Analgesic
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]
Contents
1 Uses
2 Contraindications
3 Classification
3.1 Paracetamol (acetaminophen)
3.2 NSAIDs
3.3 COX-2 inhibitors
3.4 Opioids
3.5 Alcohol
3.6 Medical cannabis
3.7 Combinations
3.8 Alternative medicine
3.9 Psychotropic agents
3.10 Other drugs
3.11 Other uses
4 List of drugs with comparison
5 Etymology
6 Research
7 See also
8 Notes
9 References
Uses
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
Each different type of analgesic has its own associated side effects.
Classification
Analgesics are typically classified based on their mechanism of action.[4]
Paracetamol (acetaminophen)
Paracetamol, also known as acetaminophen or APAP, is a medication used to treat pain and fever.[5] It is typically used for mild to moderate pain.[5] In combination with opioid pain medication, paracetamol is now used for more severe pain such as cancer pain and after surgery.[6] It is typically used either by mouth or rectally but is also available intravenously.[5][7] Effects last between two and four hours.[7] Paracetamol is classified as a mild analgesic.[7] Paracetamol is generally safe at recommended doses.[8]
NSAIDs
Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a drug class that groups together drugs that decrease pain and lower fever, and, in higher doses decrease inflammation.[9] The most prominent members of this group of drugs, aspirin, ibuprofen and naproxen, are all available over the counter in most countries.[10]
COX-2 inhibitors
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.[11]
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.[11]
Opioids
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.[12]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.[13][14][15][16]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 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, myoclonic jerks and pinpoint pupils), seizures (tramadol), but opioid-tolerant individuals usually have higher dose ceilings than patients without tolerance.[17]
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.[18]
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 suffering with chronic pain and requiring an analgesic over long periods. 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.
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 (hyperalgesia) and can even make non-painful stimuli painful (allodynia).[19]
Alcohol
Describing the effects of using alcohol to treat pain is difficult.[20] Alcohol has biological, mental, and social effects which influence the consequences of using alcohol for pain.[20] Moderate use of alcohol can lessen certain types of pain in certain circumstances.[20] Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and alcohol use disorder.[20]
Medical cannabis
Medical cannabis or medical marijuana, can refer to the use of cannabis and its cannabinoids to treat disease or improve symptoms.[21][22] 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.[23][24][25]
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 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,[26] 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.[27]
Alternative medicine
Many people use alternative medicine treatments including drugs for pain relief.[28] There is some evidence that some treatments using alternative medicine can relieve some types of pain more effectively than placebo.[29] The available research concludes that more research would be necessary to better understand the use of alternative medicine.[29]
Psychotropic agents
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
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, 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.
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.[30]
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.[31] 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.[32]
Flupirtine is a centrally acting K+ channel opener with weak NMDA antagonist properties.[33] 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.[34] However, tolerance may develop in single cases.[35]
Other uses
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.[36]); 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 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.[37]
List of drugs with comparison
