Toxicology Flashcards
Toxicological terms
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.
Five basic routes of intoxication
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
How is a poisoned animal treated?
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
Prevention of continued absorption of poison
wash- cutaneous i.e. bird covered in oil
gastric evacuation
gastric lavage
adsorbent and chelating agents
elimination
Stimulation of gastric evacuation
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.
Contraindications of gastric evacuation
seizures
depression/coma
loss of gag reflex
hypoxia
species unable to vomit
ingestion of corrosives/volatile petroleum products
recent abdominal surgery/hernia
Gastric lavage
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
Adsorbents
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
Cathartics
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.
Enhancing elimination via urinary tract
Acidify: ammonium chloride
Alkalinization: sodium bicarbonate
Close patient monitoring- acid/base balance
Symptomatic, supportive care and monitoring is often sufficient
Chelating agents
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).
Chocolate
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
Ethylene glycol
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.
Clinical signs and treatment for ethylene glycol
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.
Organophosphates
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.
Arsenic/mercury
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
Arsenic/mecury poisoning signs
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
Treatment of arsenic/mercury poisoning
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.
Illicit drugs
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).
Paracetamol
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.
Clinical signs and treatment for paracetamol toxicity
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
Anticoagulant rodenticides
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
Clinical signs and treatment for anticoagulant rodenticides
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.
Poisonous plants
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.
Common ragwort (senecio jacobea)
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.
Common ragwort- mechanism of action and symptoms
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.
Bracken (pteridium aquilinum)
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.
Symptoms of bracken poisoning
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.
Yew (taxus baccata)
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
Yew susceptibilities and treatment
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
Oak (Quercus robur)
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
Onion and garlic poisoning in dogs and cats
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
Grapes, raisins, sultanas, currants
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
Lillies
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.
