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

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


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      Mechanism of Action

       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.

      Toxicokinetics (based upon morphine – others may vary)

       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

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

      Systems Affected

       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.

SIGNALMENT/HISTORY

      Risk Factors

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

       Opioid toxicosis in the horse is usually iatrogenic.

      Historical Findings

       Iatrogenic.

       Inadvertent exposure via ingestion of fentanyl patches.

CLINICAL FEATURES

       Because toxicity would likely result from iatrogenic administration in the horse, it is imperative that the clinician is cognizant of clinical signs associated with CNS excitation then depression, GI stasis causing episodes of colic, and decreased pulmonary/cardiovascular activity.

DIFFERENTIAL DIAGNOSIS

       Dermorphin administration.

       Electrolyte imbalance.

       CNS Stimulants (amphetamine, methamphetamine).

       CNS depressants (benzodiazepine).

       Colic of other etiology.

       Ethanol.

       Ethylene glycol.

       Ivermectin.

       Marijuana toxicosis.

DIAGNOSTICS

      CBC/Serum Chemistry

       Hypoglycemia.

       Elevated BUN.

      Other Diagnostic Tests

       Arterial blood gas.

       LC‐MS.

THERAPEUTICS

      Detoxification

       Remove the source of the toxicosis.

       Provide supportive care as needed.

       If suspected, oral overdoses could be evacuated via nasogastric intubation. Once evacuated, administer activated charcoal at 1 g/kg with mineral oil and water to help decrease absorption of the medication, and assist with the potential GI stasis/impaction.

      Appropriate Health Care

       Monitor cardiovascular and respiratory activity. Assisted ventilation may be essential if severely overdosed.

       Gastrointestinal activity may be greatly compromised and monitoring for possible GI stasis should be considered.

      Antidotes

       Naloxone 0.01–0.02 mg/kg up to 0.05 mg/kg IV bolus. Note: the half life is 1–1.5 hours and may have to be repeated because its half‐life is shorter than morphine.

       Butorphanol (for pure mu agonist) – 0.01–0.1 mg/kg IV, IM.

      Drugs of Choice

       IV fluids as needed for volume expansion and dehydration.

       Cardiovascular:Atropine (anticholinergic, but will decrease gut motility) – 0.02 mg/kg IV.Glycopyrrolate (anticholinergic, but will decrease gut motility) – 0.005 mg/kg IV.

       GI Protectants:Omeprazole 2–4 mg/kg PO q24h.N‐methylnaltrexone (research only) – does not cross blood–brain barrier and may reduce negative GI effects when a mu agonist such as morphine has been given.

       CNS signs:Detomidine 0.02‐0.04 mg/kg IV or IM.Xylazine 1.1 mg/kg IV; 2.2 mg/kg IM.

      Precautions/Interactions

       Pethidine (Meperidine) is short‐acting. Can cause seizures if administered IV. Diazepam or pentobarbitone would help control these clinical signs.

       Avoid use in horses with renal insufficiency.

       Fentanyl has been noted to be a heavy respiratory depressant, and mechanical ventilation should be used with gas anesthesia.

       Caution should be used if administering other depressants with opioids as the negative side effects could increase. Benzodiazepines should be avoided.

       Ethanol is contraindicated.

       Respiratory depression in neonates has been described when morphine has been administered to mares prior to birth.


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