Text Module

Text Module (Excerpt)


Below is a cut and paste of a small portion of a text module Liz wrote to prepare pharmaceutical sales representatives to introduce a newly launched transdermal opioid analgesic to clinician customers.

Section 2.5: Overview of Pharmacologic Interventions for Chronic Pain

Learning Objectives

After completing this section you will be able to:

  • Identify the three main types of medications used to treat pain.
  • Identify nonopioid analgesics used to treat chronic pain.
  • Identify and describe opioid analgesics used to treat chronic pain.
  • Describe the role of adjuvant analgesics in treating chronic pain.
  • Describe the World Health Organization (WHO) practice guidelines for treating chronic pain.
  • Discuss some of the challenges faced by clinicians managing chronic pain.

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Pharmacologic therapies

Analgesics are drugs that relieve pain without causing a loss of consciousness. The three main types of medications used to treat pain are:

  • nonopioid analgesics
  • opioid analgesics
  • adjuvant drugs

The choice of agent(s) depends on the severity of pain and its cause.

Nonopioid analgesics

Nonopioid agents are drugs or chemical substances that have analgesic effects but do not contain opium or its derivatives. Because they are effective against common types of pain and because some are available without prescription, nonopioids are the most frequently used analgesic agents.

Fast Fact
Nonopioid agents may be used alone for mild pain (e.g., headache, muscle ache, menstrual pain), or they may be combined with opioid analgesics to treat moderate to severe pain.

 Nonopioid analgesics include:

  • acetaminophen (e.g., Tylenol®)
  • nonsteroidal anti-inflammatory drugs (NSAIDs),  salicylates (e.g., aspirin)
  •  nonselective NSAIDs (e.g., ibuprofen)
  • selective COX-2 inhibitors (e.g., celecoxib)

Aspirin, NSAIDs, and COX-2 inhibitors relieve pain by inhibiting the synthesis of hormonelike substances called prostaglandins. Prostaglandins are pain mediators that contribute to inflammation. Because aspirin, NSAIDs, and COX-2s inhibit prostaglandin synthesis, these drugs are used to treat pain associated with inflammation (e.g., rheumatoid arthritis, postoperative pain). These agents are also effective for mild to moderate headache and musculoskeletal pain.

Opioid analgesics

Opioid analgesics are potent pain medications used to treat moderate- to-severe pain. These drugs are typically used only after nonopioid agents have proven to be ineffective. (Again, opioid analgesics may sometimes be combined with nonopioid agents.)

Opioids used to treat moderate to severe chronic pain include:

  • [generic name]
  • morphine
  • methadone
  • hydromorphone
  • oxycodone
  • tramadol
  • hydrocodone

[PRODUCT NAME] ® is an opioid.

[NOTE: In all work samples Liz has substituted either [‘generic name’] or [‘PRODUCT NAME’] in place of the actual name of a client’s pharmaceutical product. She’s done this to honor confidentiality agreements.]

Opioids achieve their therapeutic effects by mimicking the action of naturally occurring pain-relieving substances (i.e., endogenous opioids) in the brain and spine and by altering the patient’s perception of pain. The most common side effects of opioid analgesics are nausea, vomiting, constipation, and sedation. A rare, but serious, side effect of opioids is respiratory depression.

Opioid analgesics are classified into four types, based on their binding characteristics at specific opioid receptors as well as their pharmacologic effects. (To review the topic of endogenous opioids and opioid receptors, please refer back to the Section 1.1 discussion of pain modulation.)

The four types of opioids are:

  • pure (full) agonists (e.g., [generic name], morphine)
  • partial agonists (e.g., buprenorphine)
  • antagonists (e.g., naloxone)
  • mixed agonist-antagonists (e.g., pentazocine)

Pure agonists bind to and enhance the natural effect of opioid receptors, primarily μ (mu) receptors. Pure agonists have a relatively straight dose-response curve. In other words, increasing the dose of a pure agonist opioid results in an increase in the analgesia, making these agents the analgesics clinicians select to treat severe pain in patients with worsening pain.

Partial agonists also bind to mu receptors but produce partial analgesic effects that are less pronounced than pure agonists. The usefulness of partial agonists is limited due to the so-called ceiling effect, where—after a certain dose level—an increase in the dose of the partial agonist does not result in an increase in the analgesic effect, but may lead to increased side effects. On account of the ceiling effect, partial agonist opioids are not recommended for the treatment of chronic, severe pain.

Antagonists bind to opioid receptors but do not activate them. In addition, antagonists with high affinities for opioid receptors can displace agonists that have lower affinities for these receptors—or, the antagonists may prevent the agonists from binding at all.

Fast Fact
[PRODUCT NAME] ® is a pure agonist.

