Chapter 49: Drug Therapy With Opioids

Pain: Definition and Clinical Importance

Pain is the most common symptom prompting individuals to seek healthcare. It is defined as an unpleasant, uncomfortable sensation that usually indicates tissue damage. Ineffective pain management can significantly impair quality of life and the ability to perform activities of daily living.

• Pain: An unpleasant sensory and emotional experience associated with actual or potential tissue damage.

• Clinical significance: Proper pain management is essential for patient comfort and recovery.

• Example: Postoperative pain following surgery requires effective management to promote healing and mobility.

Etiology of Pain

Pain can arise from various causes and is classified based on its origin, duration, and underlying cause.

• Causes:

  • Nerve damage

  • Tissue injury

  • Cancer

  • Surgery

• Classification:

  • By origin: Somatic (from skin, muscles, joints), Visceral (from internal organs), Neuropathic (from nerve injury)

  • By duration: Acute (short-term), Chronic (long-term)

  • By cause: e.g., cancer, trauma

Pathophysiology of Pain

Pain perception involves complex physiological processes beginning with tissue damage and ending with conscious awareness in the brain.

• Tissue damage activates pain receptors (nociceptors) in peripheral nerves.

• Physical causes: Heat, cold, pressure, stretch, spasm, ischemia.

• Chemical causes: Release of inflammatory substances into the extracellular fluid around nerve fibers.

• Pain signal transmission:

  • From nociceptors to spinal cord via A-delta fibers (fast, sharp pain) and C fibers (slow, dull pain).

  • Dorsal horn of the spinal cord acts as a relay station.

  • Signal continues to the thalamus (relay station in the brain) and then to the cerebral cortex where pain is perceived.

Endogenous Analgesia

The central nervous system (CNS) has its own mechanisms for relieving pain, known as endogenous analgesia.

• Opioid peptides (e.g., endorphins, enkephalins, dynorphins) interact with opioid receptors to inhibit pain perception and transmission.

• This system suppresses pain signals from peripheral nerves.

• Example: The "runner's high" is partly due to endogenous opioid release.

Clinical Manifestations and Assessment of Pain

Pain is a subjective experience, making self-reporting the gold standard for assessment.

• Influencing factors: Mood, sleep disturbances, fatigue, medications, culture, gender, age, psychosocial factors.

• Measurement tools:

  • Visual analog scales

  • Verbal or numerical rating scales

  • Picture scales

  • SOCRATES (Site, Onset, Character, Radiation, Associations, Time course, Exacerbating/relieving factors, Severity)

Drug Therapy for Pain Management

Opioid Analgesics: Mechanism and Use

Opioid analgesics are drugs used to manage moderate to severe pain by altering pain perception and emotional response.

• Mechanism:

  • Inhibit adenylate cyclase activity

  • Reduce perception of pain sensations in the brain

  • Decrease emotional upset

  • Inhibit production of pain and inflammation

• Tolerance can develop with prolonged use.

• Subgroups:

  • Opioid agonists

  • Agonists/antagonists

  • Antagonists

• Preventive analgesia: Administering analgesics before pain becomes severe.

Opioid Agonists

Opioid agonists are primarily used to relieve acute or chronic moderate to severe pain.

• Prototype: Morphine sulfate (Schedule II)

• Administration: Oral (PO), intramuscular (IM), subcutaneous, intravenous (IV)

• Patient-controlled analgesia (PCA) is a common method for self-administration.

• Pharmacokinetics: Extensively metabolized in the liver; excreted in urine; duration of action is 5–7 hours.

• Receptor binding: Binds to mu, kappa, and delta opioid receptors to block pain transmission.

• Effects:

  • Analgesia

  • CNS depression (respiratory depression, sedation)

  • Euphoria

  • Decreased gastrointestinal motility

  • Physical dependence

Indications for Opioid Use

Opioids are indicated for various conditions involving moderate to severe pain.

