Antiparasitic_drugs Flashcards
What are the purpose of antiparasitic drugs?
Antiparasitic drugs reduce parasite burdens to a tolerable level by killing parasites or inhibiting
their growth
What is an ideal antiparasitic?
An agent that ….
* Has a wide therapeutic index
→ the toxic dose is at least three times the therapeutic dose
* Is effective (after one dose) in removing parasites from body
* Is easy to administer
* Is inexpensive
* Does not leave residues
→ an important consideration for use in food-producing animals
What should you consider when using antiparasitic drugs?
- Development of resistant strains
- Inhibition of host immunity
- Cost
What is the MOA of Antiparasitic agents?
- Paralysis of parasites by mimicking the action of putative neurotransmitters
- Alteration of metabolic processes
- Alteration of parasite reproduction
Describe how Antiparasitic drugs –> Paralysis of parasites by mimicking the action of putative neurotransmitters
Describe how Antiparasitic drugs –>Alteration of metabolic processes
Describe how Antiparasitic drugs –> Alteration of parasite reproduction
List the factors that may be responsible for the therapeutic failure.
- Incorrect use of anthelmintic drugs due the insufficient knowledge of their
pharmacological features - Insufficient understanding of the relationship between pharmacological properties and
host related factors - The indiscriminate use of antiparasitic drugs has accounted for the widespread
development of drug resistance
Dictyocaulus viviparus, broncus, calf
Haemonchus contortus, abomasum, sheep
What are the antinematodal drugs used in vet med?
Antinematodal drugs: Benzimidazoles (BZDs) and probenzimidazoles (Pro-BZDs)
- Widely used in veterinary and human medicine
- Pro-BZDs are ________ _______ converted into active BZDs
- Introduced into the animal health market primarily for the control of?
- Remarkable overall safety of BZDs compounds
inactive prodrugs
GI nematodes
What is the MOA of BZD’s and pro-BZD’s?
How are BZD compounds grouped?
List the early BZD thiazolyls
Thiabendazole,
cambendazole
List the BZD methylcarbamates.
Parbendazole,
mebendazole, flubendazole,
oxibendazole,
luxabendazole, albendazole,
albendazole sulfoxide
(ricobendazole),
fenbendazole, oxfendazole
List the Halogenated BZD thiols.
Triclabendazole → it has
only flukicidal activity
against all stages of
Fasciola hepatica
List the Pro-BZD drugs.
Thiophanate → lobendazole
(hepatic metabolism)
Febantel → fenbendazole
(hepatic metabolism)
Netobimin → albendazole
(reductive reaction in the GI
tract)
- Most of the BZD compounds are white crystalline ______ insoluble or slightly _____ in water
- Their aqueous solubility is markedly higher at ____ acidic pH → _______/_______ are the appropriate site for the dissolution of BZD drug particles after oral treatment
- BZD methylcarbamate are broad-spectrum anthelmintics active against a variety of ?
powders, soluble, low, stomach/abomasum
GI and lung nematodes, tapeworm, and trematodes
List the antinematodal drugs used in ruminants.
- Albendazole
- Fenbendazole
- Albendazole sulfoxide
- Oxfendazole
What are antinematodal drugs used for in ruminants?
- Against major GI worms (in larval and adult stages)
- Lungworms
- Ineffective against filariae
List the antinematodal drugs used in horses.
- Fenbendazole
- Oxfendazole
- Oxibendazole
What are antinematodal drugs used for in horses?
- They are effective against strongyles (limited activity against immature strongyles). They are not
very effective against migrating larvae of S. vulgaris and S. edentatus → elevated multiple doses - They are effective against Oxyuris, Trichostronylus, and Parascaris
- They are not effective against Gasterophilus
List the antinematodal drugs used in companion animals.
- Febantel (Pro-BZD)
- Fenbendazole
- Mebendazole
What are antinematodal drugs used for in companion animals?
- They are effective against ascarids (Toxocara spp.), hookworms (Ancylostoma caninum),
and whipworms (Trichuris vulpis) in both adult and larva forms
List the antinematodal drugs used in companion poultry and pigs.
- Fenbendazole
- Flubendazole
What are antinematodal drugs used for in polutry and pigs?
- They are active against large roundworms, nodular worms, lungworms, whipworms, and
kidney worms (Ascaris, Oesophagostomum, hyostrongylus, Metastrongylus Trichuris, and
Stephanurus)
The anthelmintic activity of BZDs depends also on their ability to reach high and sustained
concentrations at the site of parasite location
➢ Lack of water solubility is an important limitation for the formulation of BZDs allowing mainly their preparation as:
Suspension
Paste (horses)
Granules
Tablets (dogs and cats)
Blocks
Powder, feed administration (swine and poultry)
Pellets
Poor/erratic GI absorption is a common inconvenience for the _________ availability of _______ administered BZD suspensions in most species
systemic, enterally
__________ surface in the GI tract acts as a lipid barrier for the absorption; Consider also other factors that affect the absorption!!
