Anthelmentics Flashcards
what is an anthelmentic and what are the two most important features of one
drug used to control parasites
- spectrum of activity
- safety index (ratio of toxic dose to therapeutic dose)
what class of drugs inhibit polymerization of tubulin formation in nematodes
benzimidazoles
what is a primary benzimidazole
thiabendazole (TBZ)
what are the 3 secondary benzimidazoles
cambendazole
parbendazole
oxibendazole
what are 3 tertiary benzimidazoles
Fenbendazole (FBZ)
albendazole (ABZ)
Oxfendazole (OFZ)
what can thiabendazole (TBZ) be used to treat
broad spectrum (all gastro intestinal nematodes) will kill migrating S vulgaris at 10X dosing rate 5 daily doses kills inhibited larvae of Ostertagia
what is the safety margin of TBZ
very high safety margin of above 10
non toxic
what are tertiary benzimidazoles used to treat
highly effective against inhibited ostertagia
currently in extensive use
what are some pharmacological features of the benzimidazoles
oral administration only- white drench
goes into rumen some gets to gut (depot effect)
metabolized to sulphoxidein liver->sulphone (anthelmentic activity)
OVICIDAL
what is the depot effect
metabolites of drugs also have anthelmentic effect
what species is benzimidazoles administered to and how
ruminants- drench
horses- paste
dogs, cats- tablets
pigs, poultry- powder
what is benzimidazole used to treat in ruminants
resistance?
tertiary
kills trichostrongyles and lungworms
kill inhibited and migrating larvae
widespread resistance in trichostrongyles in sheep
what is benzimidazole used to treat in horses
kill adult stages of all strongyles; kill migrating S. vulgaris larvae
NOT effective against inhibited cyathostomes (except when 5 daily doses used)
widespread resistance in cyathostomes
treatment with benzimidazole in dogs, cats, and pigs
no “depot”, must give 3-5 daily doses; mebendazole
what is imidazothiazoles- levamisole mode of action
cholinergic agonists at synaptic and extrasynaptic nicotinic acetylcholine receptors (motor end plates)
• depolarisation causes spastic paralysis
acting on the Nervous system
what does imidazothiazoles have activity against (worms)
nematodes including lung worms
not active against cestodes or trematodes
not active against inhibited larvae
Broad spectrum
how can imidazothiazoles be administered and what color is the drench
orally or parenterally, pour on (percutaneous absorbtion), intraruminally
clear drench
how does imidazothiazole act within the body
rapidly absorbed from gut in ruminants and monogastrics peak blood levels in 30 mins excreted in urine in 6 hours NOT ovicidal high safety index (easy to overdose)
is there resistance associated with imidazothiazole
widespread resistance in trichostrongyles of sheep and goats
which species are imidazothiazoles not used in and why
horses- causes excitement
Tetrahydropyrimidines - Morantel, Pyrantel mode of action
- depolarise motor end plates in muscle
* same site of action as levamisole (motor end plates)
Tetrahydropyrimidines - Morantel, Pyrantel activity
- most GINs; NOT lungworms**
* NO effect on inhibited larvae**
Tetrahydropyrimidines - Morantel, Pyrantel pharmacokinetics and safety index
• soluble • administered orally • rapidly absorbed • excreted in urine not ovicidal SI: 7x
Tetrahydropyrimidines - Morantel, Pyrantel use in sheep
widely (?) used
resistance in trichostrongyles
cross resistance with levamisole
if resistant to morantel, still susceptible to levamisole
Tetrahydropyrimidines - Morantel, Pyrantel in cattle
morantel capsule (releases drug for 90 days) widely used in Europe resistance in trichostrongyles
Tetrahydropyrimidines - Morantel, Pyrantel use in horses
not effective against inhibited cyathostomes used as also effective against cestodes
Tetrahydropyrimidines - Morantel, Pyrantel use in dogs and cats
pyrantel rather than morantel used removes hookworms
often used with oxantel to kill whipworms
macrocyclic lactones mode of Action
GABA agonists- bind with high affinity to glutamate gated chloride channels
->flaccid paralysis
macrocyclic lactones actviity
all gastrointestinal nematodes and arthropods
-not cestodes or trematodes
extremely potent- very low dose is needed
macrocyclic lactones pharmacokinetics
and safety index
oral, injectable, pour-on absorbed rapidly short half life after oral admin half life of moxidectin is 28 days- long acting SI: 20x (very good)
what effects does administering ML orally have
high drug availability at site of parasite
improved therapeutic response
effects of administering ML parenterally/sub cutaneous
high drug systemic availability
extended persistence of antiparasitic acctivity
effects of administering ML as a pour on
large skin depot of the drug
erratic percutaneous absorption
oral ingestion
large interanimal variability
what animals are MLs used in and against what
Sheep- widely used, limited resistance in trichostrongyles (cooperia and haemonchus)
cattle: kills inhibited ostertagia, resistance only to cooperia
horses: moxidectin kills up to 80%; resistance in cyathostomes
dogs, cats: oral (milbemycin) or topical (selamectin)- lung and hookworms
what is the environmental effect of ML
persists in feces killing arthropods outside of host
what is the mode of action of OP
inhibits acetylcholinesterase- spastic paralysis
what is the activity of OP
highly effective against haemonchus
higher doses needed to kill trichostrongylus and ostertagia
where is OP used
only in sheep
there is no resistance present- so use in combo where resistance is an issue
what is the mode of action of piperazine
agonist of GABA receptors->flaccid paralysis
relies on peristaltic movement to remove worms
what is the activity of piperazine
narrow spectrum- ascarids and nodule worms
given orally
low toxicity
what animals is piperazine used in and against what
horses- removes adult strongyles, does not kill inhibited cyathostomes
dogs, cats: effective against hookworms
pigs: oesophagostomum spp.
what is the mode of action of closantel
uncouples oxidative phosphorylation
how is closantel given and how long does it persist
orally
in blood for 4-6 weeks
what species is closantel used in and against what
sheep- haemonchus, resistance limited but spreading
dogs: against hookworms, but rarely used
what is the mode of action of monepantel
nematode specific ACR 23 nicotinic acetylcholine receptor sub unit-> spastic paralysis
derquantel mode of action and what is it used for
nicotinic agonist-> flaccid paralysis- does not kill nematodes
used in sheep against dictyocaulus
what treatments can be used against encysted larvae of small strongyles of horses
Fenbendazole @ 10mg/kg/day for 5 days Moxidectin @ 0.4 mg/kg
what should be the deworming regime for puppies
- treatment every 2 weeks prior to weaning
- treatment every 4 weeks after weaning
- treatment every 3 months after 6 months of age
what should be the deworming regime for pregnant bitches
• Fenbendazole @ 50 mg/kg/day from 3 weeks prepartum to 2-15 days postpartum
