Antiprotozoal Drugs

[LamiyaJannat]

Antiprotozoal

Antiprotozoal defines as drugs acts on protozoa which are single-cell organisms. several types of protozoa causing disease in poultry. Coccidiosis is the most common protozoal disease in poultry.
The life cycle of avian coccidia and the effects of anticoccidial drugs on the life cycle. All drugs are effective during the asexual cycle only, except that diclazuril is also effective during the sexual cycle.
Second generation schizonts seem to play an important role in gut damages; drugs affecting this stage can be used to treat an outbreak.

Application

Poultry is the most of the anticoccidial drugs discussed in this section and is used in chickens.
(a) Broilers are not vaccinated against coccidia because the latent infection may retard growth.
(b) Layers are vaccinated against coccidia. Outbreaks are usually treated with a sulfonamide or diclazuril on an as-needed basis.

Drugs List

Maduramycin For Poultry

Maduramycin
Maduramicin ammonium is a monovalent monoglycoside polyether ionophore that consists of 90% ammonium salt that is a fermentation product of Actinomadura yumaense. It can be grade as two types Alpha meduramycin & beta maduramycin from its definition.

Chemical Properties
Alpha meduramycin defined as that consisting of 90% ammonium salt of a polyether monocarboxylic ionophore with -OH3 at the C5 of the ring Beta maduramycin define as that consisting of the ammonium salt of a polyether monocarboxylic ionophore with –OH group at C5 of the ring.
It is (alpha & beta) does not adversely affect egg production or egg quality.  Its causes adverse effect on growth and feathering may occur at higher doses >6mg/kg (≥6 ppm).

Mode of Action
Its interfering with the transport of K+ & Na+ ions through cell membrane → influx of positively charged ions (H+) → upset of osmotic balance  Causing disturbances mitochondrial function of intracellular coccidian (Selective E. spp.)
Endogenous at sages’ effect of Emeria species
It induces anticoccidial effect on asexual stages sporozoite, trophozoite & merozoite of selective Emeria spp of poultry.

Indication
It used as a coccidiostat for the prevention & control of coccidiosis thereby increased feed efficiency, improved weight gain, reduced the number of gut lesions & mortality in poultry. It is moderately active against gram-positive bacteria.

Pharmacokinetics
Maduramycin ionophores are metabolized in the liver and are excreted mostly into bile and feces as parent compounds and metabolites in all species. It rapidly eliminated from body two-third metabolites excreted within 2 days & total 90-95% excreated within seven days that show on the animal study.

Dosages
Meduramycin is effective for the prevention of coccidiosis @ 5mg/kg body weight.  But in higher dosages, e.g 15 mg/kg body weight may cause significant weight gain depression & 8-14 mg/kg causes reduced feed efficiency in poultry. It may cause fatal toxicity in oral dosages.
For the control & prevention of coccidiosis, it may use in replacement pullets up to 16 weeks of age; turkey poults up to 12 weeks of age.

Toxicity
Maduramycin not teratogenic, Foetotoxic, carcinogenic in an animal study. It may incompatible with Tiamulin at a higher dosage above >15-20 mg/kg body weight.

Contraindication
It is used only for the prevention of coccidiosis in broiler only not use in laying birds. It does to mix with other ionophores that causing mixing error & Ionic imbalance. It does not provide horse or other equine species which causing fatal toxicosis or somehow happened mortality.

Withdrawal period
For egg & meat 5 days. It is suggested that maduramicin is acceptable without risk for use in the poultry feed @ 5mg/kg body weight for the prevention & control of coccidiosis & fattening poultry subject to mention withdrawal period.

Storage
Maduramycin should be stored under 15 degrees Celsius. Protect from direct sunlight which became causes decreased activity of maduramycin.

Available for form
It’s available as 1% & 5% as feed coccidiostat in the market.

Salinomycin in Poultry

Salinomycin
Salinomycin is a monovalent polyether ionophore anticoccidial drugs & antibacterial properties that is a fermentation product of Streptomyces albus & carries sodiam ion (Na+). Salinomycin does not adversely affect egg production or egg quality.

