Antiparasitic;

pharmacology
Mohanad AlBayati
Prof. Mohanad A. Al-Bayati, BVM&S, MSc. Physiol.,
PhD. Pharmacology and Toxicology
College of Veterinary Medicine
University of Baghdad
Al Ameria, Baghdad
Phone: 0964 7700766650
E. Mail: aumnmumu@covm.uobaghdad.edu.iq
 Anthelmintics
- Helminthic infection (gastrointestinal parasitism) in
animals is very common
- it is responsible for considerable losses to the livestock
industry, because of slow and poor growth and
development of affected animals.
- severe infection causes even death of animals.
- The most common helminths of domestic animals are
nematodes (roundworms),
cestodes (tapeworms)
trematodes (flukes).
• A large number of anthelmintic (antiparasitic
drugs) have been developed to kill or to lower
worm burden in animals
 Term anthelmintic
- an elision of anti and helminthes.
 The nematodes
 Cestodes
 Trematodes
They are collectively known as helminths.
Drugs that are effective against any one or all three groups of
helminths
 Classification of Anthelmintics
Based on type of helminths against which they are
effective: are termed as anthelmintics.
 Antinematodal drugs: Drugs effective against the
nematodes or roundworms (R).

 Anticestodal drugs: Drugs effective against the cestodes

or tapeworms (T).

 Antitrematodal drugs: Drugs effective against the

trematodes or flukes (LF).
 Ideal Anthelmintic:

i. Should have high efficacy:

1. Good efficacy: The drug must exhibit high level of
antiparasitic action. If a drug eliminates 95% of GI
nematode burden from ruminants,.
2. Poor Efficacy: It eliminates only 70%.
3. An efficacy of 100% for all stages of parasite is not
necessarily a desirable effect, since this totally eliminates
the source of antigenic stimulation by the organism and
may weaken the animals acquired resistance to the
parasite.
 Categories on the basis of their mechanism
of actions:
Drugs affecting the energy production of the
parasites: Biochemical reactions associated with
the energy production of the parasites are the
most important sites of drug action.
 Ideal Anthelmintic:
ii. Should have broad spectrum of activity against both mature
and immature parasites including larvae.

iii. Wide therapeutic index.

iv. Easy to administer to large number of animals.

v. Should not exceed approved limits of drug residue or should not

require long withdrawal period because of residue(s).

vi. Should be economic.

 Mechanisms of action
1. Drugs affecting the energy production of the parasites
a. Inhibitors of fumerate reductase enzyme and mitochondrial reactions:
In anaerobic helminthes (Ascaris) the formation of ATP (required for muscular
contraction) involves reduction of fumerate to succinate by the enzyme fumerate
reductase in the mitochondria. This reaction helps to reoxidize NADP to form ATP.

Drugs inhibit fumerate reductase enzyme action,

- block the generation of ATP
- resulting in muscular paralysis
- eventual death of the parasite:
Benzimidazoles (except mebendazole, flubendazole and triclabendazole),
benzimidazole pro drugs,
levamisole,
bithionol,
hexachlorophene.
the main pharmacokinetic features taking place after oral/intraruminal administration of
benzimidazole anthelmintics in ruminants.
(1) Route of administration: only oral or intraruminal routes can be used for the sulfide compounds (ABZ, FBZ).
(2) Rumen: marked drug dilution. The rumen’s reservoir effect is by drug adsorption to particulate digesta.
(3) Abomasum: the acidic pH facilitates drug particles dissolution and strong “ionic trapping”of the
drug/metabolite at the abomasum.
(4) Small intestine: main drug absorption site.
(5) Liver: drug oxidative metabolism.
(6) Biliary system: drug excretion (unconjugated and conjugated metabolites), enterohepatic recycling.
(7) Bloodstream: metabolites distribution to different organs/tissues, including active secretion to gastrointestinal
tract.
(8) Rumen: sulforeductive biotransformation by ruminal microflora.
ABZ, albendazole parent compound; ABZSO, albendazole sulfoxide; ABZSO2, albendazole sulfone.
the ruminal biotransformation of albendazole sulfoxide (ABZSO) enantiomers.
The width of the arrows indicates the magnitude of the metabolic reactions. The main
pharmacological features of the (+) sulfoxide enantiomer (compared to the (−) isoform) are
listed in the bottom box. The enantioselective ruminal sulforeduction of the (+) isoform is
the most relevant metabolic reaction for the formation of the parent thioether (ABZ). The
same pattern is applicable to the sulforeduction of oxfendazole (OFZ) enantiomers into
fenbendazole (FBZ) (see the text for detailed explanation). Source:
 Mechanisms of action
b. Inhibitors of tubulin polymerization and glucose uptake:
- These drugs bind to free beta-tubulin,
- inhibiting its polymerization
- thus interfering with microtubule-dependent glucose uptake.

In absence of glucose there is

- depletion of the worm's glycogen reserve,
- which renders its unable to produce ATP necessary for survival.
 benzimidazoles like mebendazole and flubendazole primarily act by inhibiting
glucose transport but these two do not inhibit fumerate reductase system.
 site of action of cambendazole and fenbendazole is fumerate reductase
inhibition. they also inhibit glucose transport. their effectiveness against
parasites lack fumerate reductase system.
 The heartworm microfilaricide, dithiazanine act by inhibiting the glucose
uptake by the parasite but the exact mechanism of inhibition of glucose
uptake is not known.
 Mechanisms of action
c. Inhibitors of electron transport mediated oxidative phosphorylation in the mitochondria of
the parasites:
 interfere with the electron transport in the mitochondria
 thereby inhibit the oxidative phosphorylation
 generation of ATP.
 The fumerate is converted to succinate but ATP is not produced.

These drugs are effective against

 flukes and
 tapeworms.
 drugs are not effective against roundworms, inspite of having similar mitochondrial
phosphorylation system because the drugs cannot penetrate tissues of the intact
roundworms.
 These drugs also uncouple oxidative phosphorylation in the mitochodria of mammals .
They are often fairly toxic (Salicylanilides, substituted phenols and halogenated
hydrocarbons: niciosamide, clioxanide, oxyclozanide, rafoxanide, closantel, resorantel;
bithionol, disophenol, dichlorophen, hexachlorophene, niclofolan, nitroxynil,
nitroscanate, bromosalans; carbontetrachloride etc).
 Mechanisms of action
d. Inhibitors of glycolysis:
 These drugs are either organic heavy metal compounds or
other chemicals,
 They have tendency to bind with the sulfhydryl SH, groups
and
 Alter the structure of proteins
 The active sites of glycolytic enzymes phosphoglycerate
kinase and phosphoglycerate mutase) of the parasite
 host (Arsenicals: Thiacetarsamide; Antimonials:
Potassium antimony tartarate and stibophen and
antitrematodal sulfonamide: Clorsulon).
 Mechanisms of action
2. Drugs Affecting the Neuromuscular System of the Parasites,
Causing Paralysis: Neuromuscular system may be affected by
 inhibiting the destruction or
 by mimicking/enhancing or antagonizing the action of
neurotransmitters .
The ultimate result is either
 spastic or flaccid paralysis of the parasite
 the paralysed parasite is expelled by the normal peristaltic
movement of the host.
The drugs affecting neuromuscular system are classified as below:
 Mechanisms of action
a. Cholinergic agonists:
These drugs affect the neuromuscular system of the parasite by
acting as cholinergic agonists: Nicotine-like action, stimulating and
subsequently blocking the neuromuscular junctions, resulting:
 sustained muscle contraction
 spastic paralysis of nematodes
 Imidazothiazoles: Butamisole, tetramisole
 levamisole;
 Pyrimidines: Morantel, oxantel
 pyrantel; Quaternary ammonium compounds: Bephenium and
thenium etc.)
Chemical structures and some comparative pharmacological properties of the imidazothiazole
(levamisole) and tetrahydropyrimidine (pyrantel, morantel) anthelmintic compounds. GI,
gastrointestinal.
 Mechanisms of action
b. Anticholinesterases:
 ACh is also a neurotransmitter in parasites just like in higher animals.
 The enzyme AChE also present in the parasite destroys ACh and thus prevents
over stimulation of smooth muscles.
 These drugs cause inhibition of acetyl cholinesterase (AChE) enzyme
 followed by constant depolarization
 due to accumulation of excess ACh at the neuromuscular junction.
 This leads to
 interference with neuromuscular transmission
 consequent paralysis
 and expulsion of the parasite,
 through enhanced intestinal peristalsis.
 The relative safety of OP compounds (Coumaphos, haloxon, dichlorvos etc) for
the host is probably related to lack of susceptibility of host AChE to the drug.
 Mechanisms of action
c. Muscle hyperpolarizers:
An anticholinergic action at the myoneural junction
in worms, producing
 competitive or
 non-depolarising type of neuromuscular
blockade like curarae.
 hyperpolarization of the muscle membrane of
the worm leading to flaccid paralysis, facilitating
its expulsion (Piperazine and avermectins).
 Mechanisms of action
d. Potentiation of inhibitory neurotransmitters (GABA agonists(sad)
The normal function of GABA in mammals and invertebrates is
inhibition of neurotransmission.
 These drugs act by potentiation of GABAergic transmission
(opening of chloride channels) between nerve and muscle.
 Potentiation of GABA leads to
 hyperpolarisation of postsynaptic cells
 leading to interference with neurotransmission to muscles
and consequent muscular paralysis
(Ivermectin, abamectin, doramectin, moxidectin, milbemycin
oxime and piperazine).
 Mechanisms of action
3. Other actions:
a. Drugs affecting parasite reproduction: Low level of feeding of these
drugs to animals constantly inhibit the egg production of the
parasites remaining in the digestive tract of the host and thereby
reduce the pasture contamination by helminthes eggs, an important
control measure in cattle and sheep management (Phenothiazine
and benzimidazoles).
b. Drugs affecting the permeability of the cells and cause vacuolation of
the tegument (praziquantel and diamfenetide).
c. Drugs cause disruption of tegument of parasites: Bunamidine,
epsíprantel and praziquantel.
d. Drugs act by unknown mechanism: Bitoscanate, paromomycin,
phenothiazine and triclabendazole.
 Anthelmintic resistance
Resistance to anthelmintics by the worms develops somewhat slowly in comparison to
antibiotic resistance in bacteria.
However, the development of resistance by nematodes to different groups of
anthelmintics is becoming widespread (resistance to benzimidazoles, levamisole and
avermectins by roundworms of cattle, sheep, goat and horses).
Continuous use of a highly effective anthelmintic results in selective removal of the most
susceptible genotypes resulting in succeeding resistant progeny.
The resistance is manifested by
passage of increased number of parasite eggs,
higher establishment rates of adult worms in the host
and greater number of larvae on the pasture after treatment than would occur if the
parasites were susceptible to the antiparasitic drug.
Cross-resistance may also occur between drugs having similar mode of action
(benzimidazoles).
Anthelmintic resistance can be prevented by:
 Anthelmintic resistance
a. Designing management practices to reduce exposure to
parasites and to minimize the frequency of use of anthelmintics.

