Anticoccidial drugs

                                       Anticoccidial drugs

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Anticoccidial drugs are agents that are used for the prevention and/or treatment of coccidiosis in chickens, cattle, sheep, goats, dogs, cats and some other species. Anticoccidial drugs either inhibit the growth of intra-cellular coccidia (coccidiostates) or destroy coccidia during their development (coccidiocidal). Pharmacological aspects of important anticoccidial drugs are discussed in the following lines.

 

1. Amprolium: It is a structural analogue of thiamine (vitamin B₁) and it is soluble in water and slightly soluble in alcohol. It is hygroscopic in nature. It mimics the action of thiamine and competitively inhibits thiamine utilization by the coccidia. It mainly acts on the early first generation schizonts preventing their differentiation of merozoites. Prolonged high doses of Amprolium can cause thiamine deficiency in the host which can be reduced or reversed by addition of excessive thiamine in the feed. It is effective against Eimeria tenella, Eimeria acervulina and Eimeria bovis. It has comparatively less efficacy against intestinal coccidia than ceacal coccidia. It is often combined with folic acid antagonists like Ethopabate or Sulphaquinoxaline to improve the spectrum. Its action is predominantly on the first generation schizonts, Amprolium has significant prophylactic properties. Excessive doses of Amprolium may give rise to encephalomalacia in sheep and inhibition of erythrocyte synthesis in calves. Amprolium toxicity can be treated by administering thiamine. It should not be concurrently administered with thiamine because of antagonistic effect. Amprolium is mainly used for the treatment and prevention of coccidiosis in poultry and cattle. It is commercially available as a soluble powder for addition to drinking water or as a premix for mixing with feed. It has zero day pre-slaughter withdrawal time.

 

 

2. Ionophore antibiotics: They are widely for the prevention of coccidiosis in livestock and poultry. The ionophores have affinity for cations principally sodium, potassium and calcium and form lipophillic complexes with them. The ionophore-cation complex renders cell membrane permeable to cations allowing their excessive entry inside the cell. The increased intracellular cation concentration interferes with certain mitochondrial functions. Alterations in membrane integrity and internal osmolarity may also upset the osmotic balance of cell affecting cellular reactions that depend on specific ions balance. Different ionophores may have different affinities for cations i.e., monovalent ionophores form complexes primarily with sodium or potassium ions while divalent ionophore form complexes with calcium, some ionophores may have affinity for both type of cations. As they affect mainly the sporozoites and merozoites, ionophores primarily have a prophylactic value. Equines and turkeys are highly susceptible to ionophores toxicity (even at very low doses) manifested by several cardiovascular effects and fatalities. High concentration of calcium in cardiac and skeletal muscles is responsible for toxic effects of ionophores in animals. Hence their use is contraindicated in equines. Ionophores are primarily used for the prophylaxis of coccidiosis in chicken and cattle and they are generally not recommended for treating established infections.

(a) Monensin: It is a monovalent ionophore which is also used as a growth promoter in cattle. Hoses, turkeys and guinea pigs are very sensitive to Monensin and must not have access to Monensin-containing feeds. The pre-slaughter withdrawal period for Monensin is 72 hours in chickens but no withdrawal period is required in goats.

(b) Lasalocid: It is a divalent ionophore that is used for the prevention of coccidiosis in poultry and livestock. It can interfere with the metabolism of divalent cations and affect excretion of water causing a wet litter at high doses.

(c) Salinomycin: It is a monovalent ioniphore but unlike Monensin and Lasalocid no pre-slaughter withdrawal time is required for its administration.

(d) Maduramycin: Maduramycin is a monovalent ionophore and its pre-slaughter withdrawal period is 5 days.

