An '''analgesic''' (colloquially known as a '''painkiller''') is any member of the diverse group of [[Medication|drugs]] used to relieve [[Pain and nociception|pain]] (achieve ''analgesia''). The word ''analgesic'' derives from Greek ''an-'' ("without") and ''-algia'' ("pain"). Analgesic drugs act in various ways on the [[peripheral nervous system|peripheral]] and [[central nervous system|central]] nervous systems; they include [[paracetamol]] (acetaminophen), the [[nonsteroidal anti-inflammatory drug]]s (NSAIDs) such as the [[salicylate]]s, [[narcotic]] drugs such as [[morphine]], synthetic drugs with narcotic properties such as [[tramadol]], and various others. Some other classes of drugs not normally considered analgesics are used to treat [[neuropathy|neuropathic]] pain syndromes; these include [[tricyclic antidepressants]] and [[anticonvulsant]]s.

==The major classes==
===Paracetamol and NSAIDs===
The exact mechanism of action of paracetamol/acetaminophen is uncertain, but it appears to be acting centrally. [[Aspirin]] and the other [[NSAIDs]] inhibit [[cyclooxygenase]], leading to a decrease in [[prostaglandin]] production; this reduces pain and also [[inflammation]] (in contrast to paracetamol and the opioids).{{Fact|date=February 2007}}

Paracetamol has few side effects, but dosing is limited by possible [[hepatotoxicity]] (potential for [[liver]] damage). NSAIDs may predispose to [[peptic ulcer]]s, [[renal failure]], [[allergy|allergic reactions]], and [[hearing loss]].{{Fact|date=February 2007}} They may also increase the risk of [[hemorrhage]] by affecting [[platelet]] function. The use of certain NSAIDs in children under 16 suffering from viral illness may contribute to [[Reye's syndrome]].

===COX-2 inhibitors===
{{main|COX-2 inhibitor}}

These drugs have been derived from NSAIDs. The [[cyclooxygenase]] enzyme inhibited by NSAIDs was discovered to have at least 2 different versions: COX1 and COX2. Research suggested that most of the adverse effects of NSAIDs were mediated by blocking the COX1 (constitutive) enzyme, with the analgesic effects being mediated by the COX2 (inducible) enzyme. The COX2 inhibitors were thus developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as [[rofecoxib]] and [[celecoxib]]) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular. However, post-launch data indicated increased risk of cardiac and cerebrovascular events with these drugs, and rofecoxib was subsequently withdrawn from the market. The role for this class of drug is [[as of 2006|currently]] hotly debated.

===Opiates and morphinomimetics===
[[Morphine]], the archetypal opioid, and various other substances (e.g. [[codeine]], [[oxycodone]], [[hydrocodone]], [[heroin|diamorphine]], [[pethidine]]) all exert a similar influence on the cerebral [[opioid receptor]] system. [[Tramadol]] and [[buprenorphine]] are thought to be [[partial agonist]]s of the opioid receptors. Dosing of all opioids may be limited by opioid toxicity (confusion, respiratory depression, [[myoclonus|myoclonic jerks]] and pinpoint pupils), but there is no dose ceiling in patients who tolerate this.

Opioids, while very effective analgesics, may have some unpleasant side-effects. Up to 1 in 3 patients starting morphine may experience [[nausea]] and [[vomiting]] (generally relieved by a short course of [[antiemetic]]s). [[Pruritus]] (itching) may require switching to a different opioid. [[Constipation]] occurs in almost all patients on opioids, and [[laxative]]s ([[lactulose]], [[macrogol]]-containing or co-danthramer) are typically co-prescribed.

When used appropriately, opioids and similar [[narcotic]] analgesics are otherwise safe and effective, carrying relatively little risk of [[addiction]]. Occasionally, gradual tapering of the dose is required to avoid withdrawal symptoms.

===Specific agents===
In patients with chronic or neuropathic pain, various other substances may have analgesic properties. [[Tricyclic antidepressant]]s, especially [[amitriptyline]], have been shown to improve pain in what appears to be a central manner. The exact mechanism of [[carbamazepine]], [[gabapentin]] and [[pregabalin]] is similarly unclear, but these [[anticonvulsant]]s are used to treat neuropathic pain with modest success.

==Specific forms and uses==
===Combinations===
Analgesics are frequently used in combination, such as the paracetamol and [[codeine]] preparations found in many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such as [[pseudoephedrine]] for [[Paranasal sinus|sinus]]-related preparations, or with [[antihistamine]] drugs for allergy sufferers.

The use of paracetamol, as well as aspirin, ibuprofen, naproxen, and other [[NSAIDS]] concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been shown to have beneficial synergistic effects by combating pain at multiple sites of action—NSAIDs reduce inflammation which, in some cases, is the cause of the pain itself while opiates dull the perception of pain—thus, in cases of mild to moderate pain caused in part by inflammation, it is generally recommended that the two be prescribed together.[http://jada.ada.org/cgi/content/abstract/133/7/861]

===Topical or systemic===
Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an [[ibuprofen]]- or [[diclofenac]]-containing gel; [[capsaicin]] also is used topically. [[Lidocaine]] and [[glucocorticoid|steroids]] may be injected into painful joints for longer-term pain relief. [[Lidocaine]] is also used for painful [[mouth sore]]s and to numb areas for [[dentistry|dental]] work and minor medical procedures.

