Role of prokinetic drugs for treatment of postoperative ileus in the horse

All horses undergoing coeliotomy for an acute abdominal crisis are at risk of developing ileus and should receive therapy aimed at promoting gastrointestinal function by restoring fluid and electrolyte balance. Adequate analgesia and prevention against peritonitis, bacteraemia and endotoxaemia should be provided. Horses that at the time of surgery have a strangulating or non-strangulating small intestinal obstruction should be considered to be at greater risk of developing a persistent ileus that is refractory to treatment than those horses with lesions involving the large intestine. In horses considered to be at greater risk of developing a persistent ileus, the use of prokinetic agents should be considered. Agents that may be used to improve gastrointestinal motility include adrenergic receptor antagonists, cholinergic agonists, benzamides, dopamine antagonists, macrolide antimicrobials, opiate receptor agonists and antagonists, somatostatin analogues and local anaesthetics. There are limited studies into the use of these agents in the horse. Until further research provides more information on motility disorders following intestinal surgery and the efficacy of prokinetic agents in this species, only selective use of some of these drugs can be recommended.     

Normal intestinal motility

Perhaps because of the inherent difficulty in using horses as experimental animals, only a relatively small amount of data is as yet available regarding normal equine gut motility. However, it is clear that the horse is fundamentally similar to other mammalian species studied. The neural and humoral control of gut activity requires much exploration; it is likely that, in the horse, some of this information will be derived during the investigation of the effects of various substances that might have clinical relevance. This is alluded to in the chapter that follows (The Effects of Pharmacological Agents on Gastrointestinal Motility). The clinical applications are likely to remain limited, though some light may be shed upon the derivation of certain disorders.     

Gastrointestinal perforation in five dogs associated with the administration of meloxicam

Objective: Five canine cases of gastrointestinal (GI) perforation and septic peritonitis associated with the routine use of meloxicam are reviewed. Series summary: Selective cyclooxygenase‐2 (COX‐2) non‐steroidal anti‐inflammatory drugs (NSAIDs) are being used more extensively and routinely for acute and chronic pain as well as for perioperative management of pain. These medications are safe and effective but can be associated with known GI and renal side effects. The patients in this case series had no significant concurrent illness, were not on any concurrent medication known to potentiate the ulcerogenic effects of NSAIDs, and in most cases did not display clinical signs that were apparent to the owners until the time of perforation. New or unique information provided: Despite the preferential selectivity for COX‐2, newer NSAIDs still carry the risk of GI performation. The incidence of GI perforation may be increased with inappropriate dosing regimens, with use of non‐veterinary products and in animals that are at high risk for toxicity. Early signs of toxicity may include alteration in appetite, and subtle signs of nausea during treatment. Warning owners to monitor their pet for vomiting, melena, and hematemesis may not be sufficient to avoid the potential disastrous consequences of GI ulceration.     

Tegaserod (HTF 919) stimulates gut motility in normal horses

REASONS FOR PERFORMING STUDY: It has been shown that the selective 5-HT4 receptor agonist tegaserod induces an increase in frequency and amplitude of contractions in isolated muscle preparations of equine ileum and pelvic flexure. OBJECTIVES: To investigate the effects of tegaserod on gut motility and transit of spheres in normal horses. METHODS: Six mature Freiberger horses were kept under standardised conditions. Effects of tegaserod (0.02 mg/kg bwt i.v. b.i.d. for 2 days) or vehicle on intestinal transit of barium-filled spheres, defaecation and gut sounds were studied in a cross-over design. Spheres were given via stomach tube prior to the first dosing of tegaserod or vehicle. Faeces were collected every 3 h and spheres eliminated were identified radiologically in the faeces. RESULTS: Tegaserod significantly accelerated the gastrointestinal (GI) transit time of spheres and increased the frequency of defaecation and scores of gut sounds compared to vehicle. The compound was well tolerated; no effects on behaviour, body temperature, heart rate, respiratory rate and clinical laboratory data were observed. CONCLUSIONS: Tegaserod efficaciously stimulated motility and accelerate GI transit in healthy horses. POTENTIAL RELEVANCE: Tegaserod may offer therapeutic potential in horses suffering from impaction or paralytic ileus.     

