Flashcards in AntiParasitic drugs Deck (153):
5 characteristics of the ideal parasiticide?
• selective toxicity
• economical to purchase
(small vs. large animal)
• hits all stages of parasite development disrupting the entire life cycle
• safe for use in “at risk” animals
• does NOT induce resistance in the parasite
** no such thing!
Food animal production
small animal/equine medical care
• Economics of anti parasitic
- food animal production
--> economic return on entire herd health
- pets & horses
= control of zoonotic disease & health of individual pet
4 categories of “at risk” patients (concerning anti-parasitics)?
Why is it difficult to prove the presence of parasite resistance in animals?
• Hard to separate out drug administration errors vs actual drug failure
• Can't culture them
How does selective pressure result in emergence of resistant populations?
- allows resistance to emerge by killing all susceptible & allowing resistant forms to remain
What is refugia?
How does it ↓ the # of resistant organisms in a population?
Does refugia try to reduce resistant organisms to zero?
- a portion of a population of parasites that survives or avoids exposure to an antiparasitic drug treatment
- subset population of population is NOT subjected to drug
--> allows susceptible parasites to compete w/ resistant forms
--> keeps resistant forms low
--> slows resistance development w/ low worm burden present
5 methods to reduce development of parasite resistance to antiparasiticides?
• Refugia = good management practice
• Use only drugs known to be effective against
the target species of parasite
• Target only health threatening parasite
species; reduce population to safe level
• Drugs that work by different mechanisms
- if combine drug
• Rotate type of drugs used over time (equine)
EPA vs. FDA
• regulatory fxns?
• What drugs or compounds would fall under each?
How does this translate to availability as OTC products?
• controls pesticides
• available OTC
• applied topically
• regulates internal drugs
• Legend drugs
• what are they?
• who regulates them?
• given internally (PO or by injection)
• prescription only
• on or by order of vet
• must have valid VCPR
- FDA regulated
-Compounds that do both internal and external parasites
Term that describes drugs against any internal worm parasite
Term used to describe drug against roundworms
Vermicide VS Vermifuge?
• paralyzes --> expulsion
Term used to describe drug against tapeworms
• what are the specific types?
Term used to describe drug against Flukes
2 groups of macrolides or macrocyclic lactones?
members of each of these groups?
1 - Avermectins
• Milbemycin oxime
Are avermectins & milbemycins lipophilic or hydrophilic type drugs?
How does this translate to the ability of the drug to reach many target sites?
• GI mucosa
** able to target migrating larvae
what receptor do macrocyclic lactones work on?
How does this actually kill the parasite?
Bind to glutamate receptor sites on chloride channels
--> open channel
--> Cl- enters cells
--> ↑ threshold
--> pharyngeal muscle paralysis
--> starve & can't hold on
--> flushed out
Why are macrolides NOT effective against cestodes & trematodes?
- Flukes & Tapes do NOT have glutamate receptors
= not susceptible
Mammalian receptor macrocyclic lactones combine with to produce toxicity?
- Why are these still safe drugs for most animals?
- Mammals don't have PERIPHERAL glutamate receptors
• Cl- gated GABA receptors in CNS
- macrolides can activate
- BBB protects most
What keeps Macrocyclic Lactones out of the brain?
- Cell membrane pump
--> transports selected drugs from INTRA to Extracellular
Where is P-gp found
- endothelial cells of BBB
- GI epithelial cells
- bile canaliculi
- renal PCT
What gene produces P-glycoprotein?
- MDR1 gene
(multiple drug resistant)
- ABCB1 gene
"ATP-binding cassette transporters” (ABC)
Why can macrocyclic lactones kill parasites for such a long period of time w/o using high dosages of drug?
1ng of drug/g of tissue
• Persistence of drug in target tissue
+ low drug concentration needed to kill parasite
--> 1 dose per month possible
• Enterohepatic circulation
Why are avermectins & milbemycin more effective at killing mites, ticks, and sucking lice,
- but less effective at killing biting lice?
• concentrations in skin sufficient to kill mites, sucking lice, and ticks
(but not superficially-feeding biting lice)
How are macrolides primarily excreted from the body?
- intact by the liver into the feces (biliary excretion)
Why is it that once a macrolide is excreted from the body, it can then re-enter the body?
What is the this process called?
impact on the duration of action?
-Because they are lipophilic
explains long lasting effect of these drugs
Why does the persistence of avermectins & milbemycin in the body have an economic impact on their use in livestock?
pour-on vs injectable w/drawl time?
- stay in tissues for a long time!
• 1% injectable = 35-50d
• 3.15% = 120d
• no withdraw
Why are there no injectable macrocyclic lactones approved for use in dairy cattle?
