Analgesic

From Wikipedia, the free encyclopedia
Jump to: navigation, search
"Painkiller" redirects here. For other uses, see Painkiller (disambiguation).
Opium poppies such as this one provide ingredients for the class of analgesics called opiates

An analgesic or painkiller is any member of the group of drugs used to achieve analgesia, relief from pain.

Analgesic drugs act in various ways on the peripheral and central nervous systems. They are distinct from anesthetics, which temporarily affect, and in some instances completely eliminate, sensation. Analgesics include paracetamol (known in North America as acetaminophen or simply APAP), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, and opioid drugs such as morphine and oxycodone.

When choosing analgesics, the severity and response to other medication determines the choice of agent; the World Health Organization (WHO) pain ladder[1] specifies mild analgesics as its first step.

Analgesic choice is also determined by the type of pain: For neuropathic pain, traditional analgesics are less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and anticonvulsants.[2]

Uses[edit]

Topical nonsteroidal anti-inflammatory drugs provided 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.[3]

Contraindications[edit]

Each different type of analgesic has its own associated side effects.

Classification[edit]

Tilidine, a type of painkiller

Drugs for pain are typically classified by chemical structure.[citation needed]

They may also be classified in other ways. Sometimes they are classified by use for various classes of medical condition.[citation needed] Other times they are sorted by the needs of special populations who would use them.[citation needed] They might be listed by availability in a geographical area, perhaps to prevent recommending a drug which is illegal in one place even if it is easily available elsewhere.[citation needed]

Paracetamol/acetaminophen[edit]

Main article: Paracetamol

Paracetamol, also known as acetaminophen or APAP, is a medication used to treat pain and fever.[4] It is typically used for mild to moderate pain.[4] In combination with opioid pain medication, paracetamol is used for more severe pain such as cancer pain and after surgery.[5] It is typically used either by mouth or rectally but is also available intravenously.[4][6] Effects last between two and four hours.[6] Paracetamol is classified as a mild analgesic.[6] Paracetamol is generally safe at recommended doses.[7]

NSAIDs[edit]

Main article: Nonsteroidal anti-inflammatory drug

Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a drug class that groups together drugs that provide analgesic (pain-killing) and antipyretic (fever-reducing) effects, and, in higher efficacies, anti-inflammatory effects. The most prominent members of this group of drugs, aspirin, ibuprofen and naproxen, are all available over the counter in most countries.[8]

COX-2 inhibitors[edit]

Main article: 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 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 (inducible) enzyme. Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as rofecoxib, celecoxib, and etoricoxib) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular.[9]

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 thrombotic events similar to that of non-coxib NSAID diclofenac.[9]

Opioids[edit]

Main article: Opioid

Morphine, the archetypal opioid, and other opioids (e.g., codeine, oxycodone, hydrocodone, dihydromorphine, pethidine) all exert a similar influence on the cerebral opioid receptor system. Buprenorphine is a partial agonist of the μ-opioid receptor, and tramadol is a serotonin norepinephrine reuptake inhibitor (SNRI) with weak μ-opioid receptor agonist properties.[10] Tramadol is structurally closer to venlafaxine than to codeine and delivers analgesia by not only delivering "opioid-like" effects (through mild agonism of the mu receptor) but also by acting as a weak but fast-acting serotonin releasing agent and norepinephrine reuptake inhibitor.[11][12][13][14] Tapentadol, 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 a 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, myoclonic jerks and pinpoint pupils), seizures (tramadol), but opioid-tolerant individuals usually have higher dose ceilings than patients without tolerance.[citation needed]

Opioids, while very effective analgesics, may have some unpleasant side-effects. Patients starting morphine may experience nausea and vomiting (generally relieved by a short course of antiemetics such as phenergan). Pruritus (itching) may require switching to a different opioid. Constipation occurs in almost all patients on opioids, and laxatives (lactulose, macrogol-containing or co-danthramer) are typically co-prescribed.[15]

When used appropriately, opioids and other central analgesics are otherwise 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 so, when safe to do so, the dosage may need to be increased to maintain effectiveness. This may be of particular concern regarding patients suffering with chronic pain.[citation needed] Opioid tolerance is often addressed with "opioid rotation therapy" 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.

