Nursing Pharmacology Chapter 13:  Pain Management:  Opioids

Pharmacodynamics

• Mechanism of Action

  • Analgesia: Specific receptor binding site localization includes:

    • Spinal cord

    • Brain

• Receptor Types:

  • Mu (μ)

  • Delta (δ)

  • Kappa (κ)

  • General Opioid Receptor Characteristics:

    • G protein coupled receptor family

    • Significant amino acid sequence homology

    • Each-receptor: subtypes

      • μ₁, μ₂

      • δ₁, δ₂

      • κ₁, κ₂

  • Receptor types and physiological effects:

    • Mu (μ):

      • Analgesia

      • Euphoria

      • Respiratory depression

      • Physiological dependence

    • Most opioid analgesics: act at the μ receptor

    • Delta (δ) and Kappa (κ) are associated with spinal analgesia

  • Drugs/endogenous opioids: Receptor types and their drug affinities:

    • Morphine (μ receptor)

    • Pentazocine (κ receptor) with some activity at the μ receptor.

    • Vndogenous opioid peptides:

      • leu-enkephalin activities associated with the δ receptor.

      • dynorphin activity involves the κ receptor.

• Cellular Action

  • Opioids responses involve G protein linkage through which the following activities may be modulated:

    • Ion channel state

    • Intracellular Ca²⁺ levels

    • Protein phosphorylations states

  • Two well-defined opioid actions:

    1. Reduce neurotransmitter release; by closing a voltage-gated Ca²⁺ channel on presynaptic neuronal terminals Or

    2. Inhibit postsynaptic neurons (hyperpolarization) by increasing and K⁺ channel conductance

• Spinal cord presynaptic sites

  • Reduced transmitter released:  affects acetylcholine, norepinephrine, glutamate, serotonin, substance P