• Acute myocardial infarction (MI)

• Biliary or renal colic

• Burns and traumatic injuries

• Postoperative pain

• Cancer pain

• Pre- and postoperative sedation and anxiety reduction

• Facilitation of anesthesia induction

• Labor and delivery (with caution)

• Treatment of acute pulmonary edema

• Treatment of gastrointestinal disorders (abdominal cramping, diarrhea)

• Treatment of severe, unproductive cough

Contraindications and Precautions for Opioid Use

Opioids should be avoided or used with caution in certain populations due to risk of adverse effects.

• Absolute contraindications:

  • Hypersensitivity to opioids

  • Existing respiratory depression

  • Acute or chronic lung disease

  • Upper airway obstruction

  • Concurrent use of monoamine oxidase inhibitors (MAOIs)

  • Pregnancy

• Use with caution:

  • Hypotension

  • Thyroid dysfunction

  • Liver or kidney disease

  • Increased intracranial pressure, head injury

  • Seizure disorder

  • Severe alcoholism

  • Concurrent use of benzodiazepines or other CNS depressants

Opioid Agonists/Antagonists

These drugs act on the same pain receptors as morphine but have mixed agonist and antagonist activity, providing pain relief with a lower risk of certain side effects.

• Prototype: Butorphanol (synthetic, Schedule IV)

• Administration: Parenteral; peak effect in 30–60 minutes

• Mechanism: Agonist at kappa receptors, partial agonist at mu receptors

• Indications:

  • Moderate to severe pain not managed by other treatments

  • Preoperative medication and anesthesia supplement

  • Pain management during labor (with fetus >37 weeks, no respiratory distress)

• Adverse effects:

  • Headache, dizziness, drowsiness, vertigo

  • Constipation, nausea, vomiting

  • Hallucinations, euphoria

  • Nasal spray: nasal congestion, cough, dyspnea, rhinitis

  • Ceiling effect on respiratory depression (less risk than full agonists)

Opioid Antagonists

Opioid antagonists are used to reverse opioid-induced CNS and respiratory depression.

• Prototype: Naloxone

• Therapeutic effects:

  • IV: onset in ~2 minutes

  • IM/Subcutaneous: 2–5 minutes

  • Intranasal: 8–13 minutes

• Mechanism: Competes with opioids for receptor sites in the brain, preventing or reversing opioid effects.

• Adverse effects: Tremors, drowsiness, sweating, decreased respirations, hypertension, nausea, vomiting.

• Contraindications: Hypersensitivity, narcotic misuse (may precipitate withdrawal: tachycardia, hypertension, violent behavior).

• Clinical note: Must be readily available in all healthcare settings where opioids are administered.

Use in Special Populations

Opioid therapy requires special consideration in certain populations due to altered pharmacokinetics and increased risk of adverse effects.

• Children: Dosing and monitoring must be carefully adjusted.

• Older adults: Require adequate analgesia with vigilant monitoring; increased sensitivity to opioids.

• Hepatic impairment: May affect drug metabolism and increase toxicity risk.

• Abnormal kidney function: May impair drug excretion.

• Critical illnesses: May alter drug response and increase risk of complications.

• Home care: Education and monitoring are essential for safe opioid use outside the hospital.

Key Medical Terminology

• Analgesia: Absence of pain in response to stimulation that would normally be painful.

• Opioid: A class of drugs that act on opioid receptors to produce morphine-like effects.

• Agonist: A substance that activates a receptor to produce a biological response.

• Antagonist: A substance that blocks or dampens a biological response by binding to and blocking a receptor.

• Physical dependence: A physiological state where abrupt cessation of a drug causes withdrawal symptoms.

• Tolerance: A state in which increased doses of a drug are required to achieve the same effect.

• Schedule II/IV drugs: Controlled substances classified by their potential for abuse and medical use (Schedule II: high potential for abuse; Schedule IV: lower potential).

Table: Comparison of Opioid Drug Classes

Additional info:

• SOCRATES is a mnemonic used for pain assessment: Site, Onset, Character, Radiation, Associations, Time course, Exacerbating/relieving factors, Severity.

• Opioid tolerance and dependence are important considerations in long-term therapy.

• Patient-controlled analgesia (PCA) allows patients to self-administer preset doses of opioids for pain control.