Introduction

The study of pharmacology in poultry and, especially, medicine application, requires a previous knowledge about the physiological characteristic, the breeding systems and the commercial use of this specie. Birds present large differences compared to other animals.

– Birds have some different physiological characteristics compared to mammals. It has an impact on their reaction to infections and medications:

• Birds do not have a regional lymph node system, which facilitates the diffusion of microorganisms through the circulatory system (septicaemia).
• Their physiological temperature is 41Âş C same to the febrile state of mammals. That is, they are animals that live in a constant feverish state.
• As a result, septicaemia occurs apparently asymptomatically, the period between infection and the first symptoms is much longer, between 10 and 15 days, than in mammals.

– The poultry industry development has promoted alterations in bird biology:

• A geneticselection has been made aimed at increasing the growth rate and prolonging the laying period between two periods of broodiness. This selection has been based on the accumulation of genes favourable to the objective, by consanguinity techniques with the fixation of grandmother lines and with hybridization of lines in the production of commercial lines.
• These geneticimprovement techniques have an important negative impact on the immune system of birds.
• Meat production parameters improvement implies an extra effort for the intestine and liver.
• Egg productionparameters improvement implies an extra effort of the liver and mineral metabolism.

– Finally, management in farms suppose significant changes in the design and preparation of avian food:

• Birds access to fresh vegetables is prevented, especially, to sprouted seeds, buds of trees, small insects… They can contain substances that, even in small quantities, are necessary for avian physiology. In this regard, pronutrientshave been defined.
• Poultryproduction have been universalized to serve the growing protein demand of a population of 7.000 million habitants (although not everyone has access to a regular and quality nutrition). Consequently, industrial agriculture has been situated in large production areas far from consumption areas (farms) and the consequent need of mechanization (grain breakage), collection chain and international transport (fungal, bacterial contamination and insect infestation). Therefore, undesirable substances appear in the food
• The high density of birds in farms increases the number of microorganisms â€�passes’ among animals of the same species. This is one of the mechanisms which can increase the pathogenicity of microorganisms towards this animal species.

Therefore, selection, industrialization and management are the origin of genetic, physiological and nutritional deficiencies which generate mass pathology. We should know these pathologies to prevent it through pharmacological treatments.

Know the pathology

To apply the pharmacology correctly, it is essential to know the pathology and, more specifically, the causes of disease. The following tables are statistics collected by teams of pathologists in different geographical areas for long periods of time.

Etiology

Table 1: 1970-1989 study of the causes of the pathology in Mississippi

MISSISSIPPI

¹Unknown., pathologies of unknown etiology.
Broiler diseases in Mississippi.: Q. Surumay, J.P. Thaxton and C.R. Sadler

• Table 2: Infectious diseases diagnosed in broilers in Australia (1977-1983)

AUSTRALIA

^ 1Mbdad:  morbidity; ²-: incidence not known; ³Neg.: Negligible;
Diseases diagnosed in broiler chicken flocks in Victoria, Australia, 1977 to 1984

• Table 3: Noninfectious diseases diagnosed in broilers in Australia (1977–1983)

AUSTRALIA

Mb: morbidity; Neg.: Negligible; -: Unknown incidence; Mt.: Mortality.
Diseases diagnosed in broiler chicken flocks in Victoria, Australia, 1977 to 1984

Main poultry pathologies

• Table 4: More frequent pathologies according different sources

 

• Table 5: Isolated microorganisms in samples of birds with different pathologies (Anditra Laboratorios)

EUROPE

Data extracted from Anditra diagnostic laboratory

Microorganisms found in higher percentage are those usually non-pathogenic, different staphylococci and E. coli. Koch’s postulates must be applied to distinguish pathogens (20-25%) from the opportunists (75-80%). Undetermined causes occupy 40-45%.

Conclusions

The following conclusions can be drawn from the reviews of the trials carried out at U.S., Australia, Europe and a global synthesis about the pathology in poultry:

1. It is necessary to screen the analytical results. In many occasions banal germs are isolated that should not be considered as a main cause of a disease. For this, techniques based on Koch’s postulates should be implemented, so that, the statistics will be related only to pathogens germs.
2. The main problems diagnosed are:

Summary of the tables 2 y 3:

The highest percentage corresponds to pathologies whose cause is complex. Together with those caused by handling and classified as “other” are almost 50% of the total.

The most important groups are:

• COMPLEXES – 38,86%
  Two or more processes are involved (virus+bacteria, mycoplasma+bacteria, protozoa+bacteria, management+virus, weather+nutrition).

• BACTERIALS – 17,47%
  Each bacterium grows in an organ where it finds the necessary nutrients for its metabolism.

• VIRAL – 10,93%
  Realated to geographical areas (migratory routes, extreme weather).

• METABOLICS – 8,76%
  Related to the extra effort of the liber, gut and calcium metabolism.

• PROTOZOARY – 8,46%
  Mainly Eimerias, Cochlosomas and Trichomonas.

• UNKNOWN ORIGIN – 7,14%
  Sporadic processes which appear without apparent cause and disappear alone.

• MANAGEMENT – 6,73%
  Linked to breeding conditions (birds/m², cm from drinking fountain, cm from the feeding…) or facilities (ventilation, temperature…).

This knowledge allows to adopt measures to improve management, nutrition and pharmacological measures, especially, preventive therapy programs that reduce medication consumption and increase its effectiveness.

Know other factors related to pharmacology

The appearance and diffusion of diseases among birds is related to anatomic and physiological characteristics. These factors, together with pathology, are important to analyse in order to apply an appropriate pharmacological treatment.

Factor related to avian anatomy and physiology

• Anatomical proximity between air sacs

Anatomical proximity between air sacs, liver, ovary and intestines that allow the transmission of germs among the organs mentioned. This is the reason for the diffusion of E. coli through gut, air sacs and liver (CRD) and in intestine, liver and ovary of Salmonella.

• Presence of nutritive yolk in the first days

Presence of nutritive yolk in the first days. Allow the spread of Salmonella, from carrier chicks to healthy chicks, through the excrement.

• High physiological temperature

High physiological temperature Initially used as a mechanism to fight infections in the first homeothermal animals, it is also the cause of the long incubation period of certain bacterial poultry infections.

• Absence of lymph node system

Absence of lymph node system, as the one developed by mammals, is the cause that many poultry infections are septicemic rather than regional.

Some of the characteristics described, allow to achieve early diagnoses of respiratory infections of a septicemic nature, frequent in 30-35 days old birds, since the causative microorganisms can be isolated in the bone marrow, between 10 and 15 days before causing clinical symptoms.

This knowledge of poultry therapy allows the use of specific antibiotics selected by antibiograms on a preventive basis if mortality 1⁰/00 is exceeded for two days.

Factors related to the active ingredients

The development of the poultry industry does not correspond with the development of knowledge in avian pharmacology. Most treatments and especially those aspects related to the dose and safety are based on empirical data derived from individual clinical experience.

It is common to use extrapolating data from experimental reports on mammals, as well as the use of products in treatments, that are not listed in the existing documentation, but based on clinical experience.

It is necessary to incorporate specific data for poultry in essential texts such as veterinary pharmacopoeia, obtained by applying the scientific method.

It is also necessary the collaboration of poultry clinicians in the development of clinical and pharmacological trial protocols, for the study of the pharmacological and toxicological parameters of each molecule, both in birds and in experimental animals.

