Download - Anthelmintics Or ‘Why I like drugs” Nick Sangster Faculty of Veterinary Science University of Sydney
Anthelmintics
Or ‘Why I like drugs”
Nick Sangster
Faculty of Veterinary Science
University of Sydney
Objectives
• Understand the need and market for anthelmintic drugs
• Describe the features of the major anthelmintic groups
• Explain spectrum of activity
Antiparasitic drugs
• Anthelmintics – helminths, worms
• Antiprotozoals – Protozoa
• Ectoparasiticides – insects and acarines
Actions and use differ, but the same principles apply to control and registration
Internet Resources
• www.sheepwormcontrol.com
• Vich.eudra.org
• www.apvma.gov.au
• http://www.worminfo.org/decision_analysis/tropical_worm_world/
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.
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
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
% Australian market
Ectoparasiticides
Anthelmintics
Vaccines
Vitamins
Antibacterials
Coccidiostats
Others
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
Discovery and dose rates
0.1
1
10
100
1000
1920 1940 1960 1980 2000 2020
Year
do
se r
ate
mg
/kg
Thiabendazole Levamisole
Ivermectin
Phenothiazine
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
Aspects of commercial anthelmintics
• Establishing a need/market
• Research
• Screening
• Refinement
• Development
• Marketing
• Technical support
Anthelmintic modes of action
Class example MOA
Benzimidazoles Albendazole Tubulin binding and cellular disruption
Tetrahydropyrimidine Levamisole Nicotinic-like agonists
Organophosphates Dichorvos Acetylcholine esterase inhibitors
Piperazines Piperazine GABA agonists
Macrocyclic lactones Ivermectin GluCl- potentiators
Praziquantel Enhance Ca++ permeability
Salicylanilides Closantel Proton ionophores
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)
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
Piperazine
• Tablet of liquid for dogs
• Used for roundworm control
• Acts like GABA to relax body muscle and paralyse worms
Macrocyclic lactones
• Ivermectin, moxidectin etc.
• Broadspectrum including ectoparasites
• Oral, injection or backline
• Act on GluCl- channels to cause paralysis of pharynx and body muscle
Salicylanilides
• Closantel
• Blood sucking parasites (Haemonchus and Fasciola)
• Oral for sheep
• Uncouples energy generation in worm mitochondria
Spectrum of activityAnthelmintics for dogs and cats
COMPOUND chemical class DOSE (mg/kg)
Piperazine piperazine 80-100 + +/-Pyrantel tetrahydropyrimidine 14 (56 in cats) + +Oxantel tetrahydropyrimidine 15 +Febantel pro-benzimidazole 25 + + +Mebendazole benzimidazole 20 (3-5 days) + + + +Flubendazole benzimidazole 22 + + + +*Fenbendazole benzimidazole 50 (3d) + + + + +aLevamisole Imidothiazole 5 or 10 + + + +/- +Nitroscanate Isothiocyanate 50 + + + +Arsenamide Arsenical 2 bid, 2d. IV +Melarsomine Arsenical IM +Thiacetarsamide Arsenical 2.2 bid, 2d. IV +Diethylcarbamazine piperazine 10 +Milbemycin oxime macrocyclic lactone 0.5 + + + +Ivermectin macrocyclic lactone 0.006 +*Ivermectin macrocyclic lactone 0.05 + +Moxidectin macrocyclic lactone 0.003 +Selamectin (dogs) macrocyclic lactone 6 +Selamectin (cats) macrocyclic lactone 6 + + +Praziquantel 5 or b + + +Niclosamide 100 + +
a, for Aelurostrongylus in cats; b, 20 mg/kg for Spirometra; * off label use; check all labels and dose rates before use.
Dipylidium
Taenia
Echinococcus
Asc
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Ancylostoma
Trichuris
Lung
wor
ms
Dirofilaria
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Dirofilaria
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Dirofilaria
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