Precautions when using opioid agonist-antagonist analgesics.

Agonist-antagonists are attractive because of their availability and absence of strict regulation. They do provide effective analgesia in many cases, and they are cost-effective. Incomplete analgesia can be noted in moderate to severe pain. Cardiopulmonary depression may be noted following agonist-antagonist administration. Interference with coadministered opiate agents may occur.     

Precautions when using opioid agonist analgesics.

Opioid agonist analgesics are effective drugs for treating postoperative pain. Contraindications for their use are primarily respiratory depression and increased intracranial pressure. Their use may mask potentially serious postoperative complications.     

Alpha-2 adrenergic agonists as analgesics in horses.

Administration of alpha-2 agonists to horses produces a variety of behavioral effects (sedation, somnolence, analgesia), and physiological effects. One of the most significant beneficial effects of administering alpha-2 agonists is the degree of analgesia they provide. Alpha-2 agonists have been the mainstay of analgesia for colic pain in horses since their introduction to clinical veterinary medicine. The increased potency of the more recently introduced alpha-2 agonists allows the provision of analgesia for conditions not previously relieved by other drugs. Unfortunately, there are significant side effects associated with alpha-2 agonist administration. Studies are underway to identify the physiologic effects associated with the stimulation of each alpha-2 receptor subtype, in hopes of developing subtype-specific alpha-2 agonists and antagonists.     

Advantages and guidelines for using opioid agonist-antagonist analgesics.

The opioid agonist-antagonists are not controlled substances requiring strict record keeping and security because of their low abuse potential. They are effective analgesics in their own right and can be used to antagonize opioid agonist-induced depression while retaining a degree of analgesia. Respiratory depression is less than that induced by opioid agonists, but degree of analgesia is somewhat limited also owing to the ceiling effect.     

The case for the routine use of analgesics.

Surgery is painful and it behooves us, as people who care for and take care of animals, to prevent their suffering whenever possible. Recent developments in the understanding of nociceptive physiology underscores this prospective, rather than retrospective, approach to the management of pain. We have the armamentarium to do this and there are very few deleterious side effects when appropriate treatments are used.     

Opioid modulation of the hypothalamo-pituitary-adrenal axis in dairy cows.

Plasma cortisol responses to an intravenous bolus treatment with 250 mg naloxone, 300 mg morphine or a combination, were studied in Holstein-Friesian cows; 4 in early lactation (29-43 d postpartum) and 7 in mid-lactation (90-155 d post-partum). Blood samples were collected every 15 min from 60 min before to 90 min after treatment. Naloxone induced an immediate increase in cortisol concentration, reaching a peak within 30 min. The cortisol response (area under the curve) was positively correlated with pre-naloxone cortisol concentrations (r = 0.7, p < 0.05). The mean increase in cortisol concentration after naloxone appeared to be lower in early lactation (1.8 ng/ml) than in mid-lactation (8.3 ng/ml). In contrast, morphine consistently suppressed mean tonic plasma cortisol concentration by 2.7 ng/ml below baseline for at least 90 min. When given with morphine, naloxone counteracted the suppressive effects; the cortisol response was similar to that after naloxone alone. A cow in mid-lactation, suffering from chronic lameness (joint infection), gave opposite results, i.e., treatment with morphine alone increased cortisol concentration, whereas morphine with naloxone did not result in the expected large increase in plasma cortisol concentration. In conclusion, the hypothalamo-pituitary-adrenal axis of dairy cows appears to be under suppressive opioidergic control. However, the opioidergic system involved in hypothalamo-pituitary-adrenal functions of an animal under chronic stress behaved in an opposite manner.     

Pharmacogenetics of opioid analgesics in dogs

Genetic variation causes interindividual variability in drug absorption, distribution, metabolism and excretion. These pharmacokinetic processes will influence the observed efficacy and toxicity of a drug. Polymorphisms in the genes encoding the metabolizing enzymes, transport proteins and receptors have been linked to the inconsistency in responses to opioid treatment in humans and laboratory animals. Pharmacogenetics is relatively less developed field in veterinary medicine compared to significant advances in knowledge on genetic basis of variation in drug responses and clinical applications in human medicine. This review discusses the opioid drug metabolism and possible genetic polymorphism of metabolizing enzymes in dogs. Polymorphism of genes encoding opioid drug transporter proteins and its effect on opioid response and opioid receptor gene variants are also discussed. Due to the scarcity of studies reported on opioid pharmacogenetics in dogs, relevant studies in humans and rodents have also been discussed to indicate current trends and potential targets for research in dogs.     

Postoperative use of analgesics in dogs and cats by Canadian veterinarians.

Four hundred and seventeen Canadian veterinarians were surveyed to determine their postoperative use of analgesics in dogs and cats following 6 surgical procedures, and to determine their opinions toward pain perception and perceived complications associated with the postoperative use of potent opioid analgesics. Three hundred and seventeen (76%) returned the questionnaire. The percentage of animals receiving analgesics postoperatively ranged from 84% of dogs and 70% of cats following orthopedic surgery to 10% of dogs and 9% of cats following castration. In general, with the exception of orthopedic surgery, roughly equal percentages of dogs and cats received postoperative analgesics. Opioids were used almost exclusively to provide postoperative analgesia, with butorphanol the most commonly administered drug to both dogs and cats. Analgesics were usually administered either once or twice postoperatively. With regard to the administration of potent opioid agonists, the 3 major concerns included respiratory depression, bradycardia, and sedation in dogs, and excitement, respiratory depression, and bradycardia in cats. Seventy-seven percent of veterinarians considered their knowledge of issues related to the recognition and control of postoperative pain to be inadequate. Experience in practice is currently the major source of knowledge, with undergraduate veterinary school and research articles in journals ranked as the least important sources. Lectures or seminars delivered at the regional level were the preferred format for continuing education.     