Alcohol[edit]

See also: Ethanol

Describing the effects of using alcohol to treat pain is difficult.[16] Alcohol has biological, mental, and social effects which influence the consequences of using alcohol for pain.[16] Moderate use of alcohol can lessen certain types of pain in certain circumstances.[16] Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and alcohol use disorder.[16]

Medical cannabis[edit]

Main article: Medical cannabis

Medical cannabis or medical marijuana, can refer to the use of cannabis and its cannabinoids to treat disease or improve symptoms.[17][18] There is evidence suggesting that cannabis can be used to treat chronic pain and muscle spasms; with some trials indicating improved relief of neuropathic pain over opioids.[19][20][21]

Combinations[edit]

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 sinus-related preparations, or with antihistamine drugs for allergy sufferers.

While the use of paracetamol, aspirin, ibuprofen, naproxen, and other NSAIDS concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been said to show beneficial synergistic effects by combatting pain at multiple sites of action,[22] 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.[23]

Alternative medicine[edit]

Many people use alternative medicine treatments including drugs for pain relief.[24] There is some evidence that some treatments using alternative medicine can relieve some types of pain more effectively than placebo.[25] The available research concludes that more research would be necessary to better understand the use of alternative medicine.[25]

Psychotropic agents[edit]

Other psychotropic analgesic agents include ketamine (an NMDA receptor antagonist), clonidine and other α2-adrenoreceptor agonists, and mexiletine and other local anaesthetic analogues.

Other drugs[edit]

Drugs that have been introduced for uses other than analgesics are also used in pain management. Both first-generation (such as amitriptyline) and newer anti-depressants (such as duloxetine) 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 hydroxyzine, promethazine, carisoprodol, or tripelennamine to increase the pain-killing ability of a given dose of opioid analgesic.

Adjuvant analgesics, also called atypical analgesics, include nefopam, orphenadrine, pregabalin, gabapentin, cyclobenzaprine, 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.

Dextromethorphan has been noted to slow the development of tolerance to opioids and exert additional analgesia by acting upon the NMDA receptors;[citation needed] some analgesics such as methadone and ketobemidone and perhaps piritramide have intrinsic NMDA action.[26]

High-alcohol liquor, two forms of which were found in the US Pharmacopoeia up until 1916 and in common use by physicians well into the 1930s, has been used in the past as an agent for dulling pain, due to the CNS depressant effects of ethyl alcohol, a notable example being the American Civil War.[citation needed] However, the ability of alcohol to relieve severe pain is likely inferior to many analgesics used today (e.g., morphine, codeine). As such, in general, the idea of alcohol for analgesia is considered a primitive 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. Stimulants such as methylphenidate, caffeine, ephedrine, dextroamphetamine, methamphetamine, and cocaine work against heavy sedation and may elevate mood in distressed patients as do the antidepressants.[citation needed] The use of medicinal cannabis remains a debated issue.

In patients with chronic or neuropathic pain, various other substances may have analgesic properties. Tricyclic antidepressants, especially clomipramine and amitriptyline, have been shown to improve pain in what appears to be a central manner.[citation needed] Nefopam is used in Europe for pain relief with concurrent opioids. The exact mechanism of carbamazepine, gabapentin, and pregabalin is similarly unclear, but these anticonvulsants are used to treat neuropathic pain with differing degrees of success. Anticonvulsants are most commonly used for neuropathic pain as their mechanism of action tends to inhibit pain sensation.[27]

Flupirtine is a centrally acting K+ channel opener with weak NMDA antagonist properties.[28] It is used in Europe for moderate to strong pain and migraine and its muscle-relaxant properties. It has no anticholinergic 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.[29] However, tolerance may develop in single cases.[30]

Other classification systems[edit]

Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an ibuprofen- or diclofenac-containing gel (The labeling for topical diclofenac has been updated to warn about drug-induced hepatotoxicity.[31]); capsaicin also is used topically. Lidocaine, an anesthetic, and steroids may be injected into painful joints for longer-term pain relief. Lidocaine is also used for painful mouth sores and to numb areas for dental work and minor medical procedures. In February 2007 the FDA notified consumers and healthcare professionals of the potential hazards of topical anesthetics entering the blood stream 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.[32]

List of drugs with comparison[edit]

Etymology[edit]

The word analgesic derives from Greek an- (ἀν-, "without"), álgos (ἄλγος, "pain"),[117] and -ikos (-ικος, forming adjectives). Such drugs were usually known as anodynes before the 20th century.[118][119]

Research[edit]

Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blockers such as funapide and raxatrigine, as well as multimodal agents such as ralfinamide.[citation needed]

See also[edit]

Notes[edit]

  1. ^ Anonymous (1990). Cancer pain relief and palliative care; report of a WHO expert committee. World Health Organization Technical Report Series, 804. Geneva, Switzerland: World Health Organization. pp. 1–75. ISBN 92-4-120804-X. 
  2. ^ Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, Bushnell MC, Farrar JT, Galer BS, Haythornthwaite JA, Hewitt DJ, Loeser JD, Max MB, Saltarelli M, Schmader KE, Stein C, Thompson D, Turk DC, Wallace MS, Watkins LR, Weinstein SM (2003). "Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations". Arch. Neurol. 60 (11): 1524–34. doi:10.1001/archneur.60.11.1524. PMID 14623723. 
  3. ^ Derry, Sheena; Moore, R. Andrew; Gaskell, Helen; McIntyre, Mairead; Wiffen, Philip J. (2015-06-11). "Topical NSAIDs for acute musculoskeletal pain in adults". The Cochrane Database of Systematic Reviews. 6 (6): CD007402. doi:10.1002/14651858.CD007402.pub3. PMID 26068955. 
  4. ^ a b c "Acetaminophen". The American Society of Health-System Pharmacists. 
  5. ^ Scottish Intercollegiate Guidelines Network (SIGN) (2008). "6.1 and 7.1.1". Guideline 106: Control of pain in adults with cancer (PDF). Scotland: National Health Service (NHS). ISBN 9781905813384. 
  6. ^ a b c Hochhauser, Daniel (2014). Cancer and its Management. John Wiley & Sons. p. 119. ISBN 9781118468715. 
  7. ^ Russell, FM; Shann, F; Curtis, N; Mulholland, K (2003). "Evidence on the use of paracetamol in febrile children.". Bulletin of the World Health Organization. 81 (5): 367–72. PMC 2572451Freely accessible. PMID 12856055. 
  8. ^ Warden SJ (April 2010). "Prophylactic Use of NSAIDs by Athletes: A Risk/Benefit Assessment". The Physician and Sports Medicine. 38 (1): 132–138. doi:10.3810/psm.2010.04.1770. PMID 20424410. 
  9. ^ a b Conaghan PG (June 2012). "A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity". Rheumatol. Int. 32 (6): 1491–502. doi:10.1007/s00296-011-2263-6. PMC 3364420Freely accessible. PMID 22193214. 
  10. ^ Smith, Howard S.; Raffa, Robert B.; Pergolizzi, Joseph V.; Taylor, Robert; Tallarida, Ronald J. (2014-07-01). "Combining opioid and adrenergic mechanisms for chronic pain". Postgraduate Medicine. 126 (4): 98–114. doi:10.3810/pgm.2014.07.2788. PMID 25141248. 
  11. ^ Driessen B, Reimann W (January 1992). "Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro". British Journal of Pharmacology. 105 (1): 147–51. doi:10.1111/j.1476-5381.1992.tb14226.x. PMC 1908625Freely accessible. PMID 1596676. 
  12. ^ Bamigbade TA, Davidson C, Langford RM, Stamford JA (September 1997). "Actions of tramadol, its enantiomers and principal metabolite, O-desmethyltramadol, on serotonin (5-HT) efflux and uptake in the rat dorsal raphe nucleus". British Journal of Anaesthesia. 79 (3): 352–6. doi:10.1093/bja/79.3.352. PMID 9389855. 
  13. ^ Reimann W, Schneider F (May 1998). "Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine". European Journal of Pharmacology. 349 (2–3): 199–203. doi:10.1016/S0014-2999(98)00195-2. PMID 9671098. 
  14. ^ Gobbi M, Moia M, Pirona L, Ceglia I, Reyes-Parada M, Scorza C, Mennini T (September 2002). "p-Methylthioamphetamine and 1-(m-chlorophenyl)piperazine, two non-neurotoxic 5-HT releasers in vivo, differ from neurotoxic amphetamine derivatives in their mode of action at 5-HT nerve endings in vitro". Journal of Neurochemistry. 82 (6): 1435–43. doi:10.1046/j.1471-4159.2002.01073.x. PMID 12354291. 
  15. ^ Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
