Analgesic: Difference between revisions

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Analgesic choice is also determined by the type of pain: For [[neuropathic pain]], recent research has suggested that classes of drugs that are not normally considered analgesics, such as [[tricyclic antidepressants]] and [[anticonvulsant]]s may be considered as an alternative.<ref name="pmid14623723">{{cite journal | vauthors = 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 | display-authors = 6 | title = Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations | journal = Archives of Neurology | volume = 60 | issue = 11 | pages = 1524–34 | date = November 2003 | pmid = 14623723 | doi = 10.1001/archneur.60.11.1524 | doi-access = free }}</ref>

=== Paracetamol (acetaminophen) ===

{{main|Paracetamol}}

===NSAIDs===

{{main|Nonsteroidal anti-inflammatory drug}}

==== COX-2 inhibitors ====

===Cannabis===

{{main|Medical cannabis}}

=== Combinations ===

===Alternative medicine===

=== Other drugs ===

=== Adjuvants ===

{{Main|Analgesic adjuvant}}

Adjuvant analgesics, also called atypical analgesics, include [[orphenadrine]], [[mexiletine]], [[pregabalin]], [[gabapentin]], [[cyclobenzaprine]], [[hyoscine]] (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.

=== Other uses ===

==Uses==

== List of drugs with comparison ==

! Physicochemistry<ref name = MD>{{cite web|title=Martindale: The Complete Drug Reference|publisher=Pharmaceutical Press|work=Medicines Complete|access-date=9 April 2014|url=http://www.medicinescomplete.com/mc/martindale/current/|editor=Brayfield, A}}</ref>

! Mechanism of action<ref name = GG/>

! style="width:100px;"| Pharmacokinetics<ref name = MD/>

|-

| colspan="7" style="text-align:center;"| '''<big>[[Nonsteroidal anti-inflammatory drug]]s</big>'''

| [[Clonixin]] || Comes in free acid and lysine salt forms. || Reversible COX-1/COX-2 inhibition. || PO, IM, IV, rectal. || No data. || Pain. || As per diclofenac.

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| [[Diethylamine salicylate]]|| Freely soluble in water; degrades upon contact with light and iron. || As per diclofenac. || Topical. || N/A. || Rheumatic and musculoskeletal pain. || As per bufexamac.

| [[Flufenamic acid]] || Comes in free acid form and aluminium salt form; anthranilic acid. || As per diclofenac. || Topical. || N/A || Soft tissue inflammation and pain. || As per bufexamac.

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| [[Glucametacin]] || Indometacin derivative. || As per diclofenac. || PO. || Not available. || Musculoskeletal, joint, peri-articular and soft-tissue disorders. || As per diclofenac.

| [[Kebuzone]] || Comes in free and sodium salt form; phenylbutazone derivative. || As per diclofenac. || IM, PO. || Not available. || As per diclofenac. || As per diclofenac.

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| [[Ketorolac]] || Comes in the [[trometamol]] salt form; highly soluble in water. Degrades in the presence of light. Acetic acid derivative. || As per diclofenac. || PO, IM, IV, intranasal, tromethamine and ophthalmologic. || Bioavailability of IM formulation = 100%; protein binding = 99%; hepatic metabolism mostly via glucoronic acid conjugation and p-hydroxylation; half-life = 5–6 hours; excretion = urine (91.4%), faeces (6.1%).<ref>{{cite web|title=NAME OF THE MEDICINE TORADOL (ketorolac trometamol)|work=TGA eBusiness Services|publisher=ROCHE PRODUCTS PTY LIMITED|date=3 February 2012|access-date=7 April 2014|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-01084-3|format=PDF|url-status=live|archive-url=https://web.archive.org/web/20151015201453/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-01084-3|archive-date=15 October 2015}}</ref> || Mild-moderate postoperative pain; acute migraine; inflammation of the eye due to cataract surgery or allergic seasonal [[conjunctivitis]]; prevention of acute pseudophakic cystoid macular oedema.<ref>{{cite journal | vauthors = McCormack PL | title = Ketorolac 0.45% ophthalmic solution | journal = Drugs & Aging | volume = 28 | issue = 7 | pages = 583–9 | date = July 2011 | pmid = 21721602 | doi = 10.2165/11207450-000000000-00000 | s2cid = 36573017 }}</ref><ref>{{cite journal | vauthors = Sinha VR, Kumar RV, Singh G | title = Ketorolac tromethamine formulations: an overview | journal = Expert Opinion on Drug Delivery | volume = 6 | issue = 9 | pages = 961–75 | date = September 2009 | pmid = 19663721 | doi = 10.1517/17425240903116006 | s2cid = 25006837 }}</ref><ref>{{cite journal | vauthors = De Oliveira GS, Agarwal D, Benzon HT | s2cid = 21022357 | title = Perioperative single dose ketorolac to prevent postoperative pain: a meta-analysis of randomized trials | journal = Anesthesia and Analgesia | volume = 114 | issue = 2 | pages = 424–33 | date = February 2012 | pmid = 21965355 | doi = 10.1213/ANE.0b013e3182334d68 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Garnock-Jones KP | title = Intranasal ketorolac: for short-term pain management | journal = Clinical Drug Investigation | volume = 32 | issue = 6 | pages = 361–71 | date = June 2012 | pmid = 22574632 | doi = 10.2165/11209240-000000000-00000 | s2cid = 41818971 }}</ref><ref>{{cite journal | vauthors = He A, Hersh EV | title = A review of intranasal ketorolac tromethamine for the short-term management of moderate to moderately severe pain that requires analgesia at the opioid level | journal = Current Medical Research and Opinion | volume = 28 | issue = 12 | pages = 1873–80 | date = December 2012 | pmid = 23098098 | doi = 10.1185/03007995.2012.744302 | s2cid = 25001604 }}</ref><ref>{{cite journal | vauthors = Taggart E, Doran S, Kokotillo A, Campbell S, Villa-Roel C, Rowe BH | title = Ketorolac in the treatment of acute migraine: a systematic review | journal = Headache | volume = 53 | issue = 2 | pages = 277–87 | date = February 2013 | pmid = 23298250 | doi = 10.1111/head.12009 | s2cid = 12843704 }}</ref><ref>{{cite journal | vauthors = Yilmaz T, Cordero-Coma M, Gallagher MJ | title = Ketorolac therapy for the prevention of acute pseudophakic cystoid macular edema: a systematic review | journal = Eye | volume = 26 | issue = 2 | pages = 252–8 | date = February 2012 | pmid = 22094296 | pmc = 3272202 | doi = 10.1038/eye.2011.296 }}</ref> || As per diclofenac.

