Drugs for Specific Purposes in the Ruminant Digestive System

Esophageal obstruction due to a foreign body leads to severe discomfort and acute free-gas bloat. Physical removal of the object may be hampered by marked spasm of the surrounding muscle. Specific spasmolytic drugs such as acepromazine may be used (0.05–0.1 mg/kg, IV, IM, or SC in cattle). Alternatively, the moderate sedative and muscle relaxant effects of a low dose of xylazine (0.05 mg/kg, IM in cattle) or detomidine (0.02–0.05 mg/kg, IM in cattle) may aid removal of obstructions. None of these compounds have been approved by the FDA for use in cattle.

Agents and mixtures that promote forestomach function (fermentation and motility) are known as ruminotorics. Formulations that contain glucogenic substrates, minerals, cofactors, and bitters (eg, nux vomica) have limited application in the current treatment of ruminoreticular indigestion. Generally, restoration of the normal ruminoreticular environment using a physiologic approach is much more satisfactory.

Specific alkalinizing or acidifying agents should not routinely be administered orally in cases of indigestion. Magnesium oxide and magnesium hydroxide are strongly alkalinizing agents able to substantially increase rumen pH and thus create a hostile environment for rumen protozoa. These compounds, when given at label dose to dairy cattle, appreciably decrease rumen fermentation and the number of rumen protozoa. Therefore, these compounds should be administered only to cattle with a confirmed diagnosis of grain overload.

Mineral oil (1–2 L) or dioctyl sodium sulfosuccinate (DSS; 90–120 mL in 1–2 L of water) administered orally or via nasogastric tube, followed by gentle ruminal massage, can help promote the dissolution and passage of impacted fibrous ruminal omasal or abomasal contents. DSS can markedly decrease numbers of rumen protozoa; thus, ruminal transfaunation should follow use of this agent if ruminal hypomotility continues.

Fresh ruminal fluid is considered to be the best available ruminotoric because it contains viable ruminal bacteria (10⁸ to 10¹¹ cells/mL) and protozoa (10⁵ to 10⁶ cells/mL) as well as many useful fermentation factors (volatile fatty acids, microbial protein, minerals, vitamins, buffers). Administration of strained fresh ruminal juice, orally or by stomach tube, is indicated in cases of ruminoreticular stasis and has been shown to improve feed intake and decrease serum beta-hydroxybutyrate concentrations in cows after correction of a left displaced abomasum.

The optimal dose of fluid is unknown, and recommendations vary widely. Doses as high as 16 L for an adult cow have been recommended; however, research has demonstrated that 1 L was as effective as 5 L at restoring normal activity of rumen flora in cases of simple indigestion in cattle.(1)

Ruminal fluid can be aspirated through a stomach tube from the ruminoreticulum of healthy animals using an extractor pump or by siphoning, or it can be collected at slaughterhouses. A rumen-cannulated donor animal is particularly convenient. It is best for the donor to be on a ration similar to that of the recipient because the ruminal microflora will then be more appropriately adapted.

As long as the initiating condition or lesion is responding favorably, improvement almost invariably follows the reestablishment of normal ruminal microbiota, with consequent normalization of the fermentation process and ruminoreticular motility.

When the ruminoreticular contents are putrefied or extremely acidic, ingesta must be removed before the transfer of fresh ruminal fluid. Ingesta can be removed by use of a large-bore stomach tube or by a rumenotomy. Acetic acid (vinegar; 4–10 L, PO) can be administered to cattle in which putrefaction of the rumen is associated with high rumen pH.

The treatment to control acute frothy bloat is to administer antifoaming agents to decrease foam stability and to promote the release of free gas, which is then promptly eructated.

Acute frothy bloat in cattle should be treated with poloxalene, which may be administered as a drench or by gastric tube (25–50 g). Frothy bloat can be prevented by administering poloxalene as a top dressing to feed (1 g/45 kg, every 24 hours) or in a molasses block (1.5 g/45 kg, every 24 hours).

