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Veterinary Pharmacology > Antinematodal Drugs, Pt. 2 > Flashcards

Antinematodal Drugs, Pt. 2 Flashcards

1
Q

What Imidathiazole is most commonly used as a an antinematodal? What is it effective against? Ineffective?

A

Levamisole, the L-isomer of tetramisole

  • lung and GI tract nematodes
  • cestodes, trematodes
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2
Q

What is the mechanism of action of Levamisole?

A

cholinergic receptor agonist (nAChR), producing spastic paralysis on nematode body wall muscles

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3
Q

Where is Levamisole metabolized? In what species is it not given?

A

liver —> oxidized and hydrolyzed

horses —> produces a metabolite that is a prohibited substance in racehorses (aminorex), has a narrow safety margin, and is not very effective against many equine nematodes

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4
Q

What is the spectrum of Levamisole?

A

broad spectrum activity against mature stages of the major GI nematodes and mature/larval stages of lungworms

  • Haemonchus, Ostertagia, Cooperia, Nematodirus, Bunostomum, Oesophagostomum, Chabertia, Dictyocaulus viviparus
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5
Q

What are 3 major therapeutic uses of Levamisole in dogs? What is it not effective against?

A
  1. GI nematodes
  2. microfilaricide against Dirofilaria immitis
  3. ascardis (Toxocara, Toxascaris) and hookworms (Ancylostoma, Uncinaria)

canine whipworms - Trichuris vulpis

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6
Q

What is the preferred administration of Levamisole in cattle? What is a common adverse effect of this way of administration?

A

injectible

levamisole hydrochloride can result in moderate to severe reaction at the injection site

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7
Q

What additional effect does Levamisole have other than an anthelmintic? When does it work best?

A

immunostimulant (can be a suppressant at higher doses)

in compromised hosts whose T-lymphocytes and phagocyte functions are below normal

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8
Q

What aspect of the immune system is not affected by Levamisole?

A

B-lymphocytes —> no direct effect on antibody production

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9
Q

What are 3 common signs of Levamisole intoxication?

A
  1. salivation
  2. defecation
  3. respiratory distress from smooth muscle contraction

similar to organophosphate poisoning

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10
Q

What way of administration is not recommended for Levamisole? What species especially tolerate it very well?

A

IV —> dangerous upon parenteral administration

chickens

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11
Q

What is the recommended administration of Levamisole in dogs and cats? Why is it not commonly given to cattle producing milk for human consumption?

A

oral (SQ administration is fatal)

no withdrawal time has been established

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12
Q

What drugs enhance the toxic effects of Levamisole?

A

nicotine-like or cholinesterase-inhibitor drugs

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13
Q

What 3 tetrahydropyrimidines are commonly used?

A
  1. Pyrantel (broad spectrum anthelmintic against GI nematodes in sheep)
  2. Morantel (methyl ester analog)
  3. Oxantel (m-oxyphenol derivative)
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14
Q

What is the mechanism of action of Pyrantel, Morantel, and Oxantel?

A

agonist at nicotinic acetylcholine receptors (nAChR) on nematode muscle cells and produce contraction and spastic paralysis

  • pyrantel and morantel are 100x more potent and ACh, but are slower in initiating contraction
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15
Q

How do pyrantel pamoate salt and pyrantel tartrate compare?

A

poorly absorbed in the GIT, allowing higher unabsorbed concentrations to reach the lower digestive tract

better absorbed in pigs and dogs compared to ruminants

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16
Q

Where are pyrantel, morantel, and oxantel excreted? What species is an exception?

A

feces

dog —> urine

17
Q

In what species is morantel poorly absorbed?

A

ruminants —> drug is undetected in bloodstream after oral treatment and is largely excreted unmetabolized in the feces

18
Q

What therapeutic use does pyrantel have in horses? What 2 species is it less efficacious against?

A

high efficacy against GI heminths

  1. Strongylus edentatus
  2. mature and immature Oxyuris equi
19
Q

What are 3 therapeutic uses of pyrantel in swine?

A
  1. removal or prevention of large roundworms (Ascaris sum)
  2. Oesophagostomum spp.
  3. stomach worms (Hyostrongylus rubidus)
20
Q

What 3 canine parasites does pyrantel work best against?

A
  1. ascarids - Toxocara cani, Toxascaris leonine
  2. hookworms- (Ancyclostoma caninum, Unicaria stenocephala
  3. stomach worm - Physalopter
21
Q

What 2 tetrahydorpyrimidines are commonly used in ruminants? What are their spectra?

A

PYRANTEL TARTRATE - adult and immature GI nematodes (Ostertagia, Haemonchus, Trichostrongylus, Nematadirus, Chabertia, Cooperia, Oesphagostomum)

MORANTEL TARTRATE - adult and immature stages of Haemonchus, Ostertagia, Trichostrongylus, Cooperia, and Nematadirus

22
Q

What formulation of pyrantel is safest?

A

pyrantel salts —> safe at doses 7x therapeutic dose

  • also safe for horses and ponies of all ages at 20x therapeutic dose
23
Q

What should tetrahydropyrimidines not be mixed with in a formulation?

A

other cholinergic anthelmintics, like Levamisole

24
Q

Is morantel or pyrantel tartrate safest?

A

morantel tartrate —> allowed for use in dairy animals without withdrawal restriction

25
Q

Levamisole vs. Pyrantel/Morantel:

A

LEVAMISOLE = lung/GI nematodes, NO IV, narrow safety in horses

P/M = GI nematodes, safe in horses

26
Q

What is Piperazine? What spectrum does it have? What parasite stage is most susceptible?

A

heterocyclic compound classified as a narrow-spectrum antinematodal against ascarids

mature worms > younger stages

27
Q

What is the mechanism of action of Piperazine? What should it not be combined with?

A

selective agonist of GABA receptors, resulting in the opening of chloride channels and hyperpolarization of nerve membranes at NMJ leading to immobilization (flaccid)

pyrantel/morantel —> antagonistic MOA

28
Q

What can large oral doses of Piperazine cause in dogs and cats? How does this compare to horses and foals?

A

emesis, diarrhea, incoordination, head pressing

no toxic effects when given 6-7x therapeutic dose

29
Q

What 4 mechanisms do parasites have to become resistant to anthelmintics?

A
  1. change in molecular target, allowing drug to accumulate at intracellular site of action
  2. production of enzymes to metabolize the drug
  3. change receptor number, structure, and/or affinity
  4. amplification of target genes, like MDR1
30
Q

What determines the rate at which anthelmintic resistance develops and spread within a population?

A

number of parasites that survive treatment and contribute resistance genes to the nect generation

31
Q

What commonly contributes to anthelmintic resistance?

A
  • parasite genetic factors
  • fecundity of adult parasites
  • parasites in refugia (on the prairie with no treatment)
  • drug features
  • grazing management
  • climatic conditions
32
Q

What 5 strategies can help fight the development of anthelmintic resistance?

A
  1. avoid under-dosing
  2. use nematocidal drug combinations of drugs of different families and MOA
  3. know the nature of the chemical and its ability to select for resistance
  4. remove feces and alternate grazing of different host
  5. keep farmers informed
33
Q

True or false: Both pyrantel and levamisole have the same MOA. They are nicotinic receptor agonists and produce flaccid paralysis on nematodes.

A

FALSE —> spastic paralysis

34
Q

Why is the combination of nematocidal drugs important?

A

allows for better efficacy while fighting resistance

35
Q

True or false: When treating nematodes in horses, the first choice would be levamisole.

A

FALSE —> Levamisole has a narrow safety margin, use Pyrantel

Veterinary Pharmacology (35 decks)

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