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Medical Pharmacology Chapter 13:  Opioid Pharmacology Lecture, slide 5

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Table of Contents: Opioids

  • Nomenclature

  • Opioids Definition

  • Source

  • Classification/Chemistry

    • Opioid Classification

    • Chemical Substitution

  • Endogenous Opioid Peptides

  • Pharmacokinetics

    • Absorption

    • Distribution

    • Metabolism

    • Excretion

  • Pharmacodynamics

    • Mechanism of Action

    • Receptor Binding

    • Receptor Types

    • General Opioid Receptor Properties

    • Opioid Receptor Subtypes: Table

    • Cellular Actions

      • G-Protein Links

      • Two well-defined Actions

      • Spinal Cord Sites of Action

        • Presynaptic Sites

    • Opioid Receptor Distribution

  • Systemic Opioid Administration

  • Tolerance and Physical Dependence

  • Opioid Effects: Degree of Tolerance Developed

Organ Systems

  • CNS

    • Analgesia

      • Spinal Cord

      • Supraspinal Sites of Action

      • Clinical Implications

    • Euphoria

    • Sedation

    •  Respiratory Depression

    • Cough Supression

    • Miosis

      • Clinical Implications

    • Truncal Rigidity

    • Nausea and Vomiting

  • Cardiovascular Effects

  • Gastrointestinal Effects

    • Constipation

  • Biliary Tract

  • Genitourinary Tract

  • Uterus

  • Neuroendocrine

  • Pentazocine  (Talwain)(and other)-- agonist-antagonists

  • Opioid Analgesics: Efficacy; Oral/Parenteral Potency Ratio

  • Summary of Opioid Analgesic Toxic Effects

Clinical Use: Opioid Analgesics

  • Analgesia

    • Obstetrical Labor

    • Renal/Biliary Colic

    • Acute Pulmonary Edema

    • Cough

    • Diarrhea

  • Opioids and Anesthesia

    • Anesthetic Premedication

    • Intraoperative Use-general

    • Intraoperative Use-regional

    • Other routes of Administration

  • Toxicity and Side Effects

    • Tolerance

    • Cross-Tolerance

    • Physiologic Dependence

    • Antagonist-Precipitated Withdrawal

    • Psychological Dependence

    • Prescribing Principles and Guidelines

    • Management/Treatment of Overdosage

    • Contraindications/Therapeutic Cautions

      • Pregnancy

      • Impaired Lung Function

      • Impaired Liver/Kidney Function

      • Endocrine Disorders

Specific Drugs

  • Strong Agonists

    • Phenanthrenes

      • Morphine

      • Hydromorphone

      • Oxymorphone (Numorphan)

    • Phenylheptylamines

      • Methadone (Dolophine)

        • pharmacodynamics

      • Levomethadyl acetate

    • Phenylpiperidines

      • Meperidine (Demerol)

      • Fentanyl Group

        • Fentanyl (Sublimaze)

        • Sufentanil  (Sufenta)

        • Alfentanil (Alfenta)

        • Remifentanil (Ultiva)

    • Morphinans: -- Levorphanol  (Levo-dromoran)

  • Mild/Moderate Agonists

    • Codeine, oxycodone (Roxicodone), dihydrocodeine, hydrocodone

    • Propoxyphene(Darvon)

    • Diphenoxylate (Lomotil)

    • Loperamide(Imodium)

  • Mixed Agonist-Antagonists & Partial Agonists

    • Nalbuphene

    • Buprenorphine (Buprenex)

    • Butorphanol

    • Pentazocine

    • Dezocine

  • Miscellaneous

    • Tramadol

  • Antitussives

  • Opioid Antagonists-Naloxone, Naltrexone, Nalmefene

    • Pharmacodynamics

    • Clinical Use


Clinical Use: opioid analgesics

  • Analgesia

    • Opioids most effective: severe, constant pain

    • Opioids less effective: sharp, intermittent pain

    • Selection and evaluation of opioids-- Factors:

      • Route of Administration (oral or parenteral)

      • Maximal efficacy

      • Therapy duration

      • Previous experience

  • Management of cancer pain; pain associated with other terminal illnesses -- Principles

    • Adequate treatment

    • Concerns about dependence and tolerance -- secondary consideration

    • Fixed-interval opioid administration: more effective than dosing on demand

      • slower released dosage forms (new) -- may provide longer and more consistent analgesia levels

    • Addition of stimulants (e.g. amphetamines): enhance opioid analgesic effects

    • Clonidine (α2 adrenergic receptor agonist): may be useful in pain management

  •  Obstetrical labor:

    • Minimize fetal/neonatal opioid depression

    • Opioid depression: reversible by naloxone

    • Phenylpiperidine agents (e.g. meperidine): may produce less depression, especially respiratory depression in the newborn compared to morphine

  • Renal/Biliary Colic:

    • Adequate pain relief: strong agonist opioid required

    • Increased dosages may be necessary to overcome increased pain secondary to increased smooth muscle tone

  • Acute Pulmonary Edema:

    • IV morphine: relieves dyspnea secondary to pulmonary edema

    • Possible mechanism of action:

      • Reduced awareness of shortness of breath

      • Reduced patient anxiety

      • Reduced preload (decreased vascular venous tone)

      • Reduced afterload (decreased peripheral resistance)

  •  Cough:

    • Cough suppression occurs at lower doses than for opioid analgesia

    • Reduced usage of opioids for cough suppression: due to non-analgesic, non-addictive synthetic agents

  • Diarrhea:

    • All diarrhea controllable with opioids

    • If diarrhea secondary to infection, treat the infection with appropriate chemotherapy

    • Current antidiarrheals utilize agents selected for the gastrointestinal tract with limited CNS actions


  •  Opioids and Anesthesia:

  • Intraoperative Use --general:

    • Adjuncts to other anesthetics

    • At high doses: primary anesthetic component

      • Cardiovascular surgery

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

  • Intraoperative Use -- regional

    • 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 --short intervals: most rapid tolerance development

        • Small doses --long intervals: 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).

Some Symptoms of Opioid Withdrawal





Muscular aches







  • 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

      • Abdominal effects -- likened to intense sexual orgasm

    • 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


  •   Management/Treatment of Opioid Overdosage:

    • Diagnosis --

      • May be straightforward (known addict; miosis; needle marks)

      • May be difficult (comatose patients -- no history available)

    • Treatment --

      • Intravenous naloxone-- rapid coma reversal if due to opioid overdose (no effect if coma is due to overdose with a sedative hypnotic)

  •   Contraindications/Therapeutic Cautions:

    • For patients receiving the opioid agonists:

      • Do not administer a mixed agonist-antagonist (e.g. pentazocine): withdrawal may be precipitated;

      • Diminishment of analgesia may occur

    •  In patients with head injuries: opioids may induce a further increase in intracranial pressure

    • Pregnancy:

      •  Pregnant women chronically using opioids:

        • Fetus may become physiologically dependent in utero

        • Withdrawal symptoms may appear in the early postpartum time frame

        • Management of fetal withdrawal symptoms:

          • Mild: management with diazepam

          • More severe: oral methadone; tincture of opium (paregoric)

    • Patients with impaired lung function:

      • Acute respiratory failure: may be precipitated by opioid-mediated respiratory depression

    • Patients with impaired hepatic or renal function:

      • Half-life may be prolonged in patients with impaired renal function; e.g. morphine and its active metabolite morphine-6-glucuronide may accumulate (reduction in dosage)

      • Since the liver is the primary metabolic site for morphine and related compounds, use in patients with pre-hepatic coma may be inappropriate

    •  Patients with endocrine disorders:

      • Adrenal-insufficiency (Addison's disease) or hypothyroidism (myxedema): prolonged, exaggerated opioid responses

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