b. Development of resistance can be delayed by slow rotation of

different chemicals with different mechanisms of action.

c. Planning treatment of whole herd/flock at a time.

d. By taking proper control measures against the parasitic phase in

the host at proper time and to the free living, nonparasitic
stages in the environment.
 Antinematodal Drugs

Classification:
a. Simple heterocyclic compounds
b. Benzimidazoles/Benzimidazole prodrugs
c. Imidazothiazoles
d. Tetrahydropyrimidines
e. Organophosphorous compounds
f. Macrocyclic lactones
g. Drugs used in the treatment of heartworm in dogs
h. Miscellaneous antinematodal compounds
a. Simple Heterocyclic Compounds
Piperazine and its Derivatives:
Chemistry:
Chemically piperzine is diethylenediamine. It is a strong
base, very unstable and consequently easily absorbs water
and carbon dioxide; thus containers should be tightly closed
and protected from light.
The simple salts of piperazine (piperazine adipate, citrate,
phosphate, sulphate, tartrate and hydrochloride) are more
stable and are used. The antiparasitic action of different salts
of piperazine is mainly due to the piperazine base.
 Anthelmintic spectrum:
All the derivatives of piperzine have similar efficacy.
They are good for ascarid and nodular worm
infections of all the species of domestic animals
(100% efficacy), moderate for pinworm (Oxyuris sp.)
infections, variable effect on other worms like
hookworms and strongyles but no effect on
whipworms (Trichuris sp), tapeworms and flukes.
They have a wide margin of safety in all domestic
animals.
 Pharmacokinetics
Piperazine compounds are readily absorbed
from the upper part of the GI tract, partly
metabolized in the tissues and the remainder is
excreted in urine within 24 hours.
 Mode of action:
The anthelmintic action of piperazine compounds is due to
a. Anticholinergic action at the myoneural junction in worms, producing a
competitive or non depolarizing type of neuromuscular blockade like curarae.
b. Blockade of succinic acid production by the worm.
c. Reversible inhibition of neuromuscular transmission in the worm by acting
like GABA, the inhibitory neurotransmitter on GABA gated chloride channels
in nematode muscle.
The end result is the flaccid paralysis of the worm.
 Worms lose motility and
 thus ability to maintain their position in the intestinal tract.
 They are passively swept along by intestinal peristalsis and
 voided live in the feces.
 Purgation is not generally advised when piperazine is used.
 Administration:
Piperazine compounds are administered orally, usually in the feed
(adipate or citrate salts) or drinking water (hexahydrate) over a 2-day
period. In horses the drug is administered by stomach tube. Dogs and
cats are usually dosed with tablets.

Dosage: Doses of piperazine compounds are expressed in terms of the

amount of piperazine base.
Horses: 110 mg/kg;
Swine, cattle, sheep and goats: 110 mg/kg;
Dogs and cats: 45-65 mg/kg;
Poultry: 32 mg/kg (about 0.3 gm for each adult bird) given each of 2
successive feedings or in drinking water for 2 days.
 Safety and toxicity:
The toxicity is
 normally very low.
 Sometimes neurotoxicity (incoordination, head
pressing)
 emesis occur in small animals at higher doses.
 The drug can be administered to pregnant
animals and
 To animals suffering from gastroenteritis.
 Contraindications:
No known contraindications except in long standing
renal or liver diseases.
In heavy ascarid infections, treatment with piperazine
or OP compounds results in intestinal blockade and
rupture due to expulsion of large masses of worm
simultaneously.
Benzimidazoles are preferred in treating such cases
because the death of worms is slow and expulsion is
delayed.
Piperazine and oxantel are mutually antagonistic.
 Phenothiazine
It was synthesized in 1885 and was one of the early drugs with a wide range
of activity against gastrointestinal nematodes.

 It was extensively used in cattle, sheep, goats, horses and chickens.

Development of truly broad-spectrum anthelmintics in 1960 has reduced the
use of phenothiazine.
 It is now primarily used in continuous low level feeding programmed for
ruminants and for formulation of mixtures with other drugs for broader
spectrum.
 It is still used in horses.
 Its toxicity has limited
 its use in swine and totally prevented
 its use in dog, cat and human.
• Chemistry: Chemically it is thiodiphenylamine.
The pure compound is a pale, green yellow
powder, insoluble in water, stable when dry
but oxidizes when wet.
Anthelmintic spectrum:
 The drug has a wide range of activity against gastrointestinal nematodes and
mainly used in ruminants and horses.
 The drug possesses good anthelmintic activity against
 stomach worms of ruminants (Haemonchus contortus, Ostertagia spp.,
Trichostrongylus axei),
 nodular worms (Oesophagostomum spp.) of ruminants and swine,
 hookworms (Bunostomum)
 small intestinal nematodes.
 Despite the greater sensitivity of horses than ruminants to phenothiazine
poisoning,
 the drug is still used in equine because of its excellent efficacy against Strongyles.
 The drug is ineffective against equine ascarids and bots.
 The drug is effective against caecal worm of chickens and turkeys (Heterakis
gallinarum).
 The drug is not effective against parasitic larval stages or immature adult worms of
any of the ruminant parasites except immature forms of Haemonchus, which are
effectively removed.
 It has no action against flukes and tapeworms.
Mode of action: The exact mechanism by which phenothiazine
destroys the worm is not known, but may be due to:

a. Inhibition of certain vital enzymes (succinoxidase, glyoxalase,

cholinesterase etc.) in the tissue cells of the parasites.
b. The drug affect the parasites reproduction and low level of
feeding of the drug to animals inhibit the egg production of
the parasite remaining in the GI tract of the host, ultimately
reduce the pasture contamination by the helminth eggs,
forms the basis of control measure in cattle and sheep
management.
Pharmacokinetics:
 Following oral administration the drug is converted to
phenothiazine sulfoxide by the cellular enzymes of the
intestinal epithelium and absorbed.
 After absorption phenothiazine sulfoxide is further oxidized in
the liver to two colorless substances, leucophenothiazone
and leucothionol and
 excreted in urine.
 These products are again oxidized in the atmosphere to
brown-red dyes, phenothiazone and thionol, which discolors
the urine and milk of the animals for several days.
Administration:
 Phenothiazine is insoluble in water so bentonite (colloidal aluminium silicate) is used to keep
the drug in suspension and it should be shaken prior to dosing animals.
 In ruminants, it is administered orally as a single drench once in a month. Powdered
phenothiazine is added to the feed generally for prophylaxis.
 Fowls are treated with single dose of the drug in feed for a 1-day treatment once a month for
control of caecal worm infections.

Dosage:
Sheep and Goats:> 27 kg: 25-30 gm; 11-23 kg: 12.5 gm; Cattle: 10 gm/45 kg (maximum 70 gm);
Single dose treatment
Calves: Minimum 10gm;
Horses: 3-5 gm/45 kg (administer half of the dose for 2 days(sad)
Chickens: 0.5 gm/bird; Turkey: 1gm/.bird.

Daily prophylactic
treatment:
Sheep and Goats: 0.25-0.5 gm/animal;
Cattle: 0.5 gm/45 kg;
Horses: Adults: 2-5 gm;
colt: 1 gm.
Toxicity:
The toxicity of phenothiazine varies among different species.
 Sheep, goats and birds are most resistant to toxic effect.
 Cattle and swine are more susceptible.
 Horses are most susceptible.
 Dogs and cats are easily poisoned and so never used in these animals.
Toxic signs in
 horses include dullness, weakness, anoraxia, oliguria, colic constipation, fever and signs
relating to haemolysis of RBC like icterus, anaemia, haemoglobinuria.
 Ruminants and fowls : Photosensitization is a side effect that may accompany pheothiazine
administration in ruminants (especially in calves) and fowls when animals are subsequently
exposed to direct sunlight.
Accumulation of unmetabolized phenothiazine sulfoxide (photodynamic agent) causes
photosensitization keratitis manifested by ulceration of cornea and blindness. Skin may show
sunburn like symptoms viz. reddening and thickening of ear and muzzle and development of
scab.
Contraindications:
a. The drug may cause poisoning in cachectic, weak, anaemic, constipated and emaciated animals and
therefore is strictly contraindicated in these animals.
b. Concurrent use of phenothiazine and organophosphates is contraindicated as phenothiazine
potentiates organophosphate toxicity.
c. The drug is contraindicated in pregnancy (during the last month of gestation). The drug causes no
interference with conception or embryonic development.

Disadvantages:

d. Pink coloration of milk due to the presence of drug metabolites (harmless) does not allow its
commercial use for human consumption for 96 hours and therefore cannot be used in lactating
animals.
e. The red coloring of urine causes permanent discoloration of hair and wool of animals resulting in
economic losses, especially to the sheep farmers.
f. There is evidence of drug resistance against some strains of Haemonchus to phenothiazine when used
for longer periods.
 b. Benzimidazoles
These antiparasitic group have
 broad spectrum of anthelmintic activity,
 high degree of efficacy,
 good margin of safety and
 have versatility of administration.

