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Pharmacology II > Antiparasitic_drugs > Flashcards

Antiparasitic_drugs Flashcards

1
Q

What are the purpose of antiparasitic drugs?

A

Antiparasitic drugs reduce parasite burdens to a tolerable level by killing parasites or inhibiting
their growth

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2
Q

What is an ideal antiparasitic?

A

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

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3
Q

What should you consider when using antiparasitic drugs?

A
  • Development of resistant strains
  • Inhibition of host immunity
  • Cost
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4
Q

What is the MOA of Antiparasitic agents?

A
  1. Paralysis of parasites by mimicking the action of putative neurotransmitters
  2. Alteration of metabolic processes
  3. Alteration of parasite reproduction
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5
Q

Describe how Antiparasitic drugs –> Paralysis of parasites by mimicking the action of putative neurotransmitters

A
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6
Q

Describe how Antiparasitic drugs –>Alteration of metabolic processes

A
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7
Q

Describe how Antiparasitic drugs –> Alteration of parasite reproduction

A
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8
Q

List the factors that may be responsible for the therapeutic failure.

A
  • 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
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9
Q
A

Dictyocaulus viviparus, broncus, calf

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10
Q
A

Haemonchus contortus, abomasum, sheep

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11
Q

What are the antinematodal drugs used in vet med?

A

Antinematodal drugs: Benzimidazoles (BZDs) and probenzimidazoles (Pro-BZDs)

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12
Q
  • 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
A

inactive prodrugs

GI nematodes

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13
Q

What is the MOA of BZD’s and pro-BZD’s?

A
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14
Q

How are BZD compounds grouped?

A
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15
Q

List the early BZD thiazolyls

A

Thiabendazole,
cambendazole

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16
Q

List the BZD methylcarbamates.

A

Parbendazole,
mebendazole, flubendazole,
oxibendazole,
luxabendazole, albendazole,
albendazole sulfoxide
(ricobendazole),
fenbendazole, oxfendazole

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17
Q

List the Halogenated BZD thiols.

A

Triclabendazole → it has
only flukicidal activity
against all stages of
Fasciola hepatica

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18
Q

List the Pro-BZD drugs.

A

Thiophanate → lobendazole
(hepatic metabolism)
Febantel → fenbendazole
(hepatic metabolism)
Netobimin → albendazole
(reductive reaction in the GI
tract)

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19
Q
  • 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 ?
A

powders, soluble, low, stomach/abomasum

GI and lung nematodes, tapeworm, and trematodes

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20
Q

List the antinematodal drugs used in ruminants.

A
  • Albendazole
  • Fenbendazole
  • Albendazole sulfoxide
  • Oxfendazole
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21
Q

What are antinematodal drugs used for in ruminants?

A
  • Against major GI worms (in larval and adult stages)
  • Lungworms
  • Ineffective against filariae
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22
Q

List the antinematodal drugs used in horses.

A
  • Fenbendazole
  • Oxfendazole
  • Oxibendazole
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23
Q

What are antinematodal drugs used for in horses?

A
  • 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
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24
Q

List the antinematodal drugs used in companion animals.

A
  • Febantel (Pro-BZD)
  • Fenbendazole
  • Mebendazole
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25
Q

What are antinematodal drugs used for in companion animals?

A
  • They are effective against ascarids (Toxocara spp.), hookworms (Ancylostoma caninum),
    and whipworms (Trichuris vulpis) in both adult and larva forms
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26
Q

List the antinematodal drugs used in companion poultry and pigs.

A
  • Fenbendazole
  • Flubendazole
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27
Q

What are antinematodal drugs used for in polutry and pigs?

