Other Anthelmintic Drugs Flashcards
What is the spectrum of Emodepside? In what animals is it used? What is its only formulation available?
ascarids and hookworms (mature and immature) of cats
topical with praziquantel for the treatment of nematodes in cats
- absorbed through the skin and deposited in adipose
What is the mechanism of action of Emodepside?
selective agonist of the presynaptic lactrophillin-receptor (LTP) in parasitic nematodes, resulting in flaccid paralysis and death
What 3 adverse effects may occur with the use of Emodepside?
- alopecia at application site
- salivation and vomiting due to licking application site
- tremors with overdose
What effect does Emodepside have on rats and rabbits?
interferes with fetal development
- pregnant women should wear gloves if product handling is necessary
When is Derquantel commonly used? What is its mechanism of action?
active against both benzimidazole and ivermectin-resistant Haemonchus contortus
acts as an antagonist of neuronal nicotinic cholinergic receptors in nematodes causing flaccid paralysis
- has a markedly lower affinity for mammalian receptors also
What are the 4 steps to the life cycle of heartworm?
- mosquito gets microfilariae while sucking blood of an infected host
- microfilaria (L1) develops into L3 inside mosquito and migrates to the oral portion of the mosquito
- mosquito punctures new host, depositing L3 that will develop into L5 to penetrate veins to reach the heart and pulmonary arteries
- adult heartworm lives in the right cardiac ventricle and in the pulmonary artery and females produce larvae into circulation
- both adults and microfilariae of Dirofilaria immitis are responsible for clinical signs associated with heartworm disease
How does a large number of Dirofilaria immitis deposition affect the heart?
cause greater pulmonary hypertension, thromboembolism, and risks vena caval syndrome
What 3 aspects are considered when treating and preventing heartworm disease?
- remove adults - adulticide
- prevent infection - larvicide
- use of microfilaricides is not common, adulticides will decrease microfilaria population
What adulticide is commonly used to treat heartworm disease? Where does it tend to concentrate? Metabolized and excreted?
Melarsomine (Immiticide)
liver and kidneys
metabolized in the liver and excreted in bile
How is Melarsomine (Immiticide) administered? When is its use contraindicated?
deep IM in L3-L5 lumbar epaxial muscles
caval syndrome where worms block the caudal vena cava, which requires immediate surgical removal
Why is it especially important to have an accurate weight before administering Melarsomine (Immiticide)? What is a possible antidote for reversing toxicity?
has a low margin of safety
Dimercaprol (BAL)
How does Dimercaprol (BAL) act as an antidote for Melarsomine (Immiticide) toxicity?
its sulfhydryl groups for heterocyclic rings and complexes with metals, principally arsenic, lead, mercury, and gold, allowing them to be excreted via renal and fecal routes
No drug is approved for use as a microfilaricide in heartworm disease. What 2 drugs tend to have microfilaricide effects?
- Ivermectin
- Milbemycin**
What larvicides are commonly used for heartworm prevention? How do they work?
macrocyclic lactones
- Ivermectin
- Moxidectin
- Milbemycin oxime
- Selamectin
kill larval stages (L3-L4) of Dilofilaria immitis in dogs and cats
How does the severity of cestode infections compare in farm animals and companion animals?
FARM ANIMALS - may be a minor problem and usually does not require treatment with specific cestocidal drugs
COMPANION ANIMALS - treatment is necessary, since dogs and cats are DH for cestodes and larval stages cause zoonosis
What is a common treatment of Anoplocephala perfoliate infections in horses?
pyrantel pamoate paste at 2x nematode dose
(most common tapeworm in horses)
What is the spectrum of action of Praziquantal?
highly efficacious against adult stages of all tapeworms in farm and companion antimals, along with trematodes
- Taenia hydatigena, T. pisiformis, T. ovis, T. taeniaeformis, D. caninum, Mesocestoides corti, E. multilocularis, E. granulosus
What is the mechanism of action of Praziquantal?
