Lecture 37 - Antiparasitics 1 Flashcards
what are the 5 ways drugs enter nematodes
- lipophilicity
- ionization
- concentration gradient
- composition of nematode
- parasites external surface
what are the 4 mechanisms of action for antohemintics
- GABA agonists
- inhibit formation of microtubules
- disrupt glutamate-gated chloride channels
- nicotinic agonists
what is the mechanism of action for piperazine
gaba agonists
activate GABA receptos to produce inhibitory effect and flaccid paralysis
what ion moves through channels for depolarization after drug binding to GABA receptor
chloride
describe piperazine:
spectrum
target species
toxicity
spectrum: narrow; ascarids
target species: horse, dog, cat, swine, poultry
toxicity: large doses cause emesis, D+, incoordination, bloating
what is the mechanism of action for benzimidazoles
binds to B-tubulin causing disruption of microtubule formation, essentially starving the nematode
if BZDs are highly potent against microtubules, why do we not have more drugs available
chemotherapeutic toxicity in humans before animal use
describe benzimidazoles
spectrum
target species
toxicity
spectrum: large
target species: horse, dogs, cat, swine, poultry, ruminants
toxicity: least toxic, only toxic to growing animals
describe the absorption of benzimidazoles
BZDs are soluble in water and allow for recycling to other active components in ruminants
what is ok to prescribe for pregnant sheep
fenbendazole
what is the mechanism of action for levamisole
cholinergic receptor agonist
muscle paralysis due to activation of excitatory nicotinic receptors
L-isomer
what neurotransmitter do cholinergic agonists mimic
acetylcholine
describe levamisole
spectrum
target species
toxicity
spectrum: broad spectrum against mature stages of GI worms
target species: cattle, sheep, goats, swine, poultry
toxicity: salivation, defecation, respiratory distress
why don’t we typically use levamisole
because the small window between therapeutic and toxic dose
describe the mechanism of action for pyrantel (tetrahydropyrimidines)
cholinergic receptor agonist
muscle paralysis due to activation of nicotinic receptors
T/F: tetrahydropyrimidines are 100x more potent than AcH
TRUE
T/F: tetrahydropyrimidines work on N-nAch receptors
FALSE - L-nAcH receptors
describe tartrate salts
- readily soluble in water
- better absorption (pigs > dogs > ruminants)
- readily excreted in feces
describe pamoate salts
- insoluble in water
- poorly absorbed in GI tract
feeding a meal with pamoate salt will help what
slow GI motility, increase contact time with worms, and overall increase efficacy
pamoate salts are safe to use in
puppies and kittens
pamoate/tartrate salts have a ____ efficacy in horse and should not be administered with ____
high; lavamisole
what is the mechanism of action for arsenicals
affect glucose uptake and metabolism
alter intestinal epithelium function
melarsomine
lower arsenic
free drug in plasma
less toxicity and better efficacy
arsenicals are active against
immature (>4month) and adult heartworms in dogs
what is the mechanism of action for macrocyclic lactones
bind to glutamate-chloride channels to increase Cl- influx that leads to flaccid paralysis of pharyngeal pumps and death
what do macrocyclic lactones not treat
cestodes (flukes) and trematodes (tapeworms)
describe doramectin
target species: beef cattle and swine
spectrum: major GI worms, lungworms, etc. in cattle, all worms in pigs
describe eprinomectin
target species: beef/dairy cattle and swine
spectrum: broad
why can eprinomectin be used in dairy cattle
only avermectin that does NOT partition into milk
what PK parameter/physiology can lead to persistent concentrations of antiparasitics in animals
- poor absorption
- storage in fat reservoir
- slow metabolism
what is the 2nd mechanism of action for ivermectin
sending inhibitory signals to motor neurons that results in paralysis
explain an MDR1 gene defect
increases Cmax and decreased elimination leading to higher brain concentrations
milbemycin oxime can be found in what products
heartworm preventative, ascarids, whipworms
what toxicity does milbemycin cause
mild cardiovascular shock due to reactions with dead microfilariae