Polymerized methyl silicone (3.3% emulsion [in cattle, 30–60 mL; in sheep, 7–15 mL]) may be used in a similar manner as poloxalene, although direct intraruminal injection via a needle or cannula may be more satisfactory in this case.

Administration of docusate sodium or administration of vegetable oils alone, such as peanut oil, sunflower oil, or soybean oil (in cattle, 60 mL; in sheep, 10–15 mL), also relieves acute frothy bloat when given orally.

The incidence of frothy bloat in feedlot cattle may be decreased by either including ionophores (eg, monensin) in the ration or administering them in controlled-release capsules.

Ruminal alkalinizing agents are used principally to treat ruminal lactic acidosis (pH < 5.5) due to grain engorgement or to soluble carbohydrate overload. The resultant systemic dehydration and acidosis necessitate immediate correction of fluid and electrolyte balance as well as restoration of a viable microbial population. Often, the latter involves removal of ruminoreticular contents and replacement with fresh ruminoreticular fluid.

Antacids include magnesium hydroxide (in cattle, 100–300 g, PO, every 6–8 hours; in sheep, 10–30 g, PO, every 6–8 hours) and magnesium carbonate (in cattle, 10–80 g, PO, every 6–8 hours; in sheep, 1–8 g, PO, every 6–8 hours). Antacids should be mixed in ~10 L of warm water to ensure adequate dispersion through the ruminoreticular contents. Oral administration of activated charcoal (2 g/kg) is believed to protect the ruminoreticular mucosa from further injury by inactivating toxins. Oral administration of sodium bicarbonate (baking soda), either as powder dissolved in water or in commercially available solutions prepared for IV infusion, rapidly neutralizes the rumen pH but is accompanied by the rapid release of large amounts of CO₂. Because of decreased rumen motility in ruminants with acute rumen acidosis, these animals are at increased risk of developing potentially life-threatening free-gas bloat.

Most research investigating the use of antiulcer agents in ruminants has focused on calves.

A combination of aluminum hydroxide and magnesium hydroxide increased abomasal pH in calves when administered at 50 or 100 mL, PO, although the higher dose was associated with diarrhea.(2)

Cimetidine (100 mg/kg, PO) and ranitidine (50 mg/kg, PO) both appear to be more effective than the AlOH-MgOH combination, with minimal adverse effects in calves.(3)

Omeprazole effectively increased abomasal pH after a single oral dose; subsequent doses, however, had minimal effect.(4) Because of important physiologic differences between preruminant calves and adult cattle, it is unclear whether this research can reasonably be extrapolated to older cattle.

Studies in adult cattle have demonstrated short increases in abomasal pH with parenteral administration of both ranitidine (6.6 mg/kg, IM) and famotidine (0.4 mg/kg, IV).(5,6) Unfortunately, the effect of either of these treatments was too short-lived to provide substantial clinical benefit.

Parenteral administration of pantoprazole (1 mg/kg, IV, or 2 mg/kg, SC) in alpacas has demonstrated a consistent increase in third-compartment pH over 3 days.(7) Whether pantoprazole is effective in true ruminants is unclear, and currently it is likely cost-prohibitive for most ruminants.

Ruminal acidifying agents are used to treat ruminal stasis or simple indigestion as well as acute ammonia intoxication. In ruminal stasis, the intraruminal pH often increases to > 7.5 because of the constant inflow of bicarbonate-rich saliva in the absence of active ruminal fermentation and formation of volatile fatty acids. Correction of the underlying cause of ruminal stasis is critical for reestablishing normal rumen fermentation and likely more important than addressing the increased pH.

In acute ammonia intoxication, the increased intraruminal pH increases the activity of urease and facilitates the absorption of free ammonia (pK_a of ammonium is 9.1). Administration of weak acids in cold water returns the pH of ruminoreticular content toward physiologic levels, promotes the uptake of volatile fatty acids, decreases the absorption of ammonia, and inhibits excessive urease activity.