Opioid dysphoria in three dogs

Objective: To describe the clinical manifestations and response to management of opioid dysphoria in 3 dogs. Case summary: Three dogs being managed for post‐operative pain were evaluated. All 3 dogs had been managed with various opioids including morphine, hydromorphone, and fentanyl following the surgical procedure. The 3 dogs exhibited vocalization that did not respond to interaction and did not change with administration of analgesic and anxiolytic agents. The dogs were treated with naloxone and, within 5 minutes of its administration, ceased vocalizing, and became aware and interactive with their environment. Further pain management consisted of non‐steroidal anti‐inflammatory medications, alpha‐2 (α₂) receptor agonists or the partial μ‐receptor opioid agonist, buprenorphine. New and unique information provided: Vocalization and lack of response to interaction with humans are clinical signs which can be seen in dogs with opioid dysphoria, and generally are not responsive to analgesics or sedation. Reversal with naloxone results in rapid resolution of vocalization and opioid‐induced dysphoria.     

Factors influencing the postoperative use of analgesics in dogs and cats by Canadian veterinarians.

Four hundred and seventeen Canadian veterinarians were surveyed to determine their postoperative use of analgesics in dogs and cats following 6 categories of surgeries, and their opinion toward pain perception and perceived complications associated with the postoperative use of potent opioid analgesics. Three hundred and seventeen (76%) returned the questionnaire. An analgesic user was defined as a veterinarian who administers analgesics to at least 50% of dogs or 50% of cats following abdominal surgery, excluding ovariohysterectomy. The veterinarians responding exhibited a bimodal distribution of analgesic use, with 49.5% being defined as analgesic users. These veterinarians tended to use analgesics in 100% of animals following abdominal surgery. Veterinarians defined as analgesic nonusers rarely used postoperative analgesics following any abdominal surgery. Pain perception was defined as the average of pain rankings (on a scale of 1 to 10) following abdominal surgery, or the value for dogs or cats if the veterinarian worked with only 1 of the 2 species. Maximum concern about the risks associated with the postoperative use of potent opioid agonists was defined as the highest ranking assigned to any of the 7 risks evaluated in either dogs or cats. Logistic regression analysis identified the pain perception score and the maximum concern regarding the use of potent opioid agonists in the postoperative period as the 2 factors that distinguished analgesic users from analgesic nonusers. This model correctly classified 68% of veterinarians as analgesic users or nonusers. Linear regression analysis identified gender and the presence of an animal health technologist in the practice as the 2 factors that influenced pain perception by veterinarians. Linear regression analysis identified working with an animal health technologist, graduation within the past 10 years, and attendance at continuing education as factors that influenced maximum concern about the postoperative use of opioid agonists.     

Non-steroidal anti-inflammatory analgesics: a review of current practice

Objective: This review is intended to update the reader on the clinical aspects of the non‐steroidal anti‐inflammatory analgesics (NSAIAs) currently used in veterinary practice. Most NSAIAs act by selectively, or preferentially, inhibiting the synthesis of cyclooxygenase (COX)‐1 or COX‐2, or both COX‐1 and COX‐2 enzymes which oxidize arachadonic acid to a series of prostenoids. The prostenoids are precursors of various prostaglandins required for many homeostatic functions throughout the body. The COX‐1 and COX‐2 enzymes are constitutive, however the COX‐2 enzyme is also induced following injury or inflammation facilitating the transmission of pain. As the newer NSAIAs focus on the inhibition of COX‐2, this review offers a more detailed discussion of this enzyme. Data synthesis: This data was obtained from recent review articles and original published reports in both the veterinary and human literature. A CAB and Medline search was also used. Conclusions: The NSAIAs are effective analgesics for managing moderate to severe pain in many species of animals; however, potential adverse effects may occur if used inappropriately. Guidelines, including indications, contraindications and dosing regimens for the commonly available NSAIAs are included.     

Effect of analgesics on the castration of male piglets

According to the current German animal welfare law, male piglets may be surgical castrated without anaesthesia up to four weeks of life. This surgical procedure is painful during and also after the operation, for newborn animals as well as for adults. This study was aimed to investigate the impact of preoperative application of analgesics (Meloxicam) on the postoperative castration - pain of four to six days old male piglets. In this investigation all animals were randomly distributed in three groups:the first one was only immobilized but had no surgery, the second one was castrated without analgesics, and the third group was castrated after application of Meloxicam. Blood samples were taken immediately before immobilization, castration or application of the analgesic as well as one, four and 28 hours afterwards to determine Cortisol-concentration in the blood serum and, via this stress-marker, to indirectly evaluate the postoperative und possible intraoperative castration-pain. As a result all piglets castrated without preoperative application of Meloxicam showed significantly increased Cortisol-concentration one and four hours after castration. In contrast, piglets castrated with analgesics resulted in no significant increase during the entire experiment.