A
  • They are active against large roundworms, nodular worms, lungworms, whipworms, and
    kidney worms (Ascaris, Oesophagostomum, hyostrongylus, Metastrongylus Trichuris, and
    Stephanurus)
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28
Q

The anthelmintic activity of BZDs depends also on their ability to reach high and sustained
concentrations at the site of parasite location

A
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29
Q

➢ Lack of water solubility is an important limitation for the formulation of BZDs allowing mainly their preparation as:

A

Suspension
Paste (horses)
Granules
Tablets (dogs and cats)
Blocks
Powder, feed administration (swine and poultry)
Pellets

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30
Q

Poor/erratic GI absorption is a common inconvenience for the _________ availability of _______ administered BZD suspensions in most species

A

systemic, enterally

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31
Q

__________ 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 ____

A

Mucous, enteric, dissolve, feces

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32
Q

BZD methylcarbamates show limited GI absorption due to their ?

A

poor solubility in water

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33
Q

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 ________.

A

rate, GI, systemic, thiazolyls

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34
Q
  • External surface of nematodes →
A

cuticle

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35
Q
  • External surface of cestodes/trematodes →
A

tegument

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36
Q

The mechanism of drug entry to
both is dependent on

A

lipophilicity

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37
Q

List The most lipophilic BZD compounds:

A
  • Fenbendazole
  • Albendazole
  • Mebendazole
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38
Q

List The least lipophilic BZD compounds:

A
  • Oxfendazole
  • Albendazole sulfoxide
  • Thiabendazole
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39
Q

Describe the Mechanisms of Drug Transfer into Target Parasites:

A
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40
Q

Some helminth parasites have the capability to biotransform anthelmintic drugs. Explain how Fasciola Hepatica does this.

A
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41
Q

Explain how the physicochemical features of the environment can affect drug access.

A
  • 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
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42
Q

How does the Ruminal esophageal groove closure affect disposition and efficacy of BZD?

A
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43
Q

How does Reduced GI transit time affect disposition and efficacy of BZD?

A
  • 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
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44
Q

How does a parasitic infection affect disposition and efficacy of BZD?

A
  • 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
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45
Q

Do we have to know this?

A
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46
Q
  • 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
A
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47
Q

List the BZDs that have been reported for potential teratogenicity. What does this mean in terms of their usage?

A

• Parbendazole
• Cambendazole
• Oxfendazole
• Febantel
• Albendazole
This limits their use in the
early stages of pregnancy

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48
Q

You learned about the effect of reduced GI transit time on disposition and efficacy of BZDs. How would it be in dogs?

A

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.

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49
Q

See other MCQ

A
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50
Q

Currently, ___________ is the worldwide imidazothiazole compound available for use in veterinary medicine

A

levamisole

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51
Q

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

A

L, tetramisole

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52
Q

Levamisole is effective against _____ and ___ tract nematodes but not against ______ and ______ parasites

A

lung, GI, cestode, trematode

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53
Q

Levamisole is a ________ receptor _____ (nAChR). It produces ______ muscle paralysis on nematode ______ _____ muscle

A

cholinergic, agonist, spastic, body wall

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54
Q

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?

A

good, route of administration, widely, rapidly, liver, oxidation, hydrolysis, urine, feces, prohibited substances (aminorex)

No, b/c it is not very effective

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55
Q

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?

A

mature, mature, larval

cattle, sheep, goats, swine, poultry, dogs, and cats

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56
Q

Adult stages of the nematodes that are usually covered by levamisole include?:

A

Haemonchus spp., Ostertagia spp., Cooperia spp., Nematodirus spp., Ostertagia spp.,
Cooperia spp., Nematodirus spp., Bunostomum spp., Oesophagostomum spp., Chabertia spp.,
and Dictyocaulus viviparus

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57
Q

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 ______

A

dogs, Dirofilaria immitis

ascarids

hookworms

whipworms

narrow, equine, horses

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58
Q

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

A

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

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59
Q

Describe the Immunomodulatory effects of Levamisole.

A

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.

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60
Q

List the signs of levasimole intoxication.

A

Signs of levamisole (or tetramisole) intoxication are like those observed during
organophosphate poisoning:
* Salivation
* Defecation
* Respiratory distress (from smooth muscle contraction)

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61
Q

Tetramisole itself has a safety margin estimated to be ____ to ____ times the therapeutic dose of 15 mg/kg

A

two, six

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62
Q

Levamisole is more dangerous when administered _______ than _____ or ____
treatments. The ___ administration is never recommended!!