Spectrum
Its act against coccidiosis associated Emeria spp & several gram-positive bacteria eg methicillin-resistant Staphylococcus aureus, staphylococcus epidermidis, Mycobacterium tuberculosis. Its acts as a anticanceral agent now a days. But not active against Fungi & mold.

Mode of action
salinomycin Na+ facilitate the transport of Na+ and H+ into cells, elevating intracellular Na+ and H+ concentrations. As a result, certain mitochondrial functions (e.g.substrate oxidations) and ATP hydrolysis are inhibited. Excess intracellular Sodium ion (Na+) concentrations accompanied by water can damage organelles as well of coccidia.

Endogenous stages effect of Emeria species
Salinomycin Na+ ionophores attack the first generation of trophozoites and schizonts.  Its active against sporozoites and early and late asexual stages of chicken.

Pharmacokinetics
Salinomycin Na+ ionophores are metabolized in the liver by cytochrome P450 enzymes, and are excreted mostly into bile and feces as parent compound and metabolites in poultry.
Following oral administration, residues are present only at very low concentrations in liver and muscle that fall below the limit of decision of the assay within 2 days in poultry.

Dosages
For prophylaxis treatment of coccidiosis 4-66g (0.004–0.0066%)/ton used in medicated poultry feed. But It is not for use with pellet binders such as bentonite clays causing severe toxicity in poultry.

Tiamulin Incompatibility
Tiamulin may interfere with the metabolism of salinomycin in chickens and cause weight suppression but not produce cardiovascular & skeletal muscle weakness in poultry. Tiamulin may interfere with the metabolism of salinomycin in chickens and cause weight suppression.

Toxicity
Salinomycin is highly toxic to turkeys at levels greater than 15g/ton and causes excessive mortality at the level recommended for use in chickens (60 g/ton).

Withdrawl Period
For meat & eggs o days.

Lasalocid in poultry

Lasalocid
Lasalocid is a not only carboxylic divalent polyether ionophore but also antibacterial & coccidiostst that is a mold fermentation product of Streptomyces lasaliensis. Its commonly used as a feed additives named lasalocid sodium (C34H53Nao8) in poultry worldwide.

Mode of action
Lasalocid Ionophores upset the osmotic balance of the protozoan cell by altering the permeability of cell membranes for alkaline metal cations. It also transports big cation called dopamine.

Endogenous stages affected of Emeria spp
Lasalocid sodium Ionophores act on against extracellular sporozoites, early tropozoite and merozoites.

Spectrum
Its acts as a broad spectrum antibacterial & coccidiostsat in poultry. It has a selective antibacterial activity in gram positive bacteria but Enteriobacteriace may naturally resistant. But it is many used coccidiostat in poultry.

Absorption
Lasalocid Ionophores absorbed orally but absorption is slower in from intestine in poultry. It is rapidly & extensively metabolized in liver & metabolites excreted through faces & bile.

Doasages
75-125g (0.0075–0.0125%)/ton medicated feed for prophylaxis of coccidiosis in poultry.

Adverse effect
Lasalocid sodium will stimulate water consumption and excretion resulting in a wet litter. With slight overdoses, it may cause depress weight gain in poultry.

Withdrawl period
For meat & eggs 3 days.

Polyether Ionophores: Resistance | Toxicity in poultry

Polyether Ionophores
It’s defined as natural & biologically active compound/ substances produced by fermentation of streptomyces or actinomadura. It destroys Emeria spp by inferring balance od most important ion specially sodium & potassium.

