Ruminant pharmacology
Ruminant Pharmacology
Reticular groove reflex
The voluminous ruminoreticular contents make the orally administered drugs less effective in a ruminant, closure of the reticular groove. With simultaneous relaxation of omasal sulcus permits entry of swallowed drug solutions directly into the abomasums, by passing ruminoreticulum. This manipulation is essential for the therapeutic efficacy of orally administered drugs in ruminants. Reflex closure of the groove is produced by chemical irritation of pharyngeal region by administering either of the following
Cattle: Copper sulfate – 5% solution
Zinc sulfate - 5% solution
Sodium bicarbonate - 10% solution
Sodium sulphat - 10% solution
Sheep: Copper sulfate – 1-2% solution
Closure of the groove takes place in about 5–10 seconds and it often remains closed for up to 60 seconds.
Suckling remains a very strong closure stimulus even in the full grown adult. It is best to allow sick calves and lambs to drink medicated milk from a nipple to assure delivery to the abomasums and rapid absorption of the drug. Oral administration of liquid medications to ruminants can result in spontaneous closure of the reticular groove in some cases.
Biochemical alteration of drugs with in Rumen (Rumen metabolism of drugs)
The environment of rumen is highly anaerobic and powerfully reductive and contains a wide diversity of microbial enzymes which catalyze, hydrolytic reactions, reductive reactions, decarboxylation, dealkylation dehalogenation, deamination and ring fission. Drugs entering rumen may get activated or inactivated.
Inactivation reactions
Chloramiphenicol – nitro group is reduced to amine.
Digitalis glycosides – destroyed.
N–Oxides of the alkaloids are rapidly reduced to tertiary bases.
Parathione – nitragroup is reduced to the primary amine.
Ruminal fluid contains oxalase, which destroys soluble oxalate in the diet. Thus ruminants are not very susceptible to oxalate poisoning.
Gossypol (a toxic phenol in cottonseed cake) is bound by a protein in the ruminal content with disappearance of the 2–E–amino group.
Phytoestogenic isoflavones which are abundant in Trifolium species are inactivated as estrogens when administered intra ruminally.
Activation Reaction
Miserotoxin (a toxic nitrosugar found in timber milk vetch, Astragalus miser) is metabolized to 3–nitro–1-propanol, which is the major toxic principle.
Microbial glucosidases release cyanide from cyanogenic glycosides with in the rumen.
Some inorganic salts may be reduced.
E.g.: Nitrate. → (Nitrite) → Ammonia.
Tryptophan and indole acetic acid are converted to 3–methylindole a toxic metabolite thought to be the cause of acute pulmonary edema and emphysema in cattle.
Polioencephalomalacia (Cerebrocortical neurosis) is a thiamine deficiency disease associated with production of high levels of thiaminase-I by ruminal microbes.
Drug effects on rumen micro flora
Drugs also exert both harmful and beneficial effects on the rumen microflora.
Harmful effects: occur from broad-spectrum antibiotics and antiprotozoan drugs suppress the bacterial fermentation and production of volatile fatty acids and increase in Acetic acid : Propionic acid ratio. Suppression of microbial growth is temporary and there will be spontaneous recovery, synthesis of B-complex group of vitamins by bacteria is also impaired by chronic use of antibiotics.
Beneficial effects: Influence of certain compounds on the ruminal micro flora may be beneficial in therapeutics.
Antibiotics in control of bloat and in treatment of ruminal lactacidosis and nitrite poisoning.
Chloral hydrate depresses cellulose digestion, with consequence fall in total VFA production but relatively increases in Propionic acid fraction. Used in treatment of acetonemia.
Some agents modify ruminal fermentation and thereby improving digestive efficiency.
a) Monensin, Lasoloid, salinomycin, polyether antibiotin a Voparcin all these alter the population of ruminal microbes and their metabolism to produce proportionally more Propionic and less acetic and butyric acid.
b) Monensin lasalocid, salinomycin amichloral these agents decrease the production of methane.
c) Diphenyliodonium – prevent degradation of amino acids, increasing the amount of free amino acids that can reach the abomasum.