Expression of the ether-a-go-go (ERG) potassium channel in smooth muscle of the equine gastrointestinal tract and influence on activity of jejunal smooth muscle

OBJECTIVE: To determine whether ether-a-go-go (ERG) potassium channels are expressed in equine gastrointestinal smooth muscle, whether ERG channel antagonists affect jejunal muscle contraction in vitro, and whether plasma cisapride concentrations in horses administered treatment for postoperative ileus (POI) are consistent with ERG channels as drug targets. SAMPLE POPULATION: Samples of intestinal smooth muscle obtained from 8 horses free of gastrointestinal tract disease and plasma samples obtained from 3 horses administered cisapride for treatment of POI. PROCEDURE: Membranes were prepared from the seromuscular layer of the duodenum, jejunum, ileum, cecum, large colon, and small colon. Immunoblotting was used to identify the ERG channel protein. Isolated jejunal muscle strips were used for isometric stress response to ERG channel blockers that included E-4031, MK-499, clofilium, and cisapride. Plasma concentrations of cisapride were determined in 3 horses administered cisapride for treatment of POI after small intestinal surgery. RESULTS: Immunoblotting identified ERG protein in all analyzed segments of the intestinal tract in all horses. The selective ERG antagonist E-4031 caused a concentration-dependent increase in jejunal contraction. Clofilium, MK-499, and cisapride also increased jejunal contraction at concentrations consistent with ERG channel block; effects of E-4031 and cisapride were not additive. Peak plasma cisapride concentrations in treated horses were consistent with ERG block as a mechanism of drug action. CONCLUSIONS AND CLINICAL RELEVANCE: The ERG potassium channels modulate motility of intestinal muscles in horses and may be a target for drugs. This finding may influence development of new prokinetic agents and impact treatment of horses with POI.     

Selected Aspects of the Clinical Pharmacology of Visceral Analgesics and Gut Motility Modifying Drugs in the Horse

Comparison of the visceral analgesic effects of xylazine, morphine, butorphanol, pentazocine, meperidine, dipyrone, and flunixin in a cecal distention model of colic pain indicated that xylazine produces the most relief from abdominal discomfort. Repeated administration of xylazine may reduce visceral pain so effectively that the seriousness of abdominal disease is obscured. Xylazine decreased propulsive motility in the jejunum and pelvic flexure of healthy ponies. Morphine and butorphanol also gave relief from visceral pain in the cecal distention model. Morphine may inhibit colonic, and butophanol jejunal, motility. Whether xylazine or opiate mediated decreases in gut motility cause clinically important slowing of ingesta transit is controversial and requires further investigation. The development of behavioral changes (i.e., apprehension and pawing) in horses given opiate therapy may limit the use of these drugs. Combinations of xylazine and morphine or butorphanol produce excellent, safe, visceral analgesia and sedation without untoward behavioral effects. Although flunixin fails to demonstrate good visceral analgesic effects in the cecal distention model, this drug produces analgesia in some cases of colic by blocking prostaglandin mediated induction of pain. Improvement of propulsive gut motility in patients with ileus may follow administration of neostigmine (which is particularly effective when the large bowel is hypomotile), naloxone (which experimentally stimulates propulsive colonic motility), and metoclopramide (which stimulates stomach and proximal small intestinal motility).     

Nutritional management of gastrointestinal disease

The gastrointestinal (GI) tract is primarily responsible for acquiring and digesting food, absorbing nutrients and water, and expelling wastes from the body as feces. A proper diet and normally functioning GI tract are integral for the delivery of nutrients, prevention of nutrient deficiencies and malnutrition, repair of damaged intestinal epithelium, restoration of normal luminal bacterial populations, promotion of normal GI motility, and maintenance of normal immune functions (eg, both tolerance and protection from pathogens). The amount of food, its form, the frequency of feeding, and the composition of diet each have important effects on GI function and may be used to help ameliorate signs of GI disease. Although both nutrients and nonnutritional components of a diet are important to GI health, they also may cause or influence the development of GI pathology (eg, antibiotic responsive diarrhea, inflammatory bowel disease, dietary intolerance, or sensitivity and/or allergy). The appropriate diet may have a profound effect on intestinal recovery and successful management of chronic or severe GI disease.     

Modifiers of gastrointestinal motility of cattle.

Little clinically relevant, evidence-based data about the effect of motility modifiers on the GI tract of cattle are currently available. Additionally, some of the published results seem to be contradictory. Three main facts explain this apparent discrepancy: (1) Results may not be transferred from one species to another, because presence, concentration, location, distribution, and function of specific receptors may differ significantly among species. (2) The lack of a significant effect on smooth muscle preparations in vitro does not necessarily exclude a certain drug's motility-modifying property on affected animals in vivo. Certain drugs bind to receptors outside the myenteric plexus. Others, such as lidocaine and adrenergic-, dopaminergic-, and opioid-antagonists increase only GI motility, if inhibitory reflexes or a hyperactive state of the inhibitory sympathetic nervous system preexists. (3) Effects of motility modifiers as found in healthy experimental animals in vivo may not be similar to those found in spontaneously diseased animals. Accurate and reliable data on the effect of modifiers of GI motility of cattle will be obtained only from double-blinded, evidence-based, in vivo studies on spontaneously affected animals. Because well-documented results from such studies are extremely rare, intensive research in this field is warranted in the future.     

