Anthelmintic

Question 1

General treatment and control goals and principles of parasites

Answer 1

We want to kill and remove life cycle stages (adults and larvae) infecting definitive hosts
We want to prevent or reduce production of parasite offspring (eggs and larvae)
We want to optimize environment to prevent transmission (ie pick up feces)
We want to optimize DH health to resist infection
We want to prevent DH contact with any I/P hosts
We want to neutralize any I/P hosts
ASSESS RISK FACTORS FOR EACH PATIENT (OR HERD) TO DETERMINE THE BEST PRACTICES
JUDICIOUS USE OF PARASITICIDES IS CRITICAL TO AVOID CREATING RESISTANCE
PREVENTION OF INFECTION, WHERE POSSIBLE, IS PREFERABLE TO TREATMENT OF INFECTIONION OR DISEASE

Question 2

What are most antiparasitics today

Answer 2

Most antiparasitics used today are neurotoxins
They are designed to target specific receptors on neurons within the parasite
These receptors work differently in mammals and birds, or are not present, and therefore the parasciticides are generally safe for the host

Question 3

Anthelmintic should be followed how

Answer 3

All have written labels
Label claims and information
What the medication will kill or control, dosage rates
Veterinarians are allowed to use drugs off-label if they deem it appropriate.

Question 4

What are the main groups of anthelmintics

Answer 4

Macrocyclic Lactones (endectocides)
Benzimadazoles
Tetrahydropyrimidines
Pyrantel/Morantels
Misc –
levamisole, piperazines, emodepside
Isoquinolones
Praziquantel
Espirantel

Question 5

The macrocyclic lactones work on

Answer 5

Safe and highly effective, first marketed in the early 1980’s
Nematodes and arthropods
Oral, in-feed, injectable, pour-on (transdermal)
This class of drugs is used in all hosts
Systemic – so some products will kill tissue stages

Question 6

How do macrocyclic lactones work

Answer 6

Ivermectin was the first - 1981
All structurally similar - complex chemicals- they originated from bacteria (some have been enhanced synthetically)
Like most antiparasitics they are neurotoxins
In parasites, the treatment results in a flaccid paralysis
worms can’t stick around in the gut if they can’t move.

Question 7

Ivermectin is and works how

Answer 7

First macrolide available in veterinary medicine
(from a bacteria, won its discoverers a Nobel prize)
Primarily available in oral,injectableor pour on forms
Wide spectrum
Endectocide – endo and ecto
only kills nematodes and arthropods
Heartworm prevention, GI nematodes, external parasites
Widely used in many species (small animal, large animal, exotics, people), both on and off label
Commonly combined with other antiparasitics to produce a product with a very wide spectrum of activity
(a recurring theme these days – hard to keep up with all the combination products)

Question 8

What are some common macrocyclic lactones

Answer 8

Selamectin (small animals)
Doramectin (large animals)
Eprinomectin (large animals)
Milbemycin oxime (small animals)
Moxidectin (both small and large animals)

Question 9

When are macrocyclic lactones used

Answer 9

All have similar modes of action as ivermectin
Highly effective, oral, injectable, topical
Used in all hosts for to treat or prevent a variety of infections/infestations (nematodes and arthropods)
A number are used as heartworm preventatives.
In food animals all these have very specific meat and milk withdrawal times
Know and comply with restrictions and communicate to producer

Question 10

The macrolides – toxicity can be cause by and when

Answer 10

Generally considered safe, with a fairly selective toxicity and high therapeutic index
HOWEVER…
They can produce toxicity (neurological signs) in susceptible animals or with significant overdose
Overdoses or genetic MDR1 mutation allows the Macrolides to cross the BBB into the brain
Hypersalivation, vomiting, ataxia/staggering,
Progresses to bradycardia, unresponsiveness, mydriasis, loss of menace response, and eventually coma

Question 11

What happens with the MDR1 genetic defect and antithelminitcs

Answer 11

Certain breeds of dogs have a defect in their MDR1 (multidrug resistance 1) gene
Primarily Collies, Australian shepherds, and other related breeds (but others)
If vets are worried about particular client dogs – genetic testing is available.

