Toxicology

Question 1

How does paracetamol toxicity occur and to what species?

Answer 1

Highly toxic to cats! Occurs via saturation of metabolic pathways. Conjugated by glutathione- glutathione promptly depleted. Cellular death. Cats lack metabolic capacity to detoxify paracetamol

Question 2

What are the clinical manifestations of paracetamol toxicity?

Answer 2

Early (<4hr)- progressive cyanosis, weakness and lethargy
4-24hr- facial and paw oedema, V+, depression, methaemoglobinaemia
Days- severe methaemoglobinaemia, hepatic necrosis

Question 3

What is the treatment for paracetamol toxicity?

Answer 3

Doesn’t respond to O2 therapy.
Emesis (optimal w/in 2hrs)- apomorphine (Ds), xylazine (Cs)
Activated charcoal
Antidote- acetylcysteine (precursor of glutathione)
Additional- SAMe, ascorbic acid

Question 4

What are the clinical manifestations of NSAID toxicity?

Answer 4

Early- GI erosion, ulceration and poss perforation, V+/D+, rarely CNS symptoms (ataxia, lethargy, drowsiness)
Late- RF, hepatic impairment
Largely due to COX-1 inhibition. Therapeutic action due to COX-2 (PG suppression)

Question 5

What is the treatment for NSAID toxicity?

Answer 5

Decontamination: emesis (optimal w/in 3hrs)- dogs apomorphine; activated charcoal (repeat doses)
Prevention of gastric ulceration: H2-R antagonists (cimetidine, ranitidine, famotidine), proton pump inhibitors (omeprazole), ulcer healing/ coating agent (sucralfate)
PG supplementation- misoprostol
Maintenance of renal function- IVFT

Question 6

What are the clinical effects of theobromine toxicity?

Answer 6

V+/ D+, PD, salivation- dehydration. CNS/ myocardial stimulation (tremor, convulsions, tachycardia, hypertension), RF. Fatal cases- severe convulsions/ circulatory failure

Question 7

What is the treatment for theobromine toxicity?

Answer 7

Emesis- apomorphine
Repeat dose activated charcoal
Adequate rehydration
Monitor vital signs, ECG, benzodiazepines for CNS stim, tx of arrhythmia (lidocaine/ B blocker)

Question 8

What are tremorgenic mycotocins?

Answer 8

Fungal metabolites produced by mould. Penitrem A may interfere w/ release of NTs (glutamate, aspartic acid and GABA). Onset of action usually w/in 3hrs- V+, ataxia, tremors, rigidity w/ hyperextension of extremities, hyperactivity, hyperaesthesia, tachycardia, panting, tachypnoea, nystagmus and blepharospasm. Svere- convulsions, coma w/ paddling, rhabdomyolysis

Question 9

What is the treatment for tremorgenic mycotoxin toxicity?

Answer 9

Decontamination: emesis (apomorphine), gastric lavage, activated charcoal (recirculation)
Anticonvulsants- benzodiazepines, barbiturates, methocarbamol
Supportive care- rehydration, cooling, ventilation, antiemetics

Question 10

What are the allium sp and what is their mechanism of toxicity?

Answer 10

Large group of plants incl leeks, onions, shallots, garlic
Contain organosulphoxides, trauma to plant converts to organic sulphur compounds. Within erythrocytes reduce the protective effect of the antioxidant, glutathione (remains in oxidative state). Mixed sulphide bond forms between Hb and glutathione–> heinz body formation. Damaged erythrocytes removed inducing anaemia.

Question 11

What are the clinical effects of allium sp toxicity?

Answer 11

Variable onset, signs of haemolysis can be delayed for 1-5d, heinz bodies w/in 24hr.
GI effects (V+, inappetance, onion smelling breath), heinz body anaemia (lethargy, pale MM, tachycardia, tachypnoea), haematurea and haemoglobinurea

Question 12

What is the management for allium sp toxicity?

