Mechanisms of Action Flashcards
Which insecticide/rodenticide has the following MOA:
• Irreversible inhibition of cholinesterases
o 1st – muscarinic receptor stimulation
o 2nd – nicotinic receptor stimulation (ganglionic & NM blockade, CNS depression)
o 3rd – nicotinic blockade (ganglionic & NM blockade, CNS depression)
Organophosphates
Which insecticide/rodenticide has the following MOA:
• Reversible inhibition of acetylcholinesterase
Carbamates
Which insecticide/rodenticide has the following MOA:
• DDT-type:
o Slow Na+ influx & inhibit K+ efflux in peripheral nerves & brain leading to partial depolarization
o Causes repetitive firing of neuron (stimulation) – axonal hyperactivity
• Aryl hydrocarbons (ex: Lindane) & cyclodienes:
o Na+ channel effects & also may inhibit GABA
• Other mechanisms:
o ↑ brain ammonia levels
o Enhanced neurotransmitter release at cholinergic synapses
o Adrenal necrosis by metabolite O,P-DDD
Chlorinated Hydrocarbons
Which insecticide/rodenticide has the following MOA:
• Delay closure of Na+ ion channels in axonal membrane of insect
o “Knockdown effect” – rapid paralysis caused by inhibition of neurons insect is immobile but not dead yet
• May inhibit ATPase leading to repetitive firing
• Allergic reactions can be seen
• Stimulation of adrenals may result in hyperglycemia (transient)
• Differences between insects & mammals:
o Bind more strongly to lower temperature (insect ambient temp ~250C compared to mammalian temp around ~380C)
o Insect Na+ channels are ~1000x more sensitive to pyrethrins than mammalian ones
o Insect Na+ channels do not recover from depolarization as quickly as mammalian Na+ channels
o Insect metabolism (esp. w/piperonyl butoxide) of pyrethrins is much slower than mammals
Pyrethrins
Which insecticide/rodenticide has the following MOA: • Similar to Pyrethrins • Type 2 pyrethroids (alpha-cyano): o Have a greater effect on Na+ channels o At ↑ concentrations interferes w/GABA
Pyrethroids
Which insecticide/rodenticide has the following MOA:
• Blocks oxidative phosphorylation in TCA cycle preventing NADH from being oxidized to NAD & thus interfering w/production of ATP
o Strong inhibitor of mitochondrial electron transport
o Cell death can occur via apoptosis when excessive levels of reactive oxygen species are made by the mitochondria
• Has an anesthetic effect when it comes in contact w/nerve axons
Rotenone
Which insecticide/rodenticide has the following MOA:
• Unknown
• May be through central & peripheral vasodilation due to an undetermined neuronal mechanism
D-Limonene
Which insecticide/rodenticide has the following MOA:
• Low doses:
o Mimics acetylcholine & stimulates post-synaptic nicotinic receptors (CNS, ganglia, NM junctions)
• High doses:
o Stimulation followed by blockage (persistent depolarization)
• Stimulates CRTZ
Nicotine
Which insecticide/rodenticide has the following MOA:
• α-2 adrenergic agonist in CNS (Main MOA)
• Weak α-1 agonist activity
• Weak Monoamine Oxidase (MAO) inhibitor
Amitraz
Which insecticide/rodenticide has the following MOA:
• Unknown
• Can cause surface irritation (skin & mucus membranes)
DEET
Which insecticide/rodenticide has the following MOA:
• Oxidation products cause methemoglobinemia & hemolysis
o Ferric Fe3+ (rather than ferrous Fe2+) in Hgb – does not bind oxygen & alters O2 binding at other heme sites
o Leads to tissue hypoxia
• Irritant
Naphthalene
Which insecticide/rodenticide has the following MOA:
• Primarily act as GABAA agonists
o GABA is a major inhibitory NT in CNS
o Binding to GABA receptors is at a different site than GABA, benzodiazepines, barbiturates
o Influx of chloride ions hyperpolarizes cell ↓ firing of neuron (CNS suppression) – Main clinical sign
• Binding to glycine & voltage-gated chloride channels also occurs in overdose situations
• Low concentrations:
o May reduce GABA & cause excitatory signs (reversed as concentrations ↑
Ivermectin
Which insecticide/rodenticide has the following MOA:
• Inhibit vitamin K epoxide reductase
o Enzyme that converts Vit K epoxide to reduced form
• Leads to depletion of reduced vitamin K
• Reduced carboxylation & activation of precursors of clotting factors II, VII, IX, X
• 2nd generation are more potent than 1st generation
Anticoagulant Rodenticides
Which insecticide/rodenticide has the following MOA:
• Causes hypercalcemia & Hyperphosphatemia
• ↑ serum calcium due to ↑ GI absorption & ↓ renal excretion of Ca2+
o ↑ tubular reabsorption
• Deposition of calcium in soft tissues (“mineralization”) such as kidney tubules, cardiac & lung tissues, vascular walls & stomach
• Leads to tissue damage, ↑ capillary permeability & hemorrhage, renal ischemia
• ↑ renal loss of Na+ & K+ (competition w/calcium for reabsorption)
Cholecalciferol
Which insecticide/rodenticide has the following MOA:
• Uncoupling of oxidative phosphorylation
• Lack of adequate ATP
• Insufficient energy for Na+/K+ ion pumps
• Brain & spinal cord are primary targets
o Rely heavily on oxidative phosphorylation
• Ion pump dysfunction leads to fluid imbalance, edema & ↑ pressure
• May cause damage through lipid peroxidation
Bromethalin