| [[Hydrocodone]] || Comes in hydrochloride/tartrate salt form; freely soluble in water, practically insoluble in most organic solvents; degrades upon contact with light/air. || Opioid receptor ligand. || PO. || Protein binding = 19%; extensively hepatically metabolised, mostly via [[CYP3A4]], but via [[CYP2D6]] to a lesser extent to [[hydromorphone]]; half-life = 8 hours; excretion = urine.<ref>{{cite web|title=Zohydro ER (hydrocodone) dosing, indications, interactions, adverse effects, and more|work=Medscape Reference|publisher=WebMD|access-date=8 April 2014|url=http://reference.medscape.com/drug/zohydro-er-hydrocodone-343312#showall|url-status=live|archive-url=https://web.archive.org/web/20140413143613/http://reference.medscape.com/drug/zohydro-er-hydrocodone-343312#showall|archive-date=13 April 2014}}</ref> || Chronic pain. || As per codeine.

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| [[Morphine]] || Comes in freebase form, hydrochloride salt, sulfate salt and tartrate salt forms; soluble in water; degrades in the presence of light. || Opioid receptor agonist (μ, δ, κ). || IM, intrathecal, PO, IV, SC, rectal. || Protein binding = 35%; extensive hepatic metabolism, with some metabolism occur in the gut after oral administration; half-life = 2 hours; excretion = urine (90%). || Moderate-severe pain. || As per codeine.

| [[Ketobemidone]] || Comes in hydrochloride salt form; freely soluble in water, soluble in ethanol and fairly insoluble in [[dichloromethane]]. || Mu opioid; NMDA antagonist. || PO, IM, IV, rectal. || Bioavailability = 34% (oral), 44% (rectal); half-life = 2–3.5 hours.<ref>{{cite journal | vauthors = Anderson P, Arnér S, Bondesson U, Boréus LO, Hartvig P | title = Single-dose kinetics and bioavailability of ketobemidone | journal = Acta Anaesthesiologica Scandinavica. Supplementum | volume = 74 | pages = 59–62 | year = 1982 | pmid = 6124079 | doi = 10.1111/j.1399-6576.1982.tb01848.x | s2cid = 35733660 }}</ref> || Moderate-severe pain. || As per other opioids.

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| colspan="7" style="text-align:center;"| '''Open-chain opioids'''

| [[Dextropropoxyphene]] || Comes in free form, hydrochloride and napsilate salt forms; very soluble in water (HCl), practically insoluble in water (napsilate); degrades upon contact with light and air. || Mu opioid. || PO. || Protein binding = 80%; hepatic metabolism; half-life = 6–12 hours, 30–36 hours (active metabolite). || Mild-moderate pain. || As per other opioids, plus ECG changes.

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| [[Levacetylmethadol]]† || Comes in hydrochloride salt form. || As above plus nicotinic acetylcholine receptor antagonist. || PO. || Protein binding = 80%; half-life = 2.6 days. || Opioid dependence. || As per other opioids, plus ventricular rhythm disorders.

==Research==

Some novel and investigational analgesics include subtype-selective [[voltage-gated sodium channel]] [[sodium channel blocker|blocker]]s such as [[funapide]] and [[raxatrigine]], as well as multimodal agents such as [[ralfinamide]].<ref>{{cite journal | vauthors = Yekkirala AS, Roberson DP, Bean BP, Woolf CJ | title = Breaking barriers to novel analgesic drug development | journal = Nature Reviews. Drug Discovery | volume = 16 | issue = 8 | pages = 545–564 | date = August 2017 | pmid = 28596533 | pmc = 5675565 | doi = 10.1038/nrd.2017.87 }}</ref>