Analgesic
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2008-07-14T21:05:05Z
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/* Paracetamol and NSAIDs */
{{redirect|Painkiller}}
An '''analgesic''' (colloquially known as a '''painkiller''') is any member of the diverse group of [[Medication|drugs]] used to relieve [[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 [[non-steroidal 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.
In choosing analgesia, the severity and response to other medication determines the choice of agent; the WHO [[pain ladder]], originally developed in [[cancer]]-related pain, is widely applied to find suitable drugs in a stepwise manner.<ref>{{cite book |last=Anonymous |title=Cancer pain relief and palliative care; report of a WHO expert committee |series=World Health Organization Technical Report Series, 804 |year=1990 |publisher=World Health Organization |location=Geneva, Switzerland |language=English |isbn=924120804X |pages=1-75}}</ref> The choice of analgesia is also determined by the type of pain: for [[neuropathic pain]], traditional analgesia is less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as [[tricyclic antidepressants]] and [[anticonvulsant]]s.<ref name="pmid14623723">{{cite journal |author=Dworkin RH, Backonja M, Rowbotham MC, ''et al'' |title=Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations |journal=Arch. Neurol. |volume=60 |issue=11 |pages=1524–34 |year=2003 |pmid=14623723 |doi=10.1001/archneur.60.11.1524|url=http://archneur.ama-assn.org/cgi/content/full/60/11/1524}}</ref>
==The major classes==
===Paracetamol and NSAIDs===
{{main|Non-steroidal anti-inflammatory drug}}
The exact mechanism of action of paracetamol/acetaminophen is uncertain, but it appears to be acting centrally. [[Aspirin]] and the other [[Non-steroidal anti-inflammatory drug|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 and is regarded as very safe, although excessive doses lead to [[nephrotoxicity|Analgesic Abuse Nephropathy]] (AAN) caused by cumulative lifetime use of large amounts (≥ 2 kg) (ref. Merck Manual) and [[hepatotoxicity]] ([[liver]] damage). NSAIDs predispose to [[peptic ulcer]]s, [[renal failure]], [[allergy|allergic reactions]], and occasionally [[hearing loss]], and they can increase the risk of [[hemorrhage]] by affecting [[platelet]] function.{{Fact|date=February 2007}} 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 due to an increased likelihood of clotting in the blood due to a decrease in the production of protoglandin around the platelets causing less clotting factor to be released, and rofecoxib was subsequently withdrawn from the market. The role for this class of drug is debated.
===Opiates and morphinomimetics===
{{main|Opioid|Opiate}}
[[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, however risks such as addiction and the body becoming used to the drug (tolerance) can occur. The effect of tolerance means that drug dosing may have to be increased if it is for a chronic disease this is where the no ceiling limit of the drug comes into play. However what must be remembered is although there is no upper limit there is a still a toxic dose even if the body has become used to lower doses.
===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 combatting 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.<ref name="pmid12148679">{{cite journal |author=Mehlisch DR |title=The efficacy of combination analgesic therapy in relieving dental pain |journal=J Am Dent Assoc |volume=133 |issue=7 |pages=861–71 |year=2002 |pmid=12148679 |url=http://jada.ada.org/cgi/content/full/133/7/861 |doi=10.1001/archneur.60.11.1524}}</ref>
===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]], an [[anesthetic]], 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 α<sub>2</sub>-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. Strong [[liquor]] has been used in the past as an agent for dulling pain, due to the [[CNS]] depressant effects of [[ethyl alcohol]], most notably during the [[Civil War]]. However, the ability of alcohol to "kill pain" is obviously inferior to virtually all of analgesics used today (e.g. morphine, codeine). As such, the idea of alcohol for analgesia is generally reguarded as being as primitive as the practice in virtually all industrialized countries today.
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. Some think it would make more sense to use the synthetic THC capsule (trade name [[Marinol]]), which is administered orally. However, in patients suffering from nausea, the swallowing of the capsule itself may provoke vomiting. Likewise, the use of medicinal [[cannabis]] remains a debated issue.
==Addiction==
{{unreferenced|article's section called "Addiction"|date=July 2008}}
In the [[United States]] in recent years, there has been a wave of new [[addiction]]s to prescription narcotics such as [[oxycodone]] (such as [[OxyContin]], or with [[acetaminophen]], as [[Percocet]]) and [[hydrocodone]] (commonly prescribed with acetaminophen, as in [[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).
==See also==
* [[Pain management]]
* [[Patient-controlled analgesia]]
* [[Co-proxamol]]
==References==
{{reflist}}
==External links==
* [http://www.jr2.ox.ac.uk/bandolier/booth/painpag/index2.html Bandolier pain site] (Oxford pain group)
{{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]]
[[ro:Substanţe analgezice]]
[[simple:Analgesic]]
[[sk:Analgézia]]
[[sl:Analgetik]]
[[sr:Аналгетик]]
[[fi:Analgeetti]]
[[sv:Analgetika]]
[[ta:வலிநீக்கி]]
[[th:ยาบรรเทาปวด]]
[[tr:Analjezik]]
[[uk:Анальгетики]]
[[ur:مُسَـکِّن]]
[[zh:镇痛药]]