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Anthelmintics Or ‘Why I like drugs”

Anthelmintics Or ‘Why I like drugs”. Nick Sangster Faculty of Veterinary Science University of Sydney. Worms. Objectives. Understand the need and market for anthelmintic drugs Describe the features of the major anthelmintic groups Explain spectrum of activity. Antiparasitic drugs.

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Anthelmintics Or ‘Why I like drugs”

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  1. Anthelmintics Or ‘Why I like drugs” Nick Sangster Faculty of Veterinary Science University of Sydney

  2. Worms

  3. Objectives • Understand the need and market for anthelmintic drugs • Describe the features of the major anthelmintic groups • Explain spectrum of activity

  4. Antiparasitic drugs • Anthelmintics – helminths, worms • Antiprotozoals – Protozoa • Ectoparasiticides – insects and acarines Actions and use differ, but the same principles apply to control and registration

  5. Internet Resources • www.sheepwormcontrol.com • Vich.eudra.org • www.apvma.gov.au • http://www.worminfo.org/decision_analysis/tropical_worm_world/

  6. What are anthelmintics? • Anti helminth drugs • Act to kill/remove/control • Nemathelminthes (roundworms) • Platyhelminthes (flatworms) • Used widely in animal and human health • A range of chemical types with different actions and efficacy.

  7. Why know about anthelmintics? • Dispel the myth ‘but they have a drug for that’ • Know how to read and understand the label • Know enough to make usage decisions in the face of: • Drug resistance (when drugs stop working) • Off label use (to use in an animal outside registration) • Antiparasitics major part of market • This sector employs a lot of vets

  8. The world animal product market 1996 $M USD Livestock Companion Parasiticides 1403 1295 Performance 310 - Antimicrobial 1705 355 Other pharms 795 585 Biologicals 1585 610

  9. % Australian market

  10. Challenges in anthelmintic discovery • Kill (or remove) worms in a single dose • Cannot target cell division • Parasite phylogenetically close to the host e.g. • some of the same neurotransmitters, • same ribosomal machinery • There are some very good drugs on the market

  11. Discovery and dose rates

  12. Requirements of anthelmintics • Effective, safe, non toxic to consumer. • Narrow spectrum, broad spectrum • Stock Medicines Act 1989 and vets • Anyone can give stock medicines to non-food producing animals (we eat horses!) • Only vets can vary label directions in food producers but MUST supply (in writing) species, withholding, dose rate, frequency of treatment, manner of administration. • No one can use an unregistered stock medicine except under permit or order

  13. Aspects of commercial anthelmintics • Establishing a need/market • Research • Screening • Refinement • Development • Marketing • Technical support

  14. Anthelmintic modes of action

  15. Benzimidazoles • Many members such as fenbendazole and albendazole • Effective against nematodes (adults and larvae) and some flukes • Given as oral liquids to all hosts • Act by binding to tubulin leading to loss of cell transport and shape • (Triclabendazole- flukicide)

  16. Levamisole • Levamisole and pyrantel • Effective against nematodes • Given as an oral liquid (levamisole-sheep; pyrantel-dogs) • Act on Acetylcholine receptors of worms to cause paralysis

  17. Piperazine • Tablet of liquid for dogs • Used for roundworm control • Acts like GABA to relax body muscle and paralyse worms

  18. Macrocyclic lactones • Ivermectin, moxidectin etc. • Broadspectrum including ectoparasites • Oral, injection or backline • Act on GluCl- channels to cause paralysis of pharynx and body muscle

  19. Salicylanilides • Closantel • Blood sucking parasites (Haemonchus and Fasciola) • Oral for sheep • Uncouples energy generation in worm mitochondria

  20. Spectrum of activity

  21. New chemicals on the horizon • Bay 44-4400 • Novel mode of action • GI nematodes at 1 mg/kg • 2-deoxyParaherquamide • Cholinergic antagonist (novel action) • GI nematodes • Sheep industry product?

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