copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 28 opioid (narcotic)...
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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Chapter 28
Opioid (Narcotic) Analgesics, Opioid Antagonists, and Nonopioid Centrally
Acting Analgesics
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Analgesics and Opioids
Analgesics are drugs that relieve pain without causing loss of consciousness.
Opioids are the most effective pain relievers available.
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Terminology
Opioid A general term defined as any drug, natural or
synthetic, that has actions similar to those of morphine
Opiate Applies only to compounds present in opium
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Opioid Receptors
Three main classes of opioid receptors Mu receptors Kappa receptors Delta receptors
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Classification of Drugs That Act as Opioid Receptors
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Morphine
Source Seedpod of the poppy plant
Overview of pharmacologic actions Receptors involved Pain relief Drowsiness Mental clouding Anxiety reduction Sense of well-being
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Morphine
Therapeutic use: relief of pain Mechanism of analgesic action Moderate to severe pain Constant dull pain vs. sharp intermittent pain Preoperative treatment of anxiety
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Morphine
Adverse effects Respiratory depression
• Infants and the elderly are especially sensitive• Onset:
IV 7 min; IM 30 min; subQ up to 90 min, may persist 4–5 hr Spinal injection—response may be delayed by hours
• Tolerance to respiratory depression can develop• Increased depression with concurrent use of other drugs
that have CNS depressant actions (eg, alcohol, barbiturates, benzodiazepines)
• Can compromise patients with impaired pulmonary function
Asthma, emphysema, kyphoscoliosis, chronic cor pulmonale, bariatric
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Morphine Adverse effects (cont’d)
Constipation Orthostatic hypotension Cough suppression Biliary colic Emesis Urinary retention Euphoria/dysphoria Sedation
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Morphine Adverse effects (cont’d)
Miosis Intracranial pressure (ICP) Birth defects Adverse effects from prolonged use
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Morphine
Pharmacokinetics Administered by several routes: PO, IM, IV, subQ,
epidural, and intrathecal Not very lipid-soluble Does not cross blood-brain barrier easily Only small fraction of each dose reaches site of
analgesic action
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Morphine
Tolerance and physical dependence Tolerance
• Increased doses needed to obtain same response• Develops with analgesia, euphoria, sedation, respiratory
depression• Cross-tolerance to other opioid agonists• No tolerance to miosis or constipation develops
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Morphine
Tolerance and physical dependence Physical dependence
• Abstinence syndrome with abrupt discontinuation• About 10 hours after last dose:
Initial reaction (yawning, rhinorrhea, sweating)• Progresses to:
Violent sneezing, weakness, nausea, vomiting, diarrhea, abdominal cramps, bone and muscle pain, muscle spasm, kicking movements
• Lasts 7–10 days if untreated• Withdrawal unpleasant but not lethal, as is possible with
CNS depressants
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Morphine
Abuse liability Precautions
Decreased respiratory reserve Pregnancy Labor and delivery Head injury Other precautions
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Morphine
Drug interactions CNS depressants Anticholinergic drugs Hypotensive drugs Monoamine oxidase inhibitors Agonist-antagonist opioids Opioid antagonists Other interactions
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Morphine
Toxicity Clinical manifestations
• Classic triad Coma Respiratory depression Pinpoint pupils
Treatment• Ventilatory support• Antagonist: naloxone (Narcan)
General guidelines• Monitor full vitals before giving• Give on a fixed schedule
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Other Strong Opioid Agonists Fentanyl (Sublimaze, Duragesic, Abstral,
Actiq, Fentora, Onsolis) 100 times the potency of morphine Five formulations in three routes
• Parenteral (Sublimaze) Surgical anesthesia
• Transdermal (Duragesic)- useful for patients with chronic, severe pain and high degree of tolerance
Patch—heat acceleration Iontophoretic system—needle-free
• Transmucosal Lozenge on a stick (Actiq) Buccal film (Onsolis) Buccal tablets (Fentora) Sublingual tablets (Abstral)
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Other Strong Opioid Agonists
Alfentanil and sufentanil Remifentanil Meperidine
Short half-life Interacts adversely with several other drugs Toxic metabolite accumulation
Methadone Treatment for pain and opioid addicts
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Other Strong Opioid Agonists
Heroin Used legally in Europe to relieve pain High abuse liability Not more effective than other opioids See Figure 28-2
Hydromorphone, oxymorphone, and levorphanol Basic pharmacology Preparations, dosage, and administration
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Fig. 28–2. Biotransformation of heroin into morphine.