The polyether ionophore antibiotics were first discovered in the early 1950s and their anticoccidial activities were recognized in the late 1960s. Because of their broad spectrum of activity and the development of drug resistance to other agents, the ionophores gained widespread usage in the poultry industry soon after their introduction. by this time gradually Polyether ionophores showing their resistance & toxicity in poultry

Resistance
Because of the unique mode of action of ionophores, development of anticoccidial resistance to ionophores was difficult to produce under experimental conditions and slow to develop after clinical use in the field. In the mid to late 1980s, ionophore-resistant strains of chicken Eimeria spp & ionophore resistance is now common.
Cross-resistance between ionophores is common, although strain differences in coccidial response to specific ionophores have been demonstrated in poultry.
In general, resistance to a monovalent polyether ionophore confers some cross-resistance to other monovalent polyether ionophores, but susceptibility to monovalent monoglycoside and divalent polyether ionophores may be retained now a days.

Toxicity
Ionophores are potentially toxic for highly susceptible species in animal studies. Horses appear to be the most sensitive species, with a monensin LD50 of 1.4 mg/kg, compared with goats (LD50 26.4 mg/kg) and chickens (LD50 214 mg/kg).
Clinical signs occur from acute myocardial and muscle degeneration. Sweating, colic, and ataxia with hindlimb paresis/paralysis are also noted are commonly observed in poultry. Pathologically, focal degenerative cardiomyopathy, skeletal muscle necrosis, and congestive heart failure may be noted.
Ionophore toxicosis can be potentiated with concurrent administration of tiamulin, chloramphenicol, macrolides, sulfonamides, and cardiac glycosides in poultry.
Exposure of horses to ionophores is usually accidental, or resulting from horses gaining access to medicated feed, particularly through feed mill errors. Care should always be taken to prevent highly susceptible animals from gaining access to feeds containing these products.

Polyether Ionophores In Poultry

Polyether Ionophores
Polyether Ionophores defined as a natural & biologically active compounds/ substances produced by fermentation of streptomyces or actinomadura. It destroys Emeria spp by inferring balance of most important ion especially sodium & potassium. There are some drugs included in this class. It’s also called coccidiostat in an earlier time. It’s only used via poultry for controlling coccidiosis in poultry.

It was first discovered in the early 1950s, and their anticoccidial activities were recognized in the late 1960s. Because of their broad spectrum of activity and the development of drug resistance to other agents, the ionophores gained widespread usage in the poultry industry soon after their introduction. Most commonly used polyether ionophores generic name given below
Classification
It is classified by two class

a) Monovalent ionophores
It’s defined as Ionophoes that have valency one called Monovalent ionophores. eg monensin, narasin and salinomycin & Monovalent glycosidic ionophores (maduramicin and semduramycin)
Monensin
Salinomycin
Narasin
Maduramycin
Samduaramycin

b) Divalent ionophores
It’s define Polyether as Ionophoes that have valency two called Divalent ionophores
for example -Lasalosid
FDA approval
Polyether Ionophores
Monensin - 1971
Lasalosid - 1976
Salinomycin - 1983
Narasin - 1988
Maduramycin - 1989
Samduaramycin - 1995

Approved Dosages
Polyether Ionophores
In here % means drugs 100 gm feed, PPM means Parts per million
Monensin - 0.01–0.0121 %
Lasalosid - 0.0075–0.0125%
Salinomycin - 0.004–0.0066%
Narasin - 54–72g/T
Maduramycin - 5–6 ppm
Samduaramycin - 25ppm

Withdrawal Period
Polyether Ionophores
Monensin -00 days
Lasalosid -03 days
Salinomycin -00 days
Narasin -00 days
Maduramycin -05 days
Samduaramycin -00 days

Adverse Effect
Polyether sodium (Na+)  ionophores Increased intracellular Na+ concentrations will damage mitochondria and Golgi body into the host.
Intracellular Na+ further exchanges for extracellular Ca2+ (calcium ion), thereby increasing intracellular Ca2+ concentrations ([Ca2+].
this higher calcium ion in cardiac & skeletal muscle responsible for inducing the main toxicity of these drugs. It also increases catecholamine secretion of chromaffin cells caused jeopardize cardiac arrhythmia. It increases various hormone secretions in endocrine cells.

Source: PoultryMania