What are opioids?

What Are Opioids?

Opioids are a class of medications that bind to opioid receptors in the body to produce analgesic (pain-relieving) effects, and include naturally occurring compounds (like morphine), semisynthetic derivatives (like oxycodone), and fully synthetic agents (like fentanyl). 1

Core Definition and Mechanism

Opioids are defined as any substance—whether naturally occurring, semisynthetic, or synthetic—that combines with opioid receptors to produce physiological effects and can be stereospecifically antagonized by naloxone 1. These medications work by binding to opioid receptors distributed throughout the central and peripheral nervous systems, blocking pain signal transmission 1.

Classification Systems

Opioids can be classified in three clinically relevant ways 1:

By Receptor Interaction

• Pure agonists (morphine, oxycodone, hydrocodone, fentanyl) - fully activate opioid receptors 2, 1
• Partial agonists (buprenorphine) - partially activate receptors with a ceiling effect 2
• Mixed agonist-antagonists (nalbuphine, pentazocine) - activate some receptors while blocking others 2
• Pure antagonists (naloxone, naltrexone) - block opioid effects 2

By Pain Intensity Indication

• For moderate pain: codeine, tramadol, dihydrocodeine (often called "weak opioids") 2
• For severe pain: morphine, oxycodone, hydromorphone, fentanyl, methadone (called "strong opioids") 2

By Duration of Action

• Short-acting/immediate-release: provide rapid onset for 3-6 hours 2
• Long-acting/extended-release: provide sustained effect over 8-24+ hours 2

Common Opioid Medications

Morphine is considered the gold standard and drug of first choice for moderate to severe cancer pain 2. Other commonly used strong opioids include oxycodone, hydrocodone, fentanyl, hydromorphone, and methadone 2. Tramadol occupies a unique position as a centrally acting analgesic with weak opioid agonist activity combined with serotonin reuptake inhibition 2.

Clinical Applications

Opioids serve as the cornerstone for managing moderate to severe acute pain, particularly from severe traumatic injuries, invasive surgeries, and cancer-related pain 2. However, opioids are NOT recommended as first-line therapy for common acute pain conditions including low back pain, neck pain, musculoskeletal injuries, minor surgeries, dental pain, kidney stones, or headaches 2. For these conditions, NSAIDs and other nonopioid therapies should be prioritized 2.

Critical Safety Concerns

Addiction and Controlled Substance Status

Opioids are Schedule II controlled substances that expose users to risks of addiction, abuse, and misuse 3, 4. The FDA defines addiction as "a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes physical withdrawal" 3.

Life-Threatening Adverse Effects

Serious, life-threatening, or fatal respiratory depression can occur with opioid use, even when used as recommended 3. Other significant adverse effects include 2, 5:

• Sedation and altered consciousness
• Nausea and vomiting (occurring in 1.5-4.8% of patients) 2
• Severe constipation (very high incidence, often without tolerance development) 5
• Urinary retention 2
• Opioid-induced hyperalgesia (paradoxical increase in pain sensitivity) 2
• Hormonal and immunologic dysfunction 5
• Risk of overdose and death, particularly with extended-release formulations 2

Physical Dependence vs. Addiction

Physical dependence is distinct from addiction 3. Physical dependence is a physiological state where the body adapts to the drug after regular exposure, resulting in withdrawal symptoms after abrupt discontinuation 3. Rapid discontinuation of opioids in physically dependent patients can lead to serious withdrawal symptoms, uncontrolled pain, and suicide 3.

Prescribing Principles

The CDC emphasizes that when opioids are warranted, clinicians should 2:

• Prescribe immediate-release formulations (not extended-release) for acute pain 2
• Use the lowest effective dose 2
• Prescribe for no longer than the expected duration of severe pain 2
• Prescribe for "as needed" use rather than scheduled dosing 2
• Maximize concurrent use of nonopioid therapies 2
• Check prescription drug monitoring programs 2
• Offer naloxone to patients at risk for overdose 2

Extended-release/long-acting opioids should be reserved for severe, continuous pain and should never be used for acute pain or as first-line therapy 2. The FDA notes that some ER/LA opioids are only appropriate for opioid-tolerant patients who have received at least 60 mg daily of oral morphine (or equianalgesic doses) for at least one week 2.

Risk Evaluation and Mitigation Strategy (REMS)

The FDA requires opioid manufacturers to provide REMS-compliant education programs for healthcare providers 3, 4. Providers must assess each patient's risk for addiction prior to prescribing, establish patient-specific treatment goals, educate patients on safe use and disposal, and routinely monitor for signs of misuse, abuse, or diversion 2, 3.