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Farm Animal Final Year > Antiparasitic agents and endoparasites > Flashcards

Antiparasitic agents and endoparasites Flashcards

1
Q

Define antiparasitics?

A

Define: Chemical compounds used to kill parasites

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2
Q

Outline types of antiparasitics?

A

Endoparasiticides (internal antiparasitics)- kill parasites living inside the animal, such as GI parasites, CRS parasites and heartworms. Endoparasiticides include anthelmintics (agents lethal to worms) and antiprotozoal (agents lethal or suppressive to protozoa)

Ectoparasiticides (external antiparasitics)- kill parasites living on the outside of an animal, including fleas, ticks, mites, and lice

Endectocides- combine the activity against internal and external parasites, offering greater convenience and broader-spectrum metazoan parasite control

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3
Q

Describe selective toxicity?

A

Paul Ehrlich –1913 •‘to succeed in identifying the chemoreceptors of parasites that have no analogue in the body’

Differential effects:

  • High toxicity to parasite
  • Low toxicity to host
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4
Q

Outline wormers (anthelmintics) of ruminants?

A

1. Group 1 (1-BZ) - benzimidazoles, white drench RW, LW, TW, LF (Adult); Oral; WP 3 d-3 wk

2. Group 2 (2-LV) - levamisole, yellow drench RW, LW; Oral & injection; WP 2-3 wk

3. Group 3 (3-ML) - the macrocyclic lactones (the avermectins and milbemycins), clear drench Ecto-Endo-parasites; Oral & injection; 1-6 wk

4. Group 4 (4-AD) – monepental (trade name Zolvix), orange drench RW; Oral; WP 2 wk

5. Group 5 (5-SI) –Derquantel + abamectin (spironoidoles) purple drench RW, LW; Oral; WP 2 wk

RW: round worm

LW: lung worm

TW: Tape worm

LF: liver fluke

WP: Withdrawal period

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5
Q

What is going to happen if you use the same class of dewormer every grazing season?

A

Resistance

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6
Q

Is there any scientific proof that drug rotation delays or enhances the development of resistance?

A

In contrast to conventional wisdom, there is no scientific evidence to go either way

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7
Q

DR what should I do?

A

Don’t use a wormer without knowing its efficacy against the intended parasites.

Due to the magnitude of DR none of the wormers can be assumed to have 100% efficacy in every circumstance.

Evaluate the efficacy of available dewormers before usage.

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8
Q

Outline wormers of the equid?

A

1.Benzimidazoles: (eg. fen/me-bendazole)

2. Tetrahydropyrimidines (eg. pyrantelembonate) specific to equines and companion animals

3. Macrocyclic lactones (eg. Iver/aver-mectins)

and for tapeworm ONLY

4. Praziquantel

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9
Q

Outline wormers of dogs and cats?

A

1.Benzimidazoles (eg. fen/me-bendazole)

2. Tetrahydropyrimidines (eg. pyrantelembonate)

3. Macrocycliclactones (eg. Iver/aver-mectins)

and for tapeworm ONLY

4. Praziquantel, Epsiprantel, Dichlorophen

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10
Q

Outline the mode of action of benzimidazoles?

A

Bind to b-tubulin and deactivate it’s function–inhibition of polymerization, causing abnormal microtubule formation and disrupts intracellular homeostasis and energy metabolism. Structural integrity of parasite compromised and it will be expelled from digestive tract.

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11
Q

Disucss resistance to benzimidazoles?

A
  • Nucleotide polymorphisms (SNPs) in the drug’s targetβ-tubulin, the most common SNP a phenylalanine to tyrosine substitution at position 200 in the gene
  • A single nucleotide change can lead to an amino acid substitution in the target protein and so change the affinity o fthe drug for the target. Such a change influences the response to the drug and might cause the drug to be less effective
  • With more frequent treatment we make DR happen quicker.
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12
Q

Discuss mode of action of imidazothiazoles (levamisole)?

A

Affect NICOTINIC acetylcholine (nAch) receptors agonists. Cholinergic agonists via mimicking Ach action they change permeability of the post-synaptic membrane, leading to depolarisation which opens voltage-gated sodium channels which allows for firing of the action potential and stimulating muscular contraction and spastic paralysis of the worms.

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13
Q

Discuss mode of action tetrahydropyrimidines (pyrantel and oxantel)?

A

Similar to imidazothiazoles

Affect NICOTINIC acetylcholine (nAch) receptors agonists. Cholinergic agonists via mimicking Ach action they change permeability of the post-synaptic membrane, leading to depolarisation which opens voltage-gated sodium channels which allows for firing of the action potential and stimulating muscular contraction and spastic paralysis of the worms.