Drug particles must dissolve in the _____ fluids to facilitate absorption. Drugs that do not ______, pass down and are excreted in the ____
Mucous, enteric, dissolve, feces
BZD methylcarbamates show limited GI absorption due to their ?
poor solubility in water
The dissolution ____ of BZD methylcarbamates, and also their passage along the ___ tract, and absorption into the ______ circulation are slower than those observed for the more hydrosoluble BZD ________.
rate, GI, systemic, thiazolyls
- External surface of nematodes →
cuticle
- External surface of cestodes/trematodes →
tegument
The mechanism of drug entry to
both is dependent on
lipophilicity
List The most lipophilic BZD compounds:
- Fenbendazole
- Albendazole
- Mebendazole
List The least lipophilic BZD compounds:
- Oxfendazole
- Albendazole sulfoxide
- Thiabendazole
Describe the Mechanisms of Drug Transfer into Target Parasites:
Some helminth parasites have the capability to biotransform anthelmintic drugs. Explain how Fasciola Hepatica does this.
Explain how the physicochemical features of the environment can affect drug access.
- The physicochemical features of the environment where the target parasite is immersed
can affect the drug access - Some helminths may be protected from the deleterious effect of an anthelmintic drug
when living in their predilected location - The partitioning of the active drug/metabolites between an aqueous GI fluid and the
lipoidal tissue of the parasite may facilitate the accumulation of drug within the parasite
How does the Ruminal esophageal groove closure affect disposition and efficacy of BZD?
How does Reduced GI transit time affect disposition and efficacy of BZD?
- An enhanced plasma availability of oxfendazole was induced by temporary feed restriction
- Fasting the animals prior to intraruminal treatment resulted in changes in the absorption and disposition of albendazole. Drug appeared to be absorbed to a greater
extent - A delayed GI transit time can decrease the rate of passage of the drug down the GI tract
How does a parasitic infection affect disposition and efficacy of BZD?
- The presence of the parasite itself could induce important changes to the PK, side-effects,
and expected efficacy of the chosen BZD - Liver disease and parasite-mediated liver damage → alteration of liver enzymes pattern
- A reduced enzymatic activity of different liver microsomal oxidases has been reported in
Fasciola hepatica-infected sheep
Do we have to know this?
- The BZD compounds have a remarkable overall safety
- All BZDs are extremely well tolerated by domestic animals and humans
- They are free of side effects at therapeutic doses, even when administered to young,
sick, or debilitated animals
List the BZDs that have been reported for potential teratogenicity. What does this mean in terms of their usage?
• Parbendazole
• Cambendazole
• Oxfendazole
• Febantel
• Albendazole
This limits their use in the
early stages of pregnancy
You learned about the effect of reduced GI transit time on disposition and efficacy of BZDs. How would it be in dogs?
A delayed GI transit time can decrease the rate of passage of the drug down the GI tract.
In ruminants it is shorter, so if you are giving this drug to a dog the issue you will see is that the drug would last for a longer period of time so you would have to give them a higher dose and also potentially repeat the treatment.
See other MCQ
Currently, ___________ is the worldwide imidazothiazole compound available for use in veterinary medicine
levamisole
Levamisole is the ___-isomer of __________ (the first imidazothiazole anthelmintic introduced). It has a broad range of activity in several host species. Its use is approved in cattle, sheep,
swine, poultry and dogs.
* Different routes of administration can be used → oral, parenteral, and topical
L, tetramisole
Levamisole is effective against _____ and ___ tract nematodes but not against ______ and ______ parasites
lung, GI, cestode, trematode
Levamisole is a ________ receptor _____ (nAChR). It produces ______ muscle paralysis on nematode ______ _____ muscle
cholinergic, agonist, spastic, body wall
Levamisole - Pharmacokinetics
* The rate of absorption is _____ and differs with the __________.
* Once systemically available, levamisole is ________ distributed in the organism
* Levamisole is ______ and extensively metabolized in the _____ → ________ and _______
* The excretion of both levamisole and metabolites is mainly in the _____ and ______ in cattle, sheep, and swine
* In horses, levamisole metabolism has been well characterized → its administration to racehorses led to the identification of trace amounts of ?