In the current situation, the clinical veterinarian should strive to find basic information on the molecules he is using, related to pharmacodynamics, pharmacokinetics, minimum inhibitory concentrations, dose/weight/metabolism ratios of different avian species and spectrum of activity.

The use of different quinolones, depending on whether they are used for the treatment of respiratory processes or for the treatment of salmonellosis, is a useful example, since their renal elimination or through the enterohepatic circuit is a decisive knowledge to recommend in each case the more suitable active ingredient.

Factors related to the route of administration

The route of administration can fundamentally influence the stability of the active substance between application and ingestion, as well as the final dose of the active substance that reaches the bird.

The most used routes of administration in poultry industry are: oral through drinking water, oral through feed, subcutaneous parenteral and intramuscular parenteral. On the contrary, the intravenous airway and parenteral route are the least frequent routes due to their difficulty.

• In the oral route through the drinking water

In the oral route through the drinking water, the stability of the active substance in water and the variation in the consumption of drinking water due to the ambient temperature acquire great influence: it can increase up to 6% for each Celsius degree that exceeds 20°C.

Fungal proliferation should be taken into account, especially polymer producing yeasts in the presence of some lactose-containing excipients that clog waterways or the presence of other products that do not dissolve well.

• The administration through the feed

The administration through the feed is influenced by the feed consumption, homogeneity of the mixture, stability of the drug during the process of preparation of the feed and, from its preparation to its consumption by the birds, and to the fixation in other feed components.

These aspects should be taken into account in medications carried out during rationed feeding phases in layers or breeders in the rearing phase, in the use of probiotics-enzymes sensitive to heat treatments or conservative agents and in the use of tetracyclines that can be fixed with calcium salts.

• In parenteral administration

In parenteral administration, the need for asepsis in instruments and in the use of sterile solvents should be taken into account, avoiding the widespread practice of using non-sterile drinking water or disinfected with chemical agents, which may have an oxidizing effect on the active substance.

• In subcutaneous parenteral administration

In subcutaneous parenteral administration, consider the possibility that the drug physically reaches the air-sacs extensions. It is important that the application is performed in the upper cervical area.

• Intramuscular parenteral administration

Intramuscular parenteral administration is frequently performed in the pectoral muscles and extremities. It should be borne in mind that the drug may cause local necrosis that affects subsequent marketing, either in single application or by repeated application.

When the active substance is nephrotoxic or excreted by the kidney, it must be applied to the pectoral musculature since the special anatomy of the renal portal system prevents correct diffusion through the body.

Factors related to management

Among the daily management guidelines on a poultry farm, the lighting program is the factor that has the greatest influence on oral medications through drinking water and feed by creating a time difference in the rhythm of administration.

The prescribing veterinarian must take into account the pharmacological concept of half-life plasma (time in which the concentration of a drug in the plasma is reduced to 50%). If this time is short, and the hours of darkness are longer, it is possible that for a few hours each day, the plasma concentration of the drug is lower than its effective concentration. Therefore, the prescribing veterinarian must know the minimum inhibitory concentration of chemotherapies that he recommends and adopt an administration schedule adapted to the light rhythm.

Factors related to the pharmacological specialty

Every pharmacological specialty is composed of active ingredients, non-active components necessary to achieve the pharmaceutical form and excipients. The non-active components and excipients can positively or negatively influence the pharmacological characteristics of the active ingredient already described above, especially absorption and stability. Veterinary drug manufacturing companies should report the characteristics of their preparations to clinical veterinarians, as they may differ from the characteristics of the active substance due to the indicated influences.

At this point, we will introduce the drug associations that constitute the majority of veterinary pharmacological specialties. There is no point in the discussion between the use of monodrugs and the use of associations, nor does the justification of associations with multiple active principles. Clinical practice requires the use of specialties composed of pharmacological associations, but it is essential that they are sufficiently documented, due to the existence of synergies demonstrated by the increase in the spectrum of activity or by lower dosage.

Taking into account the etiology, knowing the spectrum of activity and the implications due to associations or non-active principles, the clinical veterinarian can decide whether it is advisable to use a simple preparation or the simultaneous use of monodrug preparations.

Our experience is positive when two synergistic chemotherapeutic agents are used together with a symptomatic molecule. However, two conditions must be met: synergism must be demonstrated and the symptomatic molecule should not favor the diffusion of the infection (corticosteroids).

Due to the action spectra it is recommended to classify into therapeutic groups:

• Broad-spectrum chemotherapeutic agents: beta-lactams, fluorquinolones, sulfonamides and tetracyclines.
• Chemotherapeutics against G-: aminoglycosides, first-generation quinolones
• Chemotherapeutic against G +: macrolides

Among these groups, the synergism between quinolones with beta-lactams and aminoglycosides is well recognized; as well as erythromycin with sulfonamides and aminoglycosides, and sulfonamide with doxycycline.

Regarding symptomatic products, it is advisable to use pyrazole derivatives (antipyrine and phenylbutazone) and indole derivatives (indomethacin), but this last group has some liver toxicity.

Factors related to productive needs

The decision to apply treatments when it is essential is widely spread. It should be taken into account that in this situation the growth of the birds is affected and, therefore, the disease has already damaged the economy of the poultry industry, although the mortality rate is not very high.

Our criterion is to perform therapeutic action when mortality exceeds 1 per thousand daily for two consecutive days. For this, it is necessary to have the microbiological analysis carried out in advance as indicated in the section of avian anatomy and physiology.

Factors related to public health

Finally, to establish a pharmacological treatment, the clinical veterinarian must consider the knowledge related to the incidence of drug residues on public health.

The three international reference laws in force in the European Union, North American FDA and Japan define as residue any active substance or derived metabolite contained in animal feed intended for human consumption and, especially, in muscle, liver, kidney, fat and eggs.

In these laws, residues for additives (preservatives, antioxidants and probiotics) have been omitted, since their main toxicological characteristics (ADI, effects of their single administration and repeated administration) have been studied prior to their incorporation in the positive list of additives. Maximum amounts (MRLs) that cannot be exceeded have been set for each active substance and food. With this, the producing laboratories are obliged to establish for each specialty a specific withdrawal period for birds derived from the pharmacological characteristics of the active principle and the influence that the excipient and non-active principles used to achieve the pharmaceutical form have on them.

The clinical veterinarian must establish the treatments considering these withdrawal periods. This new situation, although it improves the quality of the food we consume, presents a series of difficulties that must be pointed out:

• There are difficulties in establishing the bird sacrifice calendar, since it depends more on the needs of the slaughterhouse than on the dates related to the withdrawal period.
• The production process and the market price become more expensive or business profits are reduced. The selection criteria that until now could be based only on a therapeutic criterion has totally changed.

The way to therapeutic prevention

From the criteria mentioned above, there is a need to change the mentality and clearly opt for the establishment of pharmacological treatment that we can qualify as preventive. For this we must collaborate clinicians with laboratory analysts and nutritionists.

The genetic development of the current poultry lineages and the increased presence of trichothecenes in cereals produces a significant gap between the real vitamin needs and the tables of standard needs, especially of the vitamin group B and vitamin C. In our opinion, an important part of the current avian pathology is related to these vitamins and immune deficiencies (Marek and Gumboro among others). Therefore, collaboration with the nutritionist is necessary in order to have vitamin-rich raw materials or incorporate vitamin supplements into therapeutic programs.