| Generic name (INN) | Physicochemistry[38] | Mechanism of action[39] | Routes of administration [39][40][41] | Pharmacokinetics[38] | Indications [39][40][41] | Major safety concerns [39][40][41] |
|---|---|---|---|---|---|---|
Nonsteroidal anti-inflammatory drugs | ||||||
Unselective agents | ||||||
| Aceclofenac | Comes in betadex salt and free acid forms; practically insoluble in water, soluble in many organic solvents; degrades on contact with light; phenylacetic acid derivative. | As per diclofenac. | PO. | Protein binding > 99%; half-life = 4 hours; metabolised to diclofenac (minor); excretion = urine (67%). | As per diclofenac. | As per diclofenac. |
| Acemetacin | Comes in free form; practically insoluble in water, soluble in certain organic solvents; degrades upon contact with light. Chemically related to indometacin | As per diclofenac. | PO. | Slightly metabolised to indometacin. | Rheumatoid arthritis, osteoarthritis and lower back pain. | As per diclofenac. |
| Amfenac | No available data. | As per diclofenac. | PO. | No data. | Pain and inflammation. | As diclofenac. |
| Aminophenazone | Related to phenylbutazone. | As per diclofenac. | PO. | Not available. | Musculoskeletal and joint disorders. | Agranulocytosis and cancer. |
| Ampiroxicam | Related to piroxicam. | As per diclofenac. | PO. | No data. | Rheumatoid arthritis and osteoarthritis. | Photosensitivity and other AEs typical of NSAIDs. |
| Amtolmetin guacil | Prodrug to tolmetin. | As per diclofenac. | PO. | No data. | As per diclofenac. | As per diclofenac. |
| Aspirin | Comes in free form, aluminium and lysine salt forms; fairly insoluble in water (1 in 300); highly soluble (1 in 5) in alcohol; degrades on contact with air. Salicylate. | Irreversibly inhibits COX-1 and COX-2; hence inhibiting prostaglandin synthesis. | PO, IM, IV, rectal | Bioavailability = 80–100%; protein binding = 25–95% (inversely dependent on plasma concentration); half life = 2–3 hours, 15–30 hours (higher doses); excretion = 80–100%.[42] | Blood thinning; mild-to-moderate pain; fever; rheumatic fever; migraine; rheumatoid arthritis; Kawasaki's disease | GI bleeds; ulcers; Reye syndrome; nephrotoxicity; blood dyscrasias (rarely); Stevens-Johnson syndrome (uncommon/rare) |
| Azapropazone | Comes in free form; fairly insoluble in water and chloroform, soluble in ethanol; phenylbutazone. | As per diclofenac. | PO, rectal. | No data available. | Rheumatoid arthritis; gout; ankylosing spondylitis. | As per diclofenac. |
| Bendazac | Comes in free acid and lysine salt forms. Chemically related to indometacin. | As per acetametacin. | Topical, ophthalmologic. | N/A | Skin conditions (such as contact dermatitis) and cataracts. | Hepatotoxicity reported. |
| Benorilate | Aspirin-paracetamol ester. Practically insoluble in water, sparingly soluble in ethanol and methanol, soluble in acetone and chloroform. | As per aspirin and paracetamol. | PO. | Unavailable. | Osteoarthritis; rheumatoid arthritis; soft-tissue rheumatism; mild-moderate pain and fever. | As per aspirin and paracetamol. |
| Benzydamine | Comes in free acid form; freely soluble in water. | As per diclofenac. | Topical, PO, rectal, spray and vaginal. | No data available. | Musculoskeletal disorders; soft-tissue disorders; sore throat. | As per diclofenac. |
| Bromfenac | Comes in free acid form; phenylacetic acid derivative. | Reversible COX-1/COX-2 inhibitor. | Ophthalmologic. | N/A | Postoperative pain and inflammation. | Corneal ulceration. |
| Bufexamac | Comes in free acid form; practically insoluble in water, soluble in a few organic solvents; degrades upon contact with light. | Reversible COX-1/COX-2 inhibition. | Topical. | No data. | Skin disorders. | Skin conditions, such as contact dermatitis. |
| Carbasalate | Comes in calcium salt form; fairly soluble in water. | Is metabolised to aspirin and urea. As per aspirin. | Oral. | No data. | Used for thromboembolic disorders. | As per diclofenac. |
| 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. |
| Dexibuprofen | D-isomer of ibuprofen. Propionic acid derivative. | As per diclofenac. | PO. | Bioavailability = ?; protein binding = 99%; metabolism = hepatic via carboxylation and hydroxylation; half-life = 1.8–3.5 hours; excretion = Urine (90%).[43] | Osteoarthritis; mild-moderate pain and menstrual pain.[44] | As per diclofenac. |