This characteristic accounts for the fact that antagonists can be effective agents in the treatment of opioid overdosage.

Mixed agonist-antagonists have agonistic effects at some receptors and antagonistic effects at others. Therefore, the dose of these types of opioids may determine their overall pharmacologic profile (i.e., whether they will have an overall agonistic or antagonistic effect).

Other characteristics of opioid analgesics

In addition and as a reflection of their duration of action, opioid analgesics may be characterized as:

  • long-acting opioids
  • short-acting opioids

Duration of action refers to how long pain relief persists before another dose of medication is required.

Routes of administration—that is, how medication is delivered— may be invasive (e.g., injection) or noninvasive (e.g., transdermal). Because the [PRODUCT NAME] ® patch delivers the opioid analgesic [generic name] transdermally, we will focus our discussion on this route of administration.

Advantages of transdermal delivery of opioids include:

  • convenient alternative to oral, rectal, or invasive routes
  • effective way to provide around-the-clock opioid therapy
  • useful in patients unable to swallow

Schedule (classification) is yet another way opioid analgesics are characterized. Government regulation of opioids and other drugs with high abuse potential has resulted in schedule categories being assigned to these agents, based on their medical use and their potential for abuse. Schedule I drugs have the highest potential for abuse and have no accepted medical use in the US; Schedule V drugs have the lowest potential for abuse and have accepted use in the US. Like morphine and oxycodone, [generic name] is a Schedule II drug that has accepted medical use and a high potential of abuse.

In Module 2 you will learn much more about [PRODUCT NAME] ®. For now, just be aware that the long-acting, transdermally delivered, opioid agonist [PRODUCT NAME] ® effectively treats persistent, moderate-to-severe chronic pain—and it does this without a ceiling effect.

Adjuvant drugs

Physicians may also prescribe other medications to treat pain, although many of these medications are not FDA-approved for this use. Adjuvant agents are often reserved for treating patients who do not respond well to the standard pain therapies (e.g., patients with neuropathic pain) or they may be prescribed in addition to standard therapies. Commonly used adjuvant drugs include:

  • anesthetics (e.g., ketamine)
  • topical analgesics (e.g., capsaicin)
  • antidepressants (e.g., tricyclic antidepressants (TCAs))
  • antiepileptic drugs (AEDs; e.g., gabapentin)
  • antispasmodics (muscle relaxants; e.g., cyclobenzaprine)
  • benzodiazepines (e.g., Valium®)
  • corticosteroids (e.g., prednisone)

WHO guidelines for managing chronic pain

The World Health Organization (WHO) has created a tool that helps medical professionals select an analgesic based on the severity of the patient’s pain. Originally created as a guideline for palliative care of cancer pain, the three-step WHO ladder has become a widely used practice standard for treating many forms of pain, including chronic nonmalignant pain (as well as malignant pain).

According to the WHO ladder’s stepped-approach to pain management, pain care should match the level of pain experienced by the patient. Mild pain is treated with the mildest therapies; severe pain is treated with the strongest therapies.

As illustrated in Figure 2-4, prescribed medications may be adjusted up or down this ladder based on the severity of patient pain.

Figure 2-4: WHO guidelines for managing chronic pain


Source: World Health Organization. Cancer: WHO’s pain ladder.

Figure 2-5 presents an algorithm that includes both the WHO approach and a suggested response to efficacy and safety considerations.


Figure 2-5: Pain treatment algorithm by severity (adapted from Baumann. In Pharmacotherapy: A Pathophysiologic Approach. 4th ed)

Challenges in pain management

Many challenges face clinicians prescribing pharmacologic agents for chronic pain. These include managing:

  • frail and/or elderly patients
  • renally and/or hepatically impaired patients
  • drug interactions in patients taking multiple medications for pain and other conditions
  • issues of abuse, dependence, and diversion to nonmedical usesFor example and as noted earlier, the elderly are at risk for undertreatment of chronic pain. This need not occur, because with appropriate use of analgesics and prevention of opioid-related side effects, chronic pain can be effectively managed in this population, and quality of life can be improved.

Self-Check Questions

1. List the three main types of medications used to treat pain:


B. ____________________________________________________

C. ____________________________________________________

2. Acetaminophen and NSAIDs are generally characterized as _______ analgesics.

3. List three opioid analgesics.


B. ____________________________________________________

C. ____________________________________________________

4. ________ medications may be added on to standard pain regimens to help relieve pain.

5. According to WHO guidelines for managing chronic pain, medications may be adjusted up and down the “ladder” based on the ________ of patients’ pain.

6. List three examples of challenges clinicians face when prescribing pharmacologic treatment for patients with chronic pain.