- Is this recommended in horses?
good, route of administration, widely, rapidly, liver, oxidation, hydrolysis, urine, feces, prohibited substances (aminorex)
No, b/c it is not very effective
Levamisole - Anthelmintic spectrum
* Levamisole has a broad spectrum of activity against ______ stages of the major GI nematodes
and against both _____ and _____ stages of lungworms
* It is indicated for nematodes in which species?
mature, mature, larval
cattle, sheep, goats, swine, poultry, dogs, and cats
Adult stages of the nematodes that are usually covered by levamisole include?:
Haemonchus spp., Ostertagia spp., Cooperia spp., Nematodirus spp., Ostertagia spp.,
Cooperia spp., Nematodirus spp., Bunostomum spp., Oesophagostomum spp., Chabertia spp.,
and Dictyocaulus viviparus
Levamisole has been used in _____ GI nematodes and as microfilaricide to treat ?
Levamisole can remove more than 95% of _____ (Toxocara, Toxascaris) and ________
(Ancylostoma, Uncinaria). Levamisole is not effective against canine ________ (Trichuris vulpis)
Because of its _____ safety margin and limited efficacy against many ______ parasites,
imidathiazole compounds (e.g., levamisole) are not approved for use in ______
dogs, Dirofilaria immitis
ascarids
hookworms
whipworms
narrow, equine, horses
Levamisole - Route of Administration
* Levamisole is administered as ?
* Injectable levamisole is preferred for use in ______. The original solution of levamisole hydrochloride resulted in?
* _____ and _____ solution of levamisole (5-10 mg/Kg) are in some countries approved for use in
dogs and cats
tablet, solution, oral drench, feed additive, SC or IM injectable
solutions, or topical pour-on
cattle
moderate to severe reaction at the injections site
Tablets, oral
Describe the Immunomodulatory effects of Levamisole.
Levamisole may enhance immune responsiveness.
* Levamisole modulates the immune function at 2-3 mg/Kg. When administered at higher doses,
levamisole may even suppress immune functions
* The restoration is most pronounced and consistent in compromised hosts whose T-lymphocytes or phagocyte functions are below normal
* The B-lymphocyte activity is not directly stimulated. There is no direct effect on antibody
production.
List the signs of levasimole intoxication.
Signs of levamisole (or tetramisole) intoxication are like those observed during
organophosphate poisoning:
* Salivation
* Defecation
* Respiratory distress (from smooth muscle contraction)
Tetramisole itself has a safety margin estimated to be ____ to ____ times the therapeutic dose of 15 mg/kg
two, six
Levamisole is more dangerous when administered _______ than _____ or ____
treatments. The ___ administration is never recommended!!
parenterally, oral, topical, IV
Chickens tolerate ________ and ______ very well. Minimum toxic levels exceed ____ mg/Kg
tetramisole, levamisole, 640
Dogs and cats are much tolerant to _____ than ________ administration of tetramisole. Doses of 20 mg/Kg are well tolerated (orally administered)
➢ ________ administration of tetramisole at 40 mg/Kg is fatal in dogs in 10-15 minutes → the ____ administration is recommended for dogs and cats
➢ Since no withdrawal time has been established for _____ _____, this drug should not be administered to ________ _____ producing milk for _______ consumption
Other ______-like or _______-inhibitor drugs could enhance the toxic effects of levamisole.
oral, parenteral, SC, oral, dairy cows, lactating, cattle, human
nicotine, cholinesterase
_________ was the first member introduced of the Tetrahydropyrimidines family. Initially used as a _______-spectrum anthelmintic against GI nematodes in _____
* Later it was developed for use in?
* _______ is a methyl ester analog of pyrantel with also nematocidal action
* The newest drug in this chemical family is ________ (m-oxyphenol derivate of pyrantel)
Pyrantel, broad, sheep
cattle, swine, horses, dogs, and cats
Morantel
oxantel
Tetrahydropyrimidine MOA
Tetrahydropyrimidine compounds act _________ as ________ at _______ _____________ receptors (nAChR) on
nematode ______ cells and produce _______ and ______ paralysis
selectively, agonist, nicotinic
acetylcholine, muscle, contraction, spastic
_________ and ________ are 100 times more potent than acetylcholine, although slower in initiating _________. These anthelmintics act essentially by ________ the paralytic effects of this neurotransmitter
Pyrantel, morantel, contraction, mimicking
- The _________ ______ _______ is poorly absorbed from the GI tract. Higher unabsorbed concentrations
reach the ______ digestive tract - _______ _____ is better absorbed in pigs and dogs compared to ruminants
- After absorption, drugs are rapidly metabolized and excreted into the ______
- The ______ is the only species excreting a larger proportion of the drug/metabolites in urine
compared to feces - _________ is poor absorbed in ruminants. The drug is _________ in the bloodstream in cattle
after _____ treatment → it is largely excreted __________ in the feces
pyrantel pamoate salt, lower
Pyrantel tartrate, feces
dog, Morantel, undetectable, oral, unmetabolized
In horses, the activity of pyrantel on GI helminths is characterized by ____ efficacies. A limited efficacy has been observed against _________ ______ and mature and immature ________ _____
high, Strongylus edentatus, Oxyuris equi
In swine, pyrantel is indicated for the removal or prevention of the large ____________ (?) and ____________ spp. and these family drug have also activity against the stomach
worm ?