induces the release of intracellularly stored calcium in addition to an increase in calcium influx across the tegument
- causing rapid and sustained muscle contraction and tegumental disruption
Where is Praziquantal absorbed, metabolized, and excreted?
completely absorbed in the GI tract in most species
hepatic metabolism forms a metabolite that exerts similar pharmacologic effect
renal
What is Epsiprantel (Cestex)? What is its mechanism of action?
anticestodal drug chemically related to Praziquantal that is used specifically for the treatment of common tapeworms of dogs and cats (D. caninum, T, pisiformis, T. taeniaeformis, E. granulosus, E. multilocularis)
affects calcium homeostasis within the parasite and damages the tegument, making it vulnerable to lysis and digestion
What allows for the action of Epsiprantel (Cestex) against intestinal cestodes?
poorly absorbed in the GIT and is available to act on the tapeworm and induces elimination in FECES
Praziquantel vs. Epsiprantel:
What causes fasciolosis?
liver fluke, Fasciola hepatica and Fasciola gigantica; it is the most economically important diseased caused by trematodes in domestic animals worldwide
(drugs active against one works on the other)
What rumen fluke commonly infects cattle and sheep? Why are immature stages seriously pathogenic?
Paramphistomum spp.
migrate within the gut lumen from the duodenum to the rumen, causing inflammation
What is the lung fluke of dogs and cats?
Paragonimus spp.
How are albendazole and fenbendazole used as antitrematodal drugs?
ALBENDAZOLE = used in sheep and cattle against liver flukes older than 12 weeks old
FLUBENDAZOLE = not effective against F. hepatica, but reduces F. gigantica infection
What benzimidazole has excellent efficacy against liver flukes?
Triclabendazole (TCBZ) has great efficiency against 2-day-old to mature F. hepatica
- shows no clinical efficacy against nematodes and cestodes
In what 2 ways have trematodes evolved to become resistant to Triclabendazole (TCBZ)?
- increased TCBZ oxidative metabolism by the fluke
- enhanced drug efflux mediated by ATP-dependent TM-transporter
What drug is commonly used against adult liver flukes in cattle?
Clorsulon —> highly effective against 8-week-old to mature flukes
(cattle > sheep/goats)
What is the mechanism of action of Clorsulon? What is the main route of entry into the trematode?
inhibits certain glycolytic pathways in the fluke
oral ingestion —> gut is more severely affected than the tegument
How is Corsulon distributed? Eliminated?
bound to erythrocytes
lipid soluble —> renal excretion
True or false: When treating nematodes in horses, the first choice would be levamisole.
FALSE - levamisole metabolites are dangerous to horses and not effective against most equine nematodes
Select all the common facts about praziquantel and epsiprantel.
a. spectrum of action
b. rate of GI absorption
c. mode of action
d. route of excretion
A, C
True or false: Passive diffusion is the main route of drug entry into adult liver flukes.
FALSE - ingestion
The adulticide therapy with melarsomine may result in hepatotoxicity because of…
a. its low margin of safety
b. the used route of administration
c. the number of adult parasites
d. its wide distribution and accumulation into these organs
D
What are the 2 families of endectocide compounds used as anthelmintics? What are they derived from?
- AVERMECTIN - abamectin, ivermectin, emamectin, doramectin, eprinomectin, selamectin
- MILBEMYCIN - nemadectin, moxidectin, milbemycin oxime
macrocyclic lactones produced through fermentation by actinomycetes, like Streptomyces
What are 3 important characteristics of macrocyclic latones?
- high lipophilicity
- potent broad spectrum
- persistent ectoparasitic activity
What 3 types of parasites are macrocyclic lactones effective against? What do they have no efficacy against?