Drug absorption from ruminoreticulum
The large volume of ruminoreticular content (more than 100L in an adult cow) dilutes the orally administered drug resulting delay in its absorption. The ruminoreticular epithelium is impermeable to ions, but allows lipid soluble non-ionic diffusion at normal PH of rumen 5.5–6.8 weak bases with high Pka remain ionized to a great extent and concentrated and trapped within rumino reticular contents whereas weak acids with low pka remain unionized and quickly absorbed.
Distribution of drug in ruminoreticulum
Drugs may or may not diffuse the ruminoreticulum from the blood stream. Dilution of a drug into an additional fluid space will reduce its concentration within tissues and plasma distribution into rumen fluid may result in a potential drug reservoir.
While calculating doses for an adult ruminant 20% of the body weight should be excluded (weight of rumen contents).
Drug that diffuses in to systemic circulation are sulfonamides, pentabarbitone, salicylates, ephedrine, and aminopyrin. Drugs that can not diffuse in to circulation are oxytetracyclin.
Treatment of forestomach dysfunctions
Fore stomach disorders mainly related to sudden changes in diet, production demands, management or husbandry, environment and dysfunction of other organs.
Bloat: Excessive accumulation of gas in the ruminoreticulum due to failure or inability to eructate.
Esophageal obstruction or any other factor preventing normal eructation will result in accumulation of free gas in rumen, a non frothy bloat called tympany.
Excessive foaming of ruminal ingesta causes the most commonly encountered form of bloat. Gas becomes trapped in the foam and cannot be eructed. In addition this froth inhibits eructation.
Frothy bloat is classified into two types.
Legume bloat – occurs when either alfalfa or clover are grazed.
Feed lot bloat – occurs when high concentrate rations are fed. Major causes appear to be excessive concentrate intake and feed particle size that is too fine. This is associated with increase in ruminal acidity.
Prophylaxis:
Avoid grazing animals on pastures known to produce bloat.
Poloxalene – antifoaming agents may be added to salt, protein blocks, liquid supplements or water or drench.
Antibiotics such as penicillin may be useful for several weeks, but their effectiveness wears off and other antimicrobials must then be used.
Correct feed preparation will help prevent feedlot bloat concentrates in the ration should be prepared and fed in such a manner that the animal does not consume excessive quantities of very finely ground material.
Hay or other roughages should not be ground or chopped into excessively small particles.
Dry rations poloxalene is not effective so detergents have been used.
Treatment:
Free gas bloat may be relieved by passing a stomach tube into the rumen or introducing a trocar and cannula (through left flank) and correct the causes.
Frothy bloat should be treated by drenching/administration by stomach tube of 10 g poloxalene/45 kg b.wt. gives relief with in 15-30 minits.
Acute frothy bloat can be relieved by administering the vegetable oils like peanut oil, sunflower oil and soybean oil and also by oil of terpeutine.
Ruminal atony or stasis
A number of nutritional and environmental disturbances as well as many infectious and metabolic diseases lead to disruption of forestomach digestion with a reduction in ruminoreticular motility and ultimately a ruminal stasis.
Causes:
Nutritional disease syndrome such as carbohydrate overload (starch, sugars), nitrogen overload (NPN, protein), energy deficiency (starvation) and mineral and water deficiency.
Febrile diseases and intoxications (cyanide, alkali, acid, bacterial endotoxins lead to ruminal stasis.
Systemic states like alkalosis, acidosis hypocalcemia, acetonemia.
Lesions affecting the forestomach – traumatic reticuloperitonitis, obstructive syndromes, adhesions, ruminitis.
Treatment
Provide appropriate substrate and cofactors for microbial fermentation.
Furnish large quantities of adequate microflora in a satisfactory fluid medium.
Adjust intraruminal PH accordingly.
Promote rumen motility by administering
Carbochol: 1–2 mg kg b.wt s/c repeat after 1–2 hrs.
Physostigmine: 40–45 mg kg b.wt. s/c.
Antizymotics
These are drugs used to prevent or reduce excess microbial fermentation in rumen or intestine. These are used in the treatment of bloat in ruminants and flatulent colic in horses.
