Docstoc

Worms

Document Sample
Worms Powered By Docstoc
					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
• 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
                  1000
                                Phenothiazine
dose rate mg/kg




                  100


                   10       Thiabendazole                 Levamisole


                    1

                                            Ivermectin
                   0.1
                     1920      1940         1960          1980     2000   2020
                                                   Year
  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 activity
                      Anthelmintics for dogs and cats




                                                                                                                                                                                Dirofilaria larvae
                                                                                                                                                           Dirofilaria adults
                                                                                        Echinococcus




                                                                                                                     Ancylostoma




                                                                                                                                                                                                     microfilariae
                                                                                                                                                                                                       Dirofilaria
                                                                                                                                               Lungworms
                                                                                                       Ascaridoids
                                                                  Dipylidium




                                                                                                                                   Trichuris
                                                                               Taenia
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)                          +                       +             +             +           +a
Levamisole            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.
  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?

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:0
posted:3/27/2013
language:Unknown
pages:21