Another element to consider is the information obtained through systematic analyzes that, in addition to preventive information, provide important statistics. This information studied by climatic seasons, allows to obtain an epidemiological map of antibiotic sensitivities of great value when treatments should be decided.

Therapeutic plans and their assessment

From the basic elements studied in the previous sections, we can organize a therapeutic plan in the following phases:

• Formulate balanced feed

Formulate balanced feed rich in vitamins of group B, and vitamin C.

• Incorporate mycotoxin binders in feed

Incorporate mycotoxin binders in feed that maintain the intestinal mucosa in good condition

• Perform systematic analysis on certain days of the bird’s life

Perform systematic analysis on certain days of the bird’s life. For example, in broilers, serological tests should be performed at day 1 of life (Mycoplasma and S. enteritidis), as well as bacteriological and antibiograms at 15 days of bone marrow and infraorbital sinuses, and again serological analysis at the end of bird’s life (Mycoplasma).
Administer macrolides with aminoglycosides in the first three days of life and repeat at fourteen days of life.

• Administer treatment between 24-28 days

Administer treatment between 24-28 days, if mortality increases above 1 per thousand, according to the results of the analysis of day 20.

• Administer symptomatic treatment, if necessary, beyond day 35

Administer symptomatic treatment, if necessary, beyond day 35 with or without antibiotic depending on the severity of the process and taking into account the residues.

• Finally, we must systematically assess the efficiency index

Finally, we must systematically assess the efficiency index of each breeding (EI = 350-450) in order to endorse the criteria we had chosen.

The following tables show the results of preventive therapeutic programs.

Therapeutic program for the prevention of mycoplasmosis and secondary infections: field results

It is important to evaluate the sensitivity of microorganisms against different antibiotics.

Table M1 (VILAFRANCA DEL PENEDES)

This table indicates the activity in vitro against M. gallisepticum and M. sinoviae. However, such activity cannot be extrapolated in vivo due to the circumstances of each product in its pharmacodynamics and pharmacokinetics.

Table M2 (S. JOAN DE MEDIONA – BARCELONA)

This table indicates the in vitro activity of antibiotics against 5 genera of bacteria. The data can be extrapolated to intraintestinal activity in a preventive program.

Evaluate the productive results after the application of a preventive therapeutic program.

Table M3 (FELANTIX – MALLORCA)

No significant modifications were observed when Tylosin is applied in the first three days of life, except for a slight increase in average weight (2.59 – 5.17%). The Efficiency Index (EI) comparing Tarragona and Blasi batches without preventive therapeutic program is 146.10. Comparing the batches with preventive program is 152.36.

Table M4 (FELANTIX – MALLORCA)

The oral administration of Tylosin the first three days and the repetition at 15, 16 and 17 days of life followed by the administration of gentamicin (selected by analysis) produces a 4.7% increase in the average weight, a decrease of 105.75g of the feed conversion rate, a decrease of 2.90% of mortality on a 6% (-48.33%), a reduction of the level of occupation of farm of 3.25 days by raising, as well as a reduction of 1.77 Pts. (less expense by broiler in medication).

If we compare the efficiency index of sheds without preventive treatment, an EI of 148.56 is obtained. With the preventive treatment the EI obtained is 180.09.

Table M5

• Vaccinated against H120 bronchitis at birth with spray
• B1 Plague vaccinated at 15 days through drinking water
• Vaccinated against Gumboro at 15 days through drinking water
• Medicated with commercial anti CRD of several brands, two or three times according to needs.

Table M6

• Vaccinated against H120 Bronchitison the first day by spray
• Vaccinated against Gumboro by drinking water at 15 day of life
• Medications on the first day of life with Tylosinat 1g per liter for 3 days
• Medications at 15 days with Tylosin½ g per liter for 2 days
• Preventive medications with Gentamicin at 30 days
• Medicated, (the birds that needed it), with Nalidixic Acid

Tables M1-M6 Conclusions

The above tables show that, by applying a preventive program, lower mortality, fewer days on the farm and a better efficiency index are obtained.

Benefits of applying a preventive drug program (summary).

Mortality (%)	-45.62
Final age (days)	-1.1
Average weight	+0.049 g
Feed conversion rate	-163 g
Cost per bird (Pts.)	1.57 ptas-

 

Conclusions of the application of a preventive therapeutic program against mycoplasmosis.

Studies carried out in Spain between 1982 and 1985 in broiler breeding companies.

1. Gentamicin is the most effective antimicoplasmic in the laboratory. Followed in efficiency by Josamycin, Erythromycin, Spiramycin and Tiamulin without laboratory effectiveness.
2. Erythromycinand Spiramycin show the best activity at field level against Mycoplasma synoviae and gallisepticum.
3. Tylosin, Kitasamycin, Josamycinand Tiamulin show better activity against gallisepticum than against M. sinoviae.
4. There is no direct relationship in antimicoplasmic activity between laboratory results and clinical practice derived from pharmacodynamic and pharmacokinetic aspects (such as Gentamicin) and dosage aspects influenced by economic terms.
5. Gentamicin is the most effective antibiotic in the laboratory against mycoplasmosis contaminating bacteria: coli, Proteus, Shigella, Pseudomona and Klebsiella.
6. Nalidixic Acid against coliand Shigella, Chloramphenicol against Proteus and Colimycin against Pseudomonas and Klebsiella may be drugs of choice that replace Gentamicin when the disease has become widespread.
7. The application of a medicine program based on selected substances through serological controls and antibiograms, allows, in the case of the Tylosin-Gentamicin program, to reduce mortality, feed conversionrate, farm occupancy and the cost of medication and increase the average weight of the animals.
8. It is advisable to implement prophylactic drug plans in the raising of broilers intended to fight mycoplasmic contamination during the first 2 weeks and bacterial contamination in the 4th week, in order to improve the health status, the economic outcome, as well as supply the market foods free of pharmacological residues, since these early application programs allow for adequate withdrawal periods.
9. There is no a universal preventive program. Each clinician must choose his preventive therapeutic program based on the analysis of EI and economic cost of medication.

Therapeutic program for the prevention of coccidiosis

The main factors that predispose to suffer from this disease are: the massification in industrial farms, the requirement of a very specialized management, alterations of the immunocompetent system of the birds due to suffering or having suffered some viral or bacterial infectious process, or consuming products that contaminate feed and cause immunosuppression, among other causes.

Proper handling, vector control as well as the correct design of the facilities and the use of appropriate material (boots, etc.) are main factors for the prevention of coccidiosis.

But, improvements in handling and feeding have not been enough, because risk factors in industrial poultry farming have increased, such as wet litters, certain designs of the drinking troughs that favor moisture in litter, and all substances that can cause decreased feed consumption, such as thermal stress or locomotive problems.

Coccidiostats

The coccidiostats currently allowed in the European Union are:

• Robenidine
• Lasalocid
• Halofunginone
• Salinomycin
• Maduramycin
• Diclazuril
• Narasin-Nicarbazin
• Monensin
• Decoquinate
• Narasin
• Semduramycin

Historical

When coccidiostats are used continuously and during very long periods, resistant strains of Eimeria can be created. At first, coccidiostats were used in unique programs, but as resistances began to appear, chemical and ionophore coccidiostats were combined in “Shuttle” programs (use of two different coccidiostats, one for the starting phase and one for the fattening phase).

