Anticoccidial drugs:

• These are agents used for prevention and control of coccidiosis in chicken, cattle, sheep, goats, dogs, cats, and other species.
• They exert their action either by inhibiting or arresting the growth of intracellular coccidia (coccidiostat) or destroying coccidia (coccidiocidal).
• These drugs act at different stages of coccidia life cycle and interrupt asexual, sexual or both stages.

Classification:

Based on mechanism of action and chemical structure, these drugs are classified as follows:

1. Thiamine (Vit.B₁) antagonist: Amprolium
2. Ionophores/Polyether antibiotics: Monensin, lasalocid, salinomycin, narasin, maduramicin and semiduramicin
3. Folic acid antagonist:
4. Sulphonamides: Sulphaquinoxaline, sulphaguinidine, sulphadiazine, sulphadimethoxine, sulphamethoxazole and sulphachlorpyridazine
5. Pyrimidines: Trimethoprim, Pyrimethamine, Diaveridine, Ormetoprim

• Substituted benzoic acid: Ethopabate

1. Potentiated sulphonamides: Trimethoprim-sulphadimethoxine, Trimethoprim-sulphadiazine, Ormetoprim-sulphadimethoxine, Pyremethamine-sulphadoxine, Pyremethamine-sulphadiazine
2. Quinolones: Decoquinate, methylbenzoquate, buquinolate
3. Pyridinoles: Clopidol
4. Guanidines: Robenidine
5. Nitrobenzamides: Dinitolmide and aklomide
6. Carbanilides: Nicarbazin
7. Quinazolines: Halofuginone
8. Benzeneacetonitriles: Diclazuril and clazuril
9. Triazinones: Toltrazuril
10. Benzylpurines: Arprinocid
11. Miscellaneous:
12. Nitrofurans: Furazolidone
13. Tetracyclines: Oxytetracycline and chlortetracyclines

Amprolium:

• It is structural analogue of thiamine (vit. B₁)
• It occurs as white crystalline, odourless powder, soluble in water and slightly soluble in alcohol.

Mechanism of action:

Amprolium blocks thiamine receptor in parasite

No uptake of thiamine

Prevention of synthesis of carbohydrates. Kreb’s cycle gets stopped.

Depletion of ATP production and cellular respiration

• It acts mainly on early 1^st generation schizonts, preventing differentiation of merozoites.
• It also suppress the sexual stage and sporulation of oocyst.

Antiprotozoal spectrum:

• It has good activity against Eimeria tenella and acervulina in poultry and moderate activity against other species.
• Effective against bovis and E.zurnii in cattle.

Resistance:

• Develops rapidly in susceptible coccidia.

Pharmacokinetics:

• Poorly absorbed after oral administration
• Other pharmacokinetics data are not available in domestic animal

Side effects/Adverse effects:

• Depression, anorexia, diarrhoea in dogs. These signs are infrequent and dose-related.
• Overdosage produce encephalomalacia in sheep and inhibit erythrocyte production in calves.

Contraindications:

• It should not be used for over 12 days in puppies.

Indications/clinical uses:

• In prevention and treatment of coccidiosis in poultry and cattle.
• Also used in control of coccidiosis in dogs, swine, sheep, and goats.
• Commonly used in combination with sulphonamides or ethopabate.

Dose:

Cattle: 5mg/kg, PO, for 21 days as prophylaxis

Dogs: 100-200 mg(total), PO, in food or water for 7 days

Cats: 60-100mg (total), PO, once daily for 7 days

Cattle: 10mg/kg, PO, for 5 days in feed or water

Swine: 25-65 mg/kg, PO, 1-2 times daily for 3-4 days

Sheep and goat: 55mg/kg, PO, once daily

Poultry: 0.002-0.024%, PO in water for 3 days

Polyether ionophores/Polyether Antibiotics:

• These are lipid soluble molecules synthesized from microorganisms.
• These are widely used in the prevention of coccidiosis in poultry and livestock.
• Important drugs of this class includes monensin, lasalocid, salinomycin, narasin.

Mechanism of action:

• Ionophores are basically ion transporter which facilitate transport of ions across biological membranes.
• Ionophores bind with cations. They forms a complex in such a way that ion exist in polar interiorly and exteriorly remains non-polar and lipophilic

Due to lipophilic nature of exterior part, they diffuse across cell membrane in excessive amount

They disturbs the ionic imbalance of normal cell membrane i.e. extracellular medium is high in sodium and low in potassium and in intracellular medium this is reverse.