Answer 12

Emesis. Activated charcoal. Monitor haem parameters. IVFT. Anti-emetics if needed
Supportive- high protein diet may restore glutathione, supplemental O2 in severe cases, oxyglobin/ blood transfusion in crictal

Question 13

What is the mechanism of toxicity of anticoagulant rodenticides?

Answer 13

Inhibit vit K reductase. Thus depletion of vit K and so reduction in factors II, VII, IX and X- essential for production of fibrin.

Question 14

What are the clinical effects of anticoagulant rodenticide toxicity?

Answer 14

Clinical effects rare. Delay between exposure and effects due to 1/2 life. Onset 24-72hrs. Elevation of PT time. Main effect is haemorrhage. May present w/ dyspnoea, lethargy, weakness or anorexia. Bruising, bleeding from gums, GIT, nose, wounds.

Question 15

What is the treatment for anticoagulant rodenticide toxicity?

Answer 15

Not always necc
If required- decontamination by emesis (apomorphine, xylazine) or activated charcoal. If elevation in PT/ symptomatic then Vit K therapy. In severe intoxication whole blood transfusions may be required.

Question 16

What are the clinical signs of molluscicide (metaldehyde) toxicity?

Answer 16

Hypersalivation, V+, D+, ataxia, panting, tremors, convulsions, hyperthermia.
Resp and cardiac effects less common.
Fatalities usually due to resp failure.

Question 17

What is the management for molluscicide toxicity?

Answer 17

Most common fatality for VPS. Emetics? Gastric lavage? Activated charcoal.
Management of convulsions- benzoizepines, propofol+ midazolam. Consider referral?

Question 18

What is the presentation of Vipera berus toxicity?

Answer 18

European adder- only venomous snake in UK. Can cause significant morbidity but low mortality. Dry bites. Venom- proteases, peptide hydrolases, hyalyronidase and phospholipases.
Hypovolaemia and local oedema (incr vasc perm), cardiac effects, renal impairment may be due to hypovolaemic shock.

Question 19

What is the tx for vipera berus toxicity?

Answer 19

IVFT, antivenom. Monitor BO, pulse, resp, temp, ECG, BT (check for coagulopathy), renal and hepatic parameters
Analgesia- opiod (not NSAIDs due to renal risks), abx (rare), antihistamines

Question 20

What adverse reactions can occur to vipera berus antivenom?

Answer 20

Uncommon
Early (anaphylactic)- urticaria, V+, fever, tachycardia. In severe there can be hypotension, bronchospasm. Tx- adrenaline, steroids and antihistamines
Serum sickness- days after, fever, urticaria, joint pain, lymphadenopathy. Tx- steroids and antihistamines

Question 21

What is lipid rescue therapy?

Answer 21

Used to tx dogs poisoned w/ lipophilic drugs: moxidectin, avermectin, ivermectin. Thought that lipid component formed in blood acts as a sink for lipophilic substances making them unavailable to act on their target Rs.

Question 22

What is xylitol toxicity?

Answer 22

Found in chewing gum, naturally occurring in fruit and beg. Rapid stimulator of insulin release. Requires gastric decontamination and monitoring.
Hypoglycaemia tx- frequent small meals, glucose/ dextrose, ECG monitoring
Hepatotoxicity tx- consider immediate dextrose therapy, SAMe

Question 23

What is the effect of the MDR-1 gene mutation of collies, shepherd dogs?

Answer 23

MDR-1 codes for P-gp- a large transporter protein which acts as an efflux pump. Most commonly associated w/ toxicity from MLs (ivermectin, moxidectin, doramectin, milbemycin, selamectin), loperamide, vinca alkaloids (vincristine)

Question 24

What are endotoxins vs exotoxins?

Answer 24

Endotoxins- lipid A portion of LPS of G-ve OM.
Exotoxins- classically produce by G+ve, protein and heat labile e.g. collagenases, haemolysins, also produced by some G-ve e.g. cholera toxin, E Coli enterotoxins. Useful as basis for vaccine

Question 25

What is the pathophysiological effect of endotoxins?

