Antiprotozoal Agents (2) Flashcards
Imidazothiazole (Levamisole) acts at what receptor
Nicotonic Ach receptors on nematode muscle cells —> Spastic paralysis !!
Imidzothiazoles Spectrum
A variety of GIT and lung nematodes
NOT CESTODES OR TREMATODES
Imidazothiazoles- toxicity
Cholingeric activity -> MUSCARINIC AND NICOTONIC EFFECTS
i.e. SLUD, resp distress, bradycardia, asfixia, CNS depression
Imidazothiazoles — antidote
None
Imidazothiazoles— theraeutic margin
MOST TOXIC anthelmintic
Fairly narrow therapeutic margin (safety margin may be as low as THREE TIMES the therapeutic dose)
Imidazothiazoles sheep vs cattle; chicken
Sheep seem more sensitive than cattle
Chickens tolerate it well
Imidazothiazoles forms of usage
Tablet, oral solution, oral drench, feed additive, SQ, or TOPICAL POUR ON
Imidazothiazoles herd dosing
Use SQ or IM or Pour on for the cattle
Tetrahydropyrimidines (Pyrantel, Morantel) MOA
Agonist at Nicotinic Ach receptors (like Levamisole) —> spastic paralysis
Tetrahydropyrimidines spectrum of activity (horse)
Horses- GI NEMATODES
High doses- against ileocecal TAPEWORM OF HORSES
Tetrahydropyrimidines use in cattle, dogs, cats
GI nematodes
Tetrahydropyrimidines Toxicity
High margin of safety
Doses 7x greater than therapeutic dose —> no signs of toxicity
(Vs Levimasole) !!!!
What should you not combine with Tetrahydropyrimidines
Other CHOLINERGIC agonists (Levamisole) Or antagonists (piperazine)
**spastic paralysis!
Tetrahydropyrimidines
Pyrantel tartrate vs pamoate
Pyrantel tartrate for horses
Pamoate— horses and dogs
Pyrantel tartrate usage
HORSES: continues daily administration for prolonged periods of parasite exposure
Pyrantel pamoate uses in horses vs dogs
Horses- Suspension or paste, also mixing with feed
Dogs- Suspension and tablet forms, combined in a tablet
**with FEBANTEL and PRAZIQUANTEL
Combined with a chewable containing IVERMECTIN
Morantel tartrate usage
Only approved for cattle
*sustained release bolus for beef and dairy cattle
Heterocyclic compounds (piperazine) MOA
GABA agonists — induces FLACCID paralysis
Vs levimasole and Tetrahydropyrimidines— SPASTIC paralysis
Piperazine spectrum of activity
Narrow- primarily ASCARIDS
Piperazine toxicity
Wide margin of safety, even avail OTC
Piperazine toxicity
CNS depression (ataxia, weakness, muscle tremors)
name 2 heterocyclic compounds
Piperazine
Diethylcarbamazine
Piperazine usage
Dogs cats horses for ASCARIADS
Diethylcarbamazine
First Heartworm preventive that has to be given daily
When to use Diethylcarbamazine
Limited use- for dogs that do not tolerate MONTHLY heartworm preventatives
Arsenicals
Melarsomine— heart worm adulticides
Melarsomine MOA
Presumed to affect glycolysis (metabolism of parasite)
Melarsomine spectrum of activity
Adult and 4 month old heartworms
Melarsomine efficacy of a single regimen of 2 injections
What to do for second regimen
2 administrations, ONE MONTH APART —> efficacy of >90%
Second regimen —> 4months later —> efficacy to 98% (I think he is saying in class- do 1 month administrations, for 4 months??)
Melarsomine- margin of safety and toxicity
Low margin of safety
Liver toxicity, Nephrotoxicity, adulticide induced thromboembolic pneumonia
See orange chart— side effects
**know first five effects
Injection site reactions Coughing and gagging Depression / Leth Anorexia /Inappetance Pyrexia
Also Lung congestion, V/D , dyspnea, hypersalivation, panting, hemoptysis followed
See second orange chart of onset times
Know that it isn’t immediate
But usually like a week later or so
Dimercaprol
Possible Antidote
Dimercaprol— when efficacious
If given within 3 hours of melarsomine administration (but reduces the effects of melarsomine)
Melarsomine is contraindicated for what class
Dogs with Class 4 (very severe HW diease)
MAY DIE
Melarasomine in cats
NO. Not indicated !!!!!
Where to inject immiticide
GIVE IN LUMBAR AREA ONLY (deep IM injection into epaxialmuscle group between L3-L5)
NOT SQ! If formulation stays in between skin and muscle will lead to inflammation and abscess
Melarsomine IV or IM
IM ONLY
NOT IV
AVOID SUPERFICIAL INJECTION OR LEAKAGE
Melarsomine monitoring
MONITOR DURING TX AND FOR UP TO 24 HOURS AFTER LAST INJECTION
Keep the patient in your care at LEAST 8 hours (ideal 24 hours to see adverse effects)
Melarsomine goal
Eliminate ALL ADULT heartworms with min post TX complications
Melarsomine— what stage effective
ADULTS ONLY
Emodepside MOA
Binds to a G protein coupled receptor (GPCR) which is a LATROPHILIN like receptor —> secondary messengers system —> releases an INHIBITORY NEUROPEPTIDE (possible GABA) —> FLACCID PARALYSIS
Emodepside spectrum of activity
Broad NEMATODAL ACTIVITY (larval and adult forms— including those resistance to other drugs)
Activity against TAPEWORMS
Emodepside toxicity, margin of safety
High margin of safety
Emodepside clinical use— dogs or cats
Cats as a spot on formulation (Profender)
Dogs— ORAL ONLY
Emodepside - kittens
Do not use in kittens under two months
Emodepside- Collies
If ivermectin sensitive copies, the therapeutic margin is a LOT LOWER
Treatment at 2x the therapeutic dose can cause —> discomfort, uncertain gait
Anticestodal drugs
Praziquantel and esiprantel
Also Pyrantel and Morantel
Name 2 important cestodes
Anoplocephala perfoliata— causes erosions around ileocecal valve —> intussuusception
Ecchinococcus granulosus (dogs)
Praziquantel and epsiprantel MOA (name 2 main MOA)
1) damage tegument of parasites
2) Interferes with Ca2+ homeostasis —> causes muscular contraction and paralysis
Praziquantel SOA (farm animals vs dogs)
Targets adults stages of ALL SPECIES OF TAPEWORMS of FARM AND COMPANION ANIMALS
100% activity against E granulosus in dogs, TREATMENT OF CHOICE
Some activity against trematodes
Epsiprantel SOA
labeled for TX of common tapeworms in dogs and cats
Praziquantel toxicity
GI toxicity (vomiting ) with high doses Safe in pregnant animals
Epsiprantel (Castex)
GI toxicity (vomiting) can occur with large overdoses (40x in cats) !!
No signs of toxicity with 36x in dogs
Take home message of toxicity of Praziquantel and epsiprantel
“Both drugs are relatively safe”
