27. Antihelmintics 1. (benzimidazoles. imidazothiazoles, tetrahydropyrimidines) Flashcards

1
Q

What are requirement for modern antihelmintics

A
  • should have large therapeutic index
  • considerable activity against all developmental stages (vertical spectrum)
  • broad spectrum of activity against several taxonomic groups (horizontal spectrum) - usually achieved by combining products
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2
Q

Groups of antihelmintics

A
  • benzimidazoles and probenzimidazoles (AN, AC, some AT)
  • macrocyclic lactones (AN)
  • imidazothiazoles (AN)
  • isoquinolin and benzazepin derivatives (AC, some AT)
  • organophosphates (AN)
  • piperazines (AN)
  • tetrahydropyrimidines (AN)
  • salicylanilides and substituted phenols (AT, AC, AN)
  • other (unclassified drugs) - depends on the drug
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3
Q

Benzimidazoles. Drugs. Mechanism of action

A
  • mebendazole
  • ALbendazole
  • FENbendazole
  • FLUbendazole
  • TRICLARbendazole
  • febantel
  • oxibendazole
  • oxfendazole

Inhibition of the synthesis of microtubules and energy transport
1. Inhibition of tubulin polymerisation by binding to the colchicine-sensitive site of tubulin -> degenerative combinations alterations in tegument and intestinal cells of the worm
2. Inhibition of cellular transport and energy metabolism
3. Impaired uptake of glucose -> depletion of glycogen stores
4. Degenerative changes in endoplasmic reticulum -> decreased production of ATP

Also albendazole inhibits enzyme fumarate reductase, which is helminth-specific

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4
Q

Benzimidazoles. Antihelmintics spectrum.

A
  1. Antinematodal (AN)
    Broad spectrum of activity. Larvicidal and ovicidial (alb, fenb, febantel, oxf, oxib)
  2. Anticestodal (AC)
    Febantel, fen, alb, mebendazole (larger dose), oxfendazole, flubendazole
  3. Antitrematodal effect (AT)
    Albendazole - only against older larval and adult stages of liver fluke + other flukes)
    Triclabendazole - only liver fluke (Fasciola hepatica)

Triclabendazole is not active against nematodes and cestodes!

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5
Q

Benzomidazoles. PK

A
  • PO - only limited amounts is absorbed
  • absorption lasts for 6- 30h after dosing (flub 2-7h)
  • reduced feed intake may increase activity of BZs
  • rumen acts as a drug reservoir from which plasma concentrations can be sustained for long periods
  • excretion: biliary route is the most important pathway and enterohepatic recycling of BZs to the GIT -> feces
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6
Q

Benzomidazoles. SE

A
  • PO relatively safe, non-toxic agents
  • teratogenicity (oxf, alb, feb)
  • hepatotoxicity, hair loss, feather loss, neurotoxicity (large dose/prolonged application/parenteral use)
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7
Q

Benzimidazoles. Administrative forms

A
  • not good soluble in water
  • given PO as a suspension, paste, bolus or premix (except for netobimin that can be injected)
  • WPs are between 8-14 days before slaughtering for meat (except long acting intraruminal boluses > 3 months) and 3-5 days before milking
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8
Q

Benzimidazoles in ruminants

A
  • albendazole, febantel, fenbendazole, triclabendazole
  • systemic antihelmintic activity is greater in sheep than in cattle
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9
Q

What benzimidazole can be administered topically? For what?

A

Thiabendazole.

As fungicide or against ear mites and cutaneous larva migrants

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10
Q

Special drug delivery systems in ruminants (benzimidazoles)

A

Available only in sheep and goat
- pulse-release bolus (~3 weeks in the rumen)
- sustained-release bolus (fenbendazole) - 140 days
- slow-release capsule (albendazole) - 105 days

widespread resistance among GI nematodes

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11
Q

Benzimidazoles in horses

A
  • fenbendazole, febantel, oxfendazole
  • high level and repeated administration may be necessary for extraintestinal migrating stages of large strongyles
  • resistance
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12
Q

Benzimidazoles in swine

A
  • fenbendazole, flubendazole
  • high efficacy against Ascaris suum and other swine nematodes
  • resistance in Oesophagostonum spp
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13
Q

Benzimidazoles in dogs and cats

A
  • febantel, fenbendazole, flubendazole
  • roundworms, hookworms tape tapeworms
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14
Q

Benzimidazole used in poultry

A
  • flubendazole
  • against GI and respiratory nematodes
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