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Chapter 28
Opioid (Narcotic) Analgesics, Opioid
Antagonists, and Nonopioid Centrally
Acting Analgesics
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Analgesics and Opioids
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
Analgesics are drugs that relieve pain without
causing loss of consciousness.
Opioids are the most effective pain relievers
available.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Terminology
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Opioid
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A general term defined as any drug, natural or
synthetic, that has actions similar to those of
morphine
Opiate
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Applies only to compounds present in opium
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Opioid Receptors
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Three main classes of opioid receptors
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Mu receptors
Kappa receptors
Delta receptors
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Classification of Drugs That Act as
Opioid Receptors
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Morphine
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Source
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Seedpod of the poppy plant
Overview of pharmacologic actions
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Receptors involved
Pain relief
Drowsiness
Mental clouding
Anxiety reduction
Sense of well-being
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Morphine
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Therapeutic use: relief of pain
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Mechanism of analgesic action
Moderate to severe pain
Constant dull pain vs. sharp intermittent pain
Preoperative treatment of anxiety
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Morphine
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Adverse effects
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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
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Adverse effects (cont’d)
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Constipation
Orthostatic hypotension
Cough suppression
Biliary colic
Emesis
Urinary retention
Euphoria/dysphoria
Sedation
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Morphine
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Adverse effects (cont’d)
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Miosis
Intracranial pressure (ICP)
Birth defects
Adverse effects from prolonged use
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Morphine
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Pharmacokinetics
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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
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Tolerance and physical dependence
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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
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Tolerance and physical dependence
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Physical dependence
• Abstinence syndrome with abrupt discontinuation
• About 10 hours after last dose:

Initial reaction (yawning, rhinorrhea, sweating)

Violent sneezing, weakness, nausea, vomiting, diarrhea,
abdominal cramps, bone and muscle pain, muscle spasm,
kicking movements
• Progresses to:
• Lasts 7–10 days if untreated
• Withdrawal unpleasant but not lethal, as is possible with
CNS depressants
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Morphine
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Abuse liability
Precautions
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Decreased respiratory reserve
Pregnancy
Labor and delivery
Head injury
Other precautions
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Morphine
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Drug interactions
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CNS depressants
Anticholinergic drugs
Hypotensive drugs
Monoamine oxidase inhibitors
Agonist-antagonist opioids
Opioid antagonists
Other interactions
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Morphine
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Toxicity
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Clinical manifestations
• Classic triad
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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
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Fentanyl (Sublimaze, Duragesic, Abstral,
Actiq, Fentora, Onsolis)
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100 times the potency of morphine
Five formulations in three routes
• Parenteral (Sublimaze)
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Surgical anesthesia
• Transdermal (Duragesic)- useful for patients with chronic,
severe pain and high degree of tolerance
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Patch—heat acceleration
Iontophoretic system—needle-free
• Transmucosal
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Lozenge on a stick (Actiq)
Buccal film (Onsolis)
Buccal tablets (Fentora)
Sublingual tablets (Abstral)
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Other Strong Opioid Agonists
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Alfentanil and sufentanil
Remifentanil
Meperidine
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Short half-life
Interacts adversely with several other drugs
Toxic metabolite accumulation
Methadone
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Treatment for pain and opioid addicts
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Other Strong Opioid Agonists
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Heroin
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Used legally in Europe to relieve pain
High abuse liability
Not more effective than other opioids
See Figure 28-2
Hydromorphone, oxymorphone, and
levorphanol
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
Basic pharmacology
Preparations, dosage, and administration
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Fig. 28–2. Biotransformation of heroin into morphine.
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Moderate to Strong Opioid Agonists
(hydromorphone, oxymorphone)
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Similar to morphine in most respects
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Produce analgesia, sedation, euphoria
Can cause:
• Respiratory depression, constipation, urinary retention,
cough suppression, and miosis
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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
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Codeine
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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
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Oxycodone
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Analgesic actions equivalent to those of codeine
Long-acting analgesic
• Immediate-release
• Controlled-release (OxyContin)
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
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
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Hydrocodone
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Most widely prescribed drug in the United States
Combined with aspirin, acetaminophen, or ibuprofen
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Agonist-Antagonist Opioids
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Pentazocine
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Actions and uses
Preparations, dosage, and administration
Nalbuphine
Butorphanol
Buprenorphine
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7-day patch: Butrans
Sublingual film: Suboxone
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Clinical Use of Opioids
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Pain assessment
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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
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Assessment of pain
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Dosage determination
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Opioid analgesics must be adjusted to
accommodate individual variation
Dosing schedule
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
Pain status should be evaluated before opioid
administration and about 1 hour after
As a rule, opioids should be administered on a
fixed schedule
Avoiding withdrawal
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Clinical Use of Opioids
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Physical dependence
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Abuse
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State in which an abstinence syndrome will occur
if the dependence-producing drug is abruptly
withdrawn; it is NOT equated with addiction
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
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Balance the need to provide pain relief with
the desire to minimize abuse
Minimize fears about:

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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
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Patient-controlled analgesia
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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.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Opioid Antagonists
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Drugs that block the effects of opioid agonists
Principal uses:
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Treatment of opioid overdose, relief of opioidinduced constipation
Reversal of postoperative opioid effects
Management of opioid addiction
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Pure Opioid Antagonists
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
Naloxone (Narcan)
Other pure opioid antagonists
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Methylnaltrexone (Relistor)
Alvimopan (Entereg)
Naltrexone (ReVia, Vivitrol)
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Naloxone
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Therapeutic uses

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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
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
Treatment of opioid-induced constipation in latestage disease for patients on constant opioids
Naloxegol (Movantik) for those using opioids
for chronic, non-cancer
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Nonopioid Centrally Acting
Analgesics
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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
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Mechanism of action
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Therapeutic use
Pharmacokinetics
Adverse effects and interactions
Drug interactions
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Combination of opioid and nonopioid mechanisms
CNS depressants
Abuse liability
Preparations, dosage, and administration

Immediate-release and extended-release
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