; commonly seen in cats and dogs; high mortality

has specific antidote

Toxicity: cats 1.5ml/kg, dogs 6.6ml/kg

Mechanism: metabolites are toxic (glycoaldehyde, glycolic acid and oxalic acid). Calcium+oxalic acid–>crystals in kidney–>renale failure.

Alcohol dehydrogenase=enzyme that metabolises. Can lead to metabolic acidosis– need to counteract metabolic acidosis.

Question 14

Clinical signs and treatment for ethylene glycol

Answer 14

Signs: early (1-2 hours): weakness, vomiting, incoordination

Delayed signs (24-96 hours): thirst, anuria, hematuria, convulsions, death d/t renal failure

Treatment: ethanol is an alternative substrate for enzyme alcohol dehydrogenase. Ethanol has 100x more affinity for enzyme than ethylene glycol

20% ethanol with 5% sodium bicarb (to counteract metabolic acidosis)

can also use 4-methylpyrazole but it’s not super available and it’s expensive.

Question 15

Organophosphates

Answer 15

source: ectoparasitic dips, collars, powders; insecticides

Toxicity: inhibit acetylcholinesterase–> stop ACh from being broken down. acts at muscarinic and nicotinic

Clinical signs: parasympathetic and neuromuscular activity

Treatment: atropine- blocks muscarinic receptors

oximes: regenerates acetylcholinesterase.

Question 16

Arsenic/mercury

Answer 16

sources: inorganic arsenic: weed killers, insecticide, seed dressing, wood preservatives, mineral ores
organic: growth promoter

both arsenic and mercury are heavy metals

Occurence: ant baits attractive to cats; over usage of feed additives (arsenic growth promoters banned in EU)

Toxicity: 1-25mg/kg

Mechanism: general tissue poison

• inactivation of sulphydryl groups on enzymes
• uncouple oxidative phosphorylation

cause problems in intestinal epithelium and in kidneys, liver and skin

antidote= chelating agents

Question 17

Arsenic/mecury poisoning signs

Answer 17

Acute toxicity: GIT most susceptible- severe gastroenteritis, vomiting, diarrhea, shock; massive ulceration and shedding of mucosa

Chronic toxicity: nervous signs; degeneration of peripheral nerves; ataxia, incoordination, blindness

Question 18

Treatment of arsenic/mercury poisoning

Answer 18

GI decontamination

Chelating agents: sodium thiosulphate 15-30g in 100-200ml water IV or 30-60g orally every 6 hours

Dimercaprol: 3mg/kg IM every 3-4 hours.

Question 19

Illicit drugs

Answer 19

sources: cocaine, amphetamines, narcotics

Toxicity: generally rapid CNS effects

clincial signs depend on agent

tx: decontamination, largely symptomatic, specific antagonists (i.e. naloxone for opiates).

Question 20

Paracetamol

Answer 20

cats especially susceptible, deficient in glucuronyl transferase which is required for glucuronide conjugation

Toxicity: 50-100mg/kg in cats

N-acetyl p-benzoquinone (intermediary) oxidises Hb to metHB (affects O2 carriage).

cP450- metabolises paracetamol to NAPB–> lethal to animal

Can be metabolized to mercapteric acid–> glutathione helps excrete this but there’s only a certain amount in the body.

Question 21

Clinical signs and treatment for paracetamol toxicity

Answer 21

Clinical signs: facial/pulmonary oedemia, cyanosis; liver damage (hemolysis, jaundice)

Treatment:

decontamination; supportive

N-acetylcysteine (glutathione precursor)

Sodium sulphate: helps alleviate symptoms

Vitamin C and methylene blue: help hemoglobin issues

Question 22

Anticoagulant rodenticides

Answer 22

1st gen: warfarin; 2nd gen: difenacoum, bromadiolone (highly toxic, single feeding causes problems)

toxicity depends on agent

mechanism: vitamin K antagonist (reversible)

intereferes with production of clotting factors I, II, VII, IX, and X

Question 23

Clinical signs and treatment for anticoagulant rodenticides

Answer 23

Clinical signs: depression and anorexia even before bleeding

Acute ingestion of very high doses: vascular collapse

Repeated intake: hemorrhage- internal/external (and symptoms of this e.g. weakness)

Diagnosis: prolonged clotting time, urine analysis; hemorrhage at PM

Treatment: vitamin K1 0.25-2.5 mg/kg subcut for warfarin, or 2.5-5mg/kg in case of long acting formulations

Menadione (vitamin K2) not effective.