| Diclofenac | Comes in sodium, potassium and diethylamine (topically used as a gel) salt forms; sparingly soluble in water but soluble in ethanol. Unstable in the presence of light and air. Indole acetic acid derivative. | Reversible COX-1/COX-2 inhibitor. | PO and topical. | Bioavailability = 50–60%; protein binding = 99–99.8%; hepatic metabolism; half-life = 1.2–2 hours; excretion = urine (50–70%), faeces (30–35%) | Rheumatoid arthritis; osteoarthritis; inflammatory pain (e.g. period pain); local pain/inflammation (as a gel); actinic keratoses; heavy menstrual bleeding | As per aspirin, except without Reye syndrome and with the following additions: myocardial infarctions, strokes and hypertension. More prone to causing these AEs compared to the other non-selective NSAIDs.[45] |
| 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. |
| Diflunisal | Comes in free acid and arginine salt forms; practically insoluble in water, soluble in ethanol; degrades upon contact with light. | As per diclofenac. | PO, IM, IV. | Bioavailability = 80–100%; protein binding > 99%; volume of distribution = 0.11 L/kg; hepatic metabolism; half-life = 8–12 hours; excretion = urine (90%), faeces (<5%).[38][46] | Pain; osteoarthritis; rheumatoid arthritis. | As per diclofenac. |
| Epirizole | Comes in free form. | As per diclofenac. | PO. | Not available. | Rheumatoid arthritis. | As per diclofenac. |
| Ethenzamide | Comes in free form; salicylate. | As per diclofenac. | PO. | Not available. | Musculoskeletal pain; fever. | As per diclofenac. |
| Etofenamate | Liquid; practically insoluble in water, miscible with ethyl acetate and methanol. | As per diclofenac. | Topical. | Not available. | Musculoskeletal, joint and soft-tissue disorders. | As per bufexamac. |
| Felbinac | Comes in free and diisopropanolamine salt forms; practically insoluble in water and ethanol, soluble in methanol. | As per diclofenac. | Topical. | N/A | Musculoskeletal pain and soft tissue injuries. | As per bufexamac. |
| Fenbufen | Comes as free acid; fairly insoluble in most solvents (including water); propionic acid derivative. | As per diclofenac. | PO. | Protein binding > 99%; half-life = 10–17 hours. | As per diclofenac. | As per diclofenac. |
| Fenoprofen | Comes in calcium salt; fairly insoluble in water and chloroform and fairly soluble in alcohol; sensitive to degradation by air. Propionic acid derivative. | As per diclofenac. | PO. | Bioavailability = ?; protein binding = 99%; hepatic metabolism; excretion = urine, faeces.[47] | Pain; rheumatoid arthritis and osteoarthritis. | As per diclofenac. |
| Fentiazac | Comes in free form and calcium salt; acetic acid derivative. | As per diclofenac. | PO. | No data. | As per diclofenac. | As per diclofenac. |
| Fepradinol | Comes in free acid and hydrochloride salt forms. | As per diclofenac. | Topical. | N/A | Local inflammatory response. | As per bufexamac. |
| Feprazone | Comes in free acid and piperazine salt forms. Phenylbutazone. | As per diclofenac. | PO, Rectal, topical. | Not available. | As per diclofenac. | As per bufexamac (topical use) and diclofenac (PO/rectal). |
| Floctafenine | Comes in free acid form; anthranilic acid derivative. | As per diclofenac. | Oral. | Extensively metabolised by the liver; half-life = 8 hours; excretion = urinary and biliary. | Short-term relief from pain. | As per diclofenac. |
| 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. |
| Flurbiprofen | Comes in sodium salt and free acid forms; fairly insoluble in water but soluble in ethanol; sensitive to degradation by air. Propionic acid derivative. | As per diclofenac. | PO, IM, IV, ophthalmologic. | Bioavailability = 96% (oral); protein binding > 99%; volume of distribution = 0.12 L/kg; excretion = urine (70%).[48] | Ophthalmologic: Vernal keratoconjunctivitis; postoperative ocular swelling; herpetic stromal keratitis, excimer laser photorefractive keratectomy; ocular gingivitis. Systemic use: rheumatoid arthritis; osteoarthritis.[48] | As per bromfenac (ophthalmologic) and diclofenac (PO/IM/IV). |
| Glucametacin | Indometacin derivative. | As per diclofenac. | PO. | Not available. | Musculoskeletal, joint, peri-articular and soft-tissue disorders. | As per diclofenac. |