Paradigms for pharmacologic use as a treatment component in feline behavioral medicine

Veterinary behavioral medicine remains an under-supported, under-appreciated, and under-taught specialty within veterinary medicine. Neuropsychopharmacology is the aspect that has provided the field with the most scientific legitimacy, but is also one of the most hotly debated. Paradigms for use of pharmacologic intervention include firstly ruling out any underlying medical cause. If a behavioral diagnosis can be made, treatment with psychotropic medication may be considered, although their use is most effective as part of an integrated treatment program that includes behavior modification. Used without an understanding of the mechanism of action, pharmacologic intervention may only blunt or mask behavior without altering processes or environments that produced the behavior. This paper reviews specific drugs, mechanism of action of those drugs, and relevant uses are reviewed for cats. Future advances in treatment in veterinary behavioral medicine will be pharmacological and neurophysiological. As the field of veterinary behavioral medicine expands, its paradigm will enlarge to include routine combination therapy and the implementation of neuropharmacological intervention as a diagnostic tool.     

Anesthetic management of thoracotomy

Successful anesthesia for thoracic surgery requires an understanding of the clinical disease and the physiologic changes accompanying the disease, as well as anesthetic agents available for use. The authors discuss selection of appropriate anesthetic drugs, perioperative management considerations, pharmacologic support, intraoperative monitoring and postoperative pain management.     

The role of bisphosphonates in the management of patients that have cancer.

Bisphosphonates are pharmacologic agents widely used in people for managing pathologic bone resorptive conditions. Based on their physicochemical properties, bisphosphonates concentrate within areas of active bone remodeling and induce osteoclast apoptosis. Appropriate use of bisphosphonates for treating companion animals requires a thorough understanding of how bisphosphonates exert their biologic effects. This review article highlights general properties of bisphosphonates, including their pharmacology, mechanisms of action, adverse side effects, anticancer mechanisms, surrogate markers for assessing response, and potential clinical utility for treating dogs and cats diagnosed with malignant skeletal tumors.     

Interactions between erythromycin,flunixin meglumine,levamisole and plant secondary metabolites towards bovine gastrointestinal motility—in vitro study

Continued ingestion of plant secondary metabolites by ruminants can provoke pharmacological interactions with pharmaceutical agents used in animals. As some drugs and phytocompounds affect smooth muscle activity, the aim of this study was to verify the possible interaction between selected pharmaceutical agents and plant secondary metabolites towards bovine gastrointestinal motility. The interactions between phytocompounds—apigenin, quercetin, hederagenin, medicagenic acid—and medicines—erythromycin, flunixin meglumine and levamisole—were evaluated on bovine isolated abomasal and duodenal specimens obtained from routinely slaughtered cows. The obtained results confirmed the contractile effect of all three drugs used solely. Hederagenin and medicagenic acid (0.001 μM) enhanced the contractile effect of levamisole. Hederagenin additionally increased the impact of erythromycin. Both saponins (100 μM) showed synergistic effects with all tested pharmaceuticals. Apigenin and quercetin (0.001 μM) intensified the contractile response induced by erythromycin and levamisole. Moreover, both flavonoids (100 μM) showed an antagonistic interaction with all tested drugs which in that situation were devoid of the prokinetic effect. To conclude, plant metabolic metabolites such as saponins and flavonoids are potent modifiers of the effect of drugs towards gut motility. The synergy observed between phytocompounds and selected medicines can be beneficial in the treatment of cows with hypomotility disorders.     

Muscle relaxants in canine anaesthesia 2: Clinical application

There are a variety of factors which are likely to influence the action of muscle relaxants in canine anaesthesia. These include age, body temperature and muscle diseases. Of the anaesthetic agents it is only the inhalational anaesthetic agents which significantly increase the duration of action of muscle relaxants. Antibiotic therapy particularly with the aminoglycoside antibiotics is likely to increase their duration of action. The indications for the use of muscle relaxants and the main contraindications such as the absence of anaesthetic equipment and the inability to ensure unconsciousness are discussed. The choice of anaesthetic technique together with a discussion on the premedication induction and maintenance of anaesthesia are important factors when using relaxants as is the technique of artificial ventilation. The various advantages and disadvantages of neuromuscular block monitoring are discussed as is the reversal of neuromuscular block.     

