Toxicology

Question 1

Acetaminophen toxicity MOA

Answer 1

ROS –> oxidative dmg to Hb –> methemoglobin and Heinz bodies –> hemolysis and hepatotoxicity

Question 2

Phases in ethylene glycol toxicity
Clue: 3 phases

Answer 2

Phase 1: neuro signs
Phase 2: acidosis (lactic acid, glycolic acid), cardiopulmonary signs
Phase 3: CaOx crystaluria, renal failure, halo sign on AUS of kidney

Question 3

bromethalin rodenticide

Answer 3

uncouples oxidative phosphorylation –> disrupts Na-K-ATPase pumps —> initially hyperexcitability –> then depression

Question 4

Strychnine MOA
Clue: Opisthotonus, rigidity

Answer 4

Inhibits glycine effect on motor neurons and interneurons –> tense, hyperthermic, rigid, resp. mm paralysis
Rx wth sedation, methocarbamol, ammonium Cl to trap strychnine in urine

Question 5

OP/ carbamates insecticides

Answer 5

Anticholinesterase inhibitor, prolong muscarinic signs (parasympathetic) (SLUDGE)

OP irreversible
Carbamate reversible

Rx Atropine, 2-PAM

Question 6

Botulism Vs Tetanus

Answer 6

Botulism: Clostridium botulinum, ingest PREFORMED toxin (most potent Type C), absorbed from SI to lymphatics –> bloodstream –> NMJ –> prevents release of Ach from presynaptic neuron via CA channel blockage

Tetanus: Clostridium tetani, spores form in wounds –> tetanospasmin enters axons of nearest motor nerve at NM endplate –> migrate RETROGRADE to cell body in SC/brain –> blocks inhibitory neurotransmitters (glycine, GABA)

Question 7

Acetamininophen Rx

Answer 7

1. Cimetidine: block CYP450
2. SAMe for glutathione, N acetyl cysteine for glutathione precursor
3. Vit C as antioxidant (for metHb)

Question 8

OP toxicity rx

Answer 8

2-PAM for nicotinc signs, atropine for muscarinic signs

OP = SLUDGE (anticholinesterase inhibitor)

Question 9

Inhibitory neurotransmitters

Answer 9

glycine, GABA

Question 10

Pyrethrins/pyrethroids

Answer 10

Insects:
Mammals: prolong Na conductance and continuously causes depolarization –> repetitive nerve firing

TREMORS

Question 11

Amitraz MOA

Answer 11

alpha 2 agonist

Question 12

CO poisoning

Answer 12

CO binds to Hb with 220% greater affinity than O2.
CO bound to Hb will increase the affinity of unbound Hb for O2 —> leftward shift of oxyhemoglobin disassociation curve

Question 13

What is methemoglobin?

Answer 13

Oxidized hemoglobin (Fe2+ become Fe3+)

Question 14

Compounds responsible for nervous signs associated with ethylene glycol toxicity in cats

Answer 14

EG and glycoaldehyde

Question 15

Cats and drug metabolism

Answer 15

1. Drugs that are eliminated more slowly in cats = acetaminophen, propofol, carprofen, aspirin (metabolized by conjugation)
2. Lack UGT1A6 and 1A9 (glucoronyltransferase) which glucoronidate acetaminophen and propofol, respectively.
3. Deficient glycine conjugation (and not glucuronidation) is the reason for slower aspirin clearance.
4. Lack N-acetyltransferase 2 = prone to developing methemoglobinemia (rather than hepatotoxicity) from acetaminophen.
5. Have low thiopurine methyltransferase activity = sensitive to azothioprine toxicity

Question 16

Acetaminophen MOA

Answer 16

Acetaminophen —> NAPQI (met by CYP450) (this is a toxic metabolite) —> detoxify by glutathione (cats deficient) —> metHb (Fe2+ to Fe3+) and hepatotoxicity (centrilobular hepatic necrosis)

Question 17

Lead toxicity

Answer 17

Carried on RBC, stored in bones, can also cross BBB and concentrate in brain

GI and neuro signs

Need chelation therapy: Ca EDTA, BAL, penicillamine, succimer

Question 18

EG toxicity rx

Answer 18

4MP, ethanol, supportive rx for AKI

Question 19

Cyanide poisoning
Clue: CCC

Answer 19

Inhibits cytochrome c oxidase —> prevent mitochondrial aerobic respiration

Rx: hydroxycobalamin, nitrites/thiosulfates

Question 20

Warfarin rodenticide

Answer 20

Vit K epoxide reductase
Factors 2, 7, 9, 10, proteins C and S