Blackwell's Five-Minute Veterinary Consult Clinical Companion. Группа авторов

       Natural opioids are found in the seeds of the opium poppy (Papaver somniferum). Opium powder is about 10% morphine and 0.5% codeine. Oxymorphone, codeine, hydromorphone, and heroin are derived from morphine.

       There are numerous synthetic opioids on the market manufactured primarily for human and animal pain relief and tranquilization. Most are not FDA‐approved for horses.

       The exact mode of action varies slightly by drug due to different receptor activity and affinity.

       The primary effects are seen in the CNS; however, there are opioid receptors throughout the body.

       Most pain relief is via agonists binding to mu receptors in the CNS and periphery. Mu receptors vary in location and density for horses compared with other species.

       Opioids licensed for equine patients:Butorphanol (kappa agonist and mu antagonist) – schedule IV, pain management (good for equine GI pain).Pethidine (Meperidine) – schedule II, pain management, labeled for spasmodic colic.Buprenorphine (partial mu agonist) – pain management.

       Other opioids used in equine health care, but not licensed specifically for equine patients:Fentanyl (pure mu agonist).Tramadol.Morphine (pure mu agonist).Nalbuphine (partial agonist/antagonist similar to butorphanol) – not DEA.Remifentanil.Methadone (pure mu agonist).Hydromorphone.

       Opioids easily cross the blood–brain barrier allowing for receptors causing cough reflex suppression, respiratory depression, and a depressed CNS.

       Clinical findings include decreased in gut motility and increased water absorption, causing constipation and impaction. Clinically, this is usually observed at high doses.

       Existing toxicology research is in humans, dogs, and cats with variations in the lethal doses in each species.

       Use of opioids (particularly mu agonists), historically, has been limited in the horse due to adverse side effects. In horses, clinical signs of toxicosis include excitation, agitation, increased locomotor activity and decreased gut motility. Side effects are likely due to the receptors’ affinity for the medications and how densely the receptors are in their specific locations in the equine brain.

       The major opioid receptors are mu (μ), delta (δ), and kappa (κ). Opioid receptors are found in many locations such as the CNS, autonomic nervous system, GI tract, heart, kidney, pancreas, adipocytes, and on the surface of lymphocytes.

       When the body senses pain or stress, opioid receptors are stimulated by endogenous endorphins and enkephalins.

       Similarly, opiates have various affinity and, when administered, they function as agonists, antagonists, or as both at their unique opioid‐binding site. When activated, the following specific actions occur:μ 1 – supraspinal analgesia.μ 2 – spinal analgesia, respiratory suppression, decreased gut motility.δ – higher affinity for enkephalins, spinal analgesia.κ – spinal and supraspinal analgesia, sedation, dysphoria.

       Each opiate has a unique half‐life and level of toxicity.

       Onset is 5–10 minutes after IV administration.

       Duration of action is 2–6 hours, which may be prolonged if in the extradural space.

       Poor lipid solubility.

       Hepatic metabolism.

       Renal excretion.

       Toxicity is dose‐dependent. Clinical signs, especially respiratory, are observed at therapeutic doses. Severe adverse effects and death can occur at high concentrations.

       Neurological – decreased CNS activity, initial excitation leading to depression, hypothermia, seizures, coma, death.

       Respiratory – depression.

       Gastrointestinal – decreased motility, increased water absorption.

       Cardiovascular – bradycardia, possible vasodilation, hypotension.

       Neonates have undeveloped blood–brain barrier, making them more susceptible.

       Opioid toxicosis in the horse is usually iatrogenic.

       Iatrogenic.

       Inadvertent exposure via ingestion of fentanyl patches.