• 40’s: Coccidiosisbegan to be controlled with chemicals (sulfonamides).
• 50’s: Amprolium and Nicarbazinbegan to be used.
• Subsequently, new products have appeared, such as Diclazuril in the 90’s.

Application

Some chemical coccidiostats can cause problems if contamination occurs in feed for layers or breeders:

• Robenidine in layers causes abnormal flavors
• Nicarbazinproduces unfavorable side effects in broilers when is used in periods of strong heat, and affects egg quality, discolors the eggshell and alters the yolk. Also produces embryonic mortality and severely reduces hatchability.

Once the program has been applied, its proper functioning should be monitored, checking injuries, making oocyst counts or performing coccidiograms, which are resistance tests that help to use the most appropriate program with the most useful coccidiostats.

Vaccination

To vaccinate against coccidiosis in specific avian species, it is necessary to use vaccines made with an antigen containing the pathogenic Eimeria species for that avian species in a concrete area, because there is an immunological specificity. Eimeria species that affect broilers and hens are: Eimeria acervulina, E. brunetti, E. maxim, E. mitis, E. praecox, E. necatrix and E. tenella.

The manufacture of vaccines generates many problems, since it is not easy to manufacture attenuated vaccines with all strains of pathogenic Eimeria species, because the cycles are different and immunity occurs, in most cases, during the first days of the cycle, in the asexual phase. Vaccines provide the initial inoculum and, for birds to resist field infections, two or three more cycles are necessary, which develop with the oocysts eliminated along with the feces on the litter.

Vaccines made with pathogenic Eimeria strains are not advisable because they produce clinical signs of disease, by recycling oocysts that they eliminate, and penalize zootechnical results, live weight and feed conversion rate.

Vaccination can be applied through drinking water, but it presents difficulties because oocysts are heavier than water and are located at the bottom of the ducts. It can also be administered in feed, with a spray containing the dilution of oocysts. Another way to vaccinate birds is in the incubator in 1 day old chicks.

Intestinal optimizer pronutrients

Pronutrients are active molecules from plant extracts that optimize the intestinal mucosa. They promote the activity of the local immune system of intestine which eliminates the intestinal and caecal coccidia during the first stage of reproductive cycle.

The use of intestinal optimizers pronutrients reduces mortality and lesions on intestinal mucosa, improving production parameters without creating any resistances or leaving any residues in the animals.

Trials comparing different preventive programs

Trial 1. Evaluation of intestinal optimizer pronutrients against chemical coccidiostat in poultry industry. Romania 2007

Broilers Cobb, from 0 to 42 days. Three different farms were used in the trial:

• A: Intestinal optimizer pronutrientsat 0.25 kg/Tm, from day 0 until slaughter
• B: Chemical coccidiostats. Diclazuril (200 g/Tm, from day 0 to 20), Lasalocid600 g/Tm, from day 21 to 35), withdrawal period from 35 to 42.
• C: Intestinal optimizer pronutrientsat 0.5 kg/Tm (recommended dose), from day 0 until slaughter.

The following parameters were evaluated:

• Presence of coccidia
• Daily weight gain
• Average weight
• Mortality

Results:

• Presence of coccidia:
  • FARM A: Coccidiaappeared at day 19 in the building 1 and at day 25 in the building 2. It was treated with sodium
  • FARM B: Coccidiaappeared at day 24 in the building 3 and at day 25 in the building 4. It was treated with sodium
  • FARM C: No coccidia appeared

• Daily weight gain (grams/day)

• Average weight (grams)

• Mortality

• Conclusions:

1. The best results were obtained in farm C, intestinal optimizerpronutrientes at 0.5 kg/T.
2. In the farm C, with the intestinal optimizer pronutrientes at 0.5 kg/T, is the only farm where coccidiosis was not seen.
3. In farm C, treated with the intestinal optimizerpronutrientes at 5 kg/T, achieves better weight and less mortality.
4. The intestinal optimizerpronutrientes are effective as an optimizer for the intestinal mucosa and shows better results than chemicals coccidiostats.

Comparing the results of farm C (pronutrients at 0.5 kg/T) and farm B (chemical coccidiostats), we can conclude that pronutrients can produce 231 tons more of meat, per each 1.000.000 broilers.

Trial 2. Evaluation of an intestinal optimizer against chemical coccidiostats and vaccines in local breed males (Castellana Negra breed). University of Soria (Spain) 2003.

Three batches with males of Castellana Negra breed were used in this trial:

• Batch 1: chemical coccidiostat (monensina)
• Batch 2: Intestinal optimizer
• Batch 3: Vaccine against coccidiosis

Feed was administered ad libitum, using a single feed for all animals. Weight was controlled from week 4 to week 13.

• Results:

• Conclusions:

1. Batch 1 (Chemical coccidiostat: Monensina) has lowest weight, except in the last two weeks (12-13), when the weight slightly exceeds the one of the vaccine.
2. Batch 2, intestinal optimizers, shows substantially higher weights than in the other groups.
3. The most significance differences appear at week 12.

Trial 3. Evaluation of an intestinal optimizer against chemical coccidiostats and vaccines in males of Castellana Negra (local breed) artificially infested. Soria (Spain) 2003.

Three batches with males of Castellana Negra breed were used in this trial:

• Batch 1: chemical coccidiostats (monensina)
• Batch 2: Intestinal optimizer
• Batch 3: Vaccine against coccidiosis

When animals have 9 weeks, they were infested artificially with oocysts of three Eimeria:

• 100.000 oocysts of Eimeriatenella
• 100.000 oocysts of Eimeriaacervulina
• 150.000 oocysts of Eimeriamaxima

The severity of intestinal lesions caused by coccidia with a scale of 0 (mild) to 4 (severe) was evaluated.

• Results:

Severity of the intestinal lesions (Escale 0 – 4)

• Conclusions:

1. Animals treated with the intestinal optimizerin batch 2 and the vaccinated in batch 3, show a low degree of lesions compared to batch 1, the one with the chemical coccidiostat monensina.
2. Therefore, it is convenient to propose a natural product as a substitute of chemical coccidiostats, because:
   1. Reduces the number of intestinal lesionsand their severity
   2. It is achieved a better live weight of the animal
   3. It prevents the appearance of residues in meatand does not interact with other products such as antibiotics or antioxidants.

Trial 4. Evaluation of an intestinal optimizer against the vaccination of pullets (brief of 3 trials) El Salvador 2006-2007.

Trial 4.1.

Farm of 83,000 pullets, from week 1 to 16. Batches distribution:

Results:

Conclusions:

The administration of an intestinal optimizer compared to vaccination:

1. Less mortality(%)
2. Greater uniformity
3. Simlar weight and conversion rate

Trial 4.2.

The trial was repeated in the same farm of 83,000 pullets, from week 1 to 17. Batches distribution:

• Batch 1: intestinal optimizerwithout vaccination. 16,561 birds. Average weight: 36 g
• Batch 2: Only vaccination. 15,952 birds. Average weight: 36 g

Results:

Conclusions:

The batch with intestinal optimizer achieved:

1. Better conversion rate
2. Greater uniformity
3. Similar mortalityto batch with vaccination

Trial 4.3.