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14
Q

Discuss tetrahydropyrimidines?

A
  • Active against larval & adult forms of nematodes, but are not active against migrating/arrested larvae, and no action on cestode
  • Usually formulated as tartrate or embonate salts (in the US the embonate salt is called pamoate salt). Pyrantel tartrate is more water soluble and better absorbed from the GI tract. The embonate (pamoate) salt is less water soluble and more poorly absorbed, and thus less toxic to the host, and is considered safe to administer to young, sick or pregnant animals
  • Low aqueous solubility and low uptake
  • Increases safety and efficacy
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15
Q

Discuss macrocyclic lactones?

A
  • The first class of endectocides
  • In both arthropods and nematodes
  • Cestodes, trematodes and adult heart worms are insensitive

Two groups:

  • Avermectins (ivermectin, selamectin, doramectin)
  • Milbemycins (milbemycin, moxidectin)

Very powerful and broad spectrum.

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16
Q

What is the mode of action of macrocyclic lactones?

A

MoA hyper-polarisation (inhibition)

  • Also, affect GABA-gated Cl-channels in the CNS of both vertebrates & invertebrates.
  • Protected in vertebrates by P-glycoprotein transmembrane transport pump. (If it happens in worms then become resistant)
  • Leading to hyperpolarization inhibition of movement and paralysis of worm
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17
Q

Discuss DR to macrocyclic lactones?

A

DR is reduced experimentally by calcium channel blockers so probably involves P-glycoprotein

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18
Q

Discuss monepental mode of action?

A

The nematode needs normal MPTL-1 receptors, a unique kind of Ach receptor, for its nervous system, so it can co-ordinate its movement

MoA: Spiroindoles(G5) ACH antagonist causing flaccid paralysis and expulsion of parasite.

19
Q

Discuss emodepside?

A

Cyclo-octadepsipeptides

  • Profender (emodepside/praziquantel)
  • Acts on a specific class of transmembrane G-protein coupled receptors (depsiphilins) latrophilin receptor class (GPCR largest ever class of transmembrane receptor studied)
  • Flaccid paralysis of pharynx
20
Q

Discuss cestocides?

A

Cestocides Praziquantel (specific for tapeworm treatment)

  • Binds to b -subunit of voltage gated calcium channels
  • Some helminths do not have this subunit – Fasciola sppare not susceptible
  • Spastic and tetanic muscle contractions
  • Vacuolation of the tegument
  • Key component of Echinococcus eradication
  • Instrumental tool in tape worm treatment
21
Q

Look at this?

A
22
Q

Outline the rapid development of resistance to major available antihelmentics?

A
23
Q

Why do we control parasites?

A
  • To minimize the risk of parasitic disease
  • To control parasite egg shedding
  • To maintain efficacious drugs and avoid further development of resistance
24
Q

What to consider before using anthelmintics?

A
  • What are the signs patient is presented with?
  • What is the predictable parasite that could cause this?
  • What anthelmintic that would cover this parasite?
  • What instructions should be explained when dispensing drugs?
  • What adverse effects secondary to treatment should be anticipated?
  • What drug should be avoided in patients of certain species/breeds?
25
Q

What to consider before using anthelmintics?

A
26
Q

What are the considerations for which antihelmintic to use?

A

Spectrum (If you want to target a specific parasite be specific with your parasticide choice!)

Effective in removing adult & immature forms

Therapeutic index ( wide: toxic dose is at least 3X the therapeutic dose)

Easy-to-administer e.g. in feed, injections, and pour-on

Inexpensive or economically justifiable

No residue esp. in food-producing animals

Provides specific advantages in terms of pharmacokinetics or metabolism (e.g., more convenient dosing regimen , improved drug interaction profile, etc

Drug interaction Pyrantel with piperazine–opposite modes of actions

27
Q

Discuss ADRs?

A

Adverse drug reactions (ADRs) are rare if licensed products are used at recommended dose ranges and frequencies,

BUT, ………… can cause severe reactions e.g in foals: MOXIDECTIN

28
Q

Outline diff signs of toxicosis with different antihelmintics?

A

Imidazothiazoles

Signs of toxicosis include salivation, respiratory distress, seizures, vomiting and anaphylaxis, and are related to stimulation of mammalian nicotinic cholinergic receptors

Praziquantel

Toxicity signs include anorexia, vomiting, salivation, diarrhoea, and lethargy in less than 5% of animals §

Dichlorophen

Vomiting, salivation and diarrhoea may be seen after dichlorophen administration.