roundworms, Ascaris sun, Oesophagostomum , Hyostrongylus rubidus
In dogs, pyrantel is used to control the following parasites: ?. It is useful for similar parasites in ____ → safe even in _____
ascarids (Toxocara cani, Toxascaris
leonine), hookworms (Ancylostoma caninum, Uncinaria stenocephala), and stomach worm
(Physalopter), cats, kittens
Pyrantel tartrate is an effective nematocidal in ? against
GI nematodes being highly effective against _____ and any _______ stages that dwell in the lumen.
Name these GI nematodes.
ruminants (sheep, cattle, and goats), adults, immature
GI nematodes:
Ostertagia spp., Haemonchus spp., Trichostrongylus spp., Nematadirus spp., Chabertia spp.,
Cooperia spp., and Oesphagostomum spp.
Haemonchus is one of the bad guys - very difficult to find a drug that will work against this nematode.
Morantel tartrate is good against adult and immature stages of ?
Haemonchus spp., Ostertagia
spp., Trichostrongylus spp., Cooperia spp., and Nematadirus spp.
List the formulations for the following drugs:
* Pyrantel pamoate → ?
* Pyrantel pamoate + Febantel + Praziquantel → ?
* Morantel tartrate →
- suspension and tablets (dogs)
- tablets (dogs)
- sustained-release bolus (widely used in Europe) has been
approved in many countries in America (dairy and beef cattle)
The salts of pyrantel are free of toxic effects in ?
all animal hosts at doses up to approximately seven times the therapeutic dose
In chronic toxicity studies, dogs showed ill effects when administered _______ ________ at __ or more mg/kg/day for _____ months
pyrantel tartrate, 50, three
Pyrantel is safe for horses and ponies of ?
all ages, including suckling, weanlings, pregnant
mares, and stallions
At 20 times the recommended dose in horses, ponies, and foals, pyrantel pamoate shows?
no adverse clinical effects or changes in blood cell values or serum chemistry parameters
The Tetrahydropyrimidines drug family is not recommended for use with what other drugs? Explain why. Provide an alternative drug that could be used.
This drug family is recommended not to be used concurrently with other cholinergic
anthelmintics (levamisole)
* Morantel tartrate is a safer drug than pyrantel tartrate. Its use is allowed in dairy
animals without a milk withdrawal restriction
make cards
List the Tetrahydropyrimidines used against nematodes in veterinary medicine.
Pyrantel, morantel, and oxantel
List the Heterocyclic compounds used against nematodes in veterinary medicine.
Piperazine, diethylcarbamazine citrate, and phenothiazine
The emergence of phenothiazine-resistant strains of _______ and _____ nematodes reduced the utility of this compound and they are not longer used as anthelmintic compounds
ruminant, equine
Piperazine is classified as a _______-spectrum antinematodal drug (____). Its ___ cost and ____ safety margin in all domestic animal led to its extensive worldwide use in antiparasitic
therapy
* ______ worms are more susceptible to the action of piperazine than _____ stages
narrow, ascarids, low, wide, Mature, younger
What is the MOA of Heterocyclic compounds ?
- It is a selective agonist of GABA receptors → resulting in the opening of chloride channels
- Piperazine blocks the transmission by hyperpolarizing nerve membranes at the NMJ leading to parasite immobilization
- Piperazine and pyrantel/morantel have antagonistic MOA. Do not combine them!
Large oral doses of piperazine produces what effects in cats and dogs?
Have any toxic effects been reported in foals and horses?
emesis, diarrhea, incoordination, and head pressing in cats and dogs
No toxic effects have been reported in foals and horses after they were given six or seven times the therapeutic dose
How do parasites become resistant to antihelminthic drugs?
➢ A change in the molecular target: This can affect the capacity of drug to accumulate
at intracellular site of action
➢ Activity of parasite enzymes:
➢ Receptors change: Number, structure, and/or affinity of cellular drug receptors
➢ Amplification of target gene
The rate at which anthelmintic resistance develops and spreads within a population is determined
by ?
the number of parasites that survives the treatment, and contribute with resistance genes to
the next generation
What contributes to antihelminthic resistance?
