Anticestodal drugs:

• These are drugs which are used to control tapeworms
• Those drugs which facilitate expulsion of tapeworm are called taeniafuge and those kill tapeworms in situ are called taeniacides.

Classification:

Depending on the source and chemical entity, anticestodal drugs are broadly classified into following groups and subgroups:

1. Natural anticestodal compounds
2. Organic compounds: Rhizome of male fern, Kamala, Arecoline
3. Inorganic compounds: Tin oxide, Tin chloride, Lead arsenate
4. Synthetic anticestodal compounds:
5. Isoquinolones: Praziquantel, Epsiprantel
6. Salicylanilides: Niclosamide
7. Substituted phenols: Dichlorophen, Nitroscanate, Bithionol
8. Benzimidazole and pro-benzimidazole: Albendazole, Fenbendazole, Mebendazole, Oxfendazole, Febantel, Netobimin
9. Miscellaneous: Bunamidine, Resorantel, Uredophos

# Isoquinolones:

Praziquantel:

• It is broad-spectrum anticestodal and antitrematodal drug
• Slightly soluble in water and more soluble in alcohol

Mechanism of action:

• Exact mechanism is not known clearly
• It is suggested that praziquantel interferes with regulation of intracellular Ca⁺⁺ concentration

Praziquantel after taken up by parasites causes increased membrane permeability

Rapid influx of Ca⁺⁺

High concentration of Ca⁺⁺ produces contraction and spastic paralysis of parasites

Affected worms loose the grips of intestinal mucosa and expelled

• They also produce irreversible, focal vacoulisation and destruction of protective equipment. Combined effects of paralysis and integumental destruction allows easy attack by host proteolytic enzymes causing complete/partial digestion of worms in GI tract. So, whole tapeworm rarely passed in faeces.

Antihelmintic spectrum:

• It has wide range of anticestodal activity
• It is active against all species of tapeworms including Diphylidium, Taenia, Mesocestoides and Echinococcus
• It is active against all young and larval stages of tapeworm
• It is also effective against Schistosomes and Trematodes but not active against nematodes.

Pharmacokinetics:

• Rapidly and completely absorbed from G.I tract after oral administration
• Widely distributed to all body tissues including brain, CSF, muscles, intestine, peritoneal cavity and bile ducts.
• Praziquantel after absorption is re-excreted into intestinal lumen via mucosa which provides high efficacy against GI cestodes.
• They are metabolized in liver into inactive metabolites through CYP pathway and excreted mainly in urine (70-80%).
• Elimination half-life of approximately 3 hours in dogs.

Side effects/Adverse effects:

• It is safest anticestodal drug and well tolerated at recommended dose. Majority of side effects is due to host immune reactions caused by release of contents of killed parasite
• Overdosage induces vomiting, anorexia, salivation, diarrhoea and lethargy in dogs
• Pain at injection site, drowsiness and staggering gait are infrequently reported
• No teratogenic/embryonic and reproductive effect

Contraindications and precautions:

• It is not recommended in unweaned puppies or kittens
• Safe in pregnant animals
• Injection of praziquantel is not recommended in in hounds breed of drugs

Drug interactions:

• It is rapidly metabolized when given concurrently with dexamethasone, phenytoin and carbamazepine.
• Cimetidine, inhibitor of CYP 450 isoenzymes increase blood levels of praziquantel
• Phenytoin, Rifampicin and Azole antifungals may affect the metabolism of praziquantel

Clinical uses:

• It is indicated for removal of all tapeworms in dogs & cats.

Dose:

Dogs & cats: 5 mg/kg, PO

Sheep & goats: 10-15 mg/kg, PO

Horses: 0.5-1.5 mg/kg, PO

Birds: 10-20 mg/kg, PO; repeated in 10 days

# Salicylanilides:

Niclosamide:

• It is halogenated salicylanilides derivatives introduced in 1960 as taenicide

Mechanism of action:

They inhibit oxidative phosphorylation in mitochondria

Interference with generation of ATP by susceptible cestodes

Parasite gets killed due to lack of ATP

Digestion of parasite by host proteolytic enzyme

Antihelmintic spectrum:

• It has broad-spectrum of antihelmintic activity
• Effective against Dipylidium, Taenia and Echinococcus in dogs and cats
• Also effective against Moneizia in cattle, sheep and goats
• Also useful against Paramphistomum in ruminants.

Pharmacokinetics:

• It is poorly absorbed from G.I tract after oral administration. Those bulk of unabsorbed drug in lumen of intestine is responsible for taenicidal action.
• Absorbed drug is metabolized to inactive metabolites.
• Rapidly excreted from body.

Side effects/Adverse effects:

• It has wide margin of safety.
• Occasionally, mild GI disturbances (vomiting)
• No embryotoxic or teratogenic effect.

Contraindications and precautions:

• It is not recommended in young puppies and kittens
• It is generally preferred in case of T. solium infection in place of Niclosamide.

Indications:

• For treatment of various cestodes in dogs and cats

Dose:

Dogs & cats: 100-150 mg/kg, PO

Cattle: 50 mg/kg, PO

Sheep and goats: 100 mg/kg, PO

Birds: 220 mg/kg, PO; repeated in 10-14 days

# Substituted phenols:

Dichlorophen:

• It is chlorinated analogue of diphenylmethane
• Used occasionally as fungicide, antibacterial, antiprotozoal and antihelmintic

Mechanism of action:

Dichlorophen cause uncoupling of oxidative phosphorylation in parasitic mitochondria

Depletion of energy in susceptible tapeworms

Tapeworms gets killed, digested and eliminated from host

Antihelmintic spectrum:

• Narrow spectrum of antihelmintic action
• Moderately effective against Taenia and Dipylidium in dogs and cats
• Limited activity against Echinococcus and Moniezia expansa in sheep

Pharmacokinetics:

• Poorly absorbed from GI tract after oral administration
• Unabsorbed drug exerts anticestodal action.

Side effects/Adverse effects:

• Well tolerated at recommended dosages
• Occasionally vomiting and diarrhoea
• Salivation if gelatin capsules with dichlorophen is broken

Clinical uses:

• Mostly used in small animal for removal of Taenia and Dipylidium.

Dose:

Dogs and cats: 200 mg/kg, PO

Natural antihelmintic compounds:

Arecoline:

• It is obtained from the dried ripe seeds of Areca catechu (Arecanut, Betelnut).
• It is effective against several tapeworms of dogs including Echinococcus
• It is cholinomimetic compound. It first causes transient paralysis of worms and increases peristaltic activity of intestine. This helps in expulsion of worms.
• It is usually administered in enteric-coated tablets to minimize toxicity to host.
• Side effects includes emesis, salivation & exaggerated catharsis with liquid faeces.
• High doses may produce excitation and convulsion
• It is not recommended in cats due to excessive bronchial secretions and bronchoconstriction.
• It is not recommended in young puppies and kittens.

Dose:

Arecoline hydrobromide

Dogs: 1mg/kg, PO

Arecoline acetarsal

Dogs & cats: 5 mg/kg, PO