High intracellular cation interferes with mitochondrial function (substrate oxidation) and ATP hydrolysis in susceptible bacteria.

• They affect sporozoites and merozoites in early asexual stage of parasite development.

Antiprotozoal spectrum:

• They are effective against all species of Eimeria in chickens, cattle, and sheep

Resistance:

• Resistance usually develops gradually or donot develop due to their unique mechanism of action.

Pharmacokinetics:

• Not available in domestic animal

Side effects/Adverse effects:

• Equines and turkeys are more susceptible to ionophores, even at low doses.
• Severe cardiovascular effects and fatalities in horses and other equines.
• High concentration of Ca⁺⁺ in cardiac and skeletal muscle produce toxic effects in animals.

Contraindications and precautions:

• In equines
• It shouldnot be mixed with other anticoccidials.
• They shouldnot be given 7 days before or after administration of tiamulin.

Indications/Clinical Uses:

• It is primarily used for prophylaxis of coccidiosis in chickens and cattle.
• It is used as growth promoters in cattle.
• It is not recommended for treating established infections.

Dose:

Monensin:

Chickens: 100-200g/tonne feed

Cattle: 100-360mg/animal/day

Goats: 20g/tonne feed

Lasalocid:

Chickens: 75-125g/tonne feed

Cattle: 1mg/kg, PO, once daily (max dose 360mg/animal/day)

Sheep and goats: 30g/tonne feed daily

Folic acid antagonist:

Sulphonamides:

• These were the first group of drug found to have anticoccidial activity.
• They have been widely used for the treatment and prevention of coccidiosis in various species.
• Their use in chickens have been declined due to development of drug resistance and availability of better drugs. They are still used to treat coccidia in small animals.
• Presently they are mostly used in combination with amprolium.

Mechanism of action:

• They act by blocking synthesis of folic acid.

Sulphonamides blocks utilization of PABA. Inhibit dihydropteroate synthase

Prevention of union of PABA with pteridine to form dihydropteroic acid

Inhibition of dihydropteroic acid further inhibits synthesis of dihydrofolic acid

Inhibition of synthesis of tetrahydrofolic acid (reduced form of folic acid)

Parasite metabolic process alters and ceases to multiply

• They are effective against second generation schizonts and have lesser activity against early asexual and sexual stages of coccidia.

Dose:

Sulphaquinoxaline

For prophylaxis:

Chickens and turkeys: 125ppm,PO daily in drinking water or feed for 4 weeks

Cattle: 13mg/kg, PO

For treatment of coccidiosis:

Chickens and turkeys: 500 ppm, PO, daily in drinking water for 8 weeks

Lambs: 0.025% in drinking water for 2-5 days

Pyrimidines:

• These are chemically related to pyrimethamine which inhibit dihydrofolate reductase. This enzyme is involved in synthesis of folic acid.
• Trimethoprim is used alone also but it is combined with sulphonamides.

Trimethoprim:

• Pyrimidine derivative and chemically related to pyrimethamine.

Mechanism of action:

They block enzyme dihydrofolate reductase

Inhibition of synthesis of protozoal tetrahydrofolate

Synthesis of folic acid stops which plays important role in protein synthesis

Pharmacokinetics:

• Readily absorbed after oral administration
• Peak plasma level occurs within 1-4 hours after dosing.
• They are widely distributed in body tissues and fluids.
• Excreted mainly unchanged via kidneys in urine and also in bile.

Side effects/Adverse effects:

• Myelosuppression
• Nausea, vomiting and skin rashes
• Megaloblastic anemia

Indications:

• It is used in treatment of coccidial infection.

Quinolones:

• These are important groups of anticoccidial drugs introduced in mid-1960s.
• They are insoluble in water, poorly absorbed from G.I tract and non-toxic to host.

Mechanism of action:

• They are primarily coccidiostatic.
• They act on sporozoite stage of coccidia.

Inhibition of cytochrome C mediated electron transport system in mitochondria

Inhibition of coccidial respiration

Resistance:

• Drug resistance to quinolone develop rapidly.