• whats used instead?
- MLs are heavily excreted in the milk if absorbed into the blood
BUT pour ons forms are approved for dairy because of topical route and poor absorption into body
• eprinomectin (Eprinex®)
• moxidectin (Cydectin®)
What genetic mutation results in production of poorly functioning P-glycoprotein molecules?
In what breeds is this common?
Mechanism --> ↑ susceptibility to adverse effects from drugs like ivermectin?
What does the avermectin/milbemycin molecule do to mammalian brain cells?
Homologous mutation of the MDR1 gene
- some Shetland sheepdogs
- Australian shepherds
• ↑ GI tract absorption
• ↓ liver elimination
--> ↑ drug enters CNS
--> reaches the mammalian GABA receptors
--> opening Cl- gate
What drugs can produce a collie-like susceptibility in animals that usually would not be sensitive to avermectins?
• ketoconazole (anti fungal)
• itraconazole (anti fungal)
• phenothiazine tranquilizers
• inhibits P-gp
impairs ability of P-gp to exclude macrocyclics from CNS!greater amounts avermectins and milbemycin enter CNS
How do dogs typically become intoxicated with horse avermectins?
- chew on equine paste syringe
- LA injectable used on dog/cat
--> high dose
--> overwhelming p-gp's in CNS
Clinical signs in dogs with avermectin toxicosis?
Tx of avermectin toxicosis? Is there an antidote?
How long can toxicosis last? Why do they last this long?
• CNS depression
• salivation early
• Ataxia, stupor, coma, mydriasis, blindness
Lasts DAYS to WEEKS due to adipose & enterohepatocirculation
The presence of resistance of heartworm parasites to avermectins is controversial.
Why is this a difficult issue to resolve one way or the other as to whether real resistance to avermectins used in the field exists?
What was the first avermectin approved for use in dogs?
How does the dose at which collies die from ivermectin toxicosis compare to the dose given in preventative drugs like Heartgard?
Is ivermectin safe in cats?
manufacturer recommends observing for 8 hrs after heartworm prevention
Collie death – 0.2 mg/kg
• normal dose = 0.006 mg/kg
Cats are NOT especially sensitive to ivermectin
Which avermectin heartworm preventative is only TOPICALLY applied, is approved for dogs and cats,
- also approved for control of fleas, ear mites, sarcoptic mange and ticks?
What are the 2 large animal avermectin drugs?
- Doramectin (Dectomax®)
• injectable and pour on
- Eprinomectin (Eprinex®)
• topical (pour on)
What are the 2 milbemycin type drugs used in veterinary medicine?
• Milbemycin oxime
Which milbemycin type compound is FDA approved for use in small animals for:
- monthly heartworm preventative,
-control of roundworms (ascarids),
Sentinel® - with lufenuron
Trifexis® - with spinosad
** extra lable for deomdectic mange
Which milbemycin type compound is FDA approved for use in cattle & horses to tx:
- horse stomach bots,
- Cydectin® drench
- Quest® = OTC drug
Which macrolide is approved as a 6-MONTH INJECTABLE HEARTWORM PREVENTATIVE in dogs only?
= ProHeart 6
Which group of antinematodals works by inhibiting the formation of the cell’s cytoskeleton?
What component of the cytoskeleton is disrupted?
Why are these drugs so safe for use in mammals?
• (w/ α-tubulin ) forms cell microtubules of cell’s cytoskeleton
benzimidazoles DON’T COMBINE with mammalian B-tubulin = Safe
What is the prototype drug of the benzimidazoles?
Besides the antinematodal effect, what other “anti” effect does it have?
• Also has anti-fungal effect
therefore added to otic drops!
What is one of the common uses of thiabendazole?
- otic drops
What parasite produces hydatid cysts in the liver of humans?
Which benzimidazole is: - approved for use in dogs & livestock as an antinematoda
- effective against taenia species of tapeworms
- NOT effective against Echinococcus species
- has to be given 3 consecutive doses in a row (once daily) to be effective?
Which benzimidazole is ONLY approved for EQUINE use, is given only by the oral route, and is effective against common equine nematodes
-Oxibendazole (Anthelcide EQ®)
What is the benzimidazole that is:
- a pro-drug
- is approved for canine use
- incorporated w/ anticestodal drugs & pyrantel in other products.
- Febantel (Drontal Plus®)
---> converted to fenbendazole & oxfendazole by the body
What is the very safe OTC antinematodal drug that:
- has limited spectrum of activity only against roundworms (ascarids) and hookworms,
- NOT whipworms or cestodes,
- comes in 2 FORMS, one water soluble & the other very insoluble (suspension).