Terpentine oil Horse: 15–60 ml
Cattle:15–90 ml
Sheep: 10–15 ml
Pig: 2-5 ml
Reticular groove reflex
The voluminous ruminoreticular contents make the orally administered drugs less effective in a ruminant, closure of the reticular groove. With simultaneous relaxation of omasal sulcus permits entry of swallowed drug solutions directly into the abomasums, by passing ruminoreticulum. This manipulation is essential for the therapeutic efficacy of orally administered drugs in ruminants. Reflex closure of the groove is produced by chemical irritation of pharyngeal region by administering either of the following
Cattle: Copper sulfate – 5% solution
Zinc sulfate - 5% solution
Sodium bicarbonate - 10% solution
Sodium sulphat - 10% solution
Sheep: Copper sulfate – 1-2% solution
Closure of the groove takes place in about 5–10 seconds and it often remains closed for up to 60 seconds.
Suckling remains a very strong closure stimulus even in the full grown adult. It is best to allow sick calves and lambs to drink medicated milk from a nipple to assure delivery to the abomasums and rapid absorption of the drug. Oral administration of liquid medications to ruminants can result in spontaneous closure of the reticular groove in some cases.
Biochemical alteration of drugs with in Rumen (Rumen metabolism of drugs)
The environment of rumen is highly anaerobic and powerfully reductive and contains a wide diversity of microbial enzymes which catalyze, hydrolytic reactions, reductive reactions, decarboxylation, dealkylation dehalogenation, deamination and ring fission. Drugs entering rumen may get activated or inactivated.
Inactivation reactions
Chloramiphenicol – nitro group is reduced to amine.
Digitalis glycosides – destroyed.
N–Oxides of the alkaloids are rapidly reduced to tertiary bases.
Parathione – nitragroup is reduced to the primary amine.
Ruminal fluid contains oxalase, which destroys soluble oxalate in the diet. Thus ruminants are not very susceptible to oxalate poisoning.
Gossypol (a toxic phenol in cottonseed cake) is bound by a protein in the ruminal content with disappearance of the 2–E–amino group.
Phytoestogenic isoflavones which are abundant in Trifolium species are inactivated as estrogens when administered intra ruminally.
Activation Reaction
Miserotoxin (a toxic nitrosugar found in timber milk vetch, Astragalus miser) is metabolized to 3–nitro–1-propanol, which is the major toxic principle.
Microbial glucosidases release cyanide from cyanogenic glycosides with in the rumen.
Some inorganic salts may be reduced.
E.g.: Nitrate. → (Nitrite) → Ammonia.
Tryptophan and indole acetic acid are converted to 3–methylindole a toxic metabolite thought to be the cause of acute pulmonary edema and emphysema in cattle.
Polioencephalomalacia (Cerebrocortical neurosis) is a thiamine deficiency disease associated with production of high levels of thiaminase-I by ruminal microbes.
Drug effects on rumen micro flora
Drugs also exert both harmful and beneficial effects on the rumen microflora.
Harmful effects: occur from broad-spectrum antibiotics and antiprotozoan drugs suppress the bacterial fermentation and production of volatile fatty acids and increase in Acetic acid : Propionic acid ratio. Suppression of microbial growth is temporary and there will be spontaneous recovery, synthesis of B-complex group of vitamins by bacteria is also impaired by chronic use of antibiotics.
Beneficial effects: Influence of certain compounds on the ruminal micro flora may be beneficial in therapeutics.
Antibiotics in control of bloat and in treatment of ruminal lactacidosis and nitrite poisoning.
Chloral hydrate depresses cellulose digestion, with consequence fall in total VFA production but relatively increases in Propionic acid fraction. Used in treatment of acetonemia.
Some agents modify ruminal fermentation and thereby improving digestive efficiency.
a) Monensin, Lasoloid, salinomycin, polyether antibiotin a Voparcin all these alter the population of ruminal microbes and their metabolism to produce proportionally more Propionic and less acetic and butyric acid.
b) Monensin lasalocid, salinomycin amichloral these agents decrease the production of methane.
c) Diphenyliodonium – prevent degradation of amino acids, increasing the amount of free amino acids that can reach the abomasum.