29
Q

Adverse reactions of benzimadazoles?

A

Albendazole:

Bone marrow suppression has been reported following treatment of dogs and cats and has teratogenic effects if given during pregnancy

Mebendazole and oxibendazole :

have been associated with an idiosyncratic hepatotoxic reaction in some dogs

30
Q

Which breed is at high risk from ivermectins?

A

Ivermectin and Collies

  • Increased sensitivity in collies
  • COLLIES –Deficient in P-glycoprotein
  • Signs include mydriasis, tremor, ataxia, emesis, salivation, coma
  • Safer option –Selamectin
31
Q

How to be strategic with worming treatment?

A

Winter: Treat for small Redworms larvae by using 5-day course of fenbendazole or single treatment of moxidectin

Treat for tapeworm if required (2x pyrantel embonate or single dose of praziquantel)

Spring/Summer (Grazing season): Treat for adult redworms. Select one active ingredient for each grazing season and dose based on worm egg count results

Treat for tapeworm if required (2x pyrantel embonate or single dose of praziquantel)

Autumn: Treat for small Redworms larvae by using 5-day course of fenbendazole or single treatment of moxidectin

December: Treat for Bots by using ivermectin or moxidectin

32
Q

How to handle resistance?

A
33
Q

Does pasture management help reduce worm burden?

A
34
Q

Individual horses within a herd differ greatly in the numbers of worms they harbour, the degree to which they contaminate the environment and their susceptibility to reinfection. In addition juvenille horses might harbour?

A

Paracaris equaram, which requires a separate treatment consideration, and a horse shedding very high numbers of strongyle eggs should be treated differently than a consistent low contaminator. Don’t use one standard treatment program for all horses in a stable.

35
Q

What to say to horse owners about worming?

A
36
Q

With regards to worming remember?

A

The class of agent

Refer to data sheet

Consider other aspects:

  • Public health
  • Costs
  • Combinations and interactions
  • Ease of application
  • Compliance
  • Resistance
37
Q

Therapeutic failure can be due to several common and non-resistance-related reasons:

A
  • Interactions with another drug or health condition in the patient that diminish the drug efficacy,
  • Patient immunodeficiency
  • Failure to diagnose and treat mixed infections of parasites or other infectious agents
  • Re-infection/infestation due to contaminated environment
  • Failure to deliver the correct dosage/form of product, such as compliance failures, usage of out of date products
  • Unrealistic objective (e.g it takes months to clear a flea infestation from a house not just one spot on the dog)
38
Q

Mode of Action of antiparasitics?

A
  • Paralysis of parasites via mimicking the action of neurotransmitters
  • Alteration of metabolic process
  • Alteration of parasite reproduction
  • Inhibits egg production in nematodes or multiplication in protozoas

Note, this is not an anthelmintic action, rather, consequence of an anthelmintic action

IN general they cause paralysis and starvation

39
Q

Describe movement of worms?

A

Most important antagonistic pair of neurones during locomotion are the excitatory (Ach containing) neurons and inhibitory (GABA containing) neurons

40
Q

What is going to happen if you use these two products together?

No 1 Tablet: milbmycin + Praziquantal

No2 Spot on: Moxidectin + imidacloprid

A

You will end up overdosing on macrocyclic lactones (milbemycin and moxidectin)

41
Q

Parasite refugia is the portion of a population of parasites (or stages of parasites) that?

A

Escapes selction with the drug at the time of treatment event. The sub-population includes: Encysted parasites not affected by treatment (e.g encysted abomasal nematodes in sheep and cattle, when non-larvicidal treatments are used) all free-living stages, and parasites in non- treated animals.

42
Q

The higher the proportion of worms in Refugia, the slower resistance develops. The worms in Refugia are not ‘selected’ for resistance, thus resistant worms remain?

A

diluted by susceptible ones, which continue to make up the majority of the population.

43
Q

Mixed grazing with other species, like sheep or cattle, can be used for parasite control because?

A

Sheep will graze the horses defecation areas, sheep eat the grass down around the manure, which removes the shade and moisture, so parasite are more exposed to direct sunlight and dry out –which makes it more difficult for parasite to survive. It is fine for the sheep to ingest the equine parasites as they die inside.

44
Q

Don’t treat the entire herd just prior to a move to clean pasture. Why?

A

It contradicts current knowledge about the importance of refugia. Clean pastures harbour minimal refugia and the first eggs to contaminate this new pasture will be produced by worms that survived the recent treatment. This practice introduces strong selection pressure for the development of resistance.

Farm Animal Final Year (131 decks)

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