  16. ^ a b c d Zale, Emily L.; Maisto, Stephen A.; Ditre, Joseph W. (2015). "Interrelations between pain and alcohol: An integrative review". Clinical Psychology Review. 37: 57–71. doi:10.1016/j.cpr.2015.02.005. PMC 4385458Freely accessible. PMID 25766100. 
  17. ^ Murnion, B (December 2015). "Medicinal cannabis.". Australian prescriber. 38 (6): 212–5. doi:10.18773/austprescr.2015.072. PMC 4674028Freely accessible. PMID 26843715. 
  18. ^ "What is medical marijuana?". National Institute of Drug Abuse. July 2015. Retrieved 19 April 2016. The term medical marijuana refers to using the whole unprocessed marijuana plant or its basic extracts to treat a disease or symptom. 
  19. ^ Borgelt, LM; Franson, KL; Nussbaum, AM; Wang, GS (February 2013). "The pharmacologic and clinical effects of medical cannabis.". Pharmacotherapy. 33 (2): 195–209. doi:10.1002/phar.1187. PMID 23386598. 
  20. ^ Whiting, PF; Wolff, RF; Deshpande, S; Di Nisio, M; Duffy, S; Hernandez, AV; Keurentjes, JC; Lang, S; Misso, K; Ryder, S; Schmidlkofer, S; Westwood, M; Kleijnen, J (23 June 2015). "Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.". JAMA. 313 (24): 2456–2473. doi:10.1001/jama.2015.6358. hdl:10757/558499. PMID 26103030. 
  21. ^ Jensen, Bjorn; Chen, Jeffrey; Furnish, Tim; Wallace, Mark (1 September 2015). "Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence". Current Pain and Headache Reports. 19 (10). doi:10.1007/s11916-015-0524-x. 
  22. ^ Mehlisch DR (2002). "The efficacy of combination analgesic therapy in relieving dental pain". J Am Dent Assoc. 133 (7): 861–71. doi:10.14219/jada.archive.2002.0300. PMID 12148679. 
  23. ^ Murnion B. "Combination analgesics in adults". Australian Prescriber (33): 113–5. Retrieved 12 August 2010. 
  24. ^ Thomas, Donna-Ann; Maslin, Benjamin; Legler, Aron; Springer, Erin; Asgerally, Abbas; Vadivelu, Nalini (2 April 2016). "Role of Alternative Therapies for Chronic Pain Syndromes". Current Pain and Headache Reports. 20 (5). doi:10.1007/s11916-016-0562-z. 
  25. ^ a b
    • Oltean, Hanna; Robbins, Chris; van Tulder, Maurits W; Berman, Brian M; Bombardier, Claire; Gagnier, Joel J; Gagnier, Joel J (2014). "Herbal medicine for low-back pain". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD004504.pub4. 
    • Cameron, Melainie; Gagnier, Joel J; Chrubasik, Sigrun; Cameron, Melainie (2011). "Herbal therapy for treating rheumatoid arthritis". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD002948.pub2. 
    • Cui, Xuejun; Trinh, Kien; Wang, Yong-Jun; Cui, Xuejun (2010). "Chinese herbal medicine for chronic neck pain due to cervical degenerative disc disease". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD006556.pub2. 
  26. ^ K. J. Elliott, MD; M. Brodsky, BS; A. Hynansky, BA; K. M. Foley, MD; C. E. Inturrisi, PhD. Dextromethorphan shows efficacy in experimental pain (nociception) and opioid tolerance. NEUROLOGY, 2005. 
  27. ^ Ian Eardley; Peter Whelan; Roger Kirby; Anthony Schaeffer. "Drugs Used In The Treatment Of Interstitial Cystitis". Drug Treatment in Urology. John Wiley & Sons, 2008. p. 65. 
  28. ^ Kornhuber J, Bleich S, Wiltfang J, Maler M, Parsons CG (1999). "Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. Rapid communication". J Neural Transm. 106 (9–10): 857–67. doi:10.1007/s007020050206. PMID 10599868. 
  29. ^ Klawe C, Maschke M (2009). "Flupirtine: pharmacology and clinical applications of a nonopioid analgesic and potentially neuroprotective compound". Expert opinion on pharmacotherapy. 10 (9): 1495–500. doi:10.1517/14656560902988528. PMID 19505216. 
  30. ^ Stoessel C, Heberlein A, Hillemacher T, Bleich S, Kornhuber J (August 2010). "Positive reinforcing effects of flupirtine—two case reports". Prog. Neuropsychopharmacol. Biol. Psychiatry. 34 (6): 1120–1. doi:10.1016/j.pnpbp.2010.03.031. PMID 20362025. 
