Insecticides

Question 1

OPs

Answer 1

Nerve VX agents, kind of acidic.

X-> S, O, F (structure): S-molecules => not as toxic as the ones with Oxon

Question 2

Cholinesterase inhibitors (OPs, Carbamates)

Answer 2

Routes:

Ingestion, absorption through the skin (higher LD50): OP well, Carbamates badly, inhalation (rare)

Question 3

OPs- toxicity

Answer 3

Diazinon: oral LD50 = 150-300, dermal = 900-3000 mg/kg
Chlorpiriphos: oral = 60-150, dermal = 150-1000 mg/kg
Fenthion: oral = 50-200, dermal = 200-300 mg/kg
Dichlorvos: oral = 10-80, dermal = 100-200 mg/kg

Cats: most sensitive (horses)

Question 4

Carbamates- toxicity

Answer 4

Aldicarb: LD50 = 0.1-1 mg/kg PO
Carbaril: LD50 = 300-2000 mg/kg PO
Propoxur: LD50 = 80-100 PO, LD50 - 800-1300 dermal

Dermal exposure = less toxic

Question 5

Toxokinetics

Answer 5

OPs: well absorption by any routes (Carbamates: GI well, others: worse)
Both: whole body distribution (BBB)
OPs: slower metabolism -> more/less toxic metabolites, Carbamates: faster -> less toxic metabolites
OPs: no accumulation, biological (just the effect), Carbamate: no

Question 6

Mechanism of Action

Answer 6

AChE inhibitors!! => incr of ACh (ganglion: nicotinic receptors, end: muscarinic receptors)=> endogenous ACh-intoxication

(Normal hydrolysis: acetate + choline + water)

Question 7

Clinical signs

Answer 7

SLUDGE + Myosis (eye) + Dyspnoe (bronchoconstriction) + Bradycardia
Nicotinic signs: fasciculations, mm rigidity & CNS: ataxia, convulsions, incoordination - Hyperthermia!

Question 8

Mechanism of action (OPIDN)

Answer 8

OP Induced Delayed Neuropathy: after several weeks/months
Most sensitive: humans
=> degeneration of motoric nerve axons -> demyelination => mm weakness, ataxia, paralysis

Question 9

Diagnosis

Answer 9

History & PS signs
Response to specific therapy
Lab analysis: rarely (OP detected by PLC)

Question 10

Treatment

Answer 10

Antidote:
1. Atropine 0.2-0.5 mg/kg (give 1/4 IV, 3/4 IM,SC) => only acts on muscarinic receptors => just treats DUMBSLED, but not the convulsions
Repeat after 2-4h
Cat = v sensitive

2. Pralidoxime IM & Obidoxime => only treat OP-poisoning (reversible) by reactivating the enzyme. Time-dependent
3. Detoxification: PO (activated charcoal 1-5 g/kg, emetics, laxatives, NaHCO3 5% PO, skin soap)
4. Symptomatic therapy -> anticonvulsants: Diazepam, Barbiturate, rehydration, bronchodilation, B-vitamins, ABs

Question 11

Pyrethrins & Pyrethroids

Answer 11

Sources: Chrysanthemum spp
Pyrethroids (synthetic): Permethrin, Tetramethrin, Flumethrin, Deltamethrin

Route: Antiparasitic treatment OD (occasional)

Question 12

Pyrethrins & Pyrethroids- toxicity

Answer 12

Pyrethrin LD50 = 250-1500 mg/kg PO, dermal: 1800 mg/kg

Pyrethroid LD50 = PO / dermal >1000 mg/kg

Question 13

P & P- Toxicokinetics

Answer 13

Moderate absorption: GI/skin
Rapid metabolism -> low toxicity
Rapid excretion
Mechanism of action: Neurotoxicants -> inhibition of closing of Na channels (depolarization => contractions) -> Knockout effect.
GABA- med Cl- channels (Flumetrin, Deltametrin) => receptors inhibitors

Question 14

P & P- clinical signs

Answer 14

Hypersalivation, vomiting, ataxia, convulsions (tremors), mydriasis, tachypnoe -> dyspnoe

Question 15

P & P- treatment

Answer 15

NO specific antidote => Symptomatic therapy:
1. Tremors: Diazepam 0.5-1 mg/kg IV/IM, Barbiturate. Benzodiazepines -> GABA receptors. If they don’t work give Barbiturates (propofol, inhalational anaesthetics) & fluids (convulsions)
2. Removal: dermal washing, activated charcoal, laxatives, IV lipid (20% -> binds it -> elimination)
Wait 24h, then re-evaluate

Question 16

Formamidines- Amitraz

Answer 16

Source: Antiparasitic treatment (for the 8-legged arthropods)

Question 17

Amitraz- Toxicity

Answer 17

OPs > Amitraz > Pyrethroids

V toxic for horses, relatively in cats, v toxic for Chihuahuas!!!

Question 18

Amitraz- Toxicokinetics

Answer 18

PO- well absorbed, dermal- 15-20% (peak plasma levels: after 3h)

Mechanism of action: MAO inhibition & a-2 agonists

Question 19

Amitraz- Clinical signs

Answer 19

Within 2-4h
On a-2 receptors: sedation, ataxia, hypothermia, vomiting
On a-1 + a-2 receptors: vasoconstriction -> hypertension -> reflex bradycardia -> hypotension
Hyperglycaemia, decr intestinal motility (paralytic ileus, fatal colic in horses)

Death caused by severe bradycardia, hypothermia, ileus

Question 20

Amitraz- Diagnosis & Treatment

Answer 20

History & clinical signs
Treatment: a-2 antagonists: Atipamezole, Yohimbine,
emetics, activated charcoal, fluids, electrolyte therapy.
Macrocyclic Lactones: Ivermectin (=source, most toxic), Salamectin, Moxidectin
Lipophilic agents: v good absorption & distribution (cross BBB, blood-milk), long T1/2 (several weeks)

Question 21

Molluscicides- Metaldehyde, Cu-sulfate, insecticide-carbamates

Answer 21

[]= 3-20%
Usually pellets, granules, coloring (BUT colorless to pets), vanilla smell

Mechanism of action: snail mammals (damage the NT in the synapses)

Question 22

Metaldehyde- Toxicity, Toxokinetics

Answer 22

LD50= 200-300 mg/kg (dogs)
PO: moderately toxic 3-20m/m%

Good absorption, total distribution (BBB)

Question 23

Metaldehyde- Mechanism of action

Answer 23

Local irritation (Metaldehyde -> Acetaldehyde -> Acetate => local & vomiting).
Accumulation in synapses -> damages NT: NA, GABA, Serotonin

Question 24

Metaldehyde- Clinical signs

Answer 24

Acute (1-2h): tremors, convulsions, hyperthermia -> haemoconcentration => DIC, transient blindeness
Early death: Resp.F
Late death: LF

Question 25

Metaldehyde- Diagnosis, Treatment

Answer 25

Freezing bait, vomit -> lab (chemical analysis) Treatment: intensive for 2-3 days: induce emesis, gastric lavage, sedation, anticonvulsion, mm relaxation, IV fluids, DIC