The trial is repeated in the same farm with 83,000 pullets, from week 1 to 10. This time, the intestinal optimizer is administered with an intestinal conditioner to improve the weight gain of the animals. Distribution of batches:

Results:

Conclusions:

The group with intestinal optimizers and conditioners shows:

5. Higher weight
6. Greater uniformity
7. Less mortality
8. Lower feed consumption

Therapeutic preventiveplans conclusions

• The use of medications (especially antibiotics) in health animals should be eliminated
• However, as there are processes in which the incubation period is very long, (as in respiratory conditions and coccidosis), in which the drug is administered for therapeutic and non-preventive purposes, although it is being administered to animals even without clinical manifestations.
• Therapeutic program for the prevention of necrotic enteritis and salmonellosis. Necrotic enteritis, together with mycoplasmosis, coccidia and other protozoa, are a source of pathologies and losses.

Antimicrobial Treatments

• The antimicrobial medications are used currently in poultry industry both for the control of infectious diseases to improve the poultry productivity.
• Antimicrobials are chemicals used to fight microorganisms. These agents can be nonspecific or specific.
• The nonspecific belong to the group of antiseptics and disinfectants, which act on microorganisms, both pathogenic and non-pathogenic.
• The specific ones act on microorganisms responsible for infectious diseases, which act on animals, they are chemotherapeutics and antibiotics.

Situations in which an antimicrobial can be used:

1. For the treatment of various infections.
2. For the prevention as part of the set of measures taken to protect and preserve of diseases, blocking or reducing their incidence (prophylaxis).
3. For the prevention of infections in healthy animals, in a batch where there is a risk of disease due to the existence of affected animals or suspected of being infected, and there are no other suitable alternatives (metaphylaxis). To improve the poultryproductivity, promoting a greater weight gain and a better feed conversion.

Classification of specific antimicrobials

Determining factors to choose an antimicrobial

• Etiological agent: Identify it and determine its sensibility through an antibiogram is important. When it is not possible, the clinical pictures, location of the infectious process, age and physiological phase, epidemiological and laboratory data should be considered.
• Antimicrobial properties: the properties of an ideal antimicrobial would be:
  • Destruction of the microorganism (bactericide or fungicide) instead of inhibiting its growth (bacteriostatic or fungistatic).
  • Broad spectrum of action on pathogenic microorganisms
  • High therapeutic index;
  • Activity in the presence of body fluids (exudate, pus…)
  • Non-affectation of body’s defenses (antibody synthesis, generation of defense cells)
  • Do not produce allergic sensitization reactions
  • Do not develop bacterial resistance
  • Distribution throughout the body’s tissues and fluids in adequate concentrations
  • Administration by different routes (oral, parenteral and local)
  • Accessibility
  • Also, the dosage and the duration of the treatment must be considered.
• Characteristics of the animal (bird): its organics conditions are also essential to choose the antimicrobial. Age (young or sick animals may have difficulty in biotransforming medications or eliminating them by renal route), previous pathological conditions (difficulty in nutrient absorption by the digestive tract, nephropathies or liverdiseases, etc.), genetic factors, among others, should be considered.

Common causes of misuse of antimicrobials

• Treatment of non-sensitive infections, such as virosis
• Treatment of fevers of unknown origin, the agent may be non-infectious
• Error in the choice of the antimicrobial or its dosage (dose, interval between doses, duration of treatment)
• Treatment started late, when the microorganism has already caused the lesions in the animal organism
• Presence of calcified infectious sources, necrotic tissues that hinder the arrival to the microorganism, etc.
• Infectious processes in tissues where the antimicrobial cannot reach (or cannot reach sufficient concentrations)
• Persistence, which means that the infectious agent is sensitive to the antimicrobial in vitro, but the microorganism in the tissues of the animal may be in a phase of its cycle in which it is refractory to the medication. For example, a microorganism may be in spheroplast o protoplast phase, antibiotic-resistant phases that act on the cell wall.
• Bacterial resistance, which can be natural or acquired. Natural resistance does not disturb the therapy because it is already known that a certain microorganism is naturally resistant to the antimicrobial. On the other hand, acquired resistance is a new characteristic acquired by a certain strain of microorganism, which makes it resistant to the antimicrobial. This resistance entails great inconveniencies in the clinic and in animal production.
• Bacteria can acquire resistance by transferring geneticmaterial through different systems:
  • Transformation: The bacterium takes a piece of DNA, from another bacterium, found in the medium.
  • Transduction: An accidental transfer of DNA between bacteria occurs, through a virus.
  • Conjugation: DNA transfer between bacteria occurs through communication between cells.

Antimicrobial association

The association of antimicrobial, whenever possible, should be avoided, but it is necessary in some situations:

• In the treatment of mixed infections when the etiologic agents are sensitive to different antimicrobial.
• To avoid or delay the appearance of bacterial resistance.
• For a greater therapeutic effect. Practical experience has proven that the association is more efficient, in some infectious processes.
• In the treatment of serious infections of unknown etiology. When the treatment is started before obtaining the results of the antibiogram.
• To obtain synergism, which means that the association’s antimicrobial activity is greater than that obtained when an antimicrobial is used alone. For example, use of sulfa with trimethoprim.
• Infectious processes in immunosuppressed individuals.

When an association of antimicrobials becomes necessary, it is essential to respect the dosage (dose and interval between administrations) of each of the members of the association, which should be administered as if they were administered separately.

There are several criteria to consider for the association of antimicrobials.

One is to take into account the biological action of the antimicrobial, that is, if they are bactericidal (fungicidal) or bacteriostatic (fungistatic):

• Bactericide+ bactericide ď�  synergistic or additive effect.
• Bacteriostatic + bacteriostatic ď�  additive effect
• Bactericide+ bacteriostatic ď�  synergistic, additive or antagonism effect

Another criterion is the mechanism of action:

• Cell wall + cell wall ď�  synergistic effect
• Cell wall + cytoplasmatic membrane ď�  synergistic effect
• Cell wall + defective proteinformation ď�  synergistic effect
• Cell wall + disruption of the translation of geneticinformation ď�  antagonism

Medicines and therapeutic

The most important chemotherapeutics in poultry farming are sulfonamides, diaminopyridine and quinolones.

• Sulfonamides

They are the derivatives of p-aminobenzenosulfonamide. More than a thousand sulfonamides have been synthetized, most of which have been discarded. In poultry farming, the most commonly used are sulfachinoxaline, sulfadimetoxin, sulfametazine, sulfatiazole, sulfamerazine and sulfadiazine.

Mechanism of action: Sulfonamides are competitive antagonist of p-aminobenzoic acid (PABA) and therefore interfere with their use in the biosynthesis of folic acid of the bacteria, which is structural analogue of p-aminobenzoic acid (PABA).The reduced form of folic acid (tetrahydropholic acid) is essential for the synthesis of bacterial RNA and DNA, so the sulfas interact as antimetabolic.

They are bacteriostatic in therapeutic concentrations and bactericides in high concentrations, but, with increased risk of causing adverse reactions.

By their way of action, the most susceptible organisms are those that synthetize their own folic acid, both Gram- and Gram- and, consequently, bacteria capable of using performed folates are not susceptible.

Absorption, distribution, excretion: Poultry are the species that most quickly absorb sulfas, followed by dogs and cats. Other factors tan may influence this rate are water deprivation, which delays absorption, diarrhea, etc. They have a wide distribution, biotransformation in the liver and renal elimination.

Main indications: enteritis, coccidiosis and respiratory tract infections.

