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An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for . Analgesics are conceptually distinct from , which temporarily reduce, and in some instances eliminate, , although analgesia and are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

Analgesic choice is also determined by the type of pain: For , recent research has suggested that classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and may be considered as an alternative.

Various analgesics, such as many NSAIDs, are available over the counter in most countries, whereas various others are prescription drugs owing to the substantial risks and high chances of , , and in the absence of medical supervision.

Etymology
The word analgesic derives from an- (ἀν-, "without"), álgos (ἄλγος, "pain"), and -ikos (-ικος, forming ). Such drugs were usually known as "" before the 20th century.

Classification
Analgesics are typically classified based on their mechanism of action.

Paracetamol (acetaminophen)
Paracetamol, also known as acetaminophen or APAP, is a medication used to treat and . It is typically used for mild to moderate pain. In combination with , paracetamol is now used for more severe pain such as and after surgery.
(2025). 9781905813384, National Health Service (NHS).
It is typically used either by mouth or but is also available . Effects last between two and four hours. Paracetamol is classified as a mild analgesic.
(2025). 9781118468715, John Wiley & Sons. .
Paracetamol is generally safe at recommended doses.

NSAIDs
Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a that groups together that decrease pain and , and, in higher doses, decrease . The most prominent members of this group of drugs—, and , and are all available over the counter in most countries.

COX-2 inhibitors
These drugs have been derived from NSAIDs. The enzyme inhibited by NSAIDs was discovered to have at least two different versions: COX1 and COX2. Research suggested most of the adverse effects of NSAIDs to be mediated by blocking the COX1 (constitutive) enzyme, with the analgesic effects being mediated by the COX2 () enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as , , and ) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular.

After widespread adoption of the COX-2 inhibitors, it was discovered that most of the drugs in this class increase the risk of cardiovascular events by 40% on average. This led to the withdrawal of rofecoxib and valdecoxib, and warnings on others. Etoricoxib seems relatively safe, with the risk of events similar to that of non-coxib NSAID diclofenac.

Opioids
, the archetypal , and other opioids (e.g., , , , , ) all exert a similar influence on the system. is a of the μ-opioid receptor, and is a serotonin norepinephrine reuptake inhibitor (SNRI) with weak μ-opioid receptor agonist properties. is structurally closer to than to and delivers analgesia by not only delivering "opioid-like" effects (through mild agonism of the ) but also by acting as a weak but fast-acting serotonin releasing agent and norepinephrine reuptake inhibitor. , with some structural similarities to tramadol, presents what is believed to be a novel drug working through two (and possibly three) different modes of action in the fashion of both a traditional opioid and as an SNRI. The effects of serotonin and norepinephrine on pain, while not completely understood, have had causal links established and drugs in the SNRI class are commonly used in conjunction with opioids (especially tapentadol and tramadol) with greater success in pain relief.

Dosing of all opioids may be limited by opioid toxicity (confusion, respiratory depression, and pinpoint pupils), seizures (), but opioid-tolerant individuals usually have higher dose ceilings than patients without tolerance. Opioids, while very effective analgesics, may have some unpleasant side-effects. Patients starting morphine may experience and (generally relieved by a short course of such as ). (itching) may require switching to a different opioid. occurs in almost all patients on opioids, and (, -containing or co-danthramer) are typically co-prescribed.Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).

When used appropriately, opioids and other central analgesics are safe and effective; however, risks such as addiction and the body's becoming used to the drug (tolerance) can occur. The effect of tolerance means that frequent use of the drug may result in its diminished effect. When safe to do so, the dosage may need to be increased to maintain effectiveness against tolerance, which may be of particular concern regarding patients with chronic pain and requiring an analgesic over long periods. Opioid tolerance is often addressed with in which a patient is routinely switched between two or more non-cross-tolerant opioid medications in order to prevent exceeding safe dosages in the attempt to achieve an adequate analgesic effect.

Opioid tolerance should not be confused with opioid-induced hyperalgesia. The symptoms of these two conditions can appear very similar but the mechanism of action is different. Opioid-induced hyperalgesia is when exposure to opioids increases the sensation of pain () and can even make non-painful stimuli painful ().

Alcohol
Alcohol has biological, mental, and social effects which influence the consequences of using alcohol for pain. Moderate use of alcohol can lessen certain types of pain in certain circumstances.

The majority of its analgesic effects come from antagonizing NMDA receptors, similarly to ketamine, thus decreasing the activity of the primary excitatory (signal boosting) , glutamate. It also functions as an analgesic to a lesser degree by increasing the activity of the primary inhibitory (signal reducing) neurotransmitter, GABA.

Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and alcohol use disorder.

Cannabis
Medical cannabis, or medical marijuana, refers to cannabis or its used to treat disease or improve symptoms. There is evidence suggesting that cannabis can be used to treat and , with some trials indicating improved relief of neuropathic pain over opioids.

Combinations
Analgesics are frequently used in combination, such as the and preparations found in many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such as for -related preparations, or with drugs for people with allergies.

While the use of paracetamol, aspirin, , , and other concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been said to show beneficial synergistic effects by combating pain at multiple sites of action, several combination analgesic products have been shown to have few efficacy benefits when compared to similar doses of their individual components. Moreover, these combination analgesics can often result in significant adverse events, including accidental overdoses, most often due to confusion that arises from the multiple (and often non-acting) components of these combinations.

Alternative medicine
There is some evidence that some treatments using alternative medicine can relieve some types of pain more effectively than .*
  • The available research concludes that more research would be necessary to better understand the use of alternative medicine.

Other drugs
—a monoamine reuptake inhibitor, and calcium and sodium channel modulator—is also approved for the treatment of moderate to severe pain in some countries.

is a centrally acting K+ channel opener with weak properties. It was used in Europe for moderate to strong pain, as well as its -treating and muscle-relaxant properties. It has no significant properties, and is believed to be devoid of any activity on dopamine, serotonin, or histamine receptors. It is not addictive, and tolerance usually does not develop. However, tolerance may develop in some cases.

, a blocker of potent N-type voltage-gated calcium channels, is administered for the relief of severe, usually cancer-related pain.

Adjuvants
Certain drugs that have been introduced for uses other than analgesics are also used in pain management. Both first-generation (such as ) and newer antidepressants (such as ) are used alongside NSAIDs and opioids for pain involving nerve damage and similar problems. Other agents directly potentiate the effects of analgesics, such as using , , , or to increase the pain-killing ability of a given dose of opioid analgesic.

Adjuvant analgesics, also called atypical analgesics, include , , , , , (scopolamine), and other drugs possessing anticonvulsant, anticholinergic, and/or antispasmodic properties, as well as many other drugs with CNS actions. These drugs are used along with analgesics to modulate and/or modify the action of opioids when used against pain, especially of neuropathic origin.

has been noted to slow the development of and reverse tolerance to opioids, as well as to exert additional analgesia by acting upon receptors, as does . Some analgesics such as and and perhaps have intrinsic NMDA action.

The is used to treat neuropathic pain. Similarly, the and are prescribed for neuropathic pain, and is available without prescription. Gabapentinoids work as α2δ-subunit blockers of voltage-gated calcium channels, and tend to have other mechanisms of action as well. Gabapentinoids are all , which are most commonly used for neuropathic pain, as their mechanism of action tends to inhibit pain sensation originating from the nervous system.

Other uses
Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an - or -containing gel (The labeling for topical diclofenac has been updated to warn about drug-induced hepatotoxicity. Voltaren Gel (diclofenac sodium topical gel) 1% – Hepatic Effects Labeling Changes ); also is used . , an , and may be injected into joints for longer-term pain relief. Lidocaine is also used for painful and to numb areas for work and minor medical procedures. In February 2007 the FDA notified consumers and healthcare professionals of the potential hazards of topical anesthetics entering the bloodstream when applied in large doses to the skin without medical supervision. These topical anesthetics contain anesthetic drugs such as lidocaine, tetracaine, benzocaine, and prilocaine in a cream, ointment, or gel.[2]

Uses
Topical nonsteroidal anti-inflammatory drugs provide pain relief in common conditions such as muscle sprains and overuse injuries. Since the side effects are also lesser, topical preparations could be preferred over oral medications in these conditions.