| Ibuprofen | Comes in lysine salt and free acid forms; practically insoluble in water, but soluble in ethanol, acetone, methanol, dichloromethane and chloroform. Degrades in the presence of air. Propionic acid derivative. | As per diclofenac. | PO, IV, topical | Bioavailability = 80–100%; protein binding = 90–99%; hepatic metabolism, mostly via CYP2C9 and CYP2C19-mediated oxidation; excretion = Urine (50–60%), faeces.[49] | Pain; fever; inflammatory illness; rheumatoid arthritis; osteoarthritis; heavy menstrual bleeding; patent ductus arteriosus.[40][50][51] | As per diclofenac, except with lower risk of myocardial infarction, stroke and hypertension. |
| Imidazole salicylate | Comes in free form. Salicylate. | As per diclofenac. | PO, rectal, topical. | Not available. | Muscular and rheumatic pain. | As per bufexamac (topical use) and diclofenac (PO/rectal). |
| Indometacin | Comes in free acid and sodium salt forms; practically insoluble in water and most solvents; sensitive to degradation by light. Acetic acid derivative. | As per diclofenac. | PO, IV, rectal | Bioavailability = 100% (oral); protein binding = 90%; hepatic metabolism; excretion = urine (60%), faeces (33%).[52] | Rheumatoid arthritis; osteoarthritis; gout; ankylosing spondylitis; period pain; patent ductus arteriosus.[40] | As per diclofenac. |
| Isonixin | Comes in free form. | As per diclofenac. | PO, rectal and topical. | Not available. | Musculoskeletal and joint disorders. | As per bufexamac (topical use) and diclofenac (PO/rectal). |
| Kebuzone | Comes in free and sodium salt form; phenylbutazone derivative. | As per diclofenac. | IM, PO. | Not available. | As per diclofenac. | As per diclofenac. |
| Ketoprofen | Comes in free acid, lysine salt, sodium salt and hydrochloride salt forms; the dex-enantiomer comes in trometamol salt form. Practically insoluble in water; freely soluble in most other solvents. Propionic acid derivative. | As per diclofenac. | PO, rectal, topical, transdermal, intravenous, intramuscular.[53][54] | Bioavailability > 92% (oral), 70–90% (rectal); protein binding > 99%; volume of distribution = 0.1–0.2 L/kg; hepatic metabolism; half-life = 1.5–2 hours (oral), 2.2 hours (rectal), 2 hours (intravenous).[55][56] | Rheumatoid arthritis, osteoarthritis and superficial sporting injuries (topical use).[40][57] | As per diclofenac. |
| 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%).[58] | 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.[59][60][61][62][63][64][65] | As per diclofenac. |
| Lornoxicam | Hydrochloride salt form used; oxicam derivative. | As per diclofenac. | PO. | Protein binding = 99%; volume of distribution = 0.2 L/kg; half-life = 3–5 hours; excretion = faeces (51%), urine (42%).[66][67] | Acute and chronic pain. | As per diclofenac. |
| Loxoprofen | Comes in sodium salt form. Propionic acid derivative. | As per diclofenac. | Topical. | N/A | Local inflammation and pain. | As per diclofenac. |
| Magnesium salicylate | Comes in free form; soluble in water and ethanol; salicylate. | As per diclofenac. | PO. | Not available. | As per diclofenac. | As per diclofenac. |
| Meclofenamic acid | Comes in free acid and sodium salt form, sodium salt is the form used in human medicine; practically insoluble in water (free acid) and freely soluble in water (sodium salt); sensitive to degradation by air and light. | As per diclofenac. | PO. | Protein binding > 99%; half-life = 2–4 hours; hepatically metabolised via oxidation, hydroxylation, dehalogenation and conjugation with glucuronic acid; excretion = urine, faeces (20–30%).[38] | Osteoarthritis; rheumatoid arthritis; mild-moderate pain; dysmenorrhoea; menorrhagia. | As per diclofenac. |
| Mefenamic acid | Comes in free acid form; practically insoluble in water, fairly insoluble in organic solvents; degrades on contact with air and light. Anthranilic acid derivative. | As per diclofenac. | PO. | Protein binding extensive; hepatic metabolism, mostly via CYP2C9; half-life = 2 hours; excretion = urine (66%), faeces (20–25%).[68] | Inflammatory pain and heavy menstrual bleeding.[40] | As per diclofenac. |
| Mofezolac | Comes in free form. | As per diclofenac. | PO. | Not available. | Musculoskeletal and joint pain. | As per diclofenac. |
| Morniflumate | Comes in free acid form; niflumic acid derivative. | As per diclofenac. | PO, rectal. | Not available. | Inflammatory conditions. | As per diclofenac. |