Types. Different types are presented depending on their speed of performance, characteristics and way of use. We can distinguish:

• For topical use: sulfacetamide,
• Little o non-absorbable, only active in lumen (sulfasalazine)
• Classic or fast absorption and excretion (<7h) (sulfisoxazole, sulfadiazine)
• Delayed or long-acting, fast absorption, but very slow excretion, as sulfadoxine. They can be semi-delayed, delayed (< 24 h) or ultra-delayed (up to 50 h)

Resistance: Resistance appears gradually and slowly, but when set is persistent and irreversible. Dosages vary depending on the active component and the route of administration, in poultry farming is oral.

• Diaminopyrimidines

Trimethoprim

It is a diaminopyrimidine, structural analogue of dihydrofolic acid.

Mechanisme of actions: It inhibits the enzyme dihydrofolate reductase, which transforms dihydrofolic acid into tetrahydrolofic acid.

Administration: It is administered together with sulfamides, as they have synergistic action, acting in different phases of the formation of tetrahydrofolic acid. Their joint administration has multiple advantages: they have similar pharmacokinetics, association with broad spectrom of action, lower incidence of resistance and bactericide effect.

Ormethoprim is another representative of this group, which has a longer half-life than that of the trimethoprim.

• Quinolones

In 1962, Lescher synthetized the first compound in this group, nalidixic acid, from chloroquine, and they have been improving, increasing their spectrum of action.

Types:

• First generation: The first quinolones used had a reduced spectrum of action: nalidixic acid, flumequine, oxolinic acid.
• Second generation: By associating a fluoride radical to the molecule to increase its spectrum of action, fluoroquinolones were obtained. They exhibit potent action against gran-positive and gran negative bacteria, Mycoplasma, Chlamydia and Staphylococcus. Also against gram-negative enteric bacilli.
• Third generation: They are newly developed and have a spectrum of action similar to those of the second generation, expanded with activity against Streptococcuspneumoniae, which was not sensitive to the second generation.

They are effective against a large number of pathogens, among which are cited: Escherichia coli, Salmonella, Shigella, Enterobacter, Haemophilus influenzae, Campylobacter, Neisseria, Pseudomonas aeruginosa, Enterococcus, neumococos, Chlamydia, Mycoplasma, Legionella, Brucella, Mycobacterium tuberculosis, Serratia, Moraxella catarrhalis, and others.

Mechanism of action: They have bactericidal effect. They inhibit bacterial topoisomerases type II (DNA girase), enzymes that catalyze the winding of DNA chains.

Absorption, distribution, excretion: The most used and the fastest route is oral. The máximum concentration is reached at 1.4-2.5 hours in turkeys and hens, respectively. It has a greater capacity of distribution in the body and a low interaction with plasma proteins.

Fluoroquinolones are partially biotransformed, being excreted in urine and bile. In poultry farming, the most used are enrofloxacin, norfloxacin and ciprofloxacin.

• Nitrofuran derivatives

Mechanism of action: Not fully defined.. It is believed to induce damage to bacterial DNA and, consequently, cause the death of the bacterium. They have bactericidal or bacteriostatic activity depending on their concentration. They have a broad spectrum of action on gran+ and, to a lesser extent, gram- bacteria and some protozoa and fungi. Resistances are rare.

Their use in food-producing animals presents problems with the attribution of carcinogenic effects and a period of suppression that is difficult to determine because, although they disappear rapidly from the circulating plasma, they remain in tissues and animal’ products, bound to proteins, almost three weeks.

Types:

• Nitrofurantoin: specific for the treatment of urinary tract infections.
• Furazolidone: widely used for the treatment of digestive tract infections, mainly by Salmonella, Shigellaand coli. Dosage of 100 to 200 mg/L of water or 200 mg/kg of feed.
• Nitrofurazone o nitrofural: topical use.

 

• Metronidazole

Heterocyclic nitroimidazolic compound, with nitrofuran-like chemical structure.

Mechanism of action: Not fully defined. It is administered orally, with fast absorption and wide distribution. It biotransforms in the liver.

Main indications: Used in anaerobic bacterial infections such as Clostridium, Fusobacterios and bacteroides.

• Beta-lactam antibiotics

They group penicillins and cephalosporins, which are polypeptides whose chemical structure has a beta-lactam ring.

Mechanism of action: Both are bactericidal. They prevent the synthesis of the structure of the cell wall, which is responsible for the protection and maintenance of the bacteria, by inhibiting the enzyme transpeptidase. This causes cell death of the bacteria, as the wall is critical to its survival.

PENICILLINS

They are classified into different groups:

• Natural penicillins:
  Obtained from the fungus Penicilium, called with capital letters of the alphabet. The most powerful is penicillin G.

• Penicillin V:
  Also called pehnoxymethylpenicillin. The spectrum of action is the same as that of natural ones, with the difference that its is resistant to digestive acids and can be administered orally.

• Penicillinase-resistant penicillins:
  Some microorganisms produce enzymes, called betalactamases, that can inactivate these antibiotics. The spectrum of action of resistant penicillins is wider than that of natural penicillin. All are semi-synthetic.

• Broad-spectrum penicillins:
  Semi-synthetics and sensitive to penicilinase.

• 2^nd generation penicillins:
  Ampicillin was the first broad-spectrum introduced in therapeutics. Other examples are ampicillin analogues (hetacycline, methampicillin, pivampicillin, bacampicillin), amoxicillin and ciclacillin.

• 3^rd generation penicillins:
  Sensitive to betalactamases. Intended for Pseudomonas aureginosa infections. Examples: carbecillin, indanilcarbecillin and ticarcillin.

CEPHALOSPORINS and CEPHAMYCINS

Cephalosporins are antibiotics derived from the fungus Cephalosporium acremonium, while cephamycins are fermented by Streptomyces.

Mechanism of action: similar to penicillins, prevent the synthesis on microorganisms’ wall. They can be used in poultry.

They are classified in 4 generations by their obtention, and the last one is being developed.

• First generation: action against gram+ and penicillinase-producing Staphylococcus.
• Second generation: less active than gram+, but greater activity against gram-
• Third generation: greater activity against gram-, and some resistance to betalactamase. Worse activity against gram+ agents

 

• Aminoglycosides

They are relatively small molecules, consisting of a nucleus of hexose and aminosugar, soluble in water and forming soluble salts. They are produced by Streptomyces griseus, although there are also semi-synthetic. Streptomycin, neomycin, paraneomycin, kanamycin, spectinomycin, gentamicin, tobramycin, sisomicin and netilmicin are included in this group.

Spectrum of action: Quite small, predominantly against gran-, so it is associated with penicillin to expand the spectrum of action.

Resistance: common, due to plasmids.

Absorption, diffusion, excretion: negligible intestinal absorption when administered orally. Parenteral route is used to treat systemic infections. It is excreted by the kidney in its active form.

Types:

• Narrow-spectrum:
  Streptomycin and dihydrostreptomycin, against gram- aerobes.

• Broad-spectrum:
  Neomycin, framycetin (neomycin B), pantomycin, kanamycin (against gram+ and gram– aerobes).
  Gentamicin, tobramycin, amikacin, sisomicin, netilmicin (also against P. aeruginosa).
• Varied:
  Apramycin and spectinomycin, structurally different from typical , but with the same mechanism and spectrum of action.

• Polymyxins

Polypeptide structure antibiotics produced by Bacillus polymyxa. Polymyxin B and E have therapeutic use. E is the most commonly used, being less toxic, and is also called colistin, colistimethate sodium or colimycin.