A

parenterally, oral, topical, IV

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63
Q

Chickens tolerate ________ and ______ very well. Minimum toxic levels exceed ____ mg/Kg

A

tetramisole, levamisole, 640

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64
Q

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.

A

oral, parenteral, SC, oral, dairy cows, lactating, cattle, human

nicotine, cholinesterase

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65
Q

_________ 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)

A

Pyrantel, broad, sheep

cattle, swine, horses, dogs, and cats

Morantel
oxantel

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66
Q

Tetrahydropyrimidine MOA

Tetrahydropyrimidine compounds act _________ as ________ at _______ _____________ receptors (nAChR) on
nematode ______ cells and produce _______ and ______ paralysis

A

selectively, agonist, nicotinic
acetylcholine, muscle, contraction, spastic

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67
Q

_________ and ________ are 100 times more potent than acetylcholine, although slower in initiating _________. These anthelmintics act essentially by ________ the paralytic effects of this neurotransmitter

A

Pyrantel, morantel, contraction, mimicking

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68
Q
  • 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
A

pyrantel pamoate salt, lower

Pyrantel tartrate, feces

dog, Morantel, undetectable, oral, unmetabolized

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69
Q

In horses, the activity of pyrantel on GI helminths is characterized by ____ efficacies. A limited efficacy has been observed against _________ ______ and mature and immature ________ _____

A

high, Strongylus edentatus, Oxyuris equi

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70
Q

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 ?

A

roundworms, Ascaris sun, Oesophagostomum , Hyostrongylus rubidus

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71
Q

In dogs, pyrantel is used to control the following parasites: ?. It is useful for similar parasites in ____ → safe even in _____

A

ascarids (Toxocara cani, Toxascaris
leonine), hookworms (Ancylostoma caninum, Uncinaria stenocephala), and stomach worm
(Physalopter), cats, kittens

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72
Q

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.

A

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.

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73
Q

Morantel tartrate is good against adult and immature stages of ?

A

Haemonchus spp., Ostertagia
spp., Trichostrongylus spp., Cooperia spp., and Nematadirus spp.

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74
Q

List the formulations for the following drugs:
* Pyrantel pamoate → ?
* Pyrantel pamoate + Febantel + Praziquantel → ?
* Morantel tartrate →

A
  1. suspension and tablets (dogs)
  2. tablets (dogs)
  3. sustained-release bolus (widely used in Europe) has been
    approved in many countries in America (dairy and beef cattle)
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75
Q

The salts of pyrantel are free of toxic effects in ?

A

all animal hosts at doses up to approximately seven times the therapeutic dose

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76
Q

In chronic toxicity studies, dogs showed ill effects when administered _______ ________ at __ or more mg/kg/day for _____ months

A

pyrantel tartrate, 50, three

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77
Q

Pyrantel is safe for horses and ponies of ?

A

all ages, including suckling, weanlings, pregnant
mares, and stallions

78
Q

At 20 times the recommended dose in horses, ponies, and foals, pyrantel pamoate shows?

A

no adverse clinical effects or changes in blood cell values or serum chemistry parameters

79
Q

The Tetrahydropyrimidines drug family is not recommended for use with what other drugs? Explain why. Provide an alternative drug that could be used.

A

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

80
Q

make cards

A
81
Q

List the Tetrahydropyrimidines used against nematodes in veterinary medicine.

A

Pyrantel, morantel, and oxantel

82
Q

List the Heterocyclic compounds used against nematodes in veterinary medicine.

A

Piperazine, diethylcarbamazine citrate, and phenothiazine

83
Q

The emergence of phenothiazine-resistant strains of _______ and _____ nematodes reduced the utility of this compound and they are not longer used as anthelmintic compounds

A

ruminant, equine

84
Q

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

A

narrow, ascarids, low, wide, Mature, younger

85
Q

What is the MOA of Heterocyclic compounds ?

A
  • 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!
86
Q

Large oral doses of piperazine produces what effects in cats and dogs?
Have any toxic effects been reported in foals and horses?

A

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

87
Q

How do parasites become resistant to antihelminthic drugs?