Question 24

Poisonous plants

Answer 24

occur in fields, hedgerows, hillsides, woods, gardens and in house

herbivores graze, browse, touch or are fed with them in hay or straw or other fodder

Carnivores will eat plants in house or in garden or on walks or get fed poisonous plants.

Question 25

Common ragwort (senecio jacobea)

Answer 25

very common, widely distributed in permanent pasture basal rossette of leaves (year 1 most toxic) yellow daisy like flowers (may-october) all parts of plant, including root, are poisonous. seeds are prachute types and spread easily herbicides cause wilting--\>concentrates toxin. remains poisonous even when dried and stored.

Question 26

Common ragwort- mechanism of action and symptoms

Answer 26

Toxic components are pyrrolizidine aklaloids Cattle and horses are particularly susceptible, especially young animals. Outdoor pigs and chickens are also very sensitive. Sheep, goats and deer are more tolerant. Hepatotoxic Symptoms: cattle: poor appetite, either constipation or diarrhea, juandice, head pressing horses: lethargy and yawning (sleepy staggers), blindness, animals may walk in circles or in straight lines for long distances Death after acute ingestion may be in a few days. Effects are cumulative and chronic exposure is more likely. NB: no antidotes for ragwort posisoning. No specific treatments.

Question 27

Bracken (pteridium aquilinum)

Answer 27

wide upland distribution leaves and rhizomes are toxic, even when dried young plant is most toxic mostly affects cattle but sheep, pigs and horses can also be affected. Main toxic components: thiaminase, carcinogens, cyanogenic glycosides Causes: bone marrow depletion in ruminants, thiamine deficiency in monogastrates; tumours in bladder and GI tract.

Question 28

Symptoms of bracken poisoning

Answer 28

Acute: hemorrhagic syndrom esp cattle- carcinogens affect platelets; depression weakness, anorexia, death (4-10 days) Chronic: enzootic hematuria (cattle)- bladder hemorrhage Bright blindness- retina degeneration, hyper reflectivity of tapetum (cattle and sheep) GIT tumors in conjunction with BPV-4 Thiamine deficiency (horses and pigs)- counteract by giving vitamin B Clinical features: horses- bracken staggers; pig-appears like heart failure; cattle: weakness, weight loss, bleeding, blood in feces, breathing difficulties Treatment: supportive and possible blood transfusion (cattle and sheep); thiamine supplement for pigs and horses.

Question 29

Yew (taxus baccata)

Answer 29

evergreen tree with red fruits in autumn all parts of tree are poisonous except fleshy aril; also when dried taxines=toxins; inhibit Na and Ca currents also contain irritant oils which are rapidly absorbed 60% of reported poisonings are in dogs symptoms in dogs start 2 hours after ingestion: vomiting, diarrhea, and salivation, hypothermia, bradycardia, resp. depression, convulsions, heart and resp. failure

Question 30

Yew susceptibilities and treatment

Answer 30

horses, sheep, cattle and goats are also susceptible in addition to dogs poisoning can result in sudden death, reasons may be uncertain on PM: findings may include empty right heart, and left heart, spleen, liver and luns filled with dark tarry blood no antidotes

Question 31

Oak (Quercus robur)

Answer 31

poisoning in cattle, sheep, horses and goats leaves and acorns are toxic usually seasonal tannins=poisonous compounds cause kidney damage and gastroenteritis symptoms: lack of appetite, depression, constipation, follower by diarrhea with blood in feces, blood in urine, colic not seen in pigs no antidote

Question 32

Onion and garlic poisoning in dogs and cats

Answer 32

oxidant toxins. contain thiosulphates. cats and dogs don't have enzymes to digest these. symptoms: weakness, vomiting, diarrhea, breathlessness, blood in urine eventually hemolytic anemia lag time to symptoms ~2 days

Question 33

Grapes, raisins, sultanas, currants

Answer 33

Mostly in dogs, but some in cats and ferrets Mode of action is unclear: tannins? mycotoxins? pesticides? Large invidual variation causes vomiting and diarrhea acute renal failure, casts in urine

Question 34

Lillies

Answer 34

different species, toxic to cats contain calcium oxalate and oxalic acid crystals irritate mucous membranes, may cause histamine release hypersalivation, vomiting, diarrhea, anorexia, irritation of buccal membranes--\> non specific signs lead to renal failure seen within 3-6 hours of ingestion. try to rinse calcium crystals out of mouth with water or milk.