Drug absorption from ruminoreticulum
The large volume of ruminoreticular content (more than 100L in an adult cow) dilutes the orally administered drug resulting delay in its absorption. The ruminoreticular epithelium is impermeable to ions, but allows lipid soluble non-ionic diffusion at normal PH of rumen 5.5–6.8 weak bases with high Pka remain ionized to a great extent and concentrated and trapped within rumino reticular contents whereas weak acids with low pka remain unionized and quickly absorbed.
Distribution of drug in ruminoreticulum
Drugs may or may not diffuse the ruminoreticulum from the blood stream. Dilution of a drug into an additional fluid space will reduce its concentration within tissues and plasma distribution into rumen fluid may result in a potential drug reservoir.
While calculating doses for an adult ruminant 20% of the body weight should be excluded (weight of rumen contents).
Drug that diffuses in to systemic circulation are sulfonamides, pentabarbitone, salicylates, ephedrine, and aminopyrin. Drugs that can not diffuse in to circulation are oxytetracyclin.
Treatment of forestomach dysfunctions
Fore stomach disorders mainly related to sudden changes in diet, production demands, management or husbandry, environment and dysfunction of other organs.
Bloat: Excessive accumulation of gas in the ruminoreticulum due to failure or inability to eructate.
Esophageal obstruction or any other factor preventing normal eructation will result in accumulation of free gas in rumen, a non frothy bloat called tympany.
Excessive foaming of ruminal ingesta causes the most commonly encountered form of bloat. Gas becomes trapped in the foam and cannot be eructed. In addition this froth inhibits eructation.
Frothy bloat is classified into two types.
Legume bloat – occurs when either alfalfa or clover are grazed.
Feed lot bloat – occurs when high concentrate rations are fed. Major causes appear to be excessive concentrate intake and feed particle size that is too fine. This is associated with increase in ruminal acidity.
Prophylaxis:
Avoid grazing animals on pastures known to produce bloat.
Poloxalene – antifoaming agents may be added to salt, protein blocks, liquid supplements or water or drench.
Antibiotics such as penicillin may be useful for several weeks, but their effectiveness wears off and other antimicrobials must then be used.
Correct feed preparation will help prevent feedlot bloat concentrates in the ration should be prepared and fed in such a manner that the animal does not consume excessive quantities of very finely ground material.
Hay or other roughages should not be ground or chopped into excessively small particles.
Dry rations poloxalene is not effective so detergents have been used.
Treatment:
Free gas bloat may be relieved by passing a stomach tube into the rumen or introducing a trocar and cannula (through left flank) and correct the causes.
Frothy bloat should be treated by drenching/administration by stomach tube of 10 g poloxalene/45 kg b.wt. gives relief with in 15-30 minits.
Acute frothy bloat can be relieved by administering the vegetable oils like peanut oil, sunflower oil and soybean oil and also by oil of terpeutine.
Ruminal atony or stasis
A number of nutritional and environmental disturbances as well as many infectious and metabolic diseases lead to disruption of forestomach digestion with a reduction in ruminoreticular motility and ultimately a ruminal stasis.
Causes:
Nutritional disease syndrome such as carbohydrate overload (starch, sugars), nitrogen overload (NPN, protein), energy deficiency (starvation) and mineral and water deficiency.
Febrile diseases and intoxications (cyanide, alkali, acid, bacterial endotoxins lead to ruminal stasis.
Systemic states like alkalosis, acidosis hypocalcemia, acetonemia.
Lesions affecting the forestomach – traumatic reticuloperitonitis, obstructive syndromes, adhesions, ruminitis.
Treatment
Provide appropriate substrate and cofactors for microbial fermentation.
Furnish large quantities of adequate microflora in a satisfactory fluid medium.
Adjust intraruminal PH accordingly.
Promote rumen motility by administering
Carbochol: 1–2 mg kg b.wt s/c repeat after 1–2 hrs.
Physostigmine: 40–45 mg kg b.wt. s/c.
Antizymotics
These are drugs used to prevent or reduce excess microbial fermentation in rumen or intestine. These are used in the treatment of bloat in ruminants and flatulent colic in horses.
Terpentine oil Horse: 15–60 ml
Cattle:15–90 ml
Sheep: 10–15 ml
Pig: 2-5 ml
Comments
Post a Comment