促胃肠动力药物研究现状

胃肠动力迟缓类疾病由于发病特征的不显著,在动物身上并未引起足够的重视,但随着近几年畜牧业的不断发展,其发病率不断升高,对国家已造成了不可估量的损失。从药物机制、临床研究等方面对比阐述了人用及兽用促胃肠动力药物的应用现状,旨在为兽用促胃肠动力药物的研发及兽医临床中的使用提供参考。     

Motility of the equine gastrointestinal tract: Physiology and pharmacotherapy

Normal gastrointestinal (GI) motility patterns are necessary to maintain transit of ingesta and to facilitate digestion and absorption of nutrients. Disorders of the equine GI tract are frequently encountered by the equine practitioner and these disorders are often associated with an interruption in normal intestinal motility patterns, thus complicating treatment of the primary disease. Consequently, numerous treatments have been investigated in horses to facilitate the return of normal intestinal motility. The purpose of this article is to provide a brief review of the anatomy and physiology of the GI tract in the horse and review medications available to the equine veterinarian that may potentially promote intestinal motility.     

Gastrointestinal Motility and Disease in Large Animals

An understanding of the relationship between gastrointestinal (GI) motility and disease is imperative for the proper treatment of large animal patients, especially as new therapeutic agents become available. However, the abundance of information that has become available in the last 2 decades makes gaining this understanding a formidable task. This article summarizes the changes in GI motility caused by some common diseases and conditions encountered in large animal practice, such as GI obstruction, postoperative ileus, resection and anastomosis, diarrhea, endotoxemia, GI parasitism, hypocalcemia, and pregnancy. J Vet Intern Med 1996;10:51–59. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

Epidural analgesia in the dog and cat

SUMMARY: A brief outline of the history of epidural analgesia is followed by a review of the anatomy of the epidural space with particular reference to epidural block. The technique of epidural injection in the dog is described as are the indications for the technique. These include the provision of anaesthesia for such procedures as orthopaedic surgery of the hind limb and caesarian section. The cardiovascular effects of epidural block are discussed and suggestions are made for the prevention of hypotension. The various drugs and their combinations which may be used for epidural administration are outlined. The commonest used local anaesthetic agents are bupivacaine and lidocaine. Epidural administration of opioid drugs is a relatively new technique which is used to provide intra- and post-operative analgesia. Morphine is the drug of choice for this indication.The use of other classes of drugs, such as the alpha 2 agonists and ketamine, are also considered. A variety of side-effects, contra-indications and complications are described together with methods for reducing their incidence and effects.     

Medical Management of Recurrent Seizures in Dogs and Cats

The problem of recurrent seizures is a common and challenging one in veterinary medical practice. The pathophysiology and pharmacologic suppression of focal seizure activity have been studied extensively in basic research settings, yet little is known of the genesis, modulation, and termination of generalized seizures, the most common form of seizures noted to occur in companion animals. Knowledge concerning the pharmacokinetic fate of anticonvulsant drugs currently used in veterinary medicine is adequate, though prospective clinical studies of the efficacy of these drugs in the treatment of various types of seizures are lacking. This study will review the available literature regarding the pharmacology, use, and side effects of anticonvulsant drugs currently available for control of recurrent seizures in companion animals. Alternative anticonvulsant drugs will also be described.     

GASTROINTESTINAL NUCLEAR MEDICINE

Nuclear medicine has achieved an important role in the diagnosis of gastrointestinal (GI) disease in humans. Esophageal and gastric motility problems, gastroesophageal reflux, abnormal gastric secretory function, GI bleeding, and inflammatory diseases of the GI tract can all be evaluated using nuclear scintigraphy. The use of these techniques in human medicine, their advantages and disadvantages relative to other available diagnostic tests, and their potential application to veterinary medicine are discussed. Examples of esophageal and gastric motility studies performed on normal and abnormal dogs are included.     

Drugs in salmonid aquaculture – A review

In contrast to mammalian therapeutics, the use of pharmaceutical substances is rather limited in fish. It is basically restricted to anaesthetic agents and anti-infective agents for parasitic and microbial diseases. Anaesthetic agents are used primarily in fish farm and laboratory settings to provide analgesia and immobilization of fish for minor procedures. The anti-infective agents are used for controlling disease and the choice of drug depends on efficacy, ease of application, human safety, target animal safety including stress to the fish, environmental impact, regulatory approval, costs, and implications for marketing the fish. In this article, the major drugs used in salmonids in North America and Europe will be reviewed and some insight into future directions for drug development and use for the salmonid industry will be introduced. The mechanisms of action, pharmacokinetics, side effects, and uses of the drugs are emphasized.