A

➢ 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

88
Q

The rate at which anthelmintic resistance develops and spreads within a population is determined
by ?

A

the number of parasites that survives the treatment, and contribute with resistance genes to
the next generation

89
Q

What contributes to antihelminthic resistance?

A

➢ Parasite genetic factors
➢ Fecundity of adult parasites
➢ Parasites in refugia
➢ Drug features
➢ Grazing management
➢ Climatic conditions

90
Q

What strategies affect the development of resistance?

A
  • 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
91
Q

T/F: Both tetrahydropyrimidine, pyrantel and the imidathiazole levamisole have the same MOA. They are nicotinic receptor agonist. They produce flaccid paralysis on nematodes

A

False
Produces SPASTIC

92
Q

Why is the combination of nematocidal drugs important?

A

Using drugs of different MOAs can be more effective. You want to surprise the parasite so if you use different MOA –> kill.

93
Q

xcc

A
94
Q

Cyclic Depsipeptides: Cyclodepsipeptide PF1022A is a ?

A

Emodepside used in cats

95
Q

Emodepside is effective against

A

ascarids and hookworms (mature and immature adults)

96
Q

What is the MOA of Emodepside?

A

Emodepside is a selective agonist of the presynaptic latrophilin-receptor (LTP) in
parasitic nematodes, which results in flaccid paralysis and death

97
Q

Describe the formulation of Emodepside.

A
  • 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
98
Q

List the adverse effects of Emodepside.

A
  • 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
99
Q

Emodepside may interfere with?

A

fetal development (rats and rabbits). Pregnant women
should avoid direct contact with emodepside and wear disposable gloves (if product
handling is necessary)

100
Q

Derquantel is also called?

A

2-Deoxy-paraherquamide (PHQ)

101
Q

Derquantel is active against ?

A

both BZD and ivermectin-resistant Haemonchus contortus
(adult stages)

102
Q

What is the MOA of Derquantel?

A

It acts as an antagonist of neuronal nicotinic cholinergic receptors in both nematodes
(flaccid paralysis) and mammals → it shows markedly lower affinity

103
Q

Derquantel is well absorbed and extensively distributed into tissues after oral administration

A
104
Q

Describe the heartworm lifecycle.

A
105
Q

Drugs for Heartworm Prevention and Therapy

A
  • 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
106
Q

Drugs for Heartworm Prevention and Therapy
Three aspects to be considered

A
  • Removal of adult heartworms → adulticide
  • Use of microfilaricides ???
  • Prevention of infection → it requires a larvicide
107
Q

Drugs for Heartworm Prevention and Therapy Adulticide therapy: ?

A

Melarsomine (Immiticide®

108
Q

Melarsomine is a __________ _________ compound with activity against ________ (> 4-month-old) and ____ heartworms in dogs. Its mode of action is ________.

A

trivalent arsenic , immature, adult, unknown

109
Q

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 ____.

A

IM, liver, kidneys, liver, bile

110
Q

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!

A

IV, SC, IM, L3-L5

111
Q

American Heartworm Society recommends a __ to __-dose protocol. Contraindication → ?

A

2, 3, Caval Syndrome

112
Q

Caval Syndrome (small ____, rarely ____)
worms block the _____ Vena Cava. It requires immediate _____ removal of worms

A

dogs, cats, Caudal, surgical

113
Q

List the side effects of Melarsomine (Immiticide®)

A
  • 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
114
Q

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

A
115
Q

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)

A

True

large, Macrocyclic lactones, insufficient, 90, Milbemycin, rapid

116
Q

Larvicides for heartworm prevention?

A

Macrocyclic lactones

117
Q

Which drugs are used to treat the larval stages of heartworm in dogs and cats?

A

Ivermectin, moxidectin, milbemycin oxime, and selamectin are used to kill larval stages of
Dilofilaria immitis (L3-L4) in dogs and cats

118
Q

Ivermectin and milbemycin oxime are available for ______ oral administration. Some formulations are flavored and chewable to increase patient acceptance and facilitate
administration.