• pyrantel pamoate (suspension)
- vigorously shaken before withdrawing oral dose
• pyrantel tartrate (water soluble)
Why does the parasite initially show nervous system stimulation followed by paralysis?
- nicotinic Ach receptors & excessively stimulates them
--> initial depolarization
--> NOT repolarizing
--> Spastic paralysis
What are the active ingredients in Heartgard Plus?
- ivermectin + pyrantel
What are the active ingredients in Drontal Plus?
- praziquantel + febantel + pyrantel
Which 30 day,
topically applied antinematodal works by: ↑ing intracellular Ca influx -- what does it result in?
• combined w/ praziquantel = Profender®
--> vesicles containing an inhibitory NT being released
--> flaccid paralysis of the parasite muscles
What precautions should the owner know about emodepside & aquariums or fish ponds?
- VERY Toxic to fish!
• they don't have p-gp to exclude from entering CNS
What OTC antinematodal is:
- effective ONLY against roundworms (ascarids),
- not hookworms, whipworms, or cestodes.
Is this drug a vermicide or vermifuge?
--> stimulates GABA receptor
--> Cl- channel
--> flaccid paralysis
= expulsion of roundworms
If a blood transfusion is given from a heartworm positive dog with microfilaria in the blood to a heartworm negative dog, would the transfer of microfilaria result in the blood recipient developing heartworm disease? Why or why not?
No, microfilaria aren't the infective stage.
L3 from the mosquito is infective.
What is the rickettsial organism that has a symbionic relationship with Dirofilaria immitis?
-- ovarian inhabitant
Is heartworm disease more likely produce pulmonary edema or abdominal ascites?
Why is heartworm disease not treated w/ melarsomine in cats?
- bc risk of multiple dead worm emboli killing cat is far too great
Better to allow worms to die one at a time & tx clinical signs of bronchoconstriction as needed
How does Wolbachia contribute to pathology associated with heartworm disease?
What is it about Wolbachia that produces these changes?
- Wolbachia surface protein (WPS)
= Ag assoc'd w/ stimulation of inflamm rxn
--> neutrophilic infiltration of pulmonary arteries
What is the FDA approved heartworm adulticide drug?
What age of heartworm does this kill?
Is it effective against:
- L3 (infective) larvae?
-Melarsomine = Immiticide®
• Limited to immature adult worms > 4 months & adults
Where is melarsomine injected into the dog?
What is the critical time frame in which this drug should be administered?
Why is this time frame critical?
-Deep IM injection into epaxial muscles of back
Key: 2 injections within 24 hours of each other
• Females are tough to kill (need hit 2x's w/ drug)
When does the manufacturer recommend the 2 injection protocol for melarsomine versus the 3 injection protocol?
-recommended for dogs w/ minimal or no outward clinical disease apparent
• assumes worm burden is low
• less dead worm emboli to shower lungs
Why does the American Heartworm Society state that the 2 injection protocol is “inadequate”?
- 2 injections killed 90% of worms
• NOT 90% of dogs cleared!
3 injections killed 98% of adult heartworms (% of dogs cleared of HW was much lower)
Under what circumstance is melarsomine tx contraindicated? why?
-Class 4 heartworm disease (also called “caval syndrome”)
• Too many worms to safely kill
** these animals are critically ill already!!
• Hb-emia / Hb-uria
Why is a melarsomine dosage regimen of 1 dose/month for 3 months rejected by the AHS?
-doesn’t have the required 2 injections w/in 24 hours needed to kill the tough female heartworms
Why isn’t the “slow kill” protocol for heartworm treatment recommended?
- pathology of pulmonary arteries can continue to worsen
--- unless the dog is totally confined & not allowed to exercise for the 2 years it takes for this protocol to reduce worms by 95%! (not practical)
What is the most common side effect of melarsomine?
• Pain at injection site is common
- give the 2nd injection on the other side of the spinal column
• other side effects assoc'd w/ heartworm death
What is the maximum volume of melarsomine that can be given at one site?
What if you have to give a larger volume than this?
- max volume = 4 mL
• divide into 2 volumes
• admin on same side of spinal column
-- Separate by 1 lumber full vertebrae!!
• next dose done on the other side
What clinical signs do cats show w/ heartworm disease?
What is the syndrome called?
Why is there a shortage of melarsomine in the US?
What Abx has been suggested to reduce the impact of Wolbachia?
When does the American Heartworm Society recommend giving this drug? For how long?
• lethal to 3rd and 4th larval stage & reduced microfilaria
Give doxy as 4 week course of Tx BEFORE adulticide
Why might glucocorticoids be used during heartworm treatment?