➢ Parasite genetic factors
➢ Fecundity of adult parasites
➢ Parasites in refugia
➢ Drug features
➢ Grazing management
➢ Climatic conditions
What strategies affect the development of resistance?
- Avoid under-dosing
- Use nematocidal drug combination
- Know the nature of the chemical (drug) and its ability to select for resistance
- Removal of feces and alternate grazing of different host
T/F: Both tetrahydropyrimidine, pyrantel and the imidathiazole levamisole have the same MOA. They are nicotinic receptor agonist. They produce flaccid paralysis on nematodes
False
Produces SPASTIC
Why is the combination of nematocidal drugs important?
Using drugs of different MOAs can be more effective. You want to surprise the parasite so if you use different MOA –> kill.
xcc
Cyclic Depsipeptides: Cyclodepsipeptide PF1022A is a ?
Emodepside used in cats
Emodepside is effective against
ascarids and hookworms (mature and immature adults)
What is the MOA of Emodepside?
Emodepside is a selective agonist of the presynaptic latrophilin-receptor (LTP) in
parasitic nematodes, which results in flaccid paralysis and death
Describe the formulation of Emodepside.
- It is used topically (spot-on) with the anticestodal drug praziquantel (Profender®) for the
treatment of nematodes in cats (8 weeks and older) - It is absorbed through the skin and can get deposited into adipose tissue
List the adverse effects of Emodepside.
- Alopecia may be seen at the application site
- Salivation and vomiting may occur (due to licking the application site)
- Tremors may show up when cats are overdosed with emodepside
Emodepside may interfere with?
fetal development (rats and rabbits). Pregnant women
should avoid direct contact with emodepside and wear disposable gloves (if product
handling is necessary)
Derquantel is also called?
2-Deoxy-paraherquamide (PHQ)
Derquantel is active against ?
both BZD and ivermectin-resistant Haemonchus contortus
(adult stages)
What is the MOA of Derquantel?
It acts as an antagonist of neuronal nicotinic cholinergic receptors in both nematodes
(flaccid paralysis) and mammals → it shows markedly lower affinity
Derquantel is well absorbed and extensively distributed into tissues after oral administration
Describe the heartworm lifecycle.
Drugs for Heartworm Prevention and Therapy
- Both the adult worms and the microfilariae of Dirofilaria immitis are responsible for the clinical
signs associated with heartworm disease - Heartworms live 5 to 7 years in dogs and 2 to 3 years in cats
- The severity of heartworm disease and the onset of clinical signs reflect the number of
infecting worms - Large numbers of worms are more likely to cause greater pulmonary hypertension,
thromboembolism, and risk of vena caval syndrome
Drugs for Heartworm Prevention and Therapy
Three aspects to be considered
- Removal of adult heartworms → adulticide
- Use of microfilaricides ???
- Prevention of infection → it requires a larvicide
Drugs for Heartworm Prevention and Therapy Adulticide therapy: ?
Melarsomine (Immiticide®
Melarsomine is a __________ _________ compound with activity against ________ (> 4-month-old) and ____ heartworms in dogs. Its mode of action is ________.
trivalent arsenic , immature, adult, unknown
Melasormine is rapidly absorbed after ____ injection (2.5 mg/kg). The drug is widely distributed in the body but is concentrated in the ____ and _____. It is metabolized in the _____ and excreted into ____.
IM, liver, kidneys, liver, bile
Do not give ___ or ___ of Melarsomine as significant toxicity or tissue damage may occur. Administer only deep ___ as directed (___-___ lumbar epaxial muscles) Do not administer at any other site!
IV, SC, IM, L3-L5
American Heartworm Society recommends a __ to __-dose protocol. Contraindication → ?
2, 3, Caval Syndrome
Caval Syndrome (small ____, rarely ____)
worms block the _____ Vena Cava. It requires immediate _____ removal of worms
dogs, cats, Caudal, surgical
List the side effects of Melarsomine (Immiticide®)
- The side effects provoked after injection were described as pain, swelling and tenderness at
the injection site - Coughing, gagging, depression, lethargy, lack of appetite, fever, lung congestion, and
vomiting may also appear as side effects - Melasormine has a low margin of safety. It is important to have an accurate weight before
treating - Dimercaprol (BAL) can be used as a possible antidote for reversing the toxicity of
melarsomine
Sulfhydryl groups found on dimercaprol form heterocyclic ring complexes with heavy
metals, principally arsenic, lead, mercury, and gold. The chelation to dimercaprol can be
reversible.
