Opioid Analgesics: Agonists and Agonist-Antagonists

• Two types of opioid analgesics treat pain: opioid agonists and opioid agonist-antagonists.
• Opioid agonists primarily bind to mu-type opioid receptors, producing analgesic effects.
• Opioid agonist-antagonists bind to mu and kappa receptors, simultaneously stimulating and blocking analgesic effects.
• Opioid agonist-antagonists are less effective at reducing pain but serve as alternatives for opioid-addicted clients or women in labor.
• Opioid agonists act as analgesics for moderate to severe pain.
• They are used to induce sedation and lessen anxiety in preoperative clients.

Prototype and Other Medications

• Morphine is the prototype medication for opioid agonists.
• Other medications include fentanyl, meperidine, hydromorphone, and methadone.
• Meperidine is a synthetic opioid, rarely used for postoperative pain due to interactions and poor tolerance in older adults.
• Methadone is a synthetic opioid used as a substitute for opioids in substance use disorder programs.
• Methadone blocks euphoric effects of opioids and reduces cravings.
• Other common opioid agonists include codeine, oxycodone, hydrocodone, and tapentadol.

Expected Pharmacologic Action

• Opioid agonists mimic naturally occurring opioids by binding with mu receptors.
• Stimulation of mu receptors causes analgesia, sedation, euphoria, and respiratory depression.

Adverse Drug Reactions

• Adverse reactions such as respiratory depression and sedation occur due to stimulation of mu opioid receptors.
• Sedation often causes dizziness, lightheadedness, and drowsiness.
• Constipation is a common adverse reaction due to decreased intestinal motility.
• Opioid-related medications may treat diarrhea.
• Nausea and vomiting may occur after administration.
• Opioid agonists dilate peripheral vasculature, causing orthostatic hypotension.
• Urinary retention occurs by decreasing perception of a full bladder.
• Cough suppression is an adverse reaction, unless used to suppress coughing.
• Opioids have a high misuse potential due to euphoria from mu receptor stimulation.
• Tolerance and cross-tolerance develop with chronic use, requiring larger doses.

Interventions

• Closely monitor vital signs and oxygen saturation.
• Auscultate lungs for congestion.
• Observe for decreased respiratory rate; withhold medication and stimulate breathing if below 12/min.
• Administer opioid antagonist (naloxone) to reverse respiratory depression.
• Monitor clients when ambulating due to orthostatic hypotension.
• Monitor bowel function and provide fiber supplements and stool softeners for constipation.
• Give medication with food and administer antiemetic for vomiting.
• Ensure adequate hydration.
• Monitor intake and output and watch for urinary retention.
• Encourage urination every 4 hours.
• Prepare to insert a urinary catheter if client is unable to urinate and bladder distention is evident.
• Encourage frequent coughing postoperatively to prevent respiratory secretion retention.
• Prescribe the lowest possible effective dose on a short-term basis to prevent dependence.

Administration

• Obtain baseline vital signs before administration and monitor throughout therapy.
• Opioid agonists can be given orally, intramuscularly, intravenously, subcutaneously, rectally, or epidurally.
• Instruct clients to swallow sustained-release forms whole without crushing or chewing.
• Dilute intravenous opioids and administer slowly (over 4 to 5 minutes).
• Have naloxone and resuscitation equipment available.
• Monitor client-controlled analgesia pump use and settings carefully.
• Give medications on a fixed, around-the-clock schedule for terminal cancer pain.

Safety Alert

• Clients in acute care settings are often under-medicated for pain due to dependence concerns.
• Short-term use has little to no risk of dependence.
• Physical dependency may develop with long-term opioid use with gradual withdrawal over several days can minimize withdrawal.
• Opioid withdrawal manifestations: abdominal cramps, diarrhea, agitation, anxiety, hypertension, tachycardia, tremors, muscle pain, pupil dilation, runny nose, and insomnia.
• Opioid use disorder: strong desire for medication in the absence of pain.
• Treat pain based on client's self-report.

Client Instructions

• Only take the medication when needed and on a short-term basis.
• Avoid taking opioid agonists prior to driving or activities requiring mental alertness.
• Sit or lie down immediately if feeling lightheaded.
• Rise slowly from reclining or sitting to prevent falls due to dizziness and orthostatic hypotension.
• Increase fluid and fiber intake and exercise to prevent constipation.
• Take medication with food or milk if nausea and vomiting occur.
• Report any difficulty or inability to urinate.
• Cough regularly to clear secretions and prevent pneumonia.

Contraindications and Precautions

• Contraindicated in pregnant women due to the risk of respiratory depression or neonatal opioid withdrawal.
• Contraindicated for clients with renal failure, increased intracranial pressure, biliary colic/surgery, or preterm labor.
• Use with caution in all clients as a Schedule II controlled substance.
• Administer carefully to older adults and infants.
• Administer carefully to clients with reduced respiratory reserve, head injury, inflammatory bowel disease, prostatic enlargement, hypotension, and hepatic or renal disease.

Interactions

• Opioid agonists increase CNS depressant effects when combined with CNS depressants (barbiturates, phenobarbital, benzodiazepines, alcohol).
• Anticholinergic effects increase when given with anticholinergic agents (antihistamines, tricyclic antidepressants), causing constipation and urinary retention.
• MAOIs with meperidine can cause hyperpyrexia syndrome (excitation, seizures, high temperature).
• Concurrent use with antihypertensives increases hypotensive effects.
• St. John’s wort may increase sedation.

Question

• Instructions to include when a client is about to start oral morphine:
  • Take with food
  • Rise slowly from sitting or reclining
  • Increase fluid and fiber intake
  • Do not take it before driving