Question 12

Benzimidazoles are used how as an antiparasitics

Answer 12

besides the antinematodal action, these have antitrematodal, Some anticestodal and antiprotozoal (fenbendazole) activity
Act by attacking special proteins in the parasites called β-tubulin
Disrupts normal cellular function and kills parasites
Mammals have β-tubulin, but it differs from the parasites’
Generally wide margin of safety (selective toxicity)
However, rapidly dividing mammalian cells may be affected (rely heavily on β-tubulin)
Teratogenic effects noted at high doses of some benzimidazoles
Resistance is becoming a problem in numerous hosts

Question 13

What are some common benzimidazoles

Answer 13

Thiabendazole
Fenbendazole (Panacur, Safe-Guard)
Albendazole (Valbazen)
Febantel (Drontal Plus)
Triclabendazole (Fasinex – and others)
Used in a variety of products for both small and large animals. Primarily oral (in feed or water as well as pastes and liquids)

Question 14

Pyrantel works against and how

Answer 14

Initial spastic contraction followed by paralysis and death
Numerous veterinary pharmaceuticals
Many over the counter products available

Question 15

Emodepside (Profender) is used for and how

Answer 15

Specifically for cats (nematodes and cestodes)
Topical Application

Question 16

Piperazines are used how

Answer 16

Very common in LOTS of over the counter products
narrow spectrum of activity

Question 17

What do you need to know for heartworm preventatives

Answer 17

To eliminate heartworm, multiple drugs affecting the different lifestages must me used

Question 18

How do adulticides work for heartworm

Answer 18

Adulticide – melarsomine - the only drug used to kill adult heartworms. The adulticide is not effective against microfilariae or L3 larvae

Question 19

How do Microfilaricides work for heartworm

Answer 19

drugs used to kill the circulating microfilariae in dogs prior to or post treatment with an adulticide – most often a macrocyclic lactone

Question 20

When do you use heartworm preventative and how do they work

Answer 20

– drugs used to kill larvae introduced to a dog by a mosquito (most often a macrocyclic lactone - plus these are often within combination products that also incorporate tapeworm and ectoparasite treatment) heartworm preventatives are not effective against adults
In areas of high endemicity, there is evidence of nematode resistance to these preventatives.

Question 21

Anticestodals are used when

Answer 21

Used mostly in small animal medicine as tapeworms do not have a significant effect on the feed to weight conversion in livestock.

Question 22

What is hte mechanism of action of anticestodals

Answer 22

Cause increased permeability of the cell membrane to calcium with subsequent loss of intracellular calcium resulting in paralysis of the parasite
Causes digestion of the entire worm so don’t generally see the worms passing after treatment
Praziquantel (lots of products)

Question 23

What can antiocestodals do

Answer 23

causes contractions, paralysis and tegumental lesions in tapeworms
Single dose effective against tapeworms (possible exception Diphylobothrium sp.)
Does not kill tapeworm eggs – so eggs may continue to pass in the feces for a while after treatment
Human health concern if animal has Echinococcus
Commonly combined with other anthelmintics or acaricides.
Also kills flukes (flatworms) at the proper dose

Question 24

Fenbendazole work against

Answer 24

Saw this in benzimadazoles – has a claim for Taenia sp. treatment in dogs

Question 25

Antiprotozoals are used for

Answer 25

Main protozoa we treat are Coccidians and Giardia
Some of the Anthelmintics also have antiprotozoal activity
Many of these are commonly used (often off label) for treatment of various protozoa

Question 26

What are the types of antiprotozoals common and waht do tehy do

Answer 26

Sulfonamide antibiotics
- Used to treat Coccidia (small and large animal)
Amprolium
- Feed/water additive used to treat Coccidia in calves/birds
Toltrazuril – -coccidia-calves, lambs, piglets (off label for dogs)
Ionophores(coccidiostats)
- Feed additives for poultry, cattle
- Prevent infection from happening, but will not treat an active infection.
- Very toxic to horses – causes potentially fatal muscle degeneration (skeletal and cardiac muscles)
Benzimidazoles (fenbendazole)
- Used to treat Giardia
Metronidazole (antibiotic used for anaerobic bacteria)
- Giardia in dogs and cats