- insects
- ascarines
- nematodes
cestodes and trematodes
What is the mechanism of action of macrocyclic lactones?
act on glutamate-gated chloride channels (GluCl - not present in mammals!) and GABA receptors to induce a reduction in motor activity and flaccid paralysis on the pharynx and somatic musculature
Macrocyclic lactones MOA:
What is an important aspect of the pharmacokinetics of macrocyclic lactones? What does this cause?
highly lipophilic - extensively distributed from the bloodstream to different tissues of parasites, like GI mucosa, lungs, and skin
How does doramectin and moxidectin compare?
enhances availability and prolonged time of residence in target tissues
most lipophilic endectocide agent
Where are ivermectin, moxidectin, and doramectin considerably excreted? How can this be avoided? What specific agent is used?
mammary glands
topical formulations
Eprinomectin has a good antiparasitic potency, broad spectrum, and substantially reduced distribution to milk
Where do metabolism and excretion of macrocyclic lactones occur?
liver
bile, feces, milk
What 3 macrocyclic lactones act as substrates of p-glycoprotein? Which one has a lower affinity?
- abamectin
- ivermectin
- moxidectin**
How does the duration of macrocyclic lactone persistence vary?
based on intrinsic properties and pharmacotechnical preparations
What macrocyclic lactones are commonly used to increase the protection periods between 60-150 days against cattle endoparasites?
long-acting ivermectin and moxidectin
What 4 macrocyclic lactones are commonly used in ruminants? What 3 parasites are they used against?
- Ivermectin
- Doramectin
- Moxidectin
- Eprinomectin
- GI nematodes (extremely effective against adult and larval stages***)
- lung worms
- arthropods
When is Eprinomectin most commonly used in cattle?
most commonly used as a pour-on in lactating dairy cows with zero milk withdrawal time
How are macrocyclic lactones approved for use in ruminants typically used in goats?
extra-label —> with a higher dose needed due to their higher metabolism
What 3 macrocyclic lactones are used in pigs? What 2 parasites are they most commonly used against? Which parasite can it be used with varying efficacy?
- Ivermectin
- Moxidectin
- Doramectin
- immature and adult stages of nematodes
- ectoparasites
Ivermectin has a variable efficacy against Trichuris suis
What 2 macrocyclic lactones are commonly used in horses? How do they compare? What 4 parasites are they used against?
- Ivermectin
- Moxidectin
- Moxidectin shows an extended period of protection in horses
- stomach/intestinal nematodes
- adult and larval stages of large strongyles
- adult small strongyles
- Gasterophilus intestinalis
What is Ivermectin specifically licensed for use in dogs and cats? What other 3 macrocyclic lactones may be efficacious?
preventative against dirofilariasis (L3 and L4 D. immitis) - use apart from this is considered extra-label
- Milbemycin oxime
- Moxidectin (+ Ancyclostoma caninum)
- Selamectin
What is the spectrum of Ivermectin and Moxidectin in dogs and cats considered?
limited spectrum against GI nematodes
- mostly used for heartworm
Macrocyclic lactones are highly safe compounds. When is neurotoxicity observed?
when large doses are administered, which increases GABA-mediated action in the mammalian CNS
- no effect on breeding performance, semen quality, or pregnancy
How does the safety of Abamectin and Milbemycin compounds compare to Ivermectin?
slightly more toxic —> not recommended for use in calves under 4 months
wide therapeutic margin
What is the cause of Ivermectin sensitivity seen in Collies? What are 7 signs of toxicity?
mutation causing a non-function MDR1 protein at the BBB, allowing the passage of the drug into the CNS
- depression
- ataxia
- somnolence
- salivation
- tremors
- coma
- death
What 2 macrocyclic lactones are considered safe at therapeutic doses in Collies with the MDR1 mutation?
- Moxidectin
- Selamectin
(overall efficacy and safety of MLs designed for other species should NOT be assumed for dogs and cats)
True or false: MLs are called broad-spectrum drugs because they are effective even against cestodes.
FALSE
True or false: The main MOA of MLs is caused by acting on GABA-gated chloride channels.
FALSE - glutamate-gated chloride channels (GluCl)
