Medical Pharmacology Chapter 13:  Clinical Use: opioid analgesics in pain management

• Opioids and Anesthesia

  • Anesthetic Premedication with opioids advantageous because of:

    • Sedative properties

    • Anxiolytic properties

    • Analgesic properties

• Intraoperative Use and General Uses

  • Adjuncts to other anesthetics

  • At high doses: primary anesthetic component

    • Cardiovascular surgery

    • Other high-risk surgery (desire to minimize cardiovascular depression)

• Intraoperative Use:  Regional Administration:

  • Epidural

  • Subarachnoid spaces

  • Long-lasting analgesia:

    • Catheter inserted into the epidural space

      • Analgesia following morphine or other strong opioid agonist

      • Respiratory depression may occur -- requiring naloxone

      • Common side effects: pruritus, nausea, vomiting-- naloxone reversible

• Other Routes of Administration

  • Rectal suppositories

  • Epidural: action of the spinal level

  • Transdermal patch -- systemic effects;

    • Stable drug plasma levels

    • Better pain control -- no need for repeated parenteral injections

    • Fentanyl -- most successful opioid for transdermal use; effective for management to constant pain associated with malignancies

  • Intranasal: limited use {patients who cannot tolerate oral medication or repeated parenteral drug injections

  • Patient controlled analgesia (PCA):  common use

    • Patient typically use intravenous injection

    • Effective in postoperative pain management; less opioid may be used

    • Potential problems:

      • Equipment malfunction including improper programming/set up which may lead to improper drug delivery

•   Toxicities/Side effects

  •  Tolerance and physical dependence

    • Tolerance:

      • Clinical appearance: two-three weeks following frequent administration of therapeutic doses

      • Large doses at short intervals are associated with most rapid tolerance development.

      • Small doses at long intervals are associated with least rapid tolerance development.

    • Cross-tolerance:

      • Individuals tolerant to morphine effects are also tolerant to other opioid agonists

      • Examples:

        • Meperidine, morphine, methadone, and related compounds exhibit cross-tolerance to:

          1. Analgesic action

          2. Euphoriant effects

          3. Site of actions

  • Physiologic Dependence

    • Failure to administer drug: leads to withdrawal or abstinence syndrome (significant rebound from pharmacologic opioid effects).

    • Antagonist-precipitated withdrawal: rapidly developing, powerful abstinence syndrome cause by administration of naloxone or another antagonist

    • Psychologic Dependence:

    • Basis of compulsive use:

      • Euphoria

      • Sedation

      • Indifference to stimuli

    • Despite the risk of opioid dependence, adequate pain relief should never be withheld just because the opioid has potential for abuse or because of the more complicated prescribing requirements for narcotics.

  • Prescribing Principles and Guidelines:

    1. Early establishment of therapeutic goals; limits physiologic dependence potential; involve patients in this process

    2. Attempt to limit drug dosage to the established therapeutic level

    3. Particularly for chronic pain management consider alternatives to opioids

    4. Frequently re-evaluate therapeutic needs for opioids use

1. Way, W.L., Fields, H.L. and Way, E. L. Opioid Analgesics and Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 496-515.

2. Schuckit, M.A. and Segal D.S., Opioid Drug Abuse and Dependence, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2508-2512;

3. Coda, B.A. Opioids, In Clinical Anesthesia, 3rd Edition (Barash, P.G., Cullen, B.F. and Stoelting, R.K.,eds) Lippincott-Ravin Publishers, Philadelphia, New York, 1997, pp 329-358.