Spectrum of action: reduced. Mainly against gran- enteric (E. coli, Enterobacter, Klebsiella and P. aeruginosa).

Mechanism of action: bactericidal effect. It binds to radical phosphates, disorganizing the structure of the cytoplasmic membrane, which loses selectivity and lets out small molecules.

Resistance: rarely.

Absorption, diffusion and excretion: are not absorbed oral. They bind moderately to plasma proteins and do not have a good distribution. Kidney excretion.

• Bacitracin

Polypeptide antibiotic produceb by Bacillus linchenformis with action on gram+ bacteria. It is used associated to polymyxin and/or neomycin, to increase its spectrum of action.

Mechanism of action: bactericide, prevents the synthesis of the cell wall and lyse the cytoplasmic membrane.

Main indications: It is used as growth-promoting additive in diets.

• Tetracyclines

Antibiotics produced by various species of Streptomyces. Some are semi-synthetic, with the same spectrum of action, but with better pharmacodynamics and lower toxicity

Spectrum of action: broad-spectrum antibiotics, effective against gram+ and – bacteria, clamydia, ricketsias and some protozoa.

Mechanism of action: bacteriostatic, inhibit the protein synthesis of microorganisms, binding the 30 and 50S ribosomal units.

Resistance: acquired by plasmids, which reduce the uptake of tetracyclines by bacterial cells. Some bacteria can synthesize enzymes that inhibit these antibiotics.

Absorption, diffusion and excretion: parenteral or oral administration, with absorption into the digestive tract. The presence of feed may impair oral absorption, with the exception of minocycline and doxycycline. The maximum plasma concentration is reached 1 to 3 hours after oral administration. The distribution varies depending on the solubility of the substance: doxycycline and minocycline are more soluble than tetracycline and oxytetracycline, and therefore penetrate more easily into tissues. All (except minocycline and doxycycline) are actively excreted renally.

Types:

• Natural: oxytetracycline, chlortetracycline, dimethylchlortetracycline
• Semi-synthetic: tetracycline, rolitetracycline, metacycline, minocycline, doxycycline and limecycline.

Classification:

• Short-acting: tetracycline, oxytetracycline and chlortetracycline
• Intermediate-acting: dimethylcycline and metacycline
• Long-acting: doxycycline and minocycline

The most commonly used in poultry farming are: tetracycline, oxytetracycline, chlortetracycline and doxycycline.

• Chloramphenicol and analogs

Chloramphenicol is produced by Streptomuces venezuelae o by laboratory synthesis. Tiamphenicol and florfenicol are analogs, differentiated by the presence of a methylsulfuric group in its benzene ring. The bitter taste and low solubility of these medicines limit their use. The persistence of residues for a long time has prohibited its use.

Spectrum of action: wide, efficiency over gram+ and gram-, ricketsias, spirochaetes and mycoplasma.

Mechanism of action: inhibit protein synthesis, binding the 50s subunit. They block the enzyme peptidyltransferase, preventing the prolongation of the polypeptide chain and are therefore bacteriostatic. They have action on mammalian bone marrow cells (inhibit mitochondrial protein synthesis).

Resistance: by plasmids, the ability to produce and enzyme (chloramphenicol or tiamphenicol). Cross-resistance between chloramphenicol and other antibiotics, such as macrolides and lincosamides.

Absorption, diffusion and excretion: they have good absorption in monogastrics, bind to plasma proteins (30-45%) and good distribution by all tissues. Biotransformation in liver and excretion by urine.

• Macrolides and lincosamides

Macrolides

Antibiotics with macrocyclic lactonic ring that binds to sugars. Depending on the number of atoms in that ring (consisting of C, O and N) they are divided into three groups:

• 14 atoms: erythromycin, oleandomicyn, carbomycin, clarithromycin, roxithromycin, flurithromycin and dirithromycin
• 15 atoms: azithromycin
• 16 atoms: spiramycin, josamycin, kitasamycin (leucomycin), rokitamycin, midecamycin and miocamycin.

It also includes thylosin and tiamulin, which are antibiotics made up of several constituents, one of which is a macrolide.

Types:

• Erythromycinis a complex antibiotic consisting of three components, erythromycins A, B and C, the first being the most active.
• Spiromycinis the highest spectrum macrolide, is effective against mycoplasma, has higher tolerance orally and higher concentration in tissues than erythromycin.
• Myocacinalso has good digestive tolerance and roxitromycin stands out for the half-long serum life (+12h), both being semi-synthetic.
• Tylosinwas isolated from Streptomuces fradiae, and tiamulin is a semi-synthetic derivative. Both play an important role in the control of chronic respiratory diseases, in the case of avian mycoplasma.
• Josamycinis natural, highlighting its activity against anaerobes.

Lincosamides:

Also called lincomycins or lincocinamides. They are monoglycosides attached to an aminoacid. The main representatives are lincomycin and clindamycin. Clindamycins is a semi-synthetic with a spectrum of action slightly greater than lincomycin.

Spectrum of action: it is considered “intermediate”. They are active versus gram+, mycoplasma, anaerobic bacteria. Aerobic gram- agents are resistant to both.

Mechanism of action: it prevents bacterial protein synthesis, binding the ribosomal 50S subunit and inhibitng the enzyme peptidyltransferase (prevents the extension of the polypeptide chain). Bacteriostatic acitivity.

Resistance: chromosomal resistance is developed easily. It also occurs by plasmid and is more stable. There can be cross-reaction between the same group and between two groups.

Absorption, diffusion and excretion: they are quite fat-soluble (they cros the cell barrier easily), are well absorbed orally, biotransformed in the liver and a part can be eliminated by urine completely.

• Rifamicinas

Also called rifocins. Types: rifamycin A, B, C and D. The most active is rifamycin B. Semi-synthetic derivatives: rifamycin SV, rifamide (rifamycin M) and rifampicin.

They have intermediate spectrum of action:

• Rifamycin SV: acts on gram+ agents
• Rifamida: gram+, microbacteria and some gram-
• Rifampicin: higher spectrum (gram+, gram-, microbacteria, penicillase-producing Staphylococcus)

Mechanism of action: interfere with RNA polymerase (form complexes with the enzyme), preventing the transcription of genetic information. They are bacteriostatic, but bactericidal activity is observed in microorganisms sensitive to very low concentrations.

Resistance: chromosomal resistance is developed easily, for this reason, it is associated with other antibiotics. No cross-resistance with other groups.

Main indications: rifamycin SV and rifamide are applied parenterally, and rifampicin orally.

Use of antimicrobials in poultry farming

Antiviral

• Amantadine
• Ganciclovir
• Idoxuridine
• Azidothymionine
• Interferon
• Zidovudine
• L-Lysine

Antifungals

• Amphotericin B
• Nystatin
• Ketoconazole
• Micozonazole
• Itraconazole
• Flucytosine
• Griseofulvin
• Enilconazole
• Fluconazole
• Terbinafine
• Voriconazole
• Chlorhexidine
• Iodine
• Organicacids
• Tolnaftate

Antiprotozoa and internal antiparasitics

• Anticoccidia
• Antitenias
• Antivermes
• Antihistomonas

Antiparasitics externals

• Aeriteal
• Flies
• Terrestrial
• Alphitobius
• Aerial larvae

Metabolism correctors

• Acidosis
• Rehydrations

Antitoxics 

Antitoxics are products that prevent or decrease the toxic action on the individual of products that, in poultry farming, usually enter the organism through the digestive tract or can be produced directly inside from the decomposition of some products or be produced by bacteria and fungi.