Question 27

Ectoparasiticides are used for

Answer 27

Used to control flies, grubs, mites and lice on livestock
Flies (bots and maggots) on horses
Fleas, lice, ticks and mites on companion animals
Aids in control of secondary disease transmission
Lyme, Bubonic plague, Babesiosis, Rocky Mountain Spotted Fever, etc

Question 28

Isoxazolines are and used for

Answer 28

(newest group of ectoparasite control medications)– afoxolaner, flurolaner, lotilaner, sarolaner
Flea, tick, mite and louse in small animals

Question 29

Neonicotinoids are used for

Answer 29

imidacloprid (mostly fleas)

Question 30

Fipronil is used for

Answer 30

ariety of small animal ectoparasite claims

Question 31

Pyrethroids are used for

Answer 31

pyrethrin, cyfluthrin permethrin – (from Chrysanthemums) - variety of small and large animal ectoparasite claims (cat toxicity)

Question 32

Ectoparasite treatment, routes of administration

Answer 32

Sprays
Dips
Pour-ons
Shampoos
Dusts or powders
Oral
Foggers
Spot-ons
Injectables
Impregnated ear tags

Question 33

What is anthelmintic resistance

Answer 33

A heritable (genetically passed to offspring) reduction in efficacy of a drug against a particular species and stage of a parasite
Where efficacy of a drug should be >99% resistance is confirmed where efficacy is <95%

Question 34

Classification of anthelmintics

Answer 34

Three broad groups in livestock
Benzimadazoles (BZ)
Tetrahydropyrimidines
Imidazothiazoles
Macrocyclic lactones (ML)
Resistance to any one drug in a group means resistance to all drugs in that group

Question 35

What is the current issue with anthelmintic resistance

Answer 35

Currently a major problem for parasite control in sheep (60-90% of flocks in some countries, all drug categories, seen in Canada)
Increasingly a problem in horses (BZ, LM/PY, Cyathostomins, IVM Cyathostomins, Parascaris, seen in Canada)
Increasingly a problem in cattle (BZ, IVM, Cooperia, seen in Canada)
Only sporadic reports in pigs and dogs (hookworms, heartworm)

Question 36

Some factors determining rate of resistance development

Answer 36

Underdosing
Length of time used (BZ, IVM-30 years, )
Frequency of Treatment
Pasture management
Size of in-refugia population

Question 37

Refugia means

Answer 37

Proportion of the parasite population not exposed to drug treatment
Parasites in untreated hosts
Parasites in the external environment (free-living stages)

Question 38

Why is refugia an issue

Answer 38

The larger the in refugia population the less the selection pressure
The best way to reduce the number of resistant worms the survivors produce is to make sure they breed with susceptible worms because this will dilute their resistant genes.

Question 39

How to stop refugia from happening

Answer 39

Abomasal nematodes in sheep in temperature climates
Most parasite in refugia
Only a relatively small portion of the parasites on farm are exposed to selection by one drug treatment
If you move to a clean pasture after deworming there is a strong selection for resistance
If you treat and move to contaminated pasture or leave on contaminated pasture → dilute out the resistants

Question 40

Strategies to reduce the development of anthelmintic resistance

Answer 40

Quarantine and anthelmintic treatment of purchased livestock
Treat all incoming animals – a combination of drugs is appropriate here, and isolate them for at least 12-24 hours prior to introducing to herd. And maybe test prior to introducing to herd
Avoid underdosing
Calculate dose based on heaviest in the group
Minimize anthelmintic use
Increase dosing interval, mixed grazing, good nutrition, wean lambs early and move
Targeted selective treatment
Dose only “high shedding” horses or sheep (remember overdispersion)
Dose only lambs, only ewes with poor body condition or anemia
Avoid co-grazing of sheep and goats
Monitor resistance status
Use combinations of products ????
Lower stocking densities