  31. ^ Voltaren Gel (diclofenac sodium topical gel) 1% – Hepatic Effects Labeling Changes
  32. ^ [1] Archived October 19, 2010, at the Wayback Machine.
  33. ^ a b c d e Brayfield, A (ed.). "Martindale: The Complete Drug Reference". Medicines Complete. Pharmaceutical Press. Retrieved 9 April 2014. 
  34. ^ a b c d Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8. 
  35. ^ a b c d e f g h i Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3. 
  36. ^ a b c Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8. 
  37. ^ "Zorprin, Bayer Buffered Aspirin (aspirin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 6 April 2014. 
  38. ^ "Seractil 300mg Film-Coated Tablets – Summary of Product Characteristics". electronic Medicines Compendium. Genus Pharmaceuticals. 30 September 2005. Retrieved 7 April 2014. 
  39. ^ Derry S, Best J, Moore RA (October 2013). "Single dose oral dexibuprofen [S(+)-ibuprofen] for acute postoperative pain in adults". The Cochrane Database of Systematic Reviews. 10 (10): CD007550. doi:10.1002/14651858.CD007550.pub3. PMID 24151035. 
  40. ^ a b "Cardiovascular safety of Cox-2 inhibitors and non-selective NSAIDs". MHRA. 26 July 2013. Archived from the original on April 13, 2014. Retrieved 7 April 2014. 
  41. ^ "(diflunisal) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 7 April 2014. 
  42. ^ "Nalfon (fenoprofen) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 7 April 2014. 
  43. ^ a b Abdel-Aziz AA, Al-Badr AA, Hafez GA (2012). "Flurbiprofen" (PDF). Profiles of Drug Substances, Excipients, and Related Methodology. Profiles of Drug Substances, Excipients and Related Methodology. 37: 113–81. doi:10.1016/B978-0-12-397220-0.00004-0. ISBN 9780123972200. PMID 22469318. 
  44. ^ Smith HS, Voss B (February 2012). "Pharmacokinetics of intravenous ibuprofen: implications of time of infusion in the treatment of pain and fever". Drugs. 72 (3): 327–37. doi:10.2165/11599230-000000000-00000. PMID 22316349. 
  45. ^ Neumann R, Schulzke SM, Bührer C (2012). "Oral ibuprofen versus intravenous ibuprofen or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis". Neonatology. 102 (1): 9–15. doi:10.1159/000335332. PMID 22414850. 
  46. ^ Johnston PG, Gillam-Krakauer M, Fuller MP, Reese J (March 2012). "Evidence-based use of indomethacin and ibuprofen in the neonatal intensive care unit". Clinics in Perinatology. 39 (1): 111–36. doi:10.1016/j.clp.2011.12.002. PMC 3598606Freely accessible. PMID 22341541. 
  47. ^ "Arthrexin Indomethacin PRODUCT INFORMATION" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 14 October 2011. Retrieved 7 April 2014. 
  48. ^ Coaccioli S (August 2011). "Ketoprofen 2.5% gel: a clinical overview.". European Review for Medical and Pharmacological Sciences. 15 (8): 943–9. PMID 21845805. 
  49. ^ Adachi H, Ioppolo F, Paoloni M, Santilli V (July 2011). "Physical characteristics, pharmacological properties and clinical efficacy of the ketoprofen patch: a new patch formulation". European Review for Medical and Pharmacological Sciences. 15 (7): 823–30. PMID 21780552. 
  50. ^ Kokki, H (October 2010). "Ketoprofen pharmacokinetics, efficacy, and tolerability in pediatric patients.". Paediatric drugs. 12 (5): 313–29. doi:10.2165/11534910-000000000-00000. PMID 20799760. 
  51. ^ Shohin, IE; Kulinich, JI; Ramenskaya, GV; Abrahamsson, B; Kopp, S; Langguth, P; Polli, JE; Shah, VP; et al. (October 2012). "Biowaiver monographs for immediate-release solid oral dosage forms: ketoprofen". Journal of Pharmaceutical Sciences. 101 (10): 3593–603. doi:10.1002/jps.23233. PMID 22786667. 
  52. ^ Sarzi-Puttini, P; Atzeni, F; Lanata, L; Bagnasco, M; Colombo, M; Fischer, F; D'Imporzano, M (July–September 2010). "Pain and ketoprofen: what is its role in clinical practice?". Reumatismo. 62 (3): 172–88. doi:10.4081/reumatismo.2010.172. PMID 21052564. 
