Nursing Pharmacology Chapter 13:  Pain Management:  Opioids

Pharmacokinetics

• Absorption

  • Opioid analgesics are generally well absorbed by cutaneous/intramuscular/mucosal surfaces

  • Transdermal fentanyl represents an important Route of Administration

  • Gastrointestinal absorption:

    • Some opioids are subject to first-pass effects:

    • Codeine and oxycodone exhibit high oral: parenteral potency

• Distribution

  • Various extent of plasma protein binding

  • Highest concentrations in tissues will be a  function of perfusion

  • Skeletal muscle represents the largest reservoir

  • For highly lipophilic opioids (e.g. fentanyl), there is significant concentration in adipose tissue

  • Blood Brain Barrier:

    • Amphoteric agents (possessing both an acidic and basic group, e.g. morphine {phenolic hydroxyl at C₃}: greatest difficulty for brain entry

    • Other substitutions that C₃ improve blood-brain barrier penetration: e.g., heroin, codeine

    •  Neonatal considerations: neonates lack the blood-brain barrier:

      1.    Placental opioid transfer (uses in obstetric analgesia) can result in depressed respiration in the newborn.

• Metabolism

  • Conversion to polar metabolites facilitates renal excretion.

    • Opioids with hydroxyl groups are likely conjugated with glucuronic acid

      • Examples: morphine, levorphanol (Levo-dromoran) 

      • Morphine-6-glucuronide: analgesic potency of the metabolized may be greater than that of the  parent compound, morphine.

      • In patients with compromised renal function, accumulation of metabolites occurs which prolongs  analgesia

  • Esters-type opioids are: hydrolyzed by tissue esterases:

    • Examples: heroin, remifentanil (short duration of action)

  • N-demethylation the is a minor metabolic pathway.

    • Accumulation of demethylated meperidine (Demerol)  metabolite, normeperidine:

      • Patients with decreased renal function or on high dosages may exhibit central nervous system (CNS) excitatory effects:backspace.

        •   For example, seizures may occur and are more likely observed in children.

  • Oxidative metabolism (hepatic) represents the primary route of phenylpiperidine opioid metabolism such as:

    • Fentanyl (Sublimaze)

    • Alfentanil (Alfenta)

    • Sufentanil (Sufenta)

• Excretion

  • Polar metabolites are excreted by the kidney with small amounts of drug excreted unchanged

  • Glucuronide conjugates are excreted in the bile with enterohepatic circulation contributing only to a minor extent.