Depending on the origin and action, it acts by neutralizing, blocking or preventing the formation of the toxic. Among the antitoxics used in poultry farming we can highlight the products that prevent the absorption of toxics present in food and those that prevent systemic toxic processes. In turn, among the most common toxics in food we should highlight mycotoxins and bacterial toxins.

Products that prevent the absorption of mycotoxins

Known as mycotoxin binders are feed additives, they cannot be considered as drugs, as they do not destroy or inactivate mycotoxins. These are derivatives of PVPP or silica oxides with the ability to form bonds with mycotoxin molecules so that the binder-mycotoxin complex, which forms in the gizzard at pH 2, cross along the digestive system without being absorbed. In this regard, it should be borne in mind taht these binder-mycotoxin complexes depend on the crystallography of the binder and therefore must be studied, one by one, their stability in the different pH conditions and presence of digestive juices (pancreatic and biliary).

Products that prevent the absorption of bacterial toxins

It is known that the infectious mechanism of many bacteria is based on the secretion of toxins (protein structure) whose purpose is to trick or inactivate the body’s immune system. The destruction of these proteins becomes difficult without affecting nutritional proteins so activated carbon has traditionally been used as a treatment for digestive poisonings by Clostridium, E.coli, Salmonella…

Products that prevent systemic toxic processes

This is symptomatic therapy, secondary therapy, so we refer to the clinical symptom produced by the toxic.

In this list we will include:

• Antihemorrhagic (vitaminK3) in the treatment of hemorrhagic syndrome by coumaric rings (aflatoxin, sterigmatocystin).
• Liver protectors (methionine, choline) in the treatment of cirrhosis hepatica (ochratoxin)
• Antihistamines (diphenhydramine: Antihistamine H1 by oral absorption) in the treatment of fishmeal poisonings.

Note:

In any case, the use of products against bacterial toxins and symptomatic drugs must be accompanied by the withdrawal of the food causing the poisoning.

In the case of the mycotoxin binders, it is more difficult to withdraw food, taking into account the high percentage of contaminations by one or more mycotoxins, so it is advisable to implement previous measures of cereal management (cleaning of powder, broken grain separation, mycotoxin analysis…)

Vision of Pharmacology

We reiterate some consideration made at the beggining of each section

Poultry considerations

Poultry have some physiological characteristics other than mammals, which influence their pharmacology:

1. Poultrylack regional ganglion lymphatic system which facilitates the spread of microorganisms through the circulatory system.
2. Their physiological temperature is 41ÂşC equivalent to the febrile state of mammals. That is, they are animals that live in a constant febrile state.
3. As a result, septicaemias occur in a seemingly asymptomatic manner, the period between infection and the first symptoms is much longer, between 14 and 16 days, tan in mammals.

On the other hand, the development of the poultry industry has favored some alterations in the biology of poultry:

4. Genetic selection has been made aimed at increasing the growth rate and prolonging the laying period between two periods of brooding. This selection has been base don the accumulation of genes, favorable to the objective, through techniques of inbreeding for the fixation of grandmothers’ breeds and in hibridation of lines in the production of commercial lines.
5. These geneticenhancement techniques have a significant impact on the poultry immune system.
6. The improvement of productive parameters in meatproduction imposes an overexertion on the intestine and liver.
7. The improvement of productive parameters of eggproduction imposes an overexertion on the liver and mineral metabolism.

Finally, farm management imposes significant changes in the design and processing of poultry feed:

8. Poultryare prevented from accessing fresh seasonal vegetables, especially germinated seeds, tree yolks, small insects… containing substances that are still necessary for poultry physiology in small quantities. In this sense, pronutrients have been defined.
9. Poultryproduction has been universalized to attend the growing protein demand of a population of 7 billion (although not all have access to a regular and quality nutrition). This leads to the need for industrial agriculture with large production areas of consumption (farms) and the consequent need for mechanization (grain breakage), collection chain and international transport (fungal and bacterial contaminations, insect infestations). Consequently, undesirable substances are introduced into the food
10. The high density of poultryon farms increases the number of microorganism “passes” between animals of the same species. This is one of the mechanisms that can increase the pathogenicity of microorganisms towards this animal specie.

Conclusions

• Accumulation of anatophysiological circumstances (asymptomatic septicaemias), genetics (immunodeficiency, intestinal, hepatic and mineral metabolism overexertion) and management (introduction of xenobiotics in the foodchain, restriction of access to pronutrients and increased pathogenicity for consecutive passes) have created numerous difficulties for the poultry
• Initially the poultryindustry, hand in hand with the chemical and pharmacological industry, responded to the challenges arising from industrialization by applying heat treatments to food, applying substances such as antibiotics growth promoters, coccidiostats, antioxidants, protein concentrates (meat, pen, blood or fish), phosphates, insecticides…
  • The use of these practices achieved over a long period of time (60-70-80-90’s decades of the twentieth century) a remarkable improvement of the production parameters with the consequent cheaper and popularization of meatand poultry
• This popularization also has a beneficial social effect since Access to economic proteinimproves not only human nutrition, but also influences the development of urban work by facilitating the presence of restaurants in the vicinity of the work or the use of pre-cooked foods.
• However, the increase in consumption of a food, of any food, carries with it the importance of studying the residue limits of xenobiotic substances that can reach consumers. At the end of the last century, as a first step, the need to reduce the use of antibiotics and coccidiostats was established. This was followed by a series of measures affecting the breeding conditions of poultry(space, access to water…) as well as the prohibition of incorporating certain flours of animal origin into the food.
• In parallel with these restrictions, in some countries of high purchasing power, as in others of minimum purchasing power, the breeding of indigenous poultryin either organic poultry or subsistence poultry took center stage. The result is the same, using indigenous breeds as alternative to design breeds.
• In this new context the vision of avian pharmacologyhas had to be reinvented. There are no longer mass treatments, sometimes without clinical or pharmacological criteria, we must now work in a more technical environment to respond to legal limitations and consumer requirements.
• This is why today the epidemiological knowledge of the area where the farms are located, the realization of clinical diagnoses that guide and complement them with laboratory analysis and the application of pharmacokinetic knowledge so that the drugs reach the appropriate anatomical location (enterohepatic cycle…).
• Regarding to previous practices, in our view, the use of drugs in preventive plans that meet three requirements deserve to be taken into account (to be based on semi-annual analysis of integration, to be used in presymptomatic septicaemic processes and applicable when mortalityexceeds 1 per thousand of the population for 3 days).
• Regarding to new practices we will continue the incorporation of pronutrientsinto poultry feeding programmes. Research conducted at research centers in many contries, including UCSUR, shows that the normalization of the physiological rhythm of avian tissues, through the production of specific functional protein in each tissue, significantly reduces need for medication.
• Finally, we can conclude that we are fase with a new visiĂłn of poultrypharmacology based on improvements in animal management and welfare, improvement of clinical and laboratorial diagnosis, application of pharmacokinetic concepts in the choice of drugs and application of food safety criteria with self-regulation by the poultry industry.

There is no universial preventive program. Each should seek its preventive therapeutic programa based on the analysis of EI and economic cost of medication.