  53. ^ "NAME OF THE MEDICINE TORADOL® (ketorolac trometamol)" (PDF). TGA eBusiness Services. ROCHE PRODUCTS PTY LIMITED. 3 February 2012. Retrieved 7 April 2014. 
  54. ^ McCormack PL (July 2011). "Ketorolac 0.45% ophthalmic solution.". Drugs & Aging. 28 (7): 583–9. doi:10.2165/11207450-000000000-00000. PMID 21721602. 
  55. ^ Sinha VR, Kumar RV, Singh G (September 2009). "Ketorolac tromethamine formulations: an overview". Expert Opinion on Drug Delivery. 6 (9): 961–75. doi:10.1517/17425240903116006. PMID 19663721. 
  56. ^ De Oliveira GS, Agarwal D, Benzon HT (February 2012). "Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials". Anesthesia and Analgesia. 114 (2): 424–33. doi:10.1213/ANE.0b013e3182334d68. PMID 21965355. 
  57. ^ Garnock-Jones KP (June 2012). "Intranasal ketorolac: for short-term pain management.". Clinical Drug Investigation. 32 (6): 361–71. doi:10.2165/11209240-000000000-00000. PMID 22574632. 
  58. ^ He A, Hersh EV (December 2012). "A review of intranasal ketorolac tromethamine for the short-term management of moderate to moderately severe pain that requires analgesia at the opioid level". Current Medical Research and Opinion. 28 (12): 1873–80. doi:10.1185/03007995.2012.744302. PMID 23098098. 
  59. ^ Taggart E, Doran S, Kokotillo A, Campbell S, Villa-Roel C, Rowe BH (February 2013). "Ketorolac in the treatment of acute migraine: a systematic review". Headache. 53 (2): 277–87. doi:10.1111/head.12009. PMID 23298250. 
  60. ^ Yilmaz T, Cordero-Coma M, Gallagher MJ (February 2012). "Ketorolac therapy for the prevention of acute pseudophakic cystoid macular edema: a systematic review". Eye. 26 (2): 252–8. doi:10.1038/eye.2011.296. PMC 3272202Freely accessible. PMID 22094296. 
  61. ^ Balfour JA, Fitton A, Barradell LB (April 1996). "Lornoxicam. A review of its pharmacology and therapeutic potential in the management of painful and inflammatory conditions". Drugs. 51 (4): 639–57. doi:10.2165/00003495-199651040-00008. PMID 8706598. 
  62. ^ Skjodt NM, Davies NM (June 1998). "Clinical pharmacokinetics of lornoxicam. A short half-life oxicam". Clinical Pharmacokinetics. 34 (6): 421–8. doi:10.2165/00003088-199834060-00001. PMID 9646006. 
  63. ^ "PRODUCT INFORMATION PONSTAN® CAPSULES (mefenamic acid)" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 12 October 2012. Retrieved 7 April 2014. 
  64. ^ "Relafen (nabumetone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 7 April 2014. 
  65. ^ Todd PA, Clissold SP (July 1990). "Naproxen. A reappraisal of its pharmacology, and therapeutic use in rheumatic diseases and pain states". Drugs. 40 (1): 91–137. doi:10.2165/00003495-199040010-00006. PMID 2202585. 
  66. ^ "Daypro (oxaprozin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 7 April 2014. 
  67. ^ Todd PA, Brogden RN (October 1986). "Oxaprozin. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy". Drugs. 32 (4): 291–312. doi:10.2165/00003495-198632040-00001. PMID 3536423. 
  68. ^ "CHEMMART PIROXICAM CAPSULES" (PDF). TGA eBusiness Services. Apotex Pty Ltd. 18 December 2013. Retrieved 7 April 2014. 
  69. ^ Brogden RN, Heel RC, Speight TM, Avery GS (October 1984). "Piroxicam. A reappraisal of its pharmacology and therapeutic efficacy". Drugs. 28 (4): 292–323. doi:10.2165/00003495-199448060-00007. PMID 6386426. 
  70. ^ "(salsalate) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 7 April 2014. 
  71. ^ "Aclin Sulindac" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 8 November 2011. Retrieved 7 April 2014. 
  72. ^ Gonzalez JP, Todd PA (September 1987). "Tenoxicam. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy". Drugs. 34 (3): 289–310. doi:10.2165/00003495-198734030-00001. PMID 3315620. 