Do glucocorticoids help the Dirofilaria adults survive the melarsomine treatment?
-↓ inflammation/tissue rxn from pulmonary emboli
Why is aspirin no longer recommended?
↑ chance of pulmonary hemorrhage
due to ↓ ability to control microhemorrhages
What drug is FDA approved for use as a microfilaricide?
Moxidectin = Advantage Multi®
• Newly approved!!
What drugs are used in an extralabel manner for microfilaricide treatment?
What is AMDUCA & how does it play a role in this?
-Ivermectin and Milbemycin
= Animal Med. Drug. Use Clarification Act
• allows extra-label use for specific Tx if VCPR exists
Which is typically done first:
adulticide treatment or microfilaricide treatment?
4 monthly-administered heartworm preventative ingredients
ingredient of the 1 six-month preventative drug.
1 - Milbemycin oxime
4- moxidectin tablets
Why are the use of anticestodals not of major concern in livestock production?
- usually controlled using benzimidazole antinematodals that also have anticestodal activity
What are the two main anticestodal drugs in veterinary medicine?
How do they differ as far as spectrum of activity?
Are these drugs ovicidal?
1 - Praziquantel (Droncit®)
• Echinococcus granulosus
• Dipylidium caninum
2- Epsiprantel (Cestex®)
• < Echinococcus
** not ovicidal!!! --> pass eggs
- food animal production, esp. good for coccidia in calves
• Competitive antagonism of Thiamin receptor --> thiamin deficiency for parasite --> death
For what is metronidazole used as an antiparasitic drug?
- against Giardia
--> Inhibits GABA (inhibitory NT) –> ↑ NS excitement
Side effect of metronidazole every owner should be advised about?
How reversible is this side effect?
- CNS signs in mammals: nystagmus, seizure-like activity
• Reversible quickly with 1 dose, may take up to 2 weeks with higher dose
Which benzimidazole is also a drug of choice for Tx of Giardia?
- Fenbendazole (Panacur®)
For what parasite was ponazuril developed?
- equine protozoal myeloencephalitis (EPM)
What commonly used Abx is a very effective antiprotozoal?
From what plant are pyrethrins derived
(trivial pursuit question --- worth $400 on Jeopardy)
• natural botanical
• plant in Kenya, which produces 70% world’s pyrethrum
• synthetic – stronger activity
What is piperonyl butoxide?
(what term is used to describe it)
- synergist added to many household insect sprays
--> ↑ killing power of pyrethroid
NOT insecticidal alone!!
• inhibits insect MFO (cyto P-450) that would detoxify pyrethrin/pyrethroids
• neurotoxicity in cats
Type I VS Type II pyrethroids
• effect it has on the insect (or mammalian) nervous system?
locking open Na+ channels
= most of the “thrins”
• open for shorter time
–> multiple depolarizations
= fenvalerate & deltamethrin
• Open for longer time
--> can’t repolarize after depolarizes
--> conduction blockade
--> paralysis signs
What makes pyrethrins & pyrethroids safe to use in mammals
Why is pyrethrin considered to be safe in the environment?
• Easily degraded by stomach acid & intestinal enzymes
• MFO (mixed function oxidase) enyzmes in liver --> metabolize pyrethrins/pyrethroids
• Na+ channels 1000x LESS sensitive to pyrethrins
• Readily breaks down in sunlight & oxygen
Which pyrethrin should NOT be used with cats; or cats should not contact it while it is still wet on a dog?
• clinical signs?
– cats don't have glucuronidase for conjugation
• K9 Advantix II
- muscle fasciculations
What precautions should be taken with “other pets” in the household when using pyrethrins or pyrethroids?
have few enzymes to metabolize pyrethrins
Against what external parasites is amitraz used?
(different from many other external parasite products)
• canine dip for demodectic mange
• collar kills ticks
• livestock agent used to Tx mange & lice in cattle / swine
• not dogs or horses!
Mechanism of Amitraz?
• very similar to NE
• acts like a sympathomimetic agent in insects
Amitraz inhibits the octopamine receptor
--> ↓ motility/movement
1. Ticks mouthparts stop moving
2. Movement & jumping inhibited
3. “central” NS inhibition of the insect
Stimulation of what receptor in the mammals causes the more commonly observed side effects from amitraz administration?
• Alpha 2 Agonist
--> ↓ NE release
--> Sedation, ataxia, bradycardia, hypotension, hypothermia
–> CNS depression
• MAO inhibitor (@ high dose)
--> ↓ destruction of NE & serotonin
–> get CNS excitation
What is a common way of causing Amitraz toxicosis?