| Nabumetone | Comes in free acid form; practically insoluble in water, freely soluble in acetone; degrades on contact with air and light. | As per diclofenac. | PO. | Protein binding = 99%; hepatically metabolised; half-life = 24 hours; excretion = urine (80%), faeces (9%).[69] | Osteoarthritis; rheumatoid arthritis. | As per diclofenac. |
| Naproxen | Comes in free acid and sodium form; practically insoluble in water in free form, freely soluble in water (sodium salt), fairly soluble in most organic solvents. Degrades on contact with air and light. Propionic acid derivative. | As per diclofenac. | PO. | Bioavailability = ?; protein binding > 99.5%; volume of distribution = 10% of bodyweight; half-life = 12–15 hours; excretion = urine (95%), faeces (<3%).[70] | Rheumatoid arthritis; osteoarthritis; ankylosing spondylitis; juvenile idiopathic arthritis; inflammatory pain; heavy menstrual bleeding. | As per diclofenac. less prone to causing thrombotic events compared to other non-selective NSAIDs.[45] |
| Nepafenac | Comes in free form; related to amfenac. | As per diclofenac. | Ophthalmologic. | Unavailable. | Inflammation and pain following cataract surgery. | As per bromfenac. |
| Niflumic acid | Comes in free acid form, glycinamide and ethyl ester form; practically insoluble in water, soluble in ethanol, acetone and methanol. Nicotinic acid derivative. | As per diclofenac. | PO, rectal (ethyl ester, morniflumate). | Unavailable. | Musculoskeletal, joint and mouth inflammatory disorders. | As per diclofenac. |
| Oxaprozin | Comes in potassium and free acid forms; degrades upon contact with light. Propionic acid derivative. | As per diclofenac. | PO. | Bioavailability = ?; protein binding > 99.5%; volume of distribution = 0.15–0.25 L/kg; half-life = 50–60 hours; excretion = urine (65), faeces (35%).[71][72] | Osteoarthritis; rheumatoid arthritis. | As per diclofenac. |
| Oxyphenbutazone | Comes in free form. Phenylbutazone. | As per diclofenac. | PO, Ophthalmologic. | Unavailable. | Ophthalmologic: Episcleritis. Systemic (now seldom used due to adverse effects): ankylosing spondylitis; rheumatoid arthritis; osteoarthritis. | As per bromfenac. For systemic use haematological side effects such as aplastic anaemia; agranulocytosis; leucopenia; neutropenia; etc. |
| Phenazone | No data. | As per diclofenac. | PO, otolaryngologic. | Protein binding < 10%; half-life = 12 hours; hepatic metabolised; excretion = urine (primary), faeces. | Acute otitis media. | Nephrotoxicity and haematologic toxicity and other AEs typical of NSAIDs. |
| Phenylbutazone | Comes in free form; practically insoluble in water, freely soluble in most organic solvents; degrades upon contact with light and air. | As per diclofenac. | PO, rectal, topical. | No data available. | Ankylosing spondylitis; acute gout; osteoarthritis; rheumatoid arthritis. | Haematologic toxicity (including agranulocytosis, aplastic anaemia) and AEs typical of NSAIDs. |
| Piketoprofen | Comes in free form. | As per diclofenac. | Topical. | N/A. | Musculoskeletal, joint, peri-articular and soft-tissue disorders. | As per other topical NSAIDs. |
| Piroxicam | Comes in free acid and betadex salt forms; practically insoluble in water, slightly soluble in ethanol; degrades on contact with air and light. Enolic acid derivative. | As per diclofenac. | PO, topical. | Protein binding = 99%; extensively hepatically metabolised; half-life = 36–45 hours; excretion = urine, faeces.[73][74] | Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and sports injuries (topical use).[40] | As per diclofenac. |
| Proglumetacin | Comes in maleate salt form; indometacin derivative. | As per diclofenac. | PO, rectal, topical. | Not available. | Musculoskeletal and joint disorders. | As per diclofenac. |
| Proquazone | Comes in free form. | As per diclofenac. | PO, rectal. | Not available. | As per diclofenac. | As per diclofenac. |
| Pranoprofen | No data. | As per diclofenac. | PO, ophthalmologic. | Not available. | Pain, inflammation and fever. | As per diclofenac. |
| Salamidacetic acid | Comes in sodium and diethylamine salt forms; salicylate. | As per diclofenac. | PO. | Unavailable. | Musculoskeletal disorders. | As per diclofenac. |
| Salicylamide | Fairly insoluble in water and chloroform; soluble in most other organic solvents; salicylate. | As per diclofenac. | PO, topical. | No data. | Muscular and rheumatic diseases. | As per diclofenac. |