  73. ^ Davies NM (November 1996). "Clinical pharmacokinetics of tiaprofenic acid and its enantiomers.". Clinical pharmacokinetics. 31 (5): 331–47. doi:10.2165/00003088-199631050-00002. PMID 9118583. 
  74. ^ Brogden RN, Heel RC, Speight TM, Avery GS (June 1978). "Tolmetin: a review of its pharmacological properties and therapeutic efficacy in rheumatic diseases". Drugs. 15 (6): 429–50. doi:10.2165/00003495-197815060-00002. PMID 350558. 
  75. ^ McCormack PL (December 2011). "Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.". Drugs. 71 (18): 2457–89. doi:10.2165/11208240-000000000-00000. PMID 22141388. 
  76. ^ Lynch S, Brogden RN (April 1986). "Etodolac. A preliminary review of its pharmacodynamic activity and therapeutic use". Drugs. 31 (4): 288–300. doi:10.2165/00003495-198631040-00002. PMID 2940079. 
  77. ^ Balfour JA, Buckley MM (August 1991). "Etodolac. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases and pain states". Drugs. 42 (2): 274–99. doi:10.2165/00003495-199142020-00008. PMID 1717225. 
  78. ^ Brocks DR, Jamali F (April 1994). "Etodolac clinical pharmacokinetics". Clinical pharmacokinetics. 26 (4): 259–74. doi:10.2165/00003088-199426040-00003. PMID 8013160. 
  79. ^ Takemoto JK, Reynolds JK, Remsberg CM, Vega-Villa KR, Davies NM (2008). "Clinical pharmacokinetic and pharmacodynamic profile of etoricoxib". Clinical Pharmacokinetics. 47 (11): 703–20. doi:10.2165/00003088-200847110-00002. PMID 18840026. 
  80. ^ Bannwarth B, Bérenbaum F (July 2007). "Lumiracoxib in the management of osteoarthritis and acute pain". Expert Opinion on Pharmacotherapy. 8 (10): 1551–64. doi:10.1517/14656566.8.10.1551. PMID 17661736. 
  81. ^ Davies NM, Skjodt NM (February 1999). "Clinical pharmacokinetics of meloxicam. A cyclo-oxygenase-2 preferential nonsteroidal anti-inflammatory drug". Clinical Pharmacokinetics. 36 (2): 115–26. doi:10.2165/00003088-199936020-00003. PMID 10092958. 
  82. ^ "PRODUCT INFORMATION DYNASTAT parecoxib (as sodium)" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 6 February 2013. Retrieved 7 April 2014. 
  83. ^ Scott LJ, Lamb HM (September 1999). "Rofecoxib". Drugs. 58 (3): 499–505; discussion 506–7. doi:10.2165/00003495-199958030-00016. PMID 10493277. 
  84. ^ Hillson JL, Furst DE (July 2000). "Rofecoxib". Expert Opinion on Pharmacotherapy. 1 (5): 1053–66. doi:10.1517/14656566.1.5.1053. PMID 11249495. 
  85. ^ Ormrod D, Wellington K, Wagstaff AJ (2002). "Valdecoxib". Drugs. 62 (14): 2059–71; discussion 2072–3. doi:10.2165/00003495-200262140-00005. PMID 12269850. 
  86. ^ "Buprenex, Subutex (buprenorphine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 9 April 2014. 
  87. ^ "PRODUCT INFORMATION ACTACODE" (PDF). TGA eBusiness Services. Aspen Pharma Pty Ltd. 19 September 2006. Retrieved 8 April 2014. 
  88. ^ "Zohydro ER (hydrocodone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 8 April 2014. 
  89. ^ "Dilaudid, Dilaudid HP (hydromorphone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 8 April 2014. 
  90. ^ "Roxicodone, OxyContin (oxycodone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 8 April 2014. 
  91. ^ "Opana, Opana ER (oxymorphone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 8 April 2014. 
  92. ^ "Stadol (butorphanol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 8 April 2014. 
  93. ^ a b Prommer E (March 2007). "Levorphanol: the forgotten opioid.". Supportive Care in Cancer. 15 (3): 259–64. doi:10.1007/s00520-006-0146-2. PMID 17039381. 
  94. ^ "Levo Dromoran (levorphanol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 9 April 2014. 
  95. ^ "Nubain (nalbuphine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 9 April 2014. 
