Antiparasitics Flashcards
Narrow-spectrum antiparasitics; broad calsses
- cestocides
- anti-coccidials
types of cestocides
- praziquantel
- epsiprantel
types of anti-coccidials
- sulfonamides
- amprolium
- monensin
- lasalocid
- decoquinate
- toltrazuril/ponazuril
drugs with limited cestocide activity, but not their main purpose, and what they treat
- fenbendazole - Taenia sp. (dogs)
- albendazole - Moniezia sp. (cattle)
- pyrantel - Anoplocephala sp. (horses)
Drugs with only cestocide activity and what animals they are for
- praziquantel - dogs, cats, horses
- epsiprantel - dogs, cats
Praziquantel
class
- isoquinolone
what is praziquantel licensed for?
- Dogs, cats
> Taenia spp, Dipylidium sp, Echinococcus spp - Horses
> Anoplocephala sp
Mechanism of action of praziquantel
- binds to parasite integument > rapid vacuolization
- Influx of Ca2+ > muscle contraction (in seconds)
- impaired function of scolex > paralysis, dislodgement, death
- vulnerable to host digestion > tapeworm fragments may not be seen in feces
praziquantel pharmacokinetics
- active as single dose via oral or parenteral administration
- widely distributed to all tissues via either route
Praziquantel adverse effects:
- wide margin of safety (therapeutic index >5)
- oral - vomiting, lethargy/anorexia, transient diarrhea in dogs
- excessive salivation in cats
- injection site pain (transient)
availability of praziquantel
Available singly (Droncit) and in combination formulations:
* Drontal, Milbemax, Profender, NexGard COMBO (cats),
* Quest Plus, Eqvalan Gold (horses)
* Drontal Plus, Dolpac, Interceptor Plus (dogs)
Epsiprantel class
benzazepine
epsiprantel is licensed for what?
dogs & cats – Taenia spp, Dipylidium sp
mechanism of action of epsiprantel
- thought to be similar to praziquantel
> affects Ca2+ homeostasis within parasite
epsiprantel pharmacokinetics/treatment
- active as single dose via oral administration
- practically insoluble in water – minimal absorption from gastrointestinal tract
epsiprantel adverse effects
- very wide margin of safety (therapeutic index >36)
- vomiting, anorexia, transient diarrhea = occasional
- side effects less common than with praziquantel
Note: cheaper than praziquantel
epsirantel availability
Only available as Cestex
coccidia life-cycle
Day 1: ingestion of oocysts
- Multiplication of the parasite in the small intestine without clinical signs
Day 14: Coccidia enter large intestine
Day 18-19:
>diarrhea +/- blood
> heavy infestation
> during stress
Day 18-25:
Excretion of oocysts
anti-coccidia drugs: coccidiocides
-sulfonamides
- amprolium (also coccidiostat)
- toltrazuril
anti-coccidia drugs: coccidiostats
- amprolium (also coccidiocide)
- monensin
- lasalocid
- decoquinate
sulfonamides are licensed for what animals? stat or cide? treat at what frequency and for how long?
Licensed: cattle, sheep, poultry (dogs & cats)
* coccidiocide
- first effective anti-coccidial agents
- treat daily until after > subclinical
mechanism of action of sulfonamides? synergy?
- interfere with protozoal folate synthesis:
- decreased production of nucleotides
> decreased DNA synthesis - sulfonamide + trimethoprim = synergistic
sulfonamides adverse effects
- gastrointestinal upsets (vomiting, anorexia, diarrhea)
- precipitation in renal tubules in dehydrated animals
- polyarthritis, especially Dobermans after >1 week therapy
- keratoconjunctivitis sicca (“dry eye”) in dogs
efficacy of sulfonamides?
- acquired drug resistance, especially in poultry
*still an effective anti-coccidial in small animals and ruminants - no clinical evidence that one sulfonamide more/less toxic or efficacious than another
Amprolium in licensed for what animals? cide or stat? administered how?
Licensed: cattle, poultry (sheep, dogs, cats)
* coccidiocide + coccidiostat
* administered orally - food, water, capsules
mechanism of action of amprolium?
competitively inhibits thiamine uptake
adverse effects of amprolium?
- anorexia, depression
- prolonged use can > development of thiamine deficiency > CNS dysfunction
- clinical signs may be reversed by adding thiamine to diet
- not recommended for use in puppies >12 days
Ionophore antibiotics? origin?
- monensin
- lasalocid
> streptomyces products
ionophore antibiotics are coccidiostats or cides? other effects?
Both: (a) coccidiostats (b) increase weight gain
mechanism of action of ionophore antibiotics
Action:
- Facilitate transport of cations across cell membrane:
> intracellular accumulation of cations (e.g. Ca2+ )
* selectively affect Gram +ve organisms – rumen microflora shifts to Gram –ve organisms:
> influences production of volatile fatty acids
> increased feed efficiency + increased weight gain
Ionophore antibiotics
Pharmacokinetics:
- administered orally
- absorbed: monogastrics > ruminants
monensin toxicity
- cattle, sheep (horses, dogs) – skeletal/cardiac muscle
- dose errors in mixing with feed
- accidental ingestion by susceptible species
- accidental feedmill contamination of feed
- regurgitated bolus - potentially lethal for dogs if chewed
momensin license and admin
Licensed: cattle, sheep, goats, poultry
* coccidiostat
- administered daily in feed (premix) for at risk period
monensin admin in cattle, and advantages of use
- feed premix / controlled release bolus
- promotes increased feed efficiency and weight gain
- helps prevent :
>bloat in beef cattle on pasture
> subclinical ketosis in dairy cattle - promotes increased milk production efficiency
lasalocid license and admin
Licensed: cattle, sheep, poultry
* coccidiostat
– administered daily in feed (premix) for at risk period
– incorporated into mineral block
lasalocid admin and advantages in cattle
- feed premix
- promotes increased feed efficiency and increased weight gain
Decoquinate license and admin
Licensed: cattle, sheep, poultry
* coccidiostat (quinolone)
* administered orally - in milk replacer, feed, mineral block
action of decoquinate
- inhibits cytochrome-mediated electron transport in parasite mitochondrion
safery of decoquinate? when is it most effective?
- practically insoluble in water – very safe
- most effective in calves when fed continuously in feed
effectiveness comparison between monensin, lasalocid, and decoquinate
Note: monensin, lasalocid and decoquinate at manufacturers’ recommended levels = equally effective coccidiostats
Triazine derivatives
- toltrazuril
- ponazuril
Triazine derivatives act how?
- act on apicoplast - present in apicomplexan parasites (e.g. coccidia) – exact action unknown
- coccidiocides – typically act on all intracellular stages
Toltrazuril; when to use for strong immunity
treatment in prepatent period > strong immunity
Toltrazuril is approved for treatment of:
(i) preclinical coccidiosis in neonatal pigs:
- single dose at 3-4 days of age
- 70-day meat withdrawal
(ii) preclinical coccidiosis in lambs:
- single dose ~1 week before onset of diarrhea
- 48-day meat withdrawal
(iii) preclinical coccidiosis in dairy and beef calves:
- single dose ~1 week before onset of diarrhea
- 63-day meat withdrawal
Ponazuril; what is it? what is its use and admin strategy? how effective?
- active metabolite of toltrazuril
- “aid in reducing clinical severity of Equine Protozoal Myeloencephalitis due to Sarcocystis neurona”
- daily for 28 days
- “approximately 2 horses out of 3 will respond favourably to treatment”