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Moderate to Strong Opioid Agonists (hydromorphone, oxymorphone)
Similar to morphine in most respects Produce analgesia, sedation, euphoria Can cause:
• Respiratory depression, constipation, urinary retention, cough suppression, and miosis
Can be reversed with naloxone Different from morphine
Produce less analgesia and respiratory depression than morphine
Somewhat lower potential for abuse
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Moderate to Strong Opioid Agonists
Codeine Actions and uses
• 10% converts to morphine in liver• Pain and cough suppression
Preparations, dosage, and administration• Usually oral (formulated alone or with aspirin or
acetaminophen)• 30 mg produces same effect as 325 mg acetaminophen
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Moderate to Strong Opioid Agonists
Oxycodone Analgesic actions equivalent to those of codeine Long-acting analgesic
• Immediate-release • Controlled-release (OxyContin)
Abuse: crushes and snorts or injects medication 2010 OP formulation much harder to crush and does not
dissolve into an injectable solution to decrease risk of abuse
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Moderate to Strong Opioid Agonists Hydrocodone
Most widely prescribed drug in the United States Combined with aspirin, acetaminophen, or ibuprofen
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Agonist-Antagonist Opioids
Pentazocine Actions and uses Preparations, dosage, and administration
Nalbuphine Butorphanol Buprenorphine
7-day patch: Butrans Sublingual film: Suboxone
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Clinical Use of Opioids
Pain assessment Essential component of management Based on patient’s description Evaluate:
• Pain location, characteristics, and duration; things that improve/worsen pain
• Status before drug and 1 hour after
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Dosing Guidelines
Assessment of pain Pain status should be evaluated before opioid
administration and about 1 hour after Dosage determination
Opioid analgesics must be adjusted to accommodate individual variation
Dosing schedule As a rule, opioids should be administered on a
fixed schedule Avoiding withdrawal
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Clinical Use of Opioids
Physical dependence State in which an abstinence syndrome will occur
if the dependence-producing drug is abruptly withdrawn; it is NOT equated with addiction
Abuse Drug use that is inconsistent with medical or social
norms Addiction
Behavior pattern characterized by continued use of a psychoactive substance despite physical, psychologic, or social harm
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Clinical Use of Opioids
Balance the need to provide pain relief with the desire to minimize abuse
Minimize fears about: Physical dependence Addiction- there are patients who are at higher risk
for abuse, but those taking opioids for severe pain have an extremely low incidence of addiction
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Clinical Use of Opioids
Patient-controlled analgesia PCA devices Drug selection and dosage regulations Comparison of PCA with traditional intramuscular
therapy- blood levels stay in the therapeutic range, fewer fluctuations
Patient education- instruct patient to push the “button” as soon as their pain starts to return. Reassure them that they can’t overdose.
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Fig. 28–3. Fluctuation in opioid blood levels seen with three dosing procedures.
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Opioid Antagonists
Drugs that block the effects of opioid agonists Principal uses:
Treatment of opioid overdose, relief of opioid-induced constipation
Reversal of postoperative opioid effects Management of opioid addiction
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Pure Opioid Antagonists
Naloxone (Narcan) Other pure opioid antagonists
Methylnaltrexone (Relistor) Alvimopan (Entereg) Naltrexone (ReVia, Vivitrol)
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Naloxone
Therapeutic uses Reversal of opioid overdose
• Drug of choice with pure opioid agonist overdose• Titrated cautiously with physical dependence
Reversal of postoperative opioid effects• Titrated to achieve adequate ventilation and to maintain
pain relief Reversal of neonatal respiratory depression
• Opioids given during labor and delivery may cause respiratory depression in neonate
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Other Opioid Antagonists
Methylnaltrexone Selective opioid antagonist Treatment of opioid-induced constipation in late-
stage disease for patients on constant opioids
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Nonopioid Centrally Acting Analgesics
Relieve pain by mechanisms largely or completely unrelated to opioid receptors
Do not cause respiratory depression, physical dependence, or abuse
Not regulated under the Controlled Substances Act
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Tramadol
Mechanism of action Combination of opioid and nonopioid mechanisms
Therapeutic use Pharmacokinetics Adverse effects and interactions Drug interactions
CNS depressants Abuse liability Preparations, dosage, and administration
Immediate-release and extended-release