- The first benzimidazole introduced in 1960, was thiabendazole (TBZ).

- The structure of TBZ was modified with an aim to develop related drugs with
more desirable anthelmintic properties.
- The imidazoles act as
 antibacterial,
 anthelmintic,
 antiprotozoal
 antifungal actions.
- Chemistry: All bezimidazoles have same central nucleus i.e. 1,2- diaminobenzene.
 Mode of action
All the benzimidazoles act on parasites by
interfering with their energy generating
metabolism:
a. All benzimidazoles except mebendazole and
flubendazole, are inhibitors of fumerate
reductase enzyme system and thereby inhibit
the generation of mitochondrial ATP: In the
absence of usable energy, the parasite dies.
 Mode of action
b. Mebendazole and flubendazole primarily act by
inhibiting glucose transport. They act on
1. bind to free beta tubulin,
2. inhibiting its polymerization and thus
3. interfering with microtubule-dependent glucose
uptake.
In absence of glucose there is depletion of the worm's
glycogen reserve, which renders its unable to produce
ATP necessary for survival. But these two do not
inhibit fumerate reductase system.
 Mode of action
c. The primary site of action of cambendazole and
fenbendazole is
fumerate reductase inhibition.
They also inhibit glucose transport.

Note:
the use of cambendazole and fenbendazole This
explains their effectiveness against certain parasites
that lack fumerate reductase system.
d. Thiabendazole also inhibits egg production by
helminthes by inhibiting protein synthesis.
Thiabendazole
 Thiabendazole
It is rapidly absorbed and rapidly eliminated within 48 hours.
Its zero-day withdrawl period ensures its popularity with
farmers.
It may also be used in lactating cows producing milk for human
consumption.
Dosages: Oral:
Cattle: 100 mg/kg;
Sheep: 50-75 mg/kg;
Horse: 50 mg/kg;
Poultry: 1000 mg/kg.
Other Benzimidazoles
 Other Benzimidazoles: Albendazole
The drug is metabolized to the sulphones and
sulfoxide which may act on the liver fluke and
tapeworm activity. Drug residue persists for several
days. Withdrawal period for slaughter of Cattle and
sheep is 10-14 days
lactating cows should not be treated with albenazole.
High doses may be embryotoxic and teratogenic.
Dosages: Oral:
Cattle and sheep: 7.5 mg/kg (15mg/kg for adult liver fluke);
Swine: 5-10 mg/kg.
 Cambendazole
Cambendazole Mainly used to treat pig and avian roundworms, fairly toxic,
embryotoxic and
teratogenic.
Dosages: Oral: Cattle, Horse, sheep and Swine:
20 mg/kg.

Fenbendazole

Fenbendazole: No embryotoxicity.
Dosages: Oral:
Cattle: 7.5 mg/kg;
Horse, Sheep, For Ascarids in horses and swine and Moniezia in ruminants 10 mg/kg.
Goat and Swine: 5 mg/kg; Dog and cat: 50 mg X 3 days.
Parbendazole
Parbendazole Effective against Gl nematodes and lungworms.
Embryotoxic and teratogenic.

Dosages: Oral:
Cattle, Sheep and Swine: 20-30 mg/kg.

Flubendazole
Mainly used to treat pig roundworms. No embryotoxicity.
Dosages: Oral:
Pigs: 5mg/kg or 30 ppm in feed;
Sheep: 10 mg/kg.
Mebendazole
Mebendazole: Effective against roundworms, tape worms (including
larvae). It has some antifilarial activity. No embryotoxicity.

Dosages: Oral:
Sheep and Horse: 10 mg/kg;
Pig: 30 ppm in feed for 10 days;
Dog and cat: 25-50 mg/kg twice daily for 5 days;
Poultry 10 mg/kg for 3 days.

Oxfendazole
Oxfendazole is the sulfoxide metabolite of fenbendazole and
responsible for the activity of both these anthelmintics.
 Benzimidazole Pro-Drugs
 These compounds are metabolized in vivo to
produce benzimidazoles and need to be
administered at doses high enough to produce
sufficient active metabolites.
 Their mode of action, pharmacokinetics and
spectrum of activity are similar to those of
benzimidazoles. These drugs are:
 Benzimidazole Pro-Drugs
Febantel: It is a precursor of fenbendazole. Effective against Gl
nematodes.
Dosage: Oral: Cattle: 7.5 mg/kg; Sheep & pigs: 5 mg/kg.

Netobimin It is a pro drug of albendazole. Effective against Gl

nematodes, their larvae, tapeworms and flukes. Teratogenic.
Dosage: Oral or Injection: Cattle: 7.5 mg/kg; Sheep: 7.5 mg/kg for roundworms
and 20 mg/kg for inhibited larvae, flukes and tapeworms.

Thiophanate It produces the metabolite lobendazole. Active

against most nematodes of farm animals.
Dosage: Oral: Cattle, sheep, goat and swine: 50-100mg/kg.
 Benzimidazole
 Pharmacokinetics of Benzimidazoles:
Except thiabendazole, albendazole and oxfendazole,
only limited amounts of a dose of any of the
benzimidazoles are absorbed from the GI tract of the
host as they are poorly soluble in water.

 Administration: Benzimidazoles are administered only

orally as drench, or as powder or granules in feed.
 Benzimidazole
Contradictions:

 Because of tissue and milk residues a sufficient withdrawal period

for slaughter of meat animal is required and the milk of the
treated animals should not be used for human consumption.
 Parbendazole, cambendazole and albendazole produce a
teratogenic effect in pregnant ewes in early pregnancy (first 45
days) and therefore are contraindicated during early pregnancy in
sheep and cattle.
 Mebendazole, fenbendazole, oxfendazole, flubendazole, luxa
bendazole and thiophanate are free from teratogenic effects.
 Benzimidazole
Safety and toxicity:
The benzimidazoles are extremely well tolerated
by domestic and wild animals in general at
therapeutic doses and they can be given
without side effects to even young, weak and
debilitated animals.
But some of the benzimidazoles produce
teratogenic effect during early pregnancy.
 c. Imidazothiazoles
 Butamisole Hydrochloride: It is an injectable
anthelmintic used in dogs to treat whip
worm (Trichuris vulpis) and hookworm
(Ancylostoma caninum) infections.
 It has low margin of safety.
 Toxic symptoms include vomiting, ataxia,
recumbence and convulsions.
Dose: A single SC injection 2.4 mg/kg.
 c. Imidazothiazoles
Contraindications:

1. In severely diseased or debilitated animals,

animals with renal and hepatic disorders.
2. In heartworm positive dogs as it may cause
fatality (the cause of death is not fully
known).
 Tetramisole and Levamisole:
 Levamisole was developed following the introduction of tetramisole
in 1966.

 Tetramisole is a racemic mixture of two isomers and the

anthelmintic activity of mixture rested almost solely with the l-
isomer, levamisole.

 By using levamisole the dose could be reduced to half, which

provided both a more economic formulation and an increase in
safety margin.
Chemistry: Levamisole is the levo-isomer of dl-tetramisole. It is used as hydrochloride
salt, which is highly soluble in water and therefore can be given orally or by injection.
Tetramisole and Levamisole:
Anthelmintic activity:
 Levamisole is used antinematodal drug because of its broad
range of activity in a large number of hosts (sheep, cattle, pig,
horse, chicken, dog and cat).
 It is effective against Gl nematodes, lungworms and
hookworms in ruminants, canine, horse, pig and chicken.
 Larval and immature stages of Gl parasites of ruminants are
effectively removed by levamisole.
 In poultry it is effective against Capillaria obstignata, Ascaridia
galli and H. gallinarum.
No activity against flukes, tapeworms and protozoa.
Mode of action: Tetramisole and Levamisole
1. The drug affects the neuromuscular system of the
parasite by acting as cholinergic agonist.
 It has a nicotine-like action,
 stimulating and subsequently blocking the neuromuscular
junctions.
 The result is sustained muscle contraction and paralysis of
nematodes.
 It also acts as a ganglionic stimulant
 causing muscular paralysis.
 Most nematodes are passed in the feces within 24 hours.
 Mode of action: Tetramisole and Levamisole
2. At high concentration in parasites, levamisole,
like benzimidazoles interfere with carbohydrate
metabolism by inhibiting fumerate reductase
enzyme system.
 Effect on host immune system:
Tetramisole and Levamisole

 Levamisole modulates immunity of the host

through stimulation of cell mediated immune
reactivity by enhancing the rate of T-
lymphocyte differentiation and proliferation,
 responsiveness to antigens and mitogens and
activity of effector lymphocytes.
 It is highly beneficial in immunologically
depressed animals.
 Pharmacokinetics Tetramisole and Levamisole
Pharmacokinetics:
 Levamisole is rapidly absorbed and carried to
all parts of the body.
 Mainly excreted through feces and urine, and in
small amounts also through expired gases.
 Tissue residues of the drug are not appreciable.
 Dosage and Administration
Tetramisole and Levamisole
- Administered as
 Bolus
 Soluble drench
 wet-table powder for addition todrinking water,
 SC injectable solution
 dermal spot-on.
- Levamisole: Oral: Cattle, sheep, goat and pig: 7.5 mg/kg in a single dose;
Poultry: 25-50mg/kg SC injection: 7.5 mg/kg (@ 2 ml per 50 kg of 18.2% solution);
As pour-on: 10mg/kg.
- As an immunostimulant:
2.5mg/kg oral or SC. Tetramisole: Oral or SC: Cattle, sheep, goat and pig: 15 mg/kg
in a single dose (total dose should not exceed 4.5 gm for cattle).
 Safety and toxicity
Tetramisole and Levamisole

Safety and toxicity: Compared to benzimidazoles

tetramisole and levamisole have a narrow margin
of safety. Levamisole is well tolerated at
recommended dose level.
Cattle treated orally should not be slaughtered
within 48 hrs (for oral) and 7 days (for injection)
of treatment.
The drug should not be given to dairy animals
producing milk for human consumption.
 d. Tetrahydropyrimidines
Pyrantel: An imidazothiazole derivative. It is used as tartrate or
palmoate salts.