Answer 25

Interaction w/ R on macrophage membrane, recognized by PRRs on host cells. Stimulates production of TNF and IL-1. Induces fever, leucopenia, hypotension, activation of C3, DIC, shock and death

Question 26

What are some examples of neurotoxins?

Answer 26

Botulinum toxin- blocks release of ACh at synapse and NMJ--> flaccid paralysis and death Tetanus- blocks release of NTs at inhibitory synapses causing uncontrolled excitatory synapse activity- paralysis

Question 27

What are superantigens?

Answer 27

E.g. staphylococcus aureus TSST-1. Immunomodulators which induce massive T cell activation and cytokine release. Binds to invariable regions on MHCII on APC- process of T cell activation is short circuited.

Question 28

What physiological differences in neonates influence drug handling?

Answer 28

Decr GI motility, underdeveloped gut flora and immature mucosal enzymes all lead to decr absorption of some drugs Incr total body water (polar drugs have a larger vol of distribution) Immature liver metabolic capacity Decr GFR and renal tubule function

Question 29

Describe monensin toxicity in horses?

Answer 29

From eating feed meant for sheep. CS related to neuronal, skeletal muscle and cardiac muscle effects of ionophores. Susceptibility due to low 1st pass metabolism in horses compared to ruminants making systemic bioavailability much higher than sheep.

Question 30

Why are pyrethroids toxic to cats?

Answer 30

Probably due to ineffective metabolism- lack of glucuronidyl transferase. Target is voltage dependent sodium channel- leads to repetitive firing of neurons

Question 31

What are the 5 primary agents of concern wrt food poisoning?

Answer 31

``` Camplylobacter Salmonella Listeria E Coli Norovirus Other: s.aureus, bacillus cereus, c.perfringens, c.botulinum, vibrio parahaemolyticus. TSE ```

Question 32

What is campylobacter?

Answer 32

Curved G-ve rod. C.jejuni (poultry), C.coli (pigs). Microaerophilic, thermophillic. Endemic in animals. Dx by culture of faeces (blood agar w/ abx selection, 48hrs). Zoonotic

Question 33

How does campylobacter cause dz?

Answer 33

Incubation 2-5d. Colonises the SI and causes enteritis. D+, V+, stomach pains, cramps, fever, unwell. Cooking always kills Campylobacter

Question 34

What is listeriosis?

Answer 34

Can grow at low temp. Transmitted in faeces- soil, vegetation, silage, udder. Ingestion can cause encephalitis and bacteraemia causing abortion. Grows and proliferates in epithelial cells, phagosomal escape, cytosolic replication, direct cell to cell spread. Normal adults rel resistant and cooking always kills.

Question 35

What is norovirus?

Answer 35

Winter vomiting bug (ssRNA). Person to person spread, food or food handles. Faeces. Calicivirus. Small infective dose. Resistant in environment. Cooking and disinfection always kill the virus.

Question 36

What is E coli O157?

Answer 36

Shiga toxin producing Coli= STEC. Toxin encoded by bacteriophage which infects the E COli. Toxins- ST 1 and ST 2. Some D+ and haemorrhagic colitis in calves but generally just carry. Adheres to villus surface and injects toxin into cells, causing vascular damage, oedema, thrombi. Cooking destroys pathogen. Detection by culture and latex agglutination test Carriage by calves--> beef. Can get onto cooked foods. Only need low dose--> haemorrhagic colitis and haemolytic uraemic syndrome--> RF

Question 37

What is Salmonella?

Answer 37

Many animals carry small no. Infectious dose quite high. Vaccination reduced carriage by FAs, broilers and layers. Control means incidence significantly decr. Cooking always kills. Dx by culture and serotyping.

Question 38

What are the other causes of food borne dz?

Answer 38

S.aureus- heat stable enterotoxins, must be incubated 6-12hrs for toxin to form Bacillus cereus- rice, cooking activates spores, toxin produced during subsequent incubation C.perfingens type A- 5% strains produce enterotoxin C.botulinum- faeces and soil- botulinum toxin in heated, anaerobic foods (canned/ bottled) Vibrio parahaemolyticus- shellfish