Acetic acid (4%–5%) or vinegar (in cattle, 4–8 L; in sheep, 250–500 mL) is the most common acidifying agent used.

The use of motility modifiers in cattle is controversial because evidence-based data demonstrating clinical efficacy are scarce. Several diseases, including paralytic ileus, cecal dilatation, and abomasal displacement, are accompanied by GI motility disorders. Pharmacological motility modification may hasten recovery in some cases. In most instances, however, the most effective strategy to reestablish motility is correction of the underlying disorder (hypocalcemia, endotoxemia, alkalemia, obstruction, or organ displacement), followed by restoration of the normal ruminoreticular environment through transfaunation. Furthermore, conditioned responses to the presence of feed and feeding itself are physiologic means by which ruminoreticular motility can be notably enhanced.

Motility modifiers are categorized according to their mechanism of action. Categories include cholinergics (parasympathomimetics), adrenergics, antidopaminergics, serotonergics, motilinergic receptor agonists, opioid receptor antagonists, or sodium channel blockers (lidocaine).

The use of parasympathomimetic agents (eg, neostigmine, physostigmine, bethanechol) is seldom appropriate. These drugs have cholinergic effects, which are potentially hazardous. Neostigmine (in cattle, 0.02 mg/kg, SC; in sheep, 0.01–0.02 mg/kg, SC) generally produces the fewest adverse effects; however, it tends to increase the frequency, rather than strength, of ruminoreticular contractions. Neostigmine given as a constant-rate infusion (87.5 mg in 10 L of sodium-glucose solution; infusion rate, 2 drops/s) has been used to treat cecal dilatation or dislocation. However, the stimulatory effect of neostigmine is not always reliable, and some inhibition of motility can occur, which may be due to the adrenergic component associated with ganglion stimulation by cholinergic agents.

Bethanechol (0.07 mg/kg, SC, every 8 hours, for 2 days) has been used to treat spontaneous cecal dilatation without torsion. Potential adverse effects include salivation and diarrhea. Recommendations involving neostigmine and bethanechol have not been confirmed in randomized, controlled experiments. Neither compound has been approved by the US FDA for use in cattle. Parasympathomimetics are sometimes used in practice to conservatively treat left displaced abomasum in cows, although the literature indicates that use of these compounds is of no value for this purpose.

N-butylscopolammonium bromide (hyoscine butylbromide) is a parasympatholytic agent approved for the control of diarrhea in cattle in some European countries (in nonlactating adult cattle, 0.2 mg/kg, IM or IV; in calves, 0.4 mg/kg, IM or IV). The commercial formulation is combined with an NSAID, metamizole (in nonlactating adult cattle, 25 mg/kg, IM or IV; in calves, 50 mg/kg, IM or IV). Administration of hyoscine butylbromide (80 mg/cow) in combination with dipyrone has been proposed as a conservative treatment of spontaneously occurring right displaced abomasum in cattle. Hyoscine butylbromide is not approved by the FDA, and the use of dipyrone in food animals is prohibited in the US.

Atropine (0.04 mg/kg, IV) has been found to mitigate abomasal contractions for 1–3 hours. Atropine sulfate (0.5 mg/kg, IV) administered 5 minutes before placement of a reticular magnet is suggested to prevent magnet loss into the cranial sac of the rumen.

Metoclopramide (in cattle, 0.15 mg/kg, IM; in sheep, 0.023–0.045 mg/kg) has cholinergic and antidopaminergic effects, but it does not appear to increase the myoelectric activity of the pyloric antrum in either species. However, metoclopramide at 0.5 mg/kg, IM or IV, in goats has been shown to increase myoelectric activity of the pyloric antrum but not the body of the abomasum. Because metoclopramide can cross the blood-brain barrier, restlessness and excitement are potential adverse effects. Metoclopramide has not been approved by the FDA for use in cattle.