A

monthly

119
Q

Moxidectin and selamectin are available as ______ applied liquid formulations

A

topically

120
Q

Moxidectin can also be _________ administered with a ____ dose of the slow-release (SR) formulation. It provides protection for __ months

A

subcutaneously, single, 6

121
Q
A
122
Q

Anticestodal drugs used to treat

A

tapeworm

123
Q

Tapeworm infection in farm animals may be a ____ problem and usually ______ require treatment with a specific cestocidal drug

A

minor, does not

124
Q

Some of the broad-spectrum BZD compounds are also effective against _________

A

tapeworms

125
Q

The oral administration of __________ _______ paste resulted in effective control of Anoplocephala perfoliate infections in horses (commonest _________ parasite)

A

pyrantel pamoate, tapeworm

126
Q

Treatment of tapeworm infections is necessary in _________ animals → dogs and cats are _______ hosts of tapeworms whose _____ stages cause zoonosis

A

companion, definitive, larval

127
Q

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

A
  • 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
128
Q

What is the spectrum II of action of Praziquantel ?

A
  • 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
129
Q

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

A
  • 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

130
Q
A
131
Q

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

A
  • 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
132
Q

Epsiprantel is chemically related to __________ and used specifically for the treatment of the
common ______ of dogs and cats. These include?

A

praziquantel, tapeworms

D. caninum, T. pisiformis, T. taeniaeformis, E. granulosus, E. multilocularis

133
Q

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

A

➢ 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

134
Q

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

A

dogs and cats, poorly, cestodes, feces, urine, low

135
Q
A
136
Q

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

A

Fasciola hepatica, trematode, domestic, zoonotic

137
Q

Drugs active against ____ of the species are _____ effective against the other

A

one, equally

138
Q

The tropical counterpart of F. hepatica is ?

A

F. gigantica

139
Q

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 ______

A

Paramphistomum spp., Immature, duodenum, rumen

140
Q
  • Paragonimus spp. (lung flukes) in _____ and ____.
A

dogs, cats

141
Q

________ used in sheep and cattle are active against liver flukes older than ?

A

Albendazole, 12 weeks

142
Q

Fenbendazole is not effective against ____________, but a single treatment reduced __________ infection in sheep by up 95%

A

F. hepatica, F. gigantica

143
Q

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 ?

A

F. hepatica, nematodes and cestodes

144
Q

The selection of TCBZ-resistant populations is an emerging problem in several areas of the world due to?

A

→ increased TCBZ oxidative metabolism by the fluke
→ enhanced drug efflux mediated by ATP-dependent TM-transporter

145
Q

Combined formulations containing TCBZ and different antinematodal drugs are available in different countries. Name these combinations.

A

Levamisole, abamectin, ivermectin

146
Q

TCBZ can be administered at _____ stage of pregnancy. A withdrawal time of ___ days (____) has been stablished

A

any, 56, meat

147
Q
  • Clorsulon is highly effective against ?
  • It shows good efficacy against ___-week-old and _____ flukes → following ___ and ____ administration at 4-8 mg/Kg
A

adult liver flukes in cattle > sheep and goats

8, older, SC, oral

148
Q
  • There are different combinations of clorsulon with other drugs. List these combinations.
A

➢ Clorsulon + ivermectin (Ivomec Plus®, Alverin™ Plus)
➢ Clorsulon + ivermectin + fenbendazole

149
Q

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
A
  • 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
150
Q
  • In rats, clorsulon was shown to be bound predominantly to?
A

bound predominately to erythrocytes

151
Q

Clorsulon is a ______ soluble drug. ______ excretion of the drug is thought to be the main route of elimination

A

lipid, Renal

152
Q

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

A

safe, high, breeding, pregnant, 72, 8

153
Q
  • 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
A
154
Q

The __________ and _______ are closely related macrocyclic lactones produced through fermentation by soil dwelling actinomycetes (Streptomyces)

A

avermectins, milbemycins

155
Q

List the members of the Avermectin family

A
  • Abamectin → naturally occurring avermectin
  • Ivermectin → the first marketed endectocide molecule (semisynthetic)
  • emamectin
  • Doramectin
  • Eprinomectin
  • Selamectin
156
Q

List the members of the Milbemycin family

A
  • Nemadectin
  • Moxidectin
  • Milbemycin oxime
157
Q

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

A
158
Q
A
159
Q

Avermectins nad Milbemycins are used as?

