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Medical Pharmacology Chapter 13:  Opioid Pharmacology Lecture, slide 3

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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 Suppression

    • 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

 

Organ System Effects:

  • CNS effects: mu receptor-mediated: analgesia, sedation, euphoria, respiratory depression

    • Analgesia: Pain Components

      • Affective (emotional)-- opioids have greater effect on this element

      • Sensory

      • Analgesia results from complex interactions involving:

        • Sites in the brain, spinal cord, peripheral tissue

          • Selective action on neuronal modulators and transmitters of pain (other sensory modality/motor functions: remain intact)

        • Major receptor types: μ1 and μ2

      •   Spinal cord:-- sites of action

        1. Presynaptic on primary afferent nociceptors -- decreasing substance P release.

        2. Hyperpolarization of substantia gelatinosa interneurons-- decreasing nociceptive impulse afferent transmission

        3. Spinal morphine analgesia: m2 opioid receptors

      • Supraspinal Sites of Action:

        1. Periaqueductal gray

        2. Locus ceruleus

        3. Medullary nuclei (mainly nucleus raphe magnus)

        4. Supraspinal morphine analgesia: m1 opioid receptors

      • Clinical Implications-analgesia:

        1. Bolus dosing (e.g.intramuscular): not correlated well with analgesic effects

        2. Constant/slowly changing (i.e., steady-state) plasma concentrations: well correlated with analgesic effect intensity

        3. Patients using patient-controlled analgesia delivery systems:

          • Achieve more constant plasma opioid concentration (desirable)

          • Maintained effective analgesic morphine plasma concentration

    • Euphoria:

      • Anxiolytic;pleasant; "floating sensation";

      • Individuals not in pain may experience dysphoria

    • Sedation:

      • Common consequence of opioid administration

      • Limited amnesia

      • Given as monotherapy, opioids may produce sleep from which individual can be easily awakened

      • Opioids in combination with sedative-hypnotics produce a very deep sleep

      • Significant sedation is more likely with phenanthrene derivatives (e.g., morphine, oxycodone (Roxicodone), hydrocodone, oxymorphone (Numorphan), hydromorphone (Dilaudid))

      • Significant sedation: less likely with synthetic agents (e.g. fentanyl (Sublimaze), meperidine (Demerol))

  •  Respiratory Depression:

    • All opioid analgesics: significant respiratory depression (inhibiting brain stem respiratory centers)

    • Characterized by reduced response to carbon dioxide challenge

    • Respiratory depression is:

      • dose-related

      • influenced by extent to sensory input

      • opioid induced slight respiratory depression: tolerated in patients with no prior respiratory difficulty

      • Opioid induced slight respiratory depression: poorly or not tolerated in patients with asthma, chronic obstructive pulmonary disease (COPD), cor pulmonale, and increased intracranial pressure

  • Cough Suppression

    • Significant action of opioids

    • Especially effective: codeine

      • management of pathologic cough

      • management of patients with endotracheal tubes

    • Associated with secretion accumulation which may lead to atelectasis and/or airway obstruction

  •  Miosis

    • Pupillary constriction: commonly seen with opioid agoniststhan

    • blocked by opioid antagonists

    • No tolerance develops

    • Mechanism:

      • Edinger-Westphal nucleus of the oculomotor nerve

      • Parasympathetic system:  may be blocked by atropine

    • Clinical Implications-miosis:

      •  Assuming no other drugs present: miosis correlates with opioid-induced respiratory depression

      •   Severe opioid-induced respiratory depression which causes hypoxemia will precipitate pupillary dilation

  • Truncal Rigidity:

    • Increased large trunk muscle tone-- supraspinal action

    • Decreased thoracic compliance; interferes with ventilation

    • Most often seen with highly lipophilic opioids, upon rapid IV administration:

      • Fentanyl (Sublimaze)

      • Sufentanil (Sufenta)

      • Alfentanil (Alfenta)

    • Reversal of truncal rigidity: opioid antagonists

    • Maintenance of analgesia with reduced truncal rigidity is a basis for concurrent neuromuscular blocking drug use.

  • Nausea and Vomiting:

    • Opioid analgesics: stimulate brain stem chemoreceptor trigger zone (CTZ)

    • Vestibular component may also be present

 
 
 
 
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