| Salol | No data. | As per diclofenac. | PO, topical. | No data. | Lower urinary tract infections. | As per diclofenac. |
| Salsalate | Degrades upon contact with air; salicylate derivative. | As per diclofenac. | PO. | Hepatic metabolism; half-life = 7–8 hours; excretion = urine.[75] | Rheumatoid arthritis, osteoarthritis. | As per diclofenac. |
| Sodium salicylate | Freely soluble in water; degrades upon contact with air and light; salicylate. | As per diclofenac. | PO, IV, topical. | No data. | Pain, fever and rheumatic conditions. | Cardiac problems; otherwise As per diclofenac. |
| Sulindac | Comes in free acid and sodium salt forms; practically insoluble in water and hexane, very slightly soluble in most organic solvents. Degrades upon contact with light. Acetic acid derivative. | As per diclofenac. | PO, rectal. | Bioavailability = 90%; protein binding = 93% (sulindac), 98% (active metabolite); hepatic metabolism; excretion = urine (50%), faeces (25%).[76] | Rheumatoid arthritis; osteoarthritis; gout; ankylosing spondylitis; inflammatory pain.[40] | As per diclofenac. |
| Suxibuzone | Practically insoluble in water, soluble in ethanol and acetone; phenylbutazone. | As per diclofenac. | PO, topical. | No data. | Musculoskeletal and joint disorders. | As per phenylbutazone. |
| Tenoxicam | Comes as free acid; practically insoluble in water, fairly insoluble in organic solvents; degrades upon contact with light. | As per diclofenac. | PO, rectal. | Bioavailability = 100% (oral), 80% (rectal); protein binding = 99%; volume of distribution = 0.15 L/kg; half-life = 60–75 hours; excretion = urine (67%), faeces (33%).[77] | Osteoarthritis; rheumatoid arthritis; soft tissue injury. | As per diclofenac. |
| Tetridamine | No data. | As per diclofenac. | Vaginal. | No data. | Vaginitis. | As per diclofenac. |
| Tiaprofenic acid | Comes as free acid; practically insoluble in water but freely soluble in most organic solvents; propionic acid derivative; degrades upon contact with light. Propionic acid derivative. | As per diclofenac. | PO. | Protein binding > 99%; volume of distribution = 0.1–0.2 L/kg; hepatic metabolism; half-life = 2–4 hours.[78] | Ankylosing spondylitis; osteoarthritis; rheumatoid arthritis; fibrosis; capsulitis; soft-tissue disorders. | As per diclofenac. |
| Tiaramide | No data. | As per diclofenac. | PO. | No data. | Pain; inflammation. | As per diclofenac. |
| Tinoridine | No data. | As per diclofenac. | No data. | No data. | Pain; inflammation. | As per diclofenac. |
| Tolfenamic acid | Comes as free acid; practically insoluble in water; degrades upon contact with light; anthranilic acid. | As per diclofenac. | PO. | Protein binding = 99%; half-life = 2 hours; hepatically metabolised; excretion = urine (90%), faeces. | Migraine; osteoarthritis; rheumatoid arthritis; dysmenorrhoea. | As per diclofenac. |
| Tolmetin | Comes in sodium salt form; freely soluble in water, slightly soluble in ethanol, freely soluble in methanol. Acetic acid derivative. | As per diclofenac. | PO. | Protein binding > 99%; volume of distribution = 7–10 L; half-life = 1 hour; excretion = urine (90%).[79] | Osteoarthritis; rheumatoid arthritis. | As per diclofenac. |
| Ufenamate | No data. | No data. | Topical. | No data. | Inflammatory skin disorders. | As per other topical NSAIDs. |
COX-2 selective inhibitors | ||||||
| Celecoxib | Comes in free form; practically insoluble in water, fairly soluble in organic solvents. Degrades on contact with light and moisture. Sulfonamide. | Selective COX-2 inhibitor. | PO. | Protein binding = 97%; hepatic metabolism, mostly via CYP2C9; faeces (57%), urine (27%).[80] | Rheumatoid arthritis; osteoarthritis; ankylosing spondylitis; pain due to dysmenorrhoea or injury. | As per non-selective NSAIDs. More prone to causing thrombotic events than most of them, however, except diclofenac. |
| Etodolac | Comes in free form; practically insoluble in water, freely soluble in acetone and dehydrated alcohol. Acetic acid derivative. | As per celecoxib. | PO. | Bioavailability = ?; protein binding > 99%; volume of distribution = 0.41 L/kg; half-life = 6–7 hours; excretion = urine (73%).[81][82][83] | Rheumatoid arthritis, including juvenile idiopathic arthritis; osteoarthritis; acute pain. | As per diclofenac. |
| Etoricoxib | Comes in free form; sulfonamide. | As per celecoxib. | PO