A

The broad-spectrum ecto-endoparasitic activity from both families includes
* Insects
* Ascarines
* Nematodes

160
Q

Avermectins and milbemycins do not possess efficacy against?

A

cestode and trematode parasites

161
Q

What is the MOA of Macrocyclic Lactones (MLs)?

A

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

162
Q
A
163
Q

The macrocyclic lactones are highly ___________ and extensively distributed from the bloodstream to different tissues

A

lipophilic

164
Q

Macrocyclic Lactones (MLs) are high availability in parasite location tissues such as ?

A

GI mucosal tissues, lungs, and skin

165
Q

Doramectin compared to ivermectin has an enhanced __________ and ________ time of residence in target tissues

A

availability, prolonged

“Dora last for a longer time in the forest”

166
Q

___________ is the most lipophilic endectocide agent

A

Moxidectin

167
Q

A considerable excretion of which three endectocide compounds occurs via mammary glands?

A

ivermectin, moxidectin, and doramectin

168
Q

Topical formulations of __________ are approved for use in dairy cattle in
some countries

A

moxidectin

169
Q

Eprinomectin has a good antiparasitic _______, _____ spectrum, and substantially _______ distribution to milk, compared to other MLs

A

potency, broad, reduced

170
Q

The main metabolism of MLs occurs in the ______ and they are excreted in high concentration in ?

A

liver, bile and feces

171
Q

The MLs (3?) are substrates of the P-GP transport protein. _______ has a lower affinity for P-GP compared to avermectin-type compounds

A

abamectin, ivermectin, and moxidectin, Moxidectin

172
Q

The duration of the ML persistence of antiparasitic activity vary

A
173
Q

The intrinsic properties of the MLs allow a sustainable persistence of the active drug in the
animal body → Pharmacotechnical preparations

A
174
Q

Just remember there are a different number of days

A
175
Q

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.

A

GI nematodes, Arthropods, and lung worms.

nematodes

adult, larval

Eprinomectin, moxidectin

176
Q
A
177
Q

In horses, Ivermectin and Moxidectin are used to treat?

A

Ascarids, stomach worms, lung worms, the adult and larval stages of large strongyles and adult small strongyles, and lastly the horse botfly Gastrophilus intestinalis

178
Q

Ivermectin is used in dogs and cats as a preventative against?

A

Dirofilaria immitis

179
Q

Only know which drugs effect which groups of parasites, NOT specifics.

A
180
Q

Know withdrawal times

A
181
Q

Are MLs considered to be safe compounds?

A

MLs are highly safe compounds → Pharmacodynamic action

182
Q

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!

A
183
Q

MLs do not effect on _______ performance, ____ quality, or ________ was observed when bulls or cows were treated with ivermectin at 0.4 mg/Kg

A

breeding, semen, pregnancy

184
Q

Abamectin is slightly more toxic than _______. Abamectin LD50 in mice 14-24 mg/Kg (ivermectin 25-40 mg/Kg)

A

ivermectin

185
Q

Abamectin is not recommended for use in calves under ___ months of age

A

4

186
Q

Milbemycin compounds have a ____ therapeutic margin

A

wide

187
Q

No adverse effects have been observed in cattle treated with moxidectin (SC) up to 10
times the recommended dose

A
188
Q
A

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

189
Q

Neurotoxicity to ivermectin in MDR1 defect is characterized by:

A

Depression
Ataxia
Somnolence
Salivation
Tremor
Coma
Death

“SAD CaTS DEATH”

190
Q

Which MLs are Safe at the therapeutic dose for the ivermectin sensitive collie?

A

Moxidectin, selamectin

191
Q

The overall efficacy and safety of the MLs designed for other species should not be assumed for ?

A

dogs and cats

Pharmacology II (27 decks)

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