ANTHELMINTICS

• Anthelmintics are drugs used to kill

(vermicide) or expel (vermifuge) the parasitic
worms or helminths which inhabit the GI tract
and other tissues and organs of the body.
• Used prophylactically and to treat acute or
chronic infections.
• Help to reduce worm burden and control
worm larvae on pasture or eggs in the
environment
 Helminths:
• Eukaryotic parasites live inside the body of
animals and birds
• They parasitize vertebrates
• They mainly infect GI tract and associated
structures
• Also can found in other parts of body
• Mostly feed off living hosts, receiving
nourishment and protection, causing
discomfort and weakness without mortality
• In some cases, excessive blood loss, injury to
vital organs, obstruction of intestine or
lymphatic system or secretion of toxins by
helminths cause serious diseases and
endanger life of animals
 I. Phylum Nemathelminthes
• Class Nematoda (Round worms)

• II. Phylum Platyhelminthes

• Class Cestoda (Tape worms)
• Class Trematoda (Flukes)
 Properties of Ideal Anthelmintics:
• Should have a broad spectrum of activity
(nematodes, trematodes, cestodes)
• Wide safety margin
• Selective toxicity for parasites
• Good efficacy against mature and immature
stages of parasites
• Should not interfere with normal physiological
functions, development or growth of host
• Have no/short residue period in tissues
• Easy to administer to a large number of herd
or flock
• Stable to environmental or chemical variables
• Should be economical
• Should be compatible with food and other
compounds
 Types of Anthelmintics:

• 1. Antinematodal drugs
• 2. Anticestodal drugs
• 3. Antitrematodal drugs
Classification of Antinematodal Drugs:
• 1. Benzimidazoles:
a. Benzimidazoles: albendazole, fenbendazole,
mebendazole, oxfendazole
b. Pro-benzimidazoles: febental etc.
• 2. Macrocyclic lactones/Antibiotics:
a. Avermectins: ivermectin, doramectin etc.
b. Milbemycins: milbemycin oxime, moxidectin
• 3. Imidazoles: tetramizole, levamisole etc.
• 4. Tetrahydropyrimidines: pyrantel, morental
etc.
• 5. Organophosphorus compounds: dichlorvos,
coumaphos, haloxon
• 6. Piperazines: piperazine
• 7. Arsenicals:Arsenamide
• 8. Substituted phenols and salicylanilides:
nitroxinil, closantel
• 9. Octadepsipeptides: emodepside
• 10. Aminoacetonitrile: monepental
• 11. Miscellaneous drugs: phenothiazine,
tetrachloroethylene, hygromycin B etc.
 1. Benzimidazoles: BM
• Broad spectrum anthelmintics
• Wide margin of safety
• High degree of efficacy
• Mostly given orally (suspension, paste or
powder), intraruminal injection
 MoA
• Vermicidal action
• 1. Bind to β-tubulin, a structural protein and
inhibiting its polymerization or assembly into
microtubules.
Inhibition of tubulin formation and its continual
break down disrupt the integrity and transport
functions of cells within the parasites and blocks
cell division
Binding of BM to parasite β-tubulin is reversible
and saturable
2. Inhibition of mitochondrial fumarate
reductase enzyme, blocking of glucose transport
and uncoupling of oxidative phosphorylation.
Blocking of these processes inhibit supply of
essential energy to the parasite producing
antiparasitic action
3. Also induce sterility in worms by inhibiting the
egg production and uncoupling oxidative
phosphorylation.
 Resistance:
• Acquired resistance against BM develops due
to alteration in β-tubulin isotype gene
expression, which produce altered β-tubulin
with low affinity for binding to BM.
 Albendazole:
• Broad spectrum BM
• Used widely in veterinary practice for
treatment of nematode and trematode
infections in large animals
• Effective against GI parasites of cattle and
other ruminants like Ostertagia, haemonchus,
trichostrongylus, cooperia, oesophagostomum
etc.
• Also effective against lung worm (Dictyocaulua),
tapeworms and flukes (Fasciola hepatica).
• Act by inhibiting microtubule synthesis in
nematodes
• Also has larvicidal and ovicidal effects
• Well absorbed orally
• Metabolised into albendazole sulphoxide which
shows main anthelmintic activity
• Excreted through urine
• Available in oral suspension and intraruminal
bolus for ruminants.
 Fenbendazole:
• Broad spectrum anthelmintics
• Converted into active metabolite
fenbendazole sulphoxide
• Safe drug with wide safety margin
• The withdrawal period is 14 days for meat and
72 hrs. for milk
• Not approved for lactating or food producing
animals due to long residual period
 Mebendazole:
• Broad spectrum anthelmintic
• Effective against GI nematodes
• Also effective against lungworms and
tapeworms
• Less absorbed orally
• Causes embryotoxicity and teratogenicity in
experimental animals
 Oxfendazole:
• Broad spectrum anthelmintic
• Sulphoxide metabolite of fenbendazole
• Active against many roundworms and their
larvae and tapeworms
• More readily absorbed orally
• Excreted through faeces
 Macrocyclic lactones/Antibiotics:
• Ivermectin: First commercially available
macrolide anthelmintic
• Derivaed from natural avermectins
• Effective against wide range of nematodes
• Effective against small and large strongyles,
ascarids, pinworms, hairworms, bots,
lungworms and intestinal threadworms in
horses.
• Well absorbed orally in simple stomach
animals than ruminants
• Collie breed of dog allows more penetration of
ivermectin into CNS so more ivermectin
toxicity in this breed
• Excreted in faeces
• Can be given orally or subcutaneously
• Commonly used endectocide in veterinary
practice
 Doramectin:
• Isolated from Streptomyces avermitilis
• Related pharmacologically to ivermectin and
acts as endectocide
• Used to control intestinal roundworms,
lungworms, eyeworms, grubs, mites, horn flies
and warble fly larvae
• Its activity persists for several days and
protects cattle against Ostertagia for upto 21
days
 Milbemycin oxime
• Obtained from Streptomyces hygroscopicus
• Broad spectrum endectocide
• Active against hookworms, heartworm,
roundworms and whipworms
• As ectoparasiticide, active against arthropods
• Administered orally
• Effective for at least 45 days
 Moxidectin:
• Obtained form Streptomyces cyanogrieus
• Structurally and pharmacologically similar to
ivermectin and milbemycin oxime
• Active against GI roundworms, pinworms,
lungworms, heartworms, cattle grubs, mites,
lice, horn flies and horse stomach bots.
• It is more lipophilic than other macrocyclic
lactone anthelmintics so persists longer
• Non-toxic to collies
 Levamisole:
• Primarily used for GI nematodes
• Has greater safety margin
• Acts as autonomic ganglionic stimulant and
causes activation of parasympathetic nervous
systems
• This causes sustained muscular contraction in
susceptible nematodes resulting in muscular
paralysis (nicotinic like action)
• Effective against Haemonchus,
trichostrongylus, ostertagia, cooperia,
nematodirus, oesophagostomum, chabertia
and dictyocaulus.
• Also active against Ascaris, intestinal
threadworms, lungworms, kidney worms.
• Has no activity against tapeworms, flukes and
protozoa.
• It stimulates cell-mediated immunity by
increasing T lymphocytes
• Well absorbed orally and through skin
• Metabolised in liver and excreted in urine
• After 2 days, completely eliminated from body
• No residues can be detected in tissues, blood
or urine 7-8 days after treatment.
• Side effects include muscarinic and nicotinic
cholinergic signs like salivation, constriction of
pupil, muscle tremors, excitation, ataxia, colic,
diarrhoea, urination, dyspnoea and collapse
(death)
• Atropine sulphate is best to treat the toxicity
 Pyrantel:
• Introduced in 1950
• Broad spectrum anthelmintic
• It is a nicotinic like depolarising neuromuscular
blocking agent
• It causes activation of nicotinic cholinergic
receptors and produces slowly developing
contracture and spastic paralysis of parasites.
• It also inhibits acetylcholinesterase enzyme acts
similar to acetylcholine
• The paralysed worms are slowly expelled from
the body
• Has high efficacy against GI nematodes
• Active against strongyles, ascarids, pinworms,
hookworms and stomach worms.
• Also effective against Haemonchus, ostertagia,
trichostrongylus, nematodirus, chabertia,
cooperia and oesophagostomum
 Dichlorvos:
• Organophosphorus (OP) insecticide
• Used as anthelmintic and ectoparasiticide
• Against whipworms, nodular worms,
strongyloids, hookworms, pinworms and
ascarids
 Coumaphos
• An OP compound
• Effective against Haemanchus, oestertagia,
trichostrongylus and cooperia.
• Used as feed additive
 Piperazine
• An narrow spectrum anthelmintic
• It is a GABA receptor agonist
• It increases chloride conductance at parasites
nerve membrane and produces
hyperpolarisation and reduced excitability at
neuromuscular junction
• This leads to muscle relaxation and flaccid
paralysis
• The worms paralysed and depleted of energy,
lose their grip on intestinal wall and are
expelled alive by intestinal peristalsis.
• Active against ascarids, oesophagostomum,
hookworms, strongyles, whipworms and
tapeworms etc.
• Well absorbed orally
• Excreted in urine