The dimercaprol-metal complex is excreted via renal and fecal routes
T/F: No drug is approved for use as a microfilaricide.
* Some practitioners choose not to use microfilaricide, particularly if dogs do not
harbor _____ number of microfilaria
* __________ ____ can be used, although duration of efficacy varies. A single dose
may be ________ to clear microfilariae
* Ivermectin (unapproved as a microfilaricide) is ___% effective after a single dose
(0.05 mg/Kg or 50 μg/Kg) approx. 8 times the preventive dose four weeks after
adulticide therapy is completed
* ________ is more consistently effective microfilaricide, it can be used for ____ kill
(0.5 mg/Kg)
True
large, Macrocyclic lactones, insufficient, 90, Milbemycin, rapid
Larvicides for heartworm prevention?
Macrocyclic lactones
Which drugs are used to treat the larval stages of heartworm in dogs and cats?
Ivermectin, moxidectin, milbemycin oxime, and selamectin are used to kill larval stages of
Dilofilaria immitis (L3-L4) in dogs and cats
Ivermectin and milbemycin oxime are available for ______ oral administration. Some formulations are flavored and chewable to increase patient acceptance and facilitate
administration.
monthly
Moxidectin and selamectin are available as ______ applied liquid formulations
topically
Moxidectin can also be _________ administered with a ____ dose of the slow-release (SR) formulation. It provides protection for __ months
subcutaneously, single, 6
Anticestodal drugs used to treat
tapeworm
Tapeworm infection in farm animals may be a ____ problem and usually ______ require treatment with a specific cestocidal drug
minor, does not
Some of the broad-spectrum BZD compounds are also effective against _________
tapeworms
The oral administration of __________ _______ paste resulted in effective control of Anoplocephala perfoliate infections in horses (commonest _________ parasite)
pyrantel pamoate, tapeworm
Treatment of tapeworm infections is necessary in _________ animals → dogs and cats are _______ hosts of tapeworms whose _____ stages cause zoonosis
companion, definitive, larval
Praziquantel is widely used and highly efficacious against ________ stages of all __________ in farm and companion animals and ________ parasites
* 5 mg/Kg of praziquantel in dogs and cats is completely effective against all stages of:
Spectrum of action Taenia hydatigena, T. pisiformis, T. ovis, T. taeniaeformis, D. caninum, Mesocestoides corti, E. multilocularis, and E. granulosus
- Praziquantel is widely used and highly efficacious against adult stages of all tapeworms in farm and companion animals and trematode parasites
- 5 mg/Kg of praziquantel in dogs and cats is completely effective against all stages of:
Spectrum of action Taenia hydatigena, T. pisiformis, T. ovis, T. taeniaeformis, D. caninum, Mesocestoides corti, E. multilocularis, and E. granulosus
What is the spectrum II of action of Praziquantel ?
- 25 mg/Kg on each of 2 consecutive days are necessary to treat Spirometra mansonoides
and Diphyllobothrium erinacea in dogs and cats - Praziquantel paste at 50 mg/Kg is effective for the control of Dicrocoelium dentriticum in
llamas - Praziquantel is highly effective against cestodes in ruminants. All species of Moniezia, Stilesia, and Avitellia of sheep and/or goats are eliminated by a single dose of 10-15 mg/Kg
What is the MOA of Praziquantel?
Praziquantel effects are thought to be mediated by release of intracellular stored ______, in addition to the increase of _____ influx across the _______
➢ It induces a rapid a sustained _________ muscle contraction of the parasite
➢ __________ disruption → binding and penetration of host ________ cells into the parasite
- Praziquantel effects are thought to be mediated by release of intracellular stored Ca2+, in addition to the increase of Ca2+ influx across the tegument
➢ It induces a rapid a sustained paralytic muscle contraction of the parasite
➢ tegumental disruption → binding and penetration of host immune cells into the parasite
Describe the Pharmacokinetics and safety of Praziquantel.
* Praziquantel is completely absorbed in the ____ ______ in almost all species
* Its _______ metabolite exerts similar pharmacological effect
* ________ excretion is the main route of elimination of praziquantel and its metabolites
* Praziquantel has a _____ margin of safety. Overdoses of up to _______ are tolerated without adverse effects
* Studies in pregnant rats and rabbits detected no _____ or _____ effects
- Praziquantel is completely absorbed in the GI tract in almost all species
- Its active metabolite exerts similar pharmacological effect
- Renal excretion is the main route of elimination of praziquantel and its metabolites
- Praziquantel has a wide margin of safety. Overdoses of up to fivefold are tolerated
without adverse effects - Studies in pregnant rats and rabbits detected no embryotoxic or teratogenic effects
Epsiprantel is chemically related to __________ and used specifically for the treatment of the
common ______ of dogs and cats. These include?
praziquantel, tapeworms
D. caninum, T. pisiformis, T. taeniaeformis, E. granulosus, E. multilocularis
Describe the MOA of Epsiprantel (Cestex®).