Effectiveness:
Broad-spectrum drug against Gl parasites of sheep, cattle, swine,
horse and dogs.
Mode of action: Affects neuromuscular system of the parasite
in the same way as levamisole by acting as a cholinergic agonist.
The drug causes depolarizing neuromuscular blockade resulting
in sustained muscle contraction and paralysis of nematodes.
 Pharmacokinetics Pyrantel
• Pharmacokinetics: Pyrantel tartrate is well absorbed
from the GI tract of pigs and dogs but absorption
less in ruminants.
• The drug is quickly metabolized in the body and
excreted in urine and feces. The palmoate salt is
poorly soluble in water, so less absorbed in the gut
allowing the drug to reach pinworms and be
effective against them in the lower end of large
intestine. So it is effective in the treatment of
pinworm infection of lower digestive tract in dogs.
 Administration and Dosage Pyrantel
 Orally as a drench in ruminants,
 by stomach tube in horses
 in swine it is given in feed,
 in dogs as suspension or tablets.
 Pyrantel tartrate: Dosage: Horse: 12.5 mg/kg; Swine: 22 mg/kg
(maximum 2gm/animal); Cattle, sheep and goat: 25 mg/kg.
 Pyrantel palmotate Dosage: Horses: 6.6 mg base/kg; Dogs (>2.2
kg(sad) 5mg base/kg; Dogs: (<2.2 kg(sad) 15 mg/kg.
 Pyrantel fumerate: Sheep: 12.5 mg/kg.
 Contraindications Pyrantel
In severely debilitated animals (due to nicotinic
action). Because of its cholinergic property, it
should not be administered together with other
cholinergic drugs like levamisole (may lead to
potentiation of toxicity).
 Morantel
Morantel: It is a methyl ester of pyrantel. Principally
morantel tartrate but also the fumerate salt is used as
veterinary anthelmintic.
The salts of morantel have greater anthelmintic activity
than the pyrantel.
Their pharmacological properties are similar.
Morantel tartrate is a safer drug than pyrantel tartrate.
Administration and dosage:
Morantel tartrate: Orally as aqueous solution: Dose: Sheep: 10 mg/kg; Cattle:
8.8 mg/kg. A 4% ointment of the tartrate salt is used to treat Thelazia eye infections of
cattle.
e. Organophosphorus (OP) Compounds:

The OP compounds were originally developed as

systemic insecticides.
Subsequently they are found to have also some
anthelmintic property, but their safety is often
poor.
The compounds used in farm animals are
coumaphos, crufomate, haloxon and
naphtholphos, and in horse, dog and cat are
dichlorvos and trichlorphon.
 Mode of action Organophosphorus (OP) Compounds
 The main effect of OP compounds on animal parasites is
inhibition of acetyl cholinesterase (AChE) enzyme,
 leading to an interference with neuromuscular transmission
 consequent paralysis of the parasite.
 AChE of host and parasites and of different species of
parasites vary in susceptibility to OP compounds.
 The degree of safety of OP compounds for the host is
probably related to lack of susceptibility of host AChE to the
drug. It has been found that the AChE of host and the
nematodes are not identical.
 Coumaphos Organophosphorus (OP) Compounds
Coumaphos
 Originally developed as pesticide for treatment of external
parasites of livestock and later used as an anthelmintic.
 Advantage of this drug is that it can be used in lactating animals
without requiring the milk to be discarded after treatment.
 It is effective against Haemonchus, Ostertagia, Trichostrongylus and
Coopería.
 It is mainly used as a helminthes preventive.
 The powder of the drug is given as a food supplement 2 mg/kg daily
for 6 days or as single dose 15 mg/kg for cattle and 8 mg/kg for sheep.
 The drug has narrow margin of safety and only healthy animals are
dosed.
 Dichlorvos Organophosphorus (OP) Compounds
 Dichlorvos: It is effective against Toxocara, Toxascaris, Ancylostoma,
Unciaria, Oesophagostomum spp., Ascaris suis, Trichuris suis, Parascaris
equorum, small Strongyles, Oxyuris equi, and Strongylus vulgaris.
 It is therefore a valuable anthelmintic for dogs, cats, pigs and horses." A
chief advantage of dichlorvos over many ad-spectrum anthelmintics in
dogs and swine is its efficacy against whipworms.
 It is not effective against migrating hookworms and ascarid larvae and
has no effect on tapeworms.

 Dose: Dichlorvos phosphate pellets are administered in the feed. The single treatment
doses are: Horses: 31-41 mg/kg in feed; Foals: gel formulation @ 20 mg/kg for bots and
ascarids. Swine: 11-22 mg/kg; Dogs: 27-33 mg/kg; Puppies and Cat: 11 mg/kg.
 Haloxon Organophosphorus (OP) Compounds
Haloxon: It is closely related to coumaphos. It is effective against the GI
nematodes of horse, sheep, cattle and pig. It is probably the safest OP
anthelmintic in ruminants.
Dosage and Admiminstration: Orally in bolus, drench, or paste form. Cattle:
44mg/kg; Sheep & Goat: 35-50 mg/kg.
Contraindications:
a. Haloxon, like other OP compounds should not be used simultaneously
with other cholinesterase inhibiting agents or chemicals
(carbontetrachloride).
b. Third stage of pregnancy in ewes and cows.
c. Lactating cows or goats producing milk for human consumption because
of residues.
d. Withdrawal period of seven days prior to slaughter.
 Trichlorphon Organophosphorus (OP) Compounds
 Trichlorphon: It is a pro-drug, metabolises rapidly
to dichlorvos which is responsible for its
therapeutic action.
 It is used as an insecticide as well as anthelmintic
in animals, principally in horse. It is used for the
treatment of Bots in horses, for Gl nematodes in
cattle, Haemonchus contortus and Oestrus ovis
(nasal grab) in sheep and Ascaris in pigs.
 Dose: Oral: Horse: 20-40 mg/kg for nematodes and bots; Dogs: 75 mg/kg
for each of three treatments at 3-4 days intervals; Sheep: 55 mg/kg.
 Naphtholphos Organophosphorus (OP) Compounds

 Naphtholphos: Is a medium spectrum OP

compound used in sheep and cattle mainly
against parasites of the abomasum and small
intestine, but it is ineffective against the
parasites of large intestine of ruminants. The
drug has a very low margin of safety in
chickens.
 Administration and dosages: Orally as bolus, drench or feed
additive; Cattle and sheep: 50 mg/kg.
 Crufomate Organophosphorus (OP) Compounds

 Crufomate: Its oral administration provides

anthelmintic activity in cattle and pour-on method
of application control warble fly. The drug is
• highly effective against Haemonchus, Cooperia,
Bunostomum, and Ostertagia, but
• less effective against Trichostrongylus,
Oesophagostomum, Capillaria and lungworms.
 Dosage: Cattle: Oral: 40 mg/kg, single dose.
 f. Macrocyclic lactones
Avermectins and Milbemycins Avermectins:
Avermectins are a group of chemically related anthelmintics produced by the
fermentation of actinomycete, Streptomyces avermitilis.
There are eight different components of avermectins namely
• A1a,
• A2a,
• B1a,
• B2a
• A1b, A2b, B1b
• B2b.
Each of these components has anthelmintic activity. The avermectins are
also macrocyclic lactone derivatives, but in contrast to the macrolide or
polyene antibiotics, they lack significant antibacterial or antifungal
activity.
 Ivermectin: Macrocyclic lactones
• Ivermectin is a mixture comprising 80% 22, 23 dihydroavermectin B1a and
20% 22, 23 dihydroavermectin B1b.
• It is a very potent nematocide and ectoparasiticide (endectocide) by oral and
parenteral routes.
• Activity:
 Ivermectin is effective against all stages of parasitic Gl nematodes and
lungworms including canine heartworm larvae.
 It is also a potent ectoparasicide and effective against warbles, lice and
mites.
 It has no activity against tapeworms and flukes.

Note: Dung of ivermectin treated animals does not decompose (ecological

threat).
 Ivermectin: Macrocyclic lactones
Mode of action:
 The normal function of GABA in mammals and invertebrates, is inhibition of
neurotransmission.
 Macrocyclic lactones/Avermectins cause paralysis of the worm by
potentiation of GABAergic transmission (by opening chloride channel)
between nerve and muscle.
 Potentiation of GABA leads to hyperpolarisation of postsynaptic cells and
cosequent muscular paralysis.
 Flukes and tapeworms do not use GABA as a neurotransmitter and are not
affected by avermectins. The lack of GABA related toxicity in man is explained
by its low affinity for mammalian GABA receptors and its inability to penetrate
the mammalian blood brain barrier.
 Recent evidence suggests that macrocyclic lactones act by binding to a
glutamate gated chloride channel receptor in nematode and arthropod nerve
cells. This results in opening of the channel (only in invertebrates) and influx
of chloride ions leading to flaccid paralysis. Either such glutamate gated
chloride channels are not involved in motor control of cestodes and
trematodes or such glutamate gated chloride channel receptors are not
present in cestodes or trematodes].
 Ivermectin: Macrocyclic lactones
Metabolism:
Ivermectin is readily absorbed, especially when given parenteral. High conc. of drugs the feces (98%) and urine
(2%).
Sustained in tissues for long periods and residues occur mainly in the liver and fat.
The drug is excreted in Dosage:
Cattle: 0.2mg/kg (Oral or SC);
Sheep: 0.2 mg/kg orally;
Horses: 0.2mg/kg (Oral);
Swine: 0.3 mg/kg, SC;
Dogs: 0.006-0.012 mg/kg as tablet orally or in food (monthly, as a preventive for heartworm) or 0.2 mg /kg, SC (2 injections at 14 days interval in
mange infections).