• What is the antidote for amitraz intoxication?
• what needs to be done to prevent it?
1. ingestion of tick collar remnant
2. after dipping/sponge on with Mitaban
• Alpha 2 Antagonists
• Cut extra tab off tick collar
Is fipronil a nervous system stimulator or nervous system inhibitor?
• stimulates Nervous system
FIpronil binds GABA-regulated Cl- channels
--> opens Cl- channels
--> inhibits GABA release
--> lack of inhibition
--> ↑ NS activity
How does fipronil applied in one spot cover the whole animal?
Does it kill adult fleas?
What about eggs and larvae?
What about ticks?
- spreads & sequesters in lipid membranes of the SKIN CELLS & HAIR FOLLICLES
long acting residue against:
- adult fleas
- flea eggs & larvae
What is methoprene?
What does it do to the insect?
- Added to Frontline Plus®
insect growth regulator
= Juvenile hormone mimic
--> prevents larvae development
What is a neonicotinic compound?
What drugs are considered this type of compound?
- combines w/ insects post-synaptic nicotinic cholinergic receptors in CNS
What signs are seen as a result?
highly specific for insect nicotinic receptors
--> Stimulates post-synaptic nicotinic cholinergic receptors
--> Initial stimulation (↑ed activity)
--> replaced by overstimulation
--> nicotinic receptor to lock up (flaccid paralysis)
Why can’t K9 Advantix II be used in cats?
- due to permethrin
What role does permethrin play in products like K9 Advantix II?
- tick repellent
Why does nitenpyram cause intense pruritus in some dogs after it is applied?
- Like imidacloprid, it combines with NICOTINIC RECEPTOR
--> ↑ed neuromuscular activity
--> "flea seizure"
--> eventually paralysis
• kills ONLY ADULT fleas
• Pruritus from "flea seizures" tickling skin!
What is the newest family of neonicotinoids?
in family of spinosyn products
Is spinosad safe for dogs and cats?
What is its mechanism of action?
- once-a-month Chewable TABLET
• for dogs & cats
• nicotinic receptors
--> receptor lock-up
When would you use Ivermectin @ 100X dose (extra-label)?
What flea prevention drug can it interact w/?
What clinical signs of toxicosis appear w/ this interaction?
- 100x dose for demodicosis tx
if animal is already on Spinosad (Comfortis®)
--> Ivermectin toxicosis!
• Spinosad alone is NOT a problem in Collies
What are the active ingredients in Trifexis®?
- Spinosad + Milbemycin oxime
• Flea control (spinosad)
• heartworm preventative (milbemycin) and control of canine hookworm, roundworm, whipworm
What is spinetroam?
Assurtiy® / Cheristin®
- Different member of the spinosyn
• Topical application flea adulticide for CATS!
How is indoxacarb different from all of the other mechanisms of external parasite compounds?
- No blood meal necessary
• indoxacarb = pro-drug
--> enzymes within the flea
metabolizes to active form
--> Selective Na+ channel BLOCKER (insects)
What is the “bioactivation” that the manufacturer refers to in indoxacarb?
- Enzyme w/in insect converts pro-drug to bioactive form
By what unique non-neurological mechanism does lufenuron work?
What stages does it affect?
What is the draw back to the way by which the flea acquires lufenuron?
- Flea bites for a meal
--> takes in lufenuron
--> Interferes with chiton formation
Chiton found in:
• eggs --> desiccation
• egg tooth --> can't hatch
NO ADULTICIDE ACTIVITY
Flea must bite animal (allergies)
How does afoxolaner (NexGard) kill fleas and ticks?
- Blocks GABA (inhibitory) effect
--> neuronal hyperexcitability
What is pyriproxifen?
- Juvenile Hormone Analong
- commonly included in PREMISE SPRAYS
What is a JHA?
- Juvenile Hormone Analogs
What is DEET?
- Insect repellent w/ NO insecticidal activities
• Neurotoxin (100%DEET)
--> Numbness / tingling lips
ivermectin + pyrantel
milbemycin + lufenuron
febantel + praziquantel
imidacloprid + pyriproxifen
imidacloprid + moxidectin
K9 Advantix II®
imidacloprid + permethrin
• Permethrin --> repellent
fipronil + methoprene
spinosad + milbemycin
- Member of old isoxazoline family
• LEGEND drug!!
What does non-proprietary mean?
"active drug name"
What does proprietary mean?
Why is the 3 injection protocol used on animals with larger heartworm burdens?
What is recommended for very small dogs? Why?
1st injection kills just male adult worms
- followed by month "rest"
--> males die/decay before killing females
= 3 injection protocol
• due to small pulmonary vessel size