  96. ^ Errick JK, Heel RC (September 1983). "Nalbuphine. A preliminary review of its pharmacological properties and therapeutic efficacy". Drugs. 26 (3): 191–211. doi:10.2165/00003495-198326030-00002. PMID 6137354. 
  97. ^ Brogden RN, Speight TM, Avery GS (1973). "Pentazocine: a review of its pharmacological properties, therapeutic efficacy and dependence liability". Drugs. 5 (1): 6–91. doi:10.2165/00003495-197305010-00002. PMID 4578369. 
  98. ^ "Talwin (pentazocine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 9 April 2014. 
  99. ^ Anderson P, Arnér S, Bondesson U, Boréus LO, Hartvig P (1982). "Single-dose kinetics and bioavailability of ketobemidone". Acta Anaesthesiologica Scandinavica. Supplementum. 74: 59–62. PMID 6124079. 
  100. ^ "Demerol, Pethidine (meperidine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 9 April 2014. 
  101. ^ Shipton E (March 2006). "Should New Zealand continue signing up to the Pethidine Protocol?" (PDF). The New Zealand Medical Journal. 119 (1230): U1875. PMID 16532042. Archived from the original (PDF) on April 8, 2014. 
  102. ^ Latta KS, Ginsberg B, Barkin RL (January–February 2002). "Meperidine: a critical review". American Journal of Therapeutics. 9 (1): 53–68. doi:10.1097/00045391-200201000-00010. PMID 11782820. 
  103. ^ MacPherson, RD; Duguid, MD (2008). "Strategy to Eliminate Pethidine Use in Hospitals" (PDF). Journal of Pharmacy Practice and Research. 38 (2): 88–89. 
  104. ^ Mather LE, Meffin PJ (September–October 1978). "Clinical pharmacokinetics of pethidine". Clinical Pharmacokinetics. 3 (5): 352–68. doi:10.2165/00003088-197803050-00002. PMID 359212. 
  105. ^ "Dipipanone 10mg + Cyclizine 30mg Tablets – Summary of Product Characteristics". 22 August 2012. Retrieved 9 April 2014. 
  106. ^ Holmes B, Ward A (October 1985). "Meptazinol. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy". Drugs. 30 (4): 285–312. doi:10.2165/00003495-198530040-00001. PMID 2998723. 
  107. ^ Lugo RA, Satterfield KL, Kern SE (2005). "Pharmacokinetics of methadone". Journal of Pain & Palliative Care Pharmacotherapy. 19 (4): 13–24. doi:10.1080/J354v19n04_05. PMID 16431829. 
  108. ^ "Marinol (dronabinol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 9 April 2014. 
  109. ^ "Cymbalta (duloxetine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 9 April 2014. 
  110. ^ Szelenyi I (March 2013). "Flupirtine, a re-discovered drug, revisited.". Inflammation Research. 62 (3): 251–8. doi:10.1007/s00011-013-0592-5. PMID 23322112. 
  111. ^ Devulder J (October 2010). "Flupirtine in pain management: pharmacological properties and clinical use.". CNS Drugs. 24 (10): 867–81. doi:10.2165/11536230-000000000-00000. PMID 20839897. 
  112. ^ "Savella (milnacipran) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 9 April 2014. 
  113. ^ Evans MS, Lysakowski C, Tramèr MR (November 2008). "Nefopam for the prevention of postoperative pain: quantitative systematic review" (PDF). British Journal of Anaesthesia. 101 (5): 610–7. doi:10.1093/bja/aen267. PMID 18796441. 
  114. ^ "Tylenol, Tylenol Infants' Drops (acetaminophen) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 8 April 2014. 
  115. ^ McKeage K, Keam SJ (2009). "Pregabalin: in the treatment of postherpetic neuralgia". Drugs & Aging. 26 (10): 883–92. doi:10.2165/11203750-000000000-00000. PMID 19761281. 
  116. ^ a b "Prialt (ziconotide) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 8 April 2014. 
  117. ^ Harper,D. (2001). "Online Etymology Dictionary: Analgesia". Retrieved December 3, 2012. 
  118. ^ EB (1878).
  119. ^ EB (1911).

References[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Analgesic&oldid=772568189"