➢ Epsiprantel (like ___________), affects ______ homeostasis within the parasite
➢ It damages the ________
→ making it vulnerable to _____ and _______ within the host’s gut
➢ Epsiprantel (like praziquantel), affects Ca2+ homeostasis within the parasite
➢ It damages the tegument
→ making it vulnerable to lysis and digestion within the host’s gut
Epsiprantel (Cestex®)
* It is only formulated for oral administration in ?
* Epsiprantel is ______ absorbed in the GI tract → available to act against intestinal ______,
being eliminated in ____
* Only 0.1% of the administrated drug is eliminated by _____
* Epsiprantel is a safe drug due to its ___ GI absorption. Beagle puppies (7-10 weeks ) given 100 mg/Kg once (18 times the recommended dosage) exhibited no signs of toxicity
dogs and cats, poorly, cestodes, feces, urine, low
Fasciolosis, caused by the cosmopolitan liver fluke _______ _______, is the most common and economically important disease caused by _________ parasites in _________ animals worldwide. Fasciolosis is an important _______ disease
Fasciola hepatica, trematode, domestic, zoonotic
Drugs active against ____ of the species are _____ effective against the other
one, equally
The tropical counterpart of F. hepatica is ?
F. gigantica
The Rumen fluke (?) infections are common in cattle and sheep throughout the world. ________ stages can be seriously pathogenic as they migrate within the gut lumen from the ________ to the ______
Paramphistomum spp., Immature, duodenum, rumen
- Paragonimus spp. (lung flukes) in _____ and ____.
dogs, cats
________ used in sheep and cattle are active against liver flukes older than ?
Albendazole, 12 weeks
Fenbendazole is not effective against ____________, but a single treatment reduced __________ infection in sheep by up 95%
F. hepatica, F. gigantica
Triclabendazole (TCBZ) has an excellent efficacy against ___________ (2-day-old early immature to mature fluke) and other species but does not show clinical efficacy against ?
F. hepatica, nematodes and cestodes
The selection of TCBZ-resistant populations is an emerging problem in several areas of the world due to?
→ increased TCBZ oxidative metabolism by the fluke
→ enhanced drug efflux mediated by ATP-dependent TM-transporter
Combined formulations containing TCBZ and different antinematodal drugs are available in different countries. Name these combinations.
Levamisole, abamectin, ivermectin
TCBZ can be administered at _____ stage of pregnancy. A withdrawal time of ___ days (____) has been stablished
any, 56, meat
- Clorsulon is highly effective against ?
- It shows good efficacy against ___-week-old and _____ flukes → following ___ and ____ administration at 4-8 mg/Kg
adult liver flukes in cattle > sheep and goats
8, older, SC, oral
- There are different combinations of clorsulon with other drugs. List these combinations.
➢ Clorsulon + ivermectin (Ivomec Plus®, Alverin™ Plus)
➢ Clorsulon + ivermectin + fenbendazole
Describe the MOA of Clorsulon.
- Clorsulon inhibits certain ________ pathways in the fluke
- Clorsulon-treated flukes showed
→ ______ is more severely affected than the tegument
→ ____ ingestion is a main route of entry of clorsulon into the fluke
- Clorsulon inhibits certain glycolytic pathways in the fluke
- Clorsulon-treated flukes showed
→ Gut is more severely affected than the tegument
→ Oral ingestion is a main route of entry of clorsulon into the fluke
- In rats, clorsulon was shown to be bound predominantly to?
bound predominately to erythrocytes
Clorsulon is a ______ soluble drug. ______ excretion of the drug is thought to be the main route of elimination
lipid, Renal
Clorsulon is a ____ drug with ____ therapeutic index
* Clorsulon is also considered safe for use in ______ and _______ animals
* Withdrawal times:
Milk → ___ hours (6 milkings)
Meat → __ days
safe, high, breeding, pregnant, 72, 8
- Sheep infected with flukes treated with 5 mg/kg and 100 mg/kg showed no apparent
side effects - Clorsulon is also considered safe for use in breeding and pregnant animals
- Withdrawal times:
Milk → 72 hours (6 milkings)
Meat → 8 days
The __________ and _______ are closely related macrocyclic lactones produced through fermentation by soil dwelling actinomycetes (Streptomyces)
avermectins, milbemycins
List the members of the Avermectin family
- Abamectin → naturally occurring avermectin
- Ivermectin → the first marketed endectocide molecule (semisynthetic)
- emamectin
- Doramectin
- Eprinomectin
- Selamectin
List the members of the Milbemycin family
- Nemadectin
- Moxidectin
- Milbemycin oxime
Various Avermectin and Milbemycin compounds are used in livestock, companion animals, wildlife species, and humans. They are currently marketed as injectable, pour-on, and oral formulations
Avermectins nad Milbemycins are used as?