===Psychotropic agents===
[[Tetrahydrocannabinol]] (THC) and some other [[cannabinoids]], either from the ''[[Cannabis sativa]]'' plant or synthetic, have analgesic properties, although the use of cannabis derivatives is illegal in many countries. Other psychotropic analgesic agents include [[ketamine]] (an NMDA receptor antagonist), [[clonidine]] and other α₂-adrenoreceptor agonists, and [[mexiletine]] and other local anaesthetic analogues.

===Atypical and/or adjuvant analgesics===
[[Orphenadrine]], [[cyclobenzaprine]], [[scopolamine]], [[atropine]], [[gabapentin]], first-generation [[antidepressants]] and other drugs possessing [[anticholinergic]] and/or [[antispasmodic]] properties are used in many cases along with analgesics to potentiate centrally acting analgesics such as [[opioids]] when used against pain especially of neuropathic origin and to modulate the effects of many other types of analgesics by action in the [[parasympathetic nervous system]]. [[Dextromethorphan]] has been noted to slow the development of tolerance to opioids and exert additional analgesia by acting upon the [[NMDA]] receptors; some analgesics such as [[methadone]] and [[ketobemidone]] and perhaps [[piritramide]] have intrinsic NMDA action.

The use of [[adjuvant]] analgesics is an important and growing part of the pain-control field and new discoveries are made practically every year. Many of these drugs combat the side effects of opioid analgesics, an added bonus. For example, [[antihistamines]] including orphenadrine combat the release of histamine caused by many opioids, [[methylphenidate]], [[caffeine]], [[ephedrine]], [[dextroamphetamine]], and [[cocaine]] work against heavy sedation and may elevate mood in distressed patients as do the antidepressants. A well-accepted benefit of THC to chronic pain patients on opioids is its superior anti-nauseant action. However, it would make more sense to use the Marinol capsule, or oral, rectal, or vapour administration of hash oil, rather than smoking cannabis, for the same reasons most doctors advise against smoking tobacco.

==Addiction==
In the [[United States]] in recent years, there has been a wave of new [[addiction]]s to prescription narcotics such as [[oxycodone]] (Percocet) and [[hydrocodone]] ([[Vicodin]], Lortab etc.) when available in pure formulations as opposed to combined with other medications (as in [[Percocet]] which contains both oxycodone and acetaminophen/paracetamol). Hydrocodone is only available in pure form in some European countries as the original hydrocodone pharmaceutical, Dicodid tablets. Far from reducing addiction liability, the paracetamol content of many codeine, dihydrocodeine, hydrocodone, and oxycodone pharmaceuticals in the United States only saddles users with the high risk of severe liver damage, and extraction of the opioids with cold water or solvents reduces this problem for the sophisticated abuser, self-medicator, and legitimate prescription holder alike [http://www.medicalnewstoday.com/healthnews.php?newsid=46607].

==See also==
* [[Pain management]]
* [[Patient-controlled analgesia]]
* [[Co-proxamol]]

==References==
* ''Cancer pain relief and palliative care''. Report of a WHO expert committee [World Health Organization Technical Report Series, 804] . Geneva, Switzerland: [[World Health Organization]]; 1990. pp. 1–75. ISBN 92-4-120804-X.
* [http://www.jr2.ox.ac.uk/bandolier/booth/painpag/index2.html Bandolier pain site] (Oxford pain group)

==External links==
* [http://seattlepi.nwsource.com/health/1500AP_Pain_Reliever_Warning.html FDA proposes new pain reliever warnings]

{{Analgesics}}
{{Major Drug Groups}}

[[Category:Analgesics| ]]
[[Category:Pain]]

[[ar:مسكن ألم]]
[[ca:Analgèsic]]
[[cs:Analgetikum]]
[[da:Analgesi]]
[[de:Analgetikum]]
[[es:Analgésico]]
[[fr:Analgésique]]
[[id:Analgesik]]
[[it:Analgesia]]
[[he:שיכוך כאב]]
[[ms:Analgesik]]
[[nl:Pijnstiller]]
[[ja:鎮痛剤]]
[[pl:Analgezja]]
[[pt:Analgésico]]
[[simple:Analgesic]]
[[sk:Analgézia]]
[[sl:Analgetik]]
[[fi:Analgeetti]]
[[sv:Analgetika]]
[[ta:வலிநீக்கி]]
[[th:ยาบรรเทาปวด]]
[[tr:Analjezik (Farmakolojide)]]
[[uk:Анальгетики]]
[[ur:مُسَـکِّن]]