There are two primary types of analgesics: opioid and non-opioid. Opioid analgesics act centrally in the nervous system, can cause addiction and dependence, and are controlled substances. They are more potent but carry greater risks than non-opioid analgesics like NSAIDs, which act peripherally and have a ceiling effect. Both types of analgesics work through different mechanisms - opioids bind to opioid receptors while non-opioids inhibit prostaglandin formation. Overall, opioids are more effective for severe pain but non-opioids are preferable for mild-to-moderate chronic pain due to their safer side effect profile when used long-term.

1. There are two primary types of analgesics: narcotic (opioid) and non-narcotic (nonopioid)
analgesics.
Primary differences at a glance:
Narcotic Analgesics Non-Narcotic Analgesics
Act centrally Act peripherally
Addiction, dependence, tolerance Not habit-forming
Schedule II/III controlled substances Not controlled drugs
Notable adverse effects: sedation, respiratory
depression, constipation
Notable adverse effects: gastric irritation, bleeding
problems, renal toxicity
No anti-inflammatory effect Anti-inflammatory effect
No ceiling effect Ceiling effect - increase in dose does not increase
analgesia but increases side effects
Opioid (narcotic) analgesics are derived from or related to the Opium. They bind to opioid
receptors, which present in many regions of the nervous system and are involved in pain signaling
and control. There are four groups of opioid receptors: delta, kappa, mu, and sigma.
Non-onopioid (non-narcotic) analgesics include acetaminophen, the most commonly used over-
the-counter pain medicine. Other drugs are not technically part of the analgesic family, but are
nonetheless considered analgesics in practice. These include nonsteroidal anti-inflammatory drugs
(NSAIDs). Aspirin and acetaminophen are two of the most widely used analgesics and are
effective for mild to moderate headache and pain of musculoskeletal origin.
Mechanism of Action
Opioid analgesics relieve pain by acting directly on the central nervous system. Opioids are unique
in that they not only block the incoming nociceptive signals to the brain but also act at higher brain
centers, controlling the affective components of the pain.
Non-opioid analgesics have principally analgesic, antipyretic, and anti-inflammatory actions. The
mechanism of action of traditional NSAIDs involves blockade of the production of prostaglandins by
inhibition of the enzyme cyclooxygenase (COX) at the site of injury in the periphery, thus
decreasing the formation pain mediators in the peripheral nervous system.
Nonopioids act primarily in peripheral tissues to inhibit the formation of pain-producing substances
such as prostaglandins. They do not bind to opioid receptors and are not classified under the
Controlled Substances. They are milder forms of the painkillers.
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2. Efficacy
Opioid analgesics are more effective than NSAIDs in providing pain relief.
NSAIDs provide effective relief of many types of acute and persistent pain, especially associated
with inflammation. Prescribed alone, these agents can relieve slight to moderate pain.
Alternatively, for moderate to severe pain, they can be used in combination with opioids to
enhance pain relief.
Opioids are much stronger and are used when pain signals are too severe to be controlled by non-
narcotic analgesics.
The primary difference has to do with how they produce their analgesic effects. The opioids reduce
pain by working on special pain receptors in the nervous system, primarily located in the brain and
spinal cord. The non-opioids, on the other hand, work more directly on injured body tissues. The
opioids decrease the brain's awareness of the pain, whereas the non-opioids affect some of the
chemical changes that normally take place wherever body tissues are injured or damaged. These
chemical changes at the site of the injury typically result in inflammation and increased pain
sensitivity.
Risks & Side Effects
The long-term use of opioids can lead to tolerance and necessity of dose escalation. Tolerance
occurs when chronic exposure to a drug results in diminished antinociceptive or analgesic effect,
so the larger doses are necessary to achieve the same degree of analgesia.
However, tolerance is not considered to be a problem by most pain specialists. Many persons with
chronic pain who are taking opioids are able to maintain their dosage level without continuing
escalating.
Physical dependence is an automatic consequence of taking opioids over time. Physical
dependence is apparent when a patient abruptly stops taking the drug or reduces the amount
taken. This leads to withdrawal reactions. Physical dependence is not the same as addiction and
is not considered to be a problem by most pain specialists.
Although non-opioids are often preferred for most types of chronic pain, they have two serious
drawbacks. The first drawback has to do with ceiling effects. Non-opioids have upper limit of pain
relief that can be achieved. Once that upper limit or ceiling is reached, increasing the dosage will
not provide any further pain relief. Opioids, on the other hand, tend not to have a ceiling. That is,
the more you take, the more pain relief you will get. That is the reason why non-opioids are
effective only for mild to moderate pain, whereas opioids are useful for more severe pain intensity.
The second major drawback of the non-opioids is their side effects. Although most non-opioids are
quite safe when used for temporary acute pain, problems may arise when people take them over a
long period of time (for chronic pain). This is especially true when large quantities of non-opioids
are taken. Most are aware of the adverse effects on the gastrointestinal system. However,
excessive use of the non-opioids can also damage the liver or kidneys.
Opioids have negative side effects as well. However, it is interesting that many pain specialists
now believe that opioids, when used properly, are often safer than the non-opioids.
Opioids produce respiratory depression. They reduce respiration by decreasing both the sensitivity
of the medulla to carbon dioxide concentrations and the respiratory rate. Other side effects of the
opioids include dizziness, nausea, vomiting, constipation, sedation, mental clouding, and miosis.
Many of these side effects can be minimized or eliminated with proper medical management.
Non-opioid agents differ from opioid analgesics in several ways:

3. non-opioids have a ceiling effect in analgesia (a maximum dose beyond which analgesic effect
does not increase)
do not produce tolerance or physical dependence and are not associated with abuse or
addiction
they are antipyretic and all except acetaminophen are anti-inflammatory agents
the primary mechanism of action of non-opioid analgesics is inhibition of prostaglandin
formation
opioids work by acting on receptors located on neuronal cell membranes
References & Resources
1. Pasternak GW. Pharmacological mechanisms of opioid analgesics. Clin Neuropharmacol.
1993 Feb;16(1):1-18.
2. Kay B. Narcotic analgesia--ceiling effect. Anesthesiology. 1985 Mar;62(3):371-2.
3. Sandra P. Welch, Billy R. Martin. Modern Pharmacology with Clinical Applications. Chapter
26 Opioid and Nonopioid Analgesics.
Published: May 05, 2007
Last updated: December 09, 2016
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