 

3. Folic acid antagonists: These include Sulphonamides and Diaminopyrimidines.

(a) Sulphonamides: Although the use of Sulphonamides has declined in chickens mainly due to the development of drug resistance and availability of better drugs, they still occupy an important place in the treatment of small animal and ruminants coccidia. Presently, they are commonly used in combination mixtures (often with Amprolium) and are considered effective when clinical signs are already evident. Inhibition of PABA by Sulphonamides impairs protein synthesis, metabolism and growth of susceptible coccidian. Sulphaquinoxaline is a Sulphonamide used primarily as an anticoccidial drug. It has good activity against the intestinal species of coccidian than caecal coccidia. The pre-slaughter withdrawal period for Sulphaquinoxaline is 5 days in chicken. A number of other Sulphonamides are used in veterinary practice for the treatment and prevention of coccidiosis in chicken, dogs, cats and ruminants. These include Sulphadimidine and Sulphadiazine etc.

(b) Diaminopyrimidines: These agents are highly selective inhibitors of dehydrofolate reductase, an enzyme involved in synthesis of folic acid. These drugs are mostly used in combination with Sulphonamides (as potentiated Sulphonamides), but are also available alone for therapeutic uses. Diverdine is mostly used to potentiate Sulphadimidine while Trimethoprim is used in combination with Sulphadiazine (in 1:5).

 

4. Ethopabate: It is a substituted benzoic acid anticoccidial drug that resembles structurally with PABA and interferes with folic acid synthesis. It is particularly effective against E. burnetti and E. maxima. It is mostly used in combination with Amprolium. Combinations of Amprolium and Ethopabate or Amrpolium, Sulphaquinoxaline and Ethopabate provide synergistic action and cover most of intestinal and caecal species of Eimeria.

 

Pre-slaughter withdrawal period for some common anticoccidial drugs in broilers
Drug	Pre-slaughter withdrawal period
Amprolium	0
Salinomycin	0
Monensin	72 hours
Decoquinate	3 days
Sulphaquinoxaline	5 days
Clopidol	5 days
Lasalocid	5 days
Maduramycin	5 days
Toltrazuril	21 days

 

5. Quinolones: As rapid emergence of resistance to quinolones has become a problem so they are mainly used in shuttle programs. They are primarily coccidiostatic drugs and they act on sporozoite stage of coccidia and thus inhibit coccidial respiration by interfering with cytochrome C-mediated electron transport system in mitochondria. Quinolones are selective in action because the inhibition of electron transport system occurs in coccidial mitochondria but not in the host.

Decoquinate: It is a quinolone derivative coccidistate used in poultry, goats and cattle. As it is active against invading sporozoites only and has no activity against adult coccidia, it possesses mainly prophylactic activity. The pre-slaughter period is 3 days when used in broilers.

                                                                               

6. Clopidol: It is a pyridinol compound that inhibits electron transport system within the coccidial mitochondrian. Like quinolones its action is purely coccidiostatic. Clopidol is approved for prophylaxis of coccidiosis in chickens and rabbits but not approved for laying birds as it is transmitted to the eggs. Pre-slaughter withdrawal period is 5 days in chicken.

 

7. Toltrazuril: It is a broad spectrum triazinone antiprotozoal drug that acts by inhibiting the nuclear division of schizonts and microgametes. In addition to coccidia, Toltrazuril is also active against some other protozoa like sarcocystis causing equine protozoal myeloencephalitis) and hepatozoon (causing canine hepatozoonosis). Toltrazuril appears to be compatible with other anticoccidials and antibiotics however it persists for prolonged time in host tissues and thus has a longer withdrawal period of 21 days.

 

8. Furazolidone: Furazolidone is a nitrofuran with antibacterial activity. However it also possesses anticoccidial action and is occasionally used for the treatment of coccidiosis in small animals.

 

9. Tetracyclines: In addition to antibacterial properties, some Tetracyclines like Oxytetracycline and Chlortetracycline also possess anticoccidial action. These agents are generally added in feed and are used for the prophylaxis and treatment of coccidiosis in poultry.