27. Antihelmintics 1. (benzimidazoles. imidazothiazoles, tetrahydropyrimidines) Flashcards
What are requirement for modern antihelmintics
- 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
Classification of antihelmintics
- 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
Benzimidazoles. Drugs. Mechanism of action
- 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
Benzimidazoles. Antihelmintics spectrum.
- Antinematodal (AN)
Broad spectrum of activity. Larvicidal and ovicidial (alb, fenb, febantel, oxf, oxib) - Anticestodal (AC)
Febantel, fen, alb, mebendazole (larger dose), oxfendazole, flubendazole - 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!
Benzomidazoles. PK
- 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
Benzomidazoles. SE
- PO relatively safe, non-toxic agents
- teratogenicity (oxf, alb, feb)
- hepatotoxicity, hair loss, feather loss, neurotoxicity (large dose/prolonged application/parenteral use)
Benzimidazoles. Administrative forms
- 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
Benzimidazoles in ruminants
- albendazole, febantel, fenbendazole, triclabendazole
- systemic antihelmintic activity is greater in sheep than in cattle
What benzimidazole can be administered topically? For what?
Thiabendazole.
As fungicide or against ear mites and cutaneous larva migrants
Special drug delivery systems in ruminants (benzimidazoles)
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
Benzimidazoles in horses
- fenbendazole, febantel, oxfendazole
- high level and repeated administration may be necessary for extraintestinal migrating stages of large strongyles
- resistance
Benzimidazoles in swine
- fenbendazole, flubendazole
- high efficacy against Ascaris suum and other swine nematodes
- resistance in Oesophagostonum spp
Benzimidazoles in dogs and cats
- febantel, fenbendazole, flubendazole
- roundworms, hookworms tape tapeworms
Benzimidazole used in poultry
- flubendazole
- against GI and respiratory nematodes
