Anthelmintics Flashcards
Define chemotherapy
Use of drugs to injure an invading organism without causing damage to the host (selective toxicity)
What 4 ways may anthelmintics be classified?
- Spectrum of acitivty
- Chemical group/mode of action
- Target parasites
- Method of delivery/formation
How can anthelmintics be classified based on spectrum of activity?
- Broad spec
- Narrow spec
Give an eg. of a narrow spec anthelmintic
Praziquantel - only used for hydatid disease (echinococcus)
What are the 3 main active ingredient classes/modes of action of anthelmintics? Give egs of each.
- benzimidazoles (BZ) - fenbendazole (panacur)
- imadozothiazoles (LM) - levamisole
- Macrocytic lactones (ML) - ivermectin
What are the 3 parasite specific targets?
- nematodicides
- cestodicides
- trematodicides (flukicides)
What 3 methods of delivery/formation are available?
- Oral eg. drench/tablet/bolus
- Parenterally eg. injectable
- Topically eg. pour on, spot on
What are the 3 main subgroups of broad spec anthelmintics? What will these be referred to as by farmers?
Group 1. BZ - benzimidazoles = White drenches
Group 2. LV - Imadazothiazoles = Yellow drenches
Group 3. ML - Macrocytic lactones = Clear drenches
What are the 2 newer classes of broad spec anthelmintics? What are these used for?
Group 4 (AD) Group 5 (SI) - reserved for last resort to prevent resistance developing
What are the narrow spec anthelmintics indicated for?
When specific pathogen is diagnosed. eg. Fluke drenches, tapeworms etc.
What is the mechanism of action of benzimidazoles (Group 1)?
B tubulin binding inhibited - worm starves due to inhibition of glucose uptake
What is the mechanism of action of the majority of anthelmintics?
NT interaction -> paralysis
What is the mechanism of action of Group 2 (LV) Imidazothiazoles?
Ach Ag
What is the mechanism of action of macrocyclic lactones?
Modulate glutamate-gated Cl- channels
What is a white drench?
Benzimidazoles
Give some examples of white drenches (benzimidazoles)
Albendazole, ricobendazole, fenbendazole, flubendazole, menbendazole, oxfendazole, triclabendazole
How soluable are benzimidazoles? What implications does this have?
Low water soluability - oral products available only (shake well before administered)
What levels of benzimidazoles are required for optimum potency? How does this affect dosing schedules?
- Long duration, low plasma concentration - kill worms SLOWLY by starvation.
- Multiple low doses more potent than single large dose
- potency greater in ruminants/horses [rumen/ceacum acts as reservoir] than dogs (monogastric)
- potency greater in ruminants if starved 12-24hrs -> decreases motility of gut and slows rate of passage of ingesta
- > ^ contact with parasite
What are yellow drenches?
Imidazothiazoles [levamisole]/tetrahydropyrimidines[pyrantel]
What mechanism of action do group 2 yellow drenches (imadathiazoles/tetrahydropyrimidine) ?
Cholinergic agonists -> rapid reversible spastic paralysis
How are yellow drenches administered?
Oral drenches
Which parasites is levamisole active against?
Nematodes (roundworms)
> Gut worms
- adult +++, mucosal L ++, hypobiotic L +
> Lungworms +++
(NOT trematodes, cestodes, arthropods, protozoa)
- variable activity depending on host and parasite species
What is the half-life of levamisole?
Very short
Give examples of macrocyclic lactones (ML)
Ivermectin, milbemax, milbemycin
What are clear drenches?
Macrocyclic Lactones (Avermectins, Milbemycins)
Give examples of avermectins
Abamectin, doramectin, eprinomectin, ivermectin, selamectin
Give exampls of milbemycins
Moxidectin, Milbemycin Oxime
What is the mechanism of action of macrocyclic lactones?
Affect GABA chloride channels -> flaccid paralysis
What parasites do macrocyclic lactones target?
Nematodes > Gutworms (Adults, mucosal larvae and hypobiotic larve +++) > Lungworms +++ > Arthropods ++ (esp blood sucking) (NOT trematodes, cestodes, protozoa)
Describe the pharmacokinetics of macrocyclic lactones. What impact does this have on how they are used?
Prolonged, persistent activity means good for prophylactic and metaphylactic wirm control strategies
In what forms are macrocyclic lactones available?
Oral, injection and pour on
Define metaphylaxis
Protection of animals grazing CONTAMINATED pasture - only used when there is no way around this, so metaphylaxis -> cover July - Oct to protect against the auto-infection peak from L3 which is inescapable.
Define prophylaxis
- More widely used
- treat animals April - June to PREVENT the autoinfection peak as no L3 are left on the pasture and so grass is not contaminated in the first place when cows turned out in summer
Which drugs can be used as roundwormers?
All broad spec (White, Yellow and Clear drenches; Aminoacetile Derivatices, Spiroindoles)
Narrow spec: Depsipeptides, salicylanilides, Piperazines, Phenylisothiocyanates
Which drugs can be used as tapewormers?
Broad spec: Benzimidazoles (White drench) and Tetrahydripyramidines (Yellow drench)
Narrow spec: Isoquinolones (praziquantel, epsiprantel) and Phyenylisothiocyanates (Nitroscanate)
What is the mechanism of action of praziquantel? Why do some pet owners not believe it to be effective?
Tegument destruction -> ^ membrane permeability to Ca+ ions, loss of Ca -> Spastic paralysis and malabsorption.
- Destruction of tegument means worm can be destroyed in gut and so will not be seen in faeces
What parasites do salicylanilides and substituted phenols target? Why? What negative impacts may this have?
Narrow spec - flukes and blood feeding nemotodes (eg. heamonchus contortus)
- Bind to plasma proteins -> definite intake by blood suckers.
- Also ^ plasma half life so not used in milking cattle or sheep
Give examples of salicylanilides
Closantel, oxyclozanide
Give examples of substituted phenols
Nitroxynil
What is the mechanism of action of salicylanilides and substituted phenols?
Uncouple oxidative phosphorylation pathway -> starvation
What does RDR stand for?
Recommended Dose Rate
What do anthelmintic formulations consist of?
Active compound + excipients (other ingredients to alter physical attributes and/or biological properties) eg. transport through tissues to blood stream