Toxicity:
 The drug has minimum 10-fold margin of safety for ruminants, horses, swine and dogs.
 It should not be administered parenterally to horses
 and may be toxic to certain breeds of dogs (Idiosyncratic reaction in Collies).
 It is not embryotoxic in domestic animals,
 but is teratogenic to rodents.
 Acute toxic signs are: CNS depression, listlessness, ataxia, recumbency followed by death.
Precautions:
a) Cattle must not be treated within 21 days of slaughter.
b) Ivermectin should not be used in milk producing animals or in dairy cows for 28 days
prior to calving. Abamectin and Doramectin: Pharmacological actions and dosages are
same as ivermectin.
 Milbemycins: Macrocyclic lactones
Milbemycin D:
 It is a natural product of Streptomyces hygroscopicus sp.
Aureolacrimosus,
 only used for treating dogs.
 It is active orally against dog roundworms and
prophylactic against heartworms at higher monthly
doses.
 The mode of action is similar to ivermectin. Higher doses
cause neurological disorder.in Collie breeds of dogs.
 Dose: 1mg/kg once monthly.
 Milbemycin oxime: Macrocyclic lactones
• Milbemycin oxime:
It is used is used as tablets orally in dogs at
monthly intervals for prevention of heartworm
disease and to treat hookworms.
Dose: 0.5mg/kg once monthly.
 g. Drugs Acting Against Heartworms

• Elimination of adult heartworms:

• Thiacetarsamide sodium:
Chemically it is an arsenical compound and is
the only drug used for the elimination of adult
heartworms in dogs. The drug does not affect
the circulating microfilariae.
 Thiacetarsamide sodium
Drugs Acting Against Heartworms

Mode of action:
The drug interferes with the energy production
of the parasite by inhibition of glycolysis.
The trivalent arsenic tends to bind sulfhydryl (-
SH) groups, thereby altering the tertiary
structure of proteins and the active site of
enzymes in both parasite and host.
 Thiacetarsamide sodium
Drugs Acting Against Heartworms

Effectiveness:
Following four therapeutic doses of thiacetarsamide,
adult worms die usually within 5-7 days and occasionally not until 14
days.
The dead worms are swept out of the heart by the flowing blood and
lodge in the pulmonary artery, especially in the diaphragmatic lobes,
where phagocytosis of dead worms occur during the next 2-3
months.
To avoid embolism, absolute rest during the first two weeks is
necessary.
Administration and Dosage: Dogs: IV 2.2 mg/kg twice daily for 2
days.
 Thiacetarsamide sodium
Drugs Acting Against Heartworms

Precautions:
a. The drug is hepatotoxic and nephrotoxic therefore proper
functioning of liver and kidney must be attained before starting
treatment.
b. The drug is highly irritating to subcutaneous tissues. So, during IV
injection care must be taken to avoid perivascular leakage as it
may result in local swelling and sloughing. Injection of steroids into
the area helps in reducing inflammation.
Toxicity:
The symptoms of arsenic toxicity like persistent vomiting, icterus
or orange colored urine may be seen and the toxicity can be
treated with dimercaprol 8.8mg/kg/day in 4 divided doses.
 Thiacetarsamide sodium
Drugs Acting Against Heartworms

Elimination of heartworm microfilariae:

Itis essential as they cause glomerular damage in kidney and the preventive
drug, diethylcarbamazine is not safe for use in dogs until Dithiazanine iodide:
It is an intense blue-violet powder, poorly soluble in water. It is the only drug
used as a heartworm microfilaricide in dogs. they are cleared of
microfilariae.

Mode of action:
The exact mechanism by which dithiazanine clears circulating microfilariae
from the blood is not known. It is thought that the drug inhibits the glucose
uptake by the parasite and consequently affects the ATP formation. The
parasites lose their motility, become trapped in the capillary beds and are
finally phagocytized by host cells.
 Thiacetarsamide sodium
Drugs Acting Against Heartworms

Administration and Dosages:

Available as either powder or tablet and is administration orally just after or
during feeding:
Dose: 6.6 mg/kg/day for 7-10 days as microfilariaecide. Precaution: It should be given 6
months after the adulticidal drug. The interval allows improvement in physical
condition of the dog following the stressful use of adulticidal thiacetarsamide. Toxicity:
Repeated dosing may produce vomiting, diarrhea, anorexia and asthenia.

Preventive programme for heartworm disease in dogs: Two approaches are followed:
A. The adulticidal drug is given at 6 months intervals 2.2 mg/kg IV twice daily for 2
days.
B. Using larvaecidal drugs that kill the infective 3rd stage or developing 4th stage larvae
(Diethylcarbamazine (DEC), ivermectin or milbemycin D etc). Monthly treatment with
vermectin as compared with the requirement of daily dosing with DEC, gives the
former drug the advantage as a potential preventive.
 Diethylcarbamazine citrate: (DEC)
Drugs Acting Against Heartworms

 It is a piperazine derivative.
 DEC is used as a heartworm preventive.
 The drug also act against microfilariae but unfortunately
sometimes a fatal shock type of reaction occurs if the
drug is given to microfilariae positive dogs.
 So, an infected dog must be cleared of adult heartworms
and microfilariae before starting it on DEC prophylaxis.
 In human it is used in filarial infection caused by W.
bancrofti and tropical eosinophilia.
 Diethylcarbamazine citrate: (DEC)
Drugs Acting Against Heartworms

Mode of action:
 The most important action of DEC appears to
opsonization of microfilarial membranes so that
they are readily phagocytosed by tissue fixed
monocytes, but not by circulating phagocytes.
 The drug also affects the nervous system of the
parasites and causes paralysis of the worm. It may
also interfere with the parasites arachidonate
metabolism.
 Diethylcarbamazine citrate: (DEC)
Drugs Acting Against Heartworms

Administration and Dosage:

 The drug is rapidly absorbed from the GI tract
and its rapid metabolism and excretion accounts
for its low toxicity.
 It is administered in feed or just after feeding as
tablet, syrup or powder each day throughout the
mosquito season and 2 months following.
Dosage: Dog: 6.6 mg/kg/day.
 h. Miscellaneous Antinematodal Drugs

n-Butyl chloride:
It is a colorless liquid administered in gelatin
capsules to dogs and cats after overnight fasting
for control of ascarid and hookworm infections.
It is non toxic to small animals.
Dose: Dog and Cat body wt < 2.25 kg: 1 ml; 2.25-4.5 kg: 2 ml; 4.5-
9 kg: 3 ml; 9-18 kg: 4 ml; > 18 kg: 5ml.
h. Miscellaneous Antinematodal Drugs
Toluene:
 It is a liquid coal tar hydrocarbon
(methylbenzene), and used as anthelmintic
against ascarid of hookworms of dogs and cats.
 In comparison to n-butyl chloride, it is more
efficacious but more toxic.
 Combination of these two drugs is synergistic.
Dose: Oral: Dog, cat, puppy/kitten: As gelatin capsules 0.22ml/kg.
 h. Miscellaneous Antinematodal Drugs
Tetrachloroethylene:
 It is a halogenated hydrocarbon, colorless, volatile
liquid has been used mainly against hookworm
infections of dogs, cats and humans and against Gl
nematodes of ruminants.
 Tetrachloroethylene has largely been replaced by
other better drugs because of its several
disadvantages and toxicity
dizziness, incoordination, liver damage and even death.
 h. Miscellaneous Antinematodal Drugs
Tetrachloroethylene:
Disadvantages:

a. In ruminants, rumen reduces the activity of the drug. Therefore, bypassing of the
rumen by stimulating closure of oesophageal groove is essential.
b. In small animals the animals must be kept on fat free diet for 48 hours prior dosing
as fat increases the absorption of the drug from the gut and may precipitate toxicity.
c. Food and water should be withheld 12 hours before and 4 hours respectively after
drug administration.

Contraindications:
1. In tapeworm infested animals as irritation of these worms may results in their
balling up, occlusion and even rupture of gut.
2. Febrile, debilitated, nursing animals or weighing less than 1 kg. Dose: Dog and
Cat Orally as gelatin capsules @ 0.22 ml/kg,
 Bephenium hydroxynaphthoate
Miscellaneous Antinematodal Drugs

Bephenium hydroxynaphthoate
A quaternary ammonium compound, bitter yellow
powder, insoluble in water.

Effectiveness: Most effective against mature hookworms

of dogs and cats and humans and also Gl parasites of
ruminants specially Nematodirus spp. and also
Tichostrongylus, Haemonchus, Ostertagia, Bunostomum,
Oesophagostomum and Cooperia species.
 Bephenium hydroxynaphthoate
Miscellaneous Antinematodal Drugs

Mode of action:
The drug affects the neuromuscular system of the
parasite in the same way as levamisole by acting
as a cholinergic agonist and causes depolarizing
type neuromuscular blockade resulting in
sustained muscle contraction and paralysis of
nematodes.
 Bephenium hydroxynaphthoate
Miscellaneous Antinematodal Drugs

Administration and Dosage:

Cattle and Sheep: As a drench: 250mg/kg, single dose; Dogs: as
tablets: 35 mg/kg in two divided doses. Overnight fasting and post
treatment purgatives are not required.

Precaution:
The drug produces gastric irritation, nausea and vomiting, hence an
antiemetic should be given before medication.

Toxicity:
Safe at therapeutic doses. Occasionally may cause vomiting and
diarrhea.
 Thenium closylate:
Miscellaneous Antinematodal Drugs

Thenium closylate:
It is a colorless crystalline solid, analog of bephenium.
It is particularly effective against mature and immature hookworms but has
poor action against Ascaris unless combined with piperazine.
It may cause vomiting in dogs.
Mode of Action:
Same as Bephenium.

Administration and Dosage:

As tablet, or capsule or in feed (one-day treatment). Fasting or purgation is not
required.

