Ch.6- Opiod Drugs (Narcotic drugs)

Introduction/History

  • opium: dried juice from the unripe seed capsules of the opium poppy

  • 1800s: morphine and codeine were isolated from opium

  • Until 1920: Medications containing opium were promoted

  • Oral opioids became unlawful: injection abuse began and continues today

Classification

  • smth

Mechanism of Action

  • opioids bind to receptors located in both the CNS and the spinal cord producing an altered perception of reaction to pain

  • 3 groups of endogenous substances with opioids action (in body)

    • 1. Enkephalins

    • 2. Endorphins

    • 3. Dynorphins

  • 3 important receptors

  1. Mu- stimulation produces analgesia

  2. Kappa- stimulation is responsible for dysphoria

  3. Delta- antagonist of this receptor may cause anxiety.depression

Pharmacokinetics

  • ADME

    • Absorption-

      • Most opioid analgesic agents are absorbed well orally

      • absorption also occurs from the lings the nasal and oral mucosa and the intact skin

    • Distribution

      • Opioids undergo variable first pass metabolism in the liver or intestinal cell wall

      • opioids are bound to plasma proteins and distributed throughout the body

    • Metabolism

      • Major route is in the liver in conjunction with the glucuronic acid

      • given orally most opioids have a duration of action for pain 4-6 hrs

    • Excretion

      • In the kidneys through the glomerular filtration and excreted in the urine

Pharmacologic Effects

  • A PE may also be an adverse rxn depending on the clinical use of the agent. In general the severity of the side effects is proportional to the agents efficacy or strength

    • Analgesia

    • sedation and euphoria

    • cough suppression

    • GI effects

    • adverse rxns

  • Analgesia

    • efficacy is variable among opioids depending on the strength of the agent

    • morphine is the opioid agonist by which other opioids are measured

    • strongest opioid can reduce even the most severe pain while the weaker agents like codeine with nonopiods are equivalent to the NSAIDs in their ability to relieve pain

Selected opioid analgesics

Strongest

Intermediate

Weakest

Morphone

Oxycodone

Hydrocodone

methadone

Pentazocine

Codeine

meperidine

Dihydrocodeine

hydromorphone

  • Sedation and euphoria (usual therapeutic doses)

    • kappa-Receptor stimulation

    • potentiate analgesic effect; relieve anxiety

    • additive with other CNS depressants (alcohol)

    • Remove pain; euphoria results (with larger doses)

  • Cough suppresion:

    • Depress cough center in medulla

    • antitussive effect requires lower dose than required for pain

    • least potent agents are effective (codeine)

  • GI effects

    • Increases smooth muscle tone

    • decreases GI tract propulsive contractions and motility- treatment of diarrhea; diphenoxylate (Lomotil)

ADVERSE REACTIONS

  • AR of opioids are note related to a direct damaging effect on hepatic, renal, or hematologic tissues but instreat are an extension of the PR. Adverse rxns of the opioid analgesics are proportional to their analgesic strength

    • Respiratory depression

    • Nausea and emesis

    • constipation

    • miosis

    • urinary retention

    • CNS effects

    • Biliary Tract Constriction

    • Histamine release

  • Respiratory depression

    • Not a problem with usual doses in normal pts

      • Cause of death with overdose

      • Elderly- decrease in pulmonary

  • Nausea and Emesis; constipation

    • Nausea and emesis

      • analgesic doses often cause nausea and vomiting

      • Result of direct stimulation of the chemoreceptor trigger zone in medulla

      • Side effect is reduced if the pt. does not ambulate (walk)

      • Repeat, regular doses of an opioid can prevent

    • Constipation

      • causing a tonic contraction of the GI tract (sustained contraction)

      • Small doses often have this effect

      • Duration outlast their analgesic effect