List of drugs with comparison
Nonsteroidal anti-inflammatory drugs
Unselective agents
As per diclofenac.
As per diclofenac.
As diclofenac.
Agranulocytosis and cancer.
Photosensitivity and other AEs typical of NSAIDs.
As per diclofenac.
GI bleeds; ulcers; ; nephrotoxicity; blood dyscrasias (rarely); Stevens–Johnson syndrome (uncommon/rare)
As per diclofenac.
Hepatotoxicity reported.
As per aspirin and paracetamol.
As per diclofenac.
Corneal ulceration.
Skin conditions, such as contact dermatitis.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per aspirin, except without Reye syndrome and with the following additions: myocardial infarctions, and . More prone to causing these AEs compared to the other non-selective NSAIDs.
As per bufexamac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per bufexamac.
As per bufexamac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per bufexamac.
As per bufexamac (topical use) and diclofenac (PO/rectal).
As per diclofenac.
As per bufexamac.
As per bromfenac (ophthalmologic) and diclofenac (PO/IM/IV).
As per diclofenac.
As per diclofenac, except with lower risk of myocardial infarction, stroke and hypertension.
As per bufexamac (topical use) and diclofenac (PO/rectal).
As per diclofenac.
As per bufexamac (topical use) and diclofenac (PO/rectal).
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac. less prone to causing thrombotic events compared to other non-selective NSAIDs.
As per bromfenac.
As per diclofenac.
As per diclofenac.
As per bromfenac. For systemic use haematological side effects such as aplastic anaemia; agranulocytosis; leucopenia; neutropenia; etc.
Nephrotoxicity and haematologic toxicity and other AEs typical of NSAIDs.
Haematologic toxicity (including agranulocytosis, aplastic anaemia) and AEs typical of NSAIDs.
As per other topical NSAIDs.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
Cardiac problems; otherwise As per diclofenac.
As per diclofenac.
As per phenylbutazone.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per other topical NSAIDs.
COX-2 selective inhibitors
As per non-selective NSAIDs. More prone to causing thrombotic events than most of them, however, except diclofenac.
As per diclofenac.
As per diclofenac.
As above, plus hepatotoxicity.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As per diclofenac.
As above and also potentially fatal skin reactions (e.g. toxic epidermal necrolysis).
Those with a morphine skeleton
As per codeine, respiratory effects are subject to a ceiling effect.
Constipation, dependence, sedation, itching, nausea, vomiting and respiratory depression.
As per codeine. Higher potential for abuse compared to other opioids due to its rapid penetration of the blood-brain barrier.
As per codeine.
As per codeine.
As per codeine.
As per codeine.
As per codeine.
As per codeine.
As per codeine.
As per codeine.
Morphinans
As above, but with a higher propensity for causing hallucinations and delusions. Respiratory depression is subject to ceiling effect.
As per codeine.
As per codeine. Respiratory depression is subject to ceiling effect.
Benzomorphans
As per codeine.
As per codeine.
As per codeine. Respiratory effects are subject to a ceiling effect.
As per codeine.
As per other opioids.
As per other opioids; and seizures, anxiety, mood changes and serotonin syndrome.
Open-chain opioids
As per other opioids.
As per other opioids, plus ECG changes.
Less sedating than morphine, otherwise as per morphine.
As per other opioids, plus ventricular rhythm disorders.
As per methadone.
As per pentazocine.
As per other opioids, plus QT interval prolongation.
As per other opioids.
As per other opioids; less likely to cause nausea, vomiting and constipation.
As per other opioids.
As per other opioids but with less respiratory depression and constipation. Psychiatric AEs reported. Serotonin syndrome possible if used in conjunction with other serotonergics.
Anilidopiperidines
As per other opioids. Very sedating.
As with other opioids, with less nausea, vomiting, constipation and itching and more sedation.
As with fentanyl.
As with fentanyl.
Other analgesics
Cancer; AEs of paracetamol.
Sedation, anticholinergic effects, weight gain, orthostatic hypotension, sinus tachycardia, sexual dysfunction, tremor, dizziness, sweating, agitation, insomnia, anxiety, confusion.
Dizziness, euphoria, paranoia, somnolence, abnormal thinking, abdominal pain, nausea, vomiting, depression, hallucinations, hypotension, special difficulties, emotional lability, tremors, flushing, etc.
Anticholinergic effects, GI effects, yawning, sweating, dizziness, weakness, sexual dysfunction, somnolence, insomnia, headache, tremor, decreased appetite.
Drowsiness, dizziness, heartburn, dry mouth, fatigue and nausea.
Fatigue, sedation, dizziness, ataxia, tremor, diplopia, nystagmus, amblyopia, amnesia, abnormal thinking, hypertension, vasodilation, peripheral oedema, dry mouth, weight gain and rash.
As per duloxetine, plus hypertension.
As per dronabinol.
Has antimuscarinic and sympathomimetic effects.
Hepatotoxicity; hypersensitivity reactions (rare), including Stevens–Johnson syndrome; hypotension (rare; IV).
Haematologic, nephrotoxicity, cancer and paracetamol AEs.
As per gabapentin.
As per paracetamol.
CNS toxicity (abnormal gait, abnormal vision, memory problems, etc.); GI effects.
Where † indicates products that are no longer marketed.

Research
Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blockers such as and , as well as multimodal agents such as .

See also

Citations
Sources
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