Dogs: >4.5 kg body wt.: 500 mg base as a single dose; Pups: < 4.5kg: 125 mg twice .
 Disophenol:
Miscellaneous Antinematodal Drugs

Disophenol
Chemically it is 2,6-diiodo-4-nitrophenol.
It is an injectable antihookworm compound used in dogs and cats.
Mode of Action:
The drug affects the energy production of the parasites by
inhibiting the oxidative phosphorylation in the mitochondria.
Administration and Dosage:
Dogs & cats: single SC injection: 10 mg/kg (as 4.5% solution = 45 mg/ml).
Advantages: Can be used in very young animals and even in heavily
parasitized animals without stress. No need of fasting.
 Hygromycin B:
Miscellaneous Antinematodal Drugs
Hygromycin B:
This is an antibiotic obtained from Streptomyces hygroscopicus with anthelmintic
activity.
Effectiveness:
Highly effective against A. sum and also Oesophagostomum of swine and A. galli,
Capillaría obstignata and H.gallinarum in chickens.
Administration and Dosage:
added as powder to feed of swine and chickens for several weeks. Dose: Swine: 13.2 g/
1000 kg of ration (given to weaned pigs up to 6 months of age i.e. during period of
ascarid susceptibility), intermittently (8 weeks on and 8 weeks off) to avoid toxicity;
Chickens: 8 gm/900 kg. feed.
Toxicity:
Continuous feeding of the antibiotic over 10 months may cause hearing loss and
cataract in swine. No adverse effect in chickens or on egg production at the
recommended dose level.
 3. Anticestodal Drugs
These are the drugs effective against cestodes or tapeworms and are of two types:
1. Taeniafuges: These drugs simply cause expulsion of tapeworms. They generally
paralyse the tapeworm and are combined with purgative to fecilitate expulsion
e.g. older natural organic anticestodal drugs like arecoline.

2. Taenicides: They cause actual death of the tapeworms in situ. e.g. synthetic
organic like bunamidine.

Classification:
Anticestodal drugs are classified as:

a) Natural compounds
b) Inorganic compounds and
c) Synthetic organic compounds.
 a. Natural (organic) Anticestodal Drugs
Natural Anticestodal Compounds:
Earliest anticestodal compounds:
- mostly plant origin and used for man and
animals.
- replaced by more efficacious and safer
synthetic organic anticestodal drugs.
as follows:
 a. Natural (organic) Anticestodal Drugs
• Pumkin seeds: The active principle is cucurbitine. It has low efficacy but high safety
• Male fern: (Dryopteris felix mas(sad) The powdered rhizome of this fern was best
known human cestodes. The active principle was found to be filicic acid that caused
paralysis of the tapeworm.

• Kamala: Source: Glands and hairs covering fruits of a plant Mellotus philippinensis.
It was the drug of choice for cat tapeworms like Dipylidium caninum and Taenia
taeniformis. Kamala causes paralysis of both cestodes and host intestinal muscle
and never used in veterinary medicine.

• Nicotine: Source is Nicotiana tabacum. It was given with copper sulphate for
removal of ruminant tapeworms and roundworms. The drug causes persistent
depolarization of the neuromuscular junction followed by paralysis of the worm.
The efficacy and safety of the drug are low.
 a. Natural (organic) Anticestodal Drugs
Arecoline: It is an alkaloid obtained from seeds of betel nut palm, Areca catechu.
It is used in dogs. Arecoline hydrobromide: it is a white, bitter, crystalline
substance. Effectiveness: Against all tapeworms of dogs (Taenia, Dipylidium)
including Echinococcus.

Mode of Action:
It has two folds action. Arecoline salts
- affect the neuromuscular system of the parasite probably
- by acting as a cholinergic agonist
- resulting in the paralysis and
- detachment of the worm from the intestinal mucosa.
- Its local cholinergic action also increases the peristalsitic movement of the
intestine so that the detached worm is expelled by purgation.
- The drug causes only temporary paralysis of the worm. So if purgation does
not occur within 2 hours of medication, a saline purgative is given to dogs to
induce evacuation.
 a. Natural (organic) Anticestodal Drugs
Administration and Dosage: Orally as enteric
coated tablets after overnight fasting. Dose: Dogs:
1 mg/kg.

Toxicity: Vomition, colic and diarrhea. Antidote is

atropine sulphate. The drug is contraindicated in
cats; excessively increases the tracheo-bronchial
secretion and thereby causes suffocation.
 b. Synthetic Organic compound
Anticestodal Drugs
• Bunamidine hydrochloride: It is a white crystalline powder, has good activity
against all tapeworns of dog and cat including Echinococcus granulosus.

• Mode of Action: Bunamidine salts disrupt the tegument of the parasite

resulting into reduced rate of glucose uptake and ultimate death of the
parasite. The dead v. orms are digested in the host gut. The drug does not
cause purgation.
• Dosage: Administered orally as crated tablets. Dog and Cat Single dose 25-50
mg/kg after 4 hr. fasting.
• Safety: The drug is safe in all stages of pregnancy.

• Toxicity: Vomiting and diarrhea. This can be reduced by using

hydroxynaphthoate salt. The drug may cause sensitization of heart muscle to
catecholamine and sudden death of animals.
 b. Synthetic Organic compound
Anticestodal Drugs
Niclosamide: it is 2,5-dichloro-4' nitrosalicylanilide, yellowish powder, insolubie in water.
Activity: It is widely used against the tapeworm infections (mainly for Taenia) of dog, cat
and man but it has poor efficacy against Echinococcus and variable for Dipylidium. It is
against Moniezia and Thysaosoma infections in ruminants and tapeworm infections.
animals, monkeys and reptiles .It has also activity against intestinal flukes such as
Paramphistomum in ruminants.
Mode of Action: It is a taenicide. The anticestodal activity is produced by:
a. Inhibition of glucose absorption by the worm.
b. Uncoupling of oxidative phosphorylation in the mitochondria resulting in
-blockade of Kreb's cycle
-accumulation of lactic acid in the worm and
- interference with anaerobic generation of ATP by the worm.
This results in death of tapeworm and its digestion in the gut.
c. The cestocidal action of the drug may be related to the over stimulaton of ATPase
activity of the mitochondria.
Safety and Toxicity: It has wide margin of safety. Safe at all stages of pregnancy
and in debilitated animals
 b. Synthetic Organic compound
Anticestodal Drugs
• Dichlorophen: Chemically it is 2,2-methylene bis (4-chlorophenol). It is
a white powder, insoluble in water. Most of the pharmacological
properties viz. mode of action, kinetics, safety and toxicity are similar to
niclosamide.

• Efficacy: It is mainly used as a narrow spectrum taenicide in veterinary

medicine. It is effective against Taenia and Dipylidium in dogs and cats.
But it is ineffective against Echinococcus, thus it is not the drug of
choice for this tapeworm. It has limited efficacy against Moniezia in
sheep. In addition, the drug has bactericidal and fungicidal properties.
• Administration and Dosage: Orally as tablets or suspension after
overnight fasting. Purgative is not required. Dog, Cat and Sheep: 200
mg/kg
 b. Synthetic Organic compound
Anticestodal Drugs
• Hexachlorophene:
 It is mainly used as an antitrematodal drug for the treatment of liver fluke
infection in sheep and cattle.
 The main anticestodal use of this drug is for the control of chicken tapeworms,
especially of Raillietina cesticillus.
 The drug is toxic to dogs.
Mode of Action:
 oxidative phosphorylation in the mitochondria and
 interference with anaerobic generation of ATP by the worm.
 This results in death of tapeworm and
 its digestion in the gut.
Dose: Chickens: Single dose 30-60 mg/kg after overnight fasting. The drug is
combined with phenothiazine in poultry for removal of tapeworms and Ascaris
simultaneously.
 b. Synthetic Organic compound
Anticestodal Drugs

• Resorantel: Chemically it is a hydroxynilide. It is an anticestodal

for ruminants.
Effiacy: It is highly effective against Moniezia in both sheep and
cattle and against Thysaniezia gardi in sheep. In addition, it has
efficacy in sheep and cattle against adult and immature rumen
flukes
Mode of Action:
Same as hexachlorophene (Paramphistomum spp).
Pharmacokinetics: The drug is rapidly excreted within 48 hours of
treatment.
Dose: Sheep and Cattle: Administration as drench 65 mg/kg.
 b. Synthetic Organic compound
Anticestodal Drugs
Bithionol: It is 2, 2'-thiobis (4, 6-dichlorophenol), white crystalline solid, insoluble in water. It has
anthelmintic as well as bacteriostatic and antifungal activities.
Indications and Effectiveness: It is used for the treatment of tapeworm infections (especially
Taenia) in
dogs, cats and poultry. The drug is also used for the treatment of tapeworm (Moniezia and
Thysanosoma) and rumen fluke (adult and immature Paramphistomum) infections of sheep,
cattle and goats. The drug is also effective against lung flukes (Paragonimus spp) in dogs and cats.
Mode of Action: Same as hexachlorophene
Pharmacokinetics: Absorption from host gut is poor; excreted in bile; produces purgation due to
its cholinergic effect on host gut.

Safety and Toxicity: Well tolerated by cats, dogs, cattle, sheep, goats and chickens. But sometimes
emesis is seen in dogs and diarrhea is seen in all species.

Dose: Dogs, cats, sheep and goats: Oral: 200mg/kg as tablets, gelatin capsules or boluses;
Chickens: 200 mg/kg, 2 doses, 4 days apart, in feed.
 b. Synthetic Organic compound
Anticestodal Drugs

Bithionol sulphoxide:
A derivative of bithionol. The special advantage
of this drug is that it anticestodal efficacy to
bithionol in dogs, sheep at lower therapeutic
dose level of 60 mg/kg and has excellent efficacy
against liver flukes of both sheep and cattle.
 b. Synthetic Organic compound
Anticestodal Drugs

Uredophos:
A broad spectrum anthelmintic for use against both
nematode (Ascaris and hookworms) and cestodes of dogs
and cats at the dose rate of 50 mg/kg.
The most important feature of the drug is that it is 100%
efficacy against Dipylidium caninum that is resistant to
most other anticestodal drugs except praziquantel.
Mode of Action: Anticholiesterase agent.
Toxicity: Because of severe adverse reactions and even
death the drug has been banned for clinical use.
 b. Synthetic Organic compound
Anticestodal Drugs

Nitroscanate:
It is active against tapeworms and roundworms
of dogs but not suitable for cat.
Dose: Dogs: 50 mg/kg.it is very safe and can be
given to pups and pregnant and lactating
bitches.
Side effect: Vomiting.
 b. Synthetic Organic compound
Anticestodal Drugs

Praziquantel: Chemically it is an isoquinoline and

colorless, crystalline and bitter compound.
Effectiveness: It is a new broad spectrum anthèlmintic
effective against all species of Schistosomes pathogenic to
humans and has unique, extremely high activity against
wide range of adult and larval cestodes of both animals
and man (including Cysticercosis). It is also effective
against ruminant, poultry and snake tapeworms and
certain flukes. But it has no activity against nematodes.
 b. Synthetic Organic compound
Anticestodal Drugs
Mode of Action:
 The drug is quickly taken up by the susceptible worms and act by increasing the
permeability of the nematode cell membrane to Ca.
 This causes the leakage of intracellular calcium from the membranes resulting in
 contraction of musculature and
 eventual paralysis and death of the worm.
 Praziquantel also modifies the parasite so that it becomes susceptible to hosť's
normal immune responses.

Pharmacokinetics: Orally the drug is quickly and completely absorbed and has
ubiquitous distribution (asset for its activity against adult and larval form of
parasite at different locations like brain, musculature etc.) and quickly inactivated
in liver.
 b. Synthetic Organic compound
Anticestodal Drugs

Administration and Dosage:

Administered orally or IM. Dog and cat: 5 mg/kg, by for all tapeworms;
Sheep,
Goats and Poultry: 10-15 mg/kg by either routé for all tapeworms; Snake
tapeworms: 3.5-7 mg/kg. For lungfluke infection (Paragonimus spp)
Dog: 25 mg/kg /day for three consecutive days.
Human: Oral: 10-25 mg/kg for tapeworms; For Schistosomiasis and other
flukes: 75 mg/kg. For neurocysticercosis: 50 mg/kg in three divided doses
for 15 days (alternative is albendazole).
Safety and Toxicity:
Drug has wide margin of safety. No teratogenicity or embryotoxicity orally.
 b. Synthetic Organic compound
Anticestodal Drugs
Benzimidazoles:
The cestocidal benzimidazoles are:
 Mebendazole: Taeniasis in Dog and Cat: 22 mg/kg/day for 5 days; For
adult Echinococcus granulosus: 160 mg/kg. For Moniezia in ruminants: 20
mg/kg.
 Fenbendazole: Taeniasis in Dog and Cat: 50mg/kg/day for 3 days. All the
above are ineffective against D. caninum.
 Oxfendazole, Cambendazole and Albendazole: For Moniezia in
ruminants: 7.5-15 mg/kg.
Anticestodal drugs for Horses:
The following drugs are found to be effective and safe against equine
papeworms (Anoplocephala spp)
 Mebendazole: 20 mg/kg;
 Niclosamide: 88 mg/kg
 Dichlorophen: 20 mg/kg Bithinol: 7 mg/kg;
 Pyrantel palmoate: @ 13.2 mg/kg.
c. Inorganic Compounds Anticestodal Drugs
Tin compounds:
Metallic tin with its oxide or chloride of butyl tin dilaurate: They are very
much effective against tapeworms such as
 T. solium, T. saginata and Dipylidium in dogs;
 Davinea in poultry
 anticestodal in man and domestic animals.
Mode of Action:
Tin particles form a thin layer of coating on the cuticle of the tapeworm and
rendering the strobila susceptible to digestion.

Disadvantage: Needs daily administration for several days and produces side
effects and toxic effects. So advent of more efficacious and less toxic
taenicides has limited their use.
c. Inorganic Compounds Anticestodal Drugs
Lead arsenate: I
It is highly effective against Moniezia and was in use worldwide for the
treatment of Moniezia infection in lambs, calves and kids. It has low
margin of safety and it should never be used in poultry.

Mode of Action: The drug is hydrolyzed in the gut to lead and arsenic.
The lead is transformed to lead oxide and the pentavalent arsenic to
more toxic trivalent arsenic.
Dose: Administered orally without fasting
Calves > 3 months and Lambs > 2 months: 1 gm/ animal single dose
(Lambs 2 months should not be treated);
Calves (heart) months and kids: 0.5 g/animal, single dose.
 Antitrematodal Drugs
These are the drugs effective against trematodes
or flukes.
 Fascioliosis caused by F. hepatica is most
common worldwide and has greatest
economic importance.
 The rumen fluke, Paramphistomum in cattle
and lung fluke, Paragonimus in dogs and cats
are important.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Carbon tetrachloride: It is a volatile colorless liquid, insoluble in

water.
Efficacy:
Effective against
 adult F. hepatica, well tolerated in sheep and economic. Thus it
is mainly used in sheep in the treatment of
 fascioliosis. ascariasis in dog, cat and poultry;
 Angylestome of dog and cats and
 stomach worms of cattle,

but has now replaced by more effective antinematodial drugs.

 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Mode of Action: Carbon tetrachloride

The anthelmintic action of CO is thought to be
 indirect, through its metabolites or by
 inducing formation of toxic methylsterol in the host liver due to interference with
the cholesterol bisyrithesis.
In the host, methylsterol is an itermediate metabolite in biosynthesis of cholesterol.
 CCl4 blocks the cholesterol biosynthesis
 formation and accumulation of toxic methysterols in the liver, bile and urine of
treated animals.
 This methylsterol is highly toxic to the flukes and produces lethal effects by
 interfering with the secretory and enzymatic activity of the gut epithelium of the
parasite.
 it uncouples oxidative phosphorylation in the mitochondria and
 interferes with anaerobic generation of ATP by the flukes. This results in death of the
flukes.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Carbon tetrachloride
Pharmacokinetics:
 oral administration,
 absorbed in the intestine (increased by fats and oil),
 metabolized in liver
 the active metabolite excreted in bile and urine. So
the adult flukes (12 weeks or older) living in the bile
ducts are killed but the immature flukes living in the
liver parenchyma are not affected.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Administration and Dosage:

 Sheep: Orally: 1-3 ml 300-600 ml, in before feeding; IM or SC 4 ml in liquid paraffin
containing butyl alcohol (local anaesthetic),
 Cattle: IM or SC 30ml (or 1ml/9 kg) in liquid paraffin containing butyl alcohol (local
anaesthetic);
 Dogs: 1-5 ml orally (0.1-0.2 milkg)
 Poultry: 1-5 ml orally.

Toxicity and Disadvantages:

A. Lacks activity against immature flukes.
B. Highly toxic to mammalian liver (hepatotoxic). So cannot be used in cattle, horse, pig
and cat.
C. High dose causes giddiness, unconsciousness and cardiovascular collapse.
D. Toxicity is more in debilitated animals, animals with diseased liver, high fat diet, in cold
weather (due to decrease excretion through expired air).
 a. Drugs Against Adult Flukes
Antitrematorial Drugs
Hexachlorbethane: It is a chlorinated hydrocarbon, white crystalline substance.
Effectiveness:
 Highly effective against all species of adult Fasciola in cattle and also
 against Haemonchus and Trichostrongylus. But
 it is not effective against immature flukes and intestinal nematodes of ruminants.
Mode of Action: Act by uncoupling oxidative phosphorylation in the mitochondria and
interferes with anaerobic generation of ATP by the flukes. This results in death of the
flukes.
Administration and Dosage: Orally: Sheep: 8-15 gm/ animal; Cattle: 10 gm/50 kg
(Pretreatment at
monthly interval during snail season).
Toxicity:
 Hepatotoxic but lesser than CCl4,
 so used as alternative in cattle against Fasciola infections.
Limitations: Hepatotoxicity, frequent side effects and dietary precautions in sheep and
cattle compelled replacement of the drug by newer drugs.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Hexachloroparaxylene: Chemically it is chlorinated derivative of

benzene (1,4-bis-trichloromethyl benzene).
Effectiveness:
 It is a highly effective fasciolicide against F. hepatica in sheep.
 It is combined with phenothiazine for the treatment of liver
flukes and Gl nematodes in ruminants.
Administration and Dosage: Oral: Sheep: 150mg/kg; Cattle:
125mg/kg.
Advantage: It is superior to CCl4 and hexachloroethane because:
i. High tolerance in sheep and
ii. Does not cause blood dyscrasia.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Tetrachlorodifluoroetane:
It is a halogenated hydrocarbon, effective against
only adult F.hepatica (not against immature
forms) infection and well tolerated in sheep.
Dose: Sheep: Oral: 300 mg/kg.
Disadvantage: The drug is not used in cattle since
it is less effective against liver flukes and also
produces severe toxic reactions.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Hexachlorophene Chemically it is 2,2-methylenebis (3,4,6-trichlorophenol).

Efficacy:
It is used in the treatment of mature liver fluke infections in human and ruminants
and cestode infections in canines.
The drug is 100% effective against adult F. hepatica and F. gigantica in sheep and
cattle.
This is because the drug remains in free form in bile and the host metabolite
(glucuronide) excreted in bile has high activity especially against adult flukes, as they
remain in the bile ducts.
the immature flukes (<8 weeks old) incubated in the blood of liver parenchyma, are
not affected because the free drug is less available to this immature flukes due to its
plasma protein binding.
Mode of Action: Same as hexachloroethane
Administration and Dosage: Sheep and Cattle: Oral: 25 mg/kg Safety and Toxicity: Less
safe. Overdosing causes CNS symptoms, blindness followed by even death.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Bithinol sulfoxide:

Activity: Besides anticestodal properties, bithinol and its sulfoxide has excellent
effecacy against rumen and liver flukes (Fasciola hepatica, F. gigantica, Fascioloides
magna and Paraphistomum spp) of domesticated and wild ruminants. This drug is
more effective against adult than immature flukes.
Mode of Action: Same as hexachloroethane.

Administration and Dosage: Sheep, Goat and Cattle: Oral: Administered as bolus or
in feed 60 mg/kg.

Drug combination:
Bithionol sulfoxide (30mg/kg) + Hexachlorophene (5 mg/kg(sad) 100% effective
against mature F.hepatica in cattle and sheep.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Bromosalans:
 This is the mixture of dibromosalans and tribromosalans.
 The drug has equal efficacy for adult flukes as other fasciolicidal
drugs and has been used for the treatment of F. hepatica infection.
 An extra advantage of bromosalans is that it is 100% effective
against juvenile flukes (6-10 weeks age).

Mode of Action: Same as hexachloroethane.

Dose: Sheep: Orally: 30 mg/kg (for adult flukes); 60 mg/kg (for
juvenile flukes)
Safety: It has narrow therapeutic index in sheep.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Oxyclozanide:
It is a salicylanilide compound having fasciolicidal activity. against adult liver
flukes that live in the bile duct. Like hexachlorophene and nitroxinyl, it is also
not effective against immature flukes because of protein binding in blood.
Mode of Action: Same as hexachloroethane.
Dose: Oral: Cattle and Sheep: 15 mg/kg.
Advantages:
a. The drug is equally effective as CCl4, hexachloroethane and
hexachlorophene and is less toxic.
b. Drug has zero withdrawal for milk and short withdrawal period for
slaughter.
c. It can be given in therapeutic doses to debilitated and pregnant animals
without any side effects.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Clioxanide:
Chemically it is 4'-chloro-3,5- diodobenzanilide
acetate.
It is highly effective against adult and immature
F.hepatica in sheep but the doses needed for
immature flukes are less safe.
Dose: Orally for adult flukes: 15 mg/kg.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Niclofolan:
It is an analogue of hexachlorophene.
 It is effective against adult F.hepatica in sheep, cattle and pigs at
safe doses.
 It is also effective against immature flukes at higher doses but is
less safe. The drug is mostly used in sheep.
Mode of Action: Same as hexachloroethane.
Administration and Dose: Oral: For adult flukes: Sheep: 2.7 mg/kg;
Cattle: 3mg/kg; Parenteral: Sheep and Cattle: SC 0.6-1 mg/kg.
Precaution: Niclofolan is excreted in milk. Milk should not be
consumed for 4-5days of post treatment.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Nitroxynil:
Chemically it is 4-hydroxy-3-iodo-5-nitrobenzonitrile. It is an injectable fasciolicide,
 effective adult liver flukes (F.hepatica and F. gigantica) in cattle and sheep,
 with some activity against fly larvae (Oesterous ovis) and
 blood sucking nematodes.
 It is also used to treat gapeworms (Syngamus) in poultry.
Mode of Action: Same as hexachloroethane.
Administration and Dosage: SC route. Since, when given orally, reduction of nitro group by
microorganisms in rumen causes loss of anthelmintic activity.
Dose:
Sheep and Cattle: SC 10 mg/kg;
Poultry: 150-400 ppm in water. Precaution: The drug is slowly excreted. So, withdrawal period
for slaughter is 31 days and should not be used in cows producing milk for human consumption.
Advantage: Easy to administer SC than other fasciolicides that are given orally.
Safety: Margin of safety is only 4.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs
Rafoxanide:
Chemically it is a halogenated salicylanilide.
Activity:
 Effective against adult and young (6-10 weeks old) liver flukes in sheep.
 It is also indicated in the treatment of blood sucking nematode
infections (haemonchosis, bunostomiasis) and
 for tissue invading fly maggots (sheep nasal bot).
Mode of Action: Same as hexachloroethane.
Dose:
Sheep: 7.5 mg/kg orally;
Cattle: 7.5 mg/kg orally or 3mg/kg SC.
Pharmacokinetics: The drug is well absorbed, but slowly eliminated. So
the drug cannot be used in lactating cows and requires 28 days
withdrawal period for meat.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Bromophenophos:
It is an organophosphoric acid ester, used for the treatment
of
 mature F.hepatica infections in cattle.
 good efficacy against immature liver flukes.
Mode of Action: Same as hexachloroethanc.
Dose: Cattle orally 12 mg/kg.
Toxicity: Safety index is 3. The toxicity of niclofolan,
nitroxynil and bromophenophos is due to uncoupling
of oxidative phosphorylation in the host also.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Clorsulon:
Chemically it is benzene sulfonamide. It is an oral fasciolicide.
Activity: It is active against adult and young immature liver flukes (6-8 weeks old).
Mode of Action: The drug inhibits the glycolysis by
 inhibiting the glycolytic enzymes,
 3-phosphoglycerate kinase
 phosphogleromutase of F.hepatica.
 This enzymatic inhibition causes
 blockade of the Embden Myerhof glycolytic pathway in the parasite and
 deprives the fluke of essential metabolic energy.
 This ultimately leads to death of the fluke.
Dose: Cattle and Sheep: 7 mg/kg orally as drench or 4 mg/kg SC.
Safety: Safe for using in breeding and pregnant animals.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Closantel:
Closantel has a broad range of anthelmintic activity, affecting both
 endoparasites
 ectoparasites (endectocide) of animals.
The drug is effective against
 adult
 juvenile (6-10 weeks old) liver flukes,
 blood sucking nematodes,
 parasitic larvae of flies and
 some extent against tapeworms,
 mange, mites and ticks.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Mode of Action: Same as hexachloroethane.

Pharmacokinetics: It is well absorbed both orally
and SC. Administration and Dosage: Orally or SC.
Dose: Sheep and Cattle: 5mg/kg SC or 10 mg/kg
orally.
Safety and Toxicity: It has therapeutic index of 6.
It is not carcinogenic, teratogenic or embryotoxic.
 a. Drugs Against Adult Flukes
Antitrematorial Drugs

Benzimidazoles:
Albendazole:
 Highly effective against adult F. hepatica and Fascioloides
magna in sheep and cattle and used therapeutically.
 Dose: Oral: Single dose: Cattle: 10 mg/kg; Sheep: 7.5
mg/kg. For Dicrocoelium infection in sheep (Single oral
dose)
 Cambendazole: 50-100 mg/kg ;
 Thiabendazole: 100 mg/kg;
 fenbendazole: 100 mg/kg.
 b. Drugs Against Immature Flukes
Antitrematorial Drugs

Diamfenetide:
Chemically it is 3,3-bis (4-acetamidophenyloxy) ethyl
ether.
Activity: In contrast to other fasciolicides,
 less active against immature flukes
 high activity against the immature stages of liver
flukes especially in sheep
 comparatively less activity against adult flukes.
 It is inactive in cattle.
 b. Drugs Against Immature Flukes
Antitrematorial Drugs

Mode of Action:
The drug undergoes de-acylation in the liver of the host by hepatic enzymes
(deacylase) and a high conc. of an active amine metabolite is formed in the
hepatic parenchyma which is responsible for its activity.
This amine metabolite causes rapid killing of immature flukes that are also
located in the liver parenchyma until they are seven weeks of age.
The flukicidal effect is due to affecting permeability of cells
and vacuolation of tegument.
The amine metabolite is also rapidly inactivated by liver.
Therefore, the drug is less effective against adult flukes as only a small amount
of the active drug reaches to the mature flukes, located in the bile ducts.
Use: For prophylaxis of liver fluke disease in sheep and for the treatment of acute
fascioliosis (due to immature F. hepatica in liver parenchyma) in sheep.
 b. Drugs Against Immature Flukes
Antitrematorial Drugs

Administration and Dosage:

Curative: Sheep: Orally as suspension (100 mg/kg, single dose.
Subsequent use of an adulticidal drug is useful.

Prophylaxis: Combination of rafoxanide (effective against four

weeks old to adult flukes) and diamfenetide (effective against day
old to 10 weeks flukes) forms an ideal fasciolicide and is best for
chemoprophylaxis of facioliosis.
Precaution: The drug should not be given to sheep producing milk
for human consumption. It has a 7-day withdrawal period for meat.
Safety: Safe at recommended dose.
 c. Drugs Against Mature and Immature Flukes
Antitrematorial Drugs

The only drug available is the triclabendazole.

Triclabendazole:
Has a quite different spectrum of activity directed against liver flukes.
It is highly potent against liver fluke F.hepatica from day old to adult. But it has no
antinematodal activity.
Mode of Action: Not known. But it is thought to be different from that of other
benzimidazoles.
Pharmacokinetics: The major metabolites of triclabendazole are corresponding
sulphoxide and sulphone and the former is the major metabolite excreted in bile.
Administration and Dosage: Oral: Sheep and Goats 10 mg/kg; Cattle; 12 mg/kg.
Toxicity & Safety: The drug is tolerated orally in sheep and cattle. It is neither
teratogenic nor embryotoxic .
Precaution: The drug should not be given to animals producing milk for human
consumption. It has a 28 day withdrawal period for meat.
 d. Drugs Used in Paramphistomiasis
Antitrematorial Drugs

The following drugs are used effectively in the

treatment of paramphistomiasis in sheep and
cattle.
Niclosamide: 90 mg/kg, oral Resorantel: 65
mg/kg, oral
Bithionol: 70 mg/kg, 2 doses orally at 48 hours
interval.
Bithionol sulfoxide: 60 mg/kg, single dose
 e. Drugs Used in Paragonimiasis
Antitrematorial Drugs
The drugs available for treatment of paragonimiasis in
dog and cat:

Praziquantel: Drug of choice in dogs: Dose: 25

mg/kg/day for three consecutive days.
Albendazole: Cat Dose: 50 mg/kg for 21 days.
Fenbendazole: Dog: Dose: 50 mg/kg twice daily for 10
days (for adult flukes).
Bithionol: Effective at high doses, but efficacy is
unpredictable (produces undesirable side effects).