Decoquinate:

• These are quinolone derivative coccidiostat insoluble in water.
• They are active against several species of Eimeria in poultry, cattle, goats.
• They are poorly absorbed from G.I tract.
• Rapidly distributed into blood and tissues.
• It is used mainly for treatment and prophylaxis of coccidiosis in calves and lambs, chickens, cattle, goat, sheep
• It is also used for toxoplasmosis in sheep.
• It is not approved for turkeys, laying and breeding birds or lactating animals.

Doses:

For treatment:

Calves and lambs: 1mg/kg, PO, for 28 days

Sheep and goats: 0.5mg/kg, PO

For prophylaxis:

Cattle, calves, goats, and sheep: 0.5mg/kg, PO, for 28 days

Broiler chickens: 20-40g/tonne feed

Pyridinoles:

Clopidol:

• It is sole member of pyridinoles marketed as anticoccidial agent.
• It acts against sporozoite stages and halts their development in host enterocyte.
• It acts by inhibiting electron transport system within coccidial mitochondrian.
• It is purely coccidiostatic against wide range of Eimeria species.
• It is used for prophylaxis of coccidiosis in chickens and rabbits.
• It is contraindicated in laying birds as it is transmitted to eggs.
• Overdosage of clopidol is associated with inappetence in treated birds.
• It should not be mixed with other coccidiostats, except methylbenzoquate.

Dose:

Broilers, chickens, and game birds: 125g/tonne feed

Rabbits: 200g/tonne feed

Guanidines:

Robenidine:

• It is guanidine derivative synthetic anticoccidial drugs.
• It is available commercially as hydrochloride salt.

Mechanism of action:

• They act by inhibition of oxidative phosphorylation in protozoa. Due to inhibition of oxidative phosphorylation, ATP production ceases. Due to decrease in ATP, protozoa cannot divide.
• It mainly affect late first-generation and second-generation stage schizonts.

Antiprotozoal spectrum:

• It is both coccidiostat and coccidiocidal.
• It is effective against all poultry coccidia and rabbit intestinal coccidia.

Pharmacokinetics:

• Not well documented.

Side effects/Adverse effects:

• Well tolerated at recommended dosages.
• It imparts unpleasant taste to flesh of broilers if therapy is not terminated 5 days before slaughter.

Contraindications and precautions:

• It should not be used in laying birds.
• It shouldnot be mixed with other anticoccidials.

Dose:

Broiler chickens and turkeys: 30g/tonne feed

Rabbits: 50-65g/tonne feed

Carbanilides:

Nicarbazin:

• It is an equimolar mixture of 4,4-dinitrocarbanilide and 2-hydroxy-4,6- dimethyl pyrimidine.

Mechanism of action:

• Exact mechanism of action is not known.
• It is suggested that it acts via inhibition of succinate-linked nadide reduction and energy dependent transhydrogenase and accumulation of calcium in presence of ATP.
• It acts primarily on second-generation schizonts.

Antiprotozoal spectrum:

• It has both coccidiostat and coccidiocidal properties, but it is mainly coccidiostat.
• Effective against all Eimeria species.

Pharmacokinetics:

• After oral administration, DNC and HDP are absorbed separately from G.I tract.
• DNC is absorbed rapidly but disappear more slowly from tissues than HDP.

Side effects/Adverse effects:

• It may bleach brown-shelled eggs.
• Mottled egg yolks
• Reduce eggshell thickness
• Depressed egg weight
• Hatchability reduced
• Impairment of products.
• Medicated birds are susceptible to heat stress.

Contraindications and precautions:

• In laying and breeding birds.
• It shouldnot be used during hotter months.
• It shouldnot be mixed with other anticoccidials.

Clinical uses/Indications:

• In prevention of coccidiosis outbreak.
• In shuttle programmes.
• It is not recommended for treatment of coccidiosis.

Dose:

Broiler chickens: 100-125 g/tonne feed given continuously

Replacement birds: 125g/tonne feed upto 16 weeks of age

Quinazolines:

Halofuginone:

• Potent and effective against most species of Eimeria in poultry.
• It has both coccidiostatic and coccidiocidal effects.
• It inhibits early asexual stages of coccidia.
• It is used in prevention and treatment of coccidiosis in chickens and turkeys.
• Side effects include skin ruptures, irritation to skin or eye, inappetence.
• Toxic to fish and other aquatic animals and must not be fed to water fowl.

Dose:

Chickens: 3g/tonne feed

Turkeys: 3g/tonne feed