B. ____________________________________________________

C. ____________________________________________________

Self-Check Answers


A. nonopioid analgesics

B. opioid analgesics

C. adjuvant drugs

2. nonopioid

3.  Any three of the following are correct:

  • [generic name] morphine
  • methadone
  • hydromorphone
  • oxycodone

4.  Adjuvant

5.  Severity
6. Any three of the following are correct:

  • Managing frail and/or elderly patients
  • Managing renally and/or hepatically impaired patients
  • Managing drug interactions in patients taking multiple medications for pain and other conditions
  • Managing issues of abuse and dependence

Take Home Points

[Note: The following bullet points capture need-t0-know information from the entire text module written by Liz, not just key points from Section 2.5 cut and pasted, above.]

  • Pain is defined by the IASP as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
  • The neurophysiologic processes involved in pain are referred to collectively as nociception; nociception begins with the release of chemical mediators and includes:
    • transduction of the chemical signal into an electrical impulse
    • transmission of the impulse to the spinal cord and brain
    • perception (processing and interpretation of the signal in the brain)
    • modulation of pain signals through the release of endogenous opioids (endorphins)
  • Continued stimulation of nociceptors may induce sensitization to further stimuli and may be a factor in the development of chronic pain.
  • During modulation, endogenous opioids (endorphins) bind to opioid receptors and help ameliorate pain; types of opioid receptors include mu (μ), delta (δ), and kappa (κ) receptors.
  • Pain can be classified based on its duration, quality (e.g., sharp, dull, burning), and source. Nociceptive pain refers to pain mediated via nociceptors; neuropathic pain is caused by damage or dysfunction of the nerves themselves.
  • Chronic pain refers to pain lasting at least 3 months. New definitions refer to chronic pain as pain that persists after the injury has healed and the cause, or etiology, is not certain. Nonmalignant disease states and disorders associated with chronic pain include low back pain, osteoarthritis, and fibromyalgia. Chronic pain may also be associated with cancer (malignant chronic pain).
  • Chronic pain affects millions of Americans and costs billions of dollars in direct and incorrect costs (e.g., lost productivity) each year.
  • Despite advances in pain management, chronic pain is often undertreated; barriers to treatment include myths and misunderstandings about chronic pain and its management; patient barriers, such as concerns about side effects and risk of dependency and poor access to care; clinical and practice barriers, such as lack of adherence to clinical practice guidelines and inadequate or inaccurate clinical knowledge
  • Evaluation of chronic pain begins with collection of the patient’s medical history, assessment of pain using pain rating scales and/or self-reporting tools, physical examination, and diagnostic tests as appropriate.
  • Pain rating scales may use verbal descriptors, numeric scales, or visual scales; self-reporting tools include the Brief Pain Inventory (BPI) and McGill Pain Questionnaire (MPQ); all are designed to help quantify and objectify the patient’s pain.
  • Following treatment, pain should be reassessed, ideally using the same tools. Many experts also feel that pain should be treated as the “fifth vital sign,” and should be assessed whenever vital signs are taken.
  • The goals of treating chronic pain are diminish physical and emotional suffering, improve/restore daily functioning, optimize health, and improve the patient’s ability to cope with pain. Chronic pain often benefits from a multimodal approach that includes pharmacologic and nonpharmacologic therapies.
  • Any underlying cause of pain should be promptly identified and treated (e.g., with surgery).
  • Nonpharmacologic treatments for pain include cognitive behavioral therapy (CBT), physical rehabilitation, and alternative therapies (e.g., acupuncture, acupressure). Surgical techniques such as neuroablation and tumor debulking may also be used.
  • Analgesics may be classified as nonopioid analgesics, opioid analgesics, and adjuvant drugs.
  • Nonopioid analgesics include acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Opioid analgesics include [generic name], morphine, methadone, hydromorphone, oxycodone, tramadol, and hydrocodone T-2
  • Adjuvant drugs include anesthetics, topical analgesics, antidepressants, antiepileptic drugs (AEDs), benzodiazepines, antispasmodics, and corticosteroids.
  • Opioids are classified as pure agonists, partial agonists, antagonists, and mixed agonist-antagonists, depending on how they interact with opioid receptors. [generic name], the active ingredient in [PRODUCT NAME] ®, is a pure agonist.
  • Opioids analgesics are also classified as long-acting vs. short- acting and according to route of administration.
  • The World Health Organization (WHO) issues guidelines for managing chronic pain, including a “pain ladder” that specifies recommended treatments according to the severity of pain.
  • Challenges in pain management include how to best manage frail and/or elderly patients, renally and/or hepatically impaired patients, avoiding drug interactions, and dealing with issues of abuse, dependence, and diversion.

Image Credits:
Hand holding pills, Ayena, Wikimedia Commons
Pain-relief ladder, WHO