Opioids are commonly used in veterinary medicine for their analgesic, sedative, and anti-diarrheal properties. Opioids are
also effective antitussive agents and in appropriate doses opioids can provide anxiolytic effects. The analgesic effects of
opioids are mediated primarily through activity in the central nervous system (CNS) including the spinal cord and brain. Effects
on the gastrointestinal tract (GIT) are primarily local effects and include decreased propulsive contractions, increased segmental
contractions, and decreased fluid secretions. Local analgesic effects can also be obtained by direct injection into the synovium.
Leukocytes, which have opiate receptors, are also affected by opioids eliciting a range of effects, from immunostimulation
to immunosuppression. Studies in humans have demonstrated that withholding opioids in painful patients that are immunocompromised
results in worsened immune function.
Mu opioid agonists (morphine, hydromorphone, fentanyl) result in dose-dependent analgesia with larger doses eliciting a greater
effect. Mu opioids are effective in treating mild to severe pain. In contrast the partial mu agonist buprenorphine and kappa
agonists (butorphanol, nalbuphine) have a ceiling effect, in which a sub-maximum level of analgesia is achieved and additional
doses do not result in increased analgesic effects. Partial agonists are effective in treating mild to moderate pain.
Respiratory Effects
Mu opioid agonists produce a dose-dependent respiratory depression in animals while partial mu agonists and kappa agonists
produce sub-maximum respiratory depression. In contrast to humans, the respiratory depressant effects of opioids in healthy
animals administered clinically recommended doses produce minimal respiratory depression. Doses as high as 50 to 100 times
the clinically recommended doses of morphine resulted in severe respiratory depression, but not death in animals. However
animals with underlying respiratory disease (bronchitis, asthma, pleural effusion, cor pulmonale, etc.) are at in increased
risk for respiratory adverse effects. Animals with head trauma are at an increased risk of cerebral edema when administered
opioids as the opioids decrease the animal's response to increasing carbon dioxide levels which can potentially worsen cerebral
edema.
Antitussive Effects
Opioids also have antitussive effects which are independent of the respiratory depressant effects. Mu opioid agonists (morphine,
hydrocodone, codeine, et al), buprenorphine, and kappa agonists (butorphanol) are effective antitussive agents. Tramadol also
has antitussive effects in experimental models, but its effectiveness has not been investigated clinically. The efficacy of
tramadol in dogs as an antitussive is expected to be less than other species as the active metabolite is not produced in consistent
or high concentrations.
Cardiovascular Effects
Clinically recommended dosages of opioids have minimal effects on the cardiovascular system in animals. The effects of IV
morphine at clinically recommended doses on the blood pressure of dogs have been variable ranging from mild decreases to mild
increases. Histamine concentrations increase following IV morphine injection, but the clinical relevance appears to be minimal
as changes in cardiovascular parameters, including blood pressure, are minimal. In contrast to humans, dogs administered morphine
(at higher than recommended doses) had increased coronary vascular resistance and decreased coronary blood flow. Therefore,
routine administration of morphine for the treatment of congestive heart failure is not recommended. Opioids result in minimal
effects on cardiac output, however decreased heart rate is routinely observed in dogs. Morphine also exerts protective effects
towards ventricular tachycardia.
Thermoregulation
Panting commonly occurs in dogs after administration of opioids. Opioids affect the thermoregulatory center in the hypothalamus
in dogs which results in a decrease in body temperature due to the increased panting. It is not uncommon for dogs to become
hypothermic when administered opioids. In cats, the opposite effect is occasionally seen, in which the body temperature increases,
and may occur more frequently with hydromorphone.
Emesis
Opioids (primarily morphine, hydromorphone) can result in emesis following administration to dogs and cats that is thought
to be primarily due to stimulation of the chemoreceptor trigger zone (CRTZ). Conversely, some opioids act as antiemetics on
the emetic center in the brain. Butorphanol (0.2 - 0.4 mg/kg IV, IM, SC) has been used as an antiemetic in dogs and cats receiving
chemotherapy in which the vomiting is not controlled with standard antiemetic drugs. Fentanyl also has demonstrated antiemetic
effects. Chronic administration of opioids may result in GI stasis and ileus with vomiting resulting from decreased GIT motility.