The broad-spectrum ecto-endoparasitic activity from both families includes
* Insects
* Ascarines
* Nematodes
Avermectins and milbemycins do not possess efficacy against?
cestode and trematode parasites
What is the MOA of Macrocyclic Lactones (MLs)?
MLs act on glutamate-gated chloride
channels (GluCl) and GABA receptors.
They induce reduction in motor activity → flaccid paralytic effects on the pharynx and somatic musculature
The macrocyclic lactones are highly ___________ and extensively distributed from the bloodstream to different tissues
lipophilic
Macrocyclic Lactones (MLs) are high availability in parasite location tissues such as ?
GI mucosal tissues, lungs, and skin
Doramectin compared to ivermectin has an enhanced __________ and ________ time of residence in target tissues
availability, prolonged
“Dora last for a longer time in the forest”
___________ is the most lipophilic endectocide agent
Moxidectin
A considerable excretion of which three endectocide compounds occurs via mammary glands?
ivermectin, moxidectin, and doramectin
Topical formulations of __________ are approved for use in dairy cattle in
some countries
moxidectin
Eprinomectin has a good antiparasitic _______, _____ spectrum, and substantially _______ distribution to milk, compared to other MLs
potency, broad, reduced
The main metabolism of MLs occurs in the ______ and they are excreted in high concentration in ?
liver, bile and feces
The MLs (3?) are substrates of the P-GP transport protein. _______ has a lower affinity for P-GP compared to avermectin-type compounds
abamectin, ivermectin, and moxidectin, Moxidectin
The duration of the ML persistence of antiparasitic activity vary
The intrinsic properties of the MLs allow a sustainable persistence of the active drug in the
animal body → Pharmacotechnical preparations
Just remember there are a different number of days
In ruminants, Ivermectin, Doramectin, Moxidectin, and Iprinomectin are used to treat?
MLs are active against most of the _________ parasites affecting goats (extralabel).
MLs are extremely effective against _____ and ____ stages of most GI nematodes in cattle.
___________ and __________ (pour-on) are indicated in lactating dairy cows with 0 milk withdrawal time in some countries.
GI nematodes, Arthropods, and lung worms.
nematodes
adult, larval
Eprinomectin, moxidectin
In horses, Ivermectin and Moxidectin are used to treat?
Ascarids, stomach worms, lung worms, the adult and larval stages of large strongyles and adult small strongyles, and lastly the horse botfly Gastrophilus intestinalis
Ivermectin is used in dogs and cats as a preventative against?
Dirofilaria immitis
Only know which drugs effect which groups of parasites, NOT specifics.
Know withdrawal times
Are MLs considered to be safe compounds?
MLs are highly safe compounds → Pharmacodynamic action
Avermectins have at least a 10-fold safety margin in ruminants, horses, swine, and most of dog breeds
➢ GABA-mediated action in the mammalian central nervous system
Neuro-toxicity observed when large toxic doses are administered!
MLs do not effect on _______ performance, ____ quality, or ________ was observed when bulls or cows were treated with ivermectin at 0.4 mg/Kg
breeding, semen, pregnancy
Abamectin is slightly more toxic than _______. Abamectin LD50 in mice 14-24 mg/Kg (ivermectin 25-40 mg/Kg)
ivermectin
Abamectin is not recommended for use in calves under ___ months of age
4
Milbemycin compounds have a ____ therapeutic margin
wide
No adverse effects have been observed in cattle treated with moxidectin (SC) up to 10
times the recommended dose
The Ivermectin sensitive Collie
The mutation causes a non-functional MDR1 protein at the blood brain barrier, which causes the
passage of drugs into the CNS
Neurotoxicity to ivermectin in MDR1 defect is characterized by:
Depression
Ataxia
Somnolence
Salivation
Tremor
Coma
Death
“SAD CaTS DEATH”
Which MLs are Safe at the therapeutic dose for the ivermectin sensitive collie?
Moxidectin, selamectin
The overall efficacy and safety of the MLs designed for other species should not be assumed for ?
dogs and cats