Erythromycin lactobionate is a macrolide antimicrobial that increases gut myoelectric activity by binding to motilin receptors in intestinal smooth muscle cells. In cows, erythromycin (0.1 mg/kg, IV; or 1 mg/kg, IM) was found to increase myoelectric activity in the abomasum and duodenum for > 2 hours.(8) This effect was increased to 6–8 hours when erythromycin was administered in polyethylene glycol at 10 mg/kg, IM. While other macrolides, including tulathromycin and spiramycin, have demonstrated positive effects on abomasal motility, erythromycin appears to be the most effective. Erythromycin is approved by the FDA only for the treatment of shipping fever, pneumonia, foot rot, and metritis at 2.2 mg/kg, IM. Deep IM injection in the neck is recommended because of the risk of pain, swelling, and tissue blemishes at the injection site.

The prokinetic serotoninergic drug cisapride (in cattle, 0.5 mg/kg, PO) appears to increase abomasal emptying in calves; however, consequential prokinetic effects have not been conclusively demonstrated in ruminants. Anecdotally, administration of lidocaine as a constant-rate infusion in doses similar to those used in horses (loading dose, 1.3 mg/kg, IV; infusion rate, 0.05 mg/kg/min) is safe and may be effective in treating small intestinal ileus in both cattle and small ruminants.

1. Steiner S, Linhart N, Neidl A, Baumgartner W, Tichy A, Wittek T. Evaluation of the therapeutic efficacy of rumen transfaunation. J Anim Physiol Anim Nutr (Berl). 2020;104(1):56–63. doi: 10.1111/jpn.13232. Epub 2019 Oct 31. PMID: 31667911; PMCID: PMC7004065.

2. Ahmed AE, Constable PD, Misk NA. Effect of an orally administered antacid agent containing aluminum hydroxide and magnesium hydroxide on abomasal luminal pH in clinically normal milk-fed calves. J Am Vet Med Assoc. 2002 Jan 1;220(1):74-9. doi: 10.2460/javma.2002.220.74. PMID: 12680452.

3. Ahmed AF, Constable PD, Misk NA. Effect of orally administered cimetidine and ranitidine on abomasal luminal pH in clinically normal milk-fed calves. Am J Vet Res. 2001 Oct;62(10):1531-8. doi: 10.2460/ajvr.2001.62.1531. PMID: 11592315.

4. Ahmed AF, Constable PD, Misk NA. Effect of orally administered omeprazole on abomasal luminal pH in dairy calves fed milk replacer. J Vet Med A Physiol Pathol Clin Med. 2005 Jun;52(5):238-43. doi: 10.1111/j.1439-0442.2005.00715.x. PMID: 15943608.

5. Wallace LL, Reecy J, Williams JE. The effect of ranitidine hydrochloride on abomasal fluid pH in young steers. Agri Pract. 1994;15:34–38.

6. Balcomb CC, Heller MC, Chigerwe M, Knych HK, Meyer AM. Pharmacokinetics and efficacy of intravenous famotidine in adult cattle. J Vet Intern Med. 2018 May;32(3):1283-1289. doi: 10.1111/jvim.15080. Epub 2018 Mar 23. PMID: 29572958; PMCID: PMC5980459.

7. Smith GW, Davis JL, Smith SM, Gerard MP, Campbell NB, Foster DM. Efficacy and pharmacokinetics of pantoprazole in alpacas. J Vet Intern Med. 2010 Jul-Aug;24(4):949-55. doi: 10.1111/j.1939-1676.2010.0508.x. Epub 2010 Apr 6. PMID: 20384953.

8. Huhn, J. C., Nelson, D. R., Constable, P. D., & Morin, D. E. (1998). Prokinetic properties of erythromycin lactobionate in cattle. In Proceedings (pp. 177-180). World Buiatrics Cong.