copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 28 opioid (narcotic)...

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 28

Opioid (Narcotic) Analgesics, Opioid Antagonists, and Nonopioid Centrally

Acting Analgesics

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Analgesics and Opioids

Analgesics are drugs that relieve pain without causing loss of consciousness.

Opioids are the most effective pain relievers available.


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


Opioid Receptors

Three main classes of opioid receptors Mu receptors Kappa receptors Delta receptors

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Classification of Drugs That Act as Opioid Receptors

5


Morphine

Source Seedpod of the poppy plant

Overview of pharmacologic actions Receptors involved Pain relief Drowsiness Mental clouding Anxiety reduction Sense of well-being


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


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


Morphine Adverse effects (cont’d)

Constipation Orthostatic hypotension Cough suppression Biliary colic Emesis Urinary retention Euphoria/dysphoria Sedation


Morphine Adverse effects (cont’d)

Miosis Intracranial pressure (ICP) Birth defects Adverse effects from prolonged use


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


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


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


Morphine

Abuse liability Precautions

Decreased respiratory reserve Pregnancy Labor and delivery Head injury Other precautions


Morphine

Drug interactions CNS depressants Anticholinergic drugs Hypotensive drugs Monoamine oxidase inhibitors Agonist-antagonist opioids Opioid antagonists Other interactions


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


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)


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


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


Fig. 28–2. Biotransformation of heroin into morphine.


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


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


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


Moderate to Strong Opioid Agonists Hydrocodone

Most widely prescribed drug in the United States Combined with aspirin, acetaminophen, or ibuprofen


Agonist-Antagonist Opioids

Pentazocine Actions and uses Preparations, dosage, and administration

Nalbuphine Butorphanol Buprenorphine

7-day patch: Butrans Sublingual film: Suboxone


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


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



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



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



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.


Fig. 28–3. Fluctuation in opioid blood levels seen with three dosing procedures.


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


Pure Opioid Antagonists

Naloxone (Narcan) Other pure opioid antagonists

Methylnaltrexone (Relistor) Alvimopan (Entereg) Naltrexone (ReVia, Vivitrol)


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


Other Opioid Antagonists

Methylnaltrexone Selective opioid antagonist Treatment of opioid-induced constipation in late-

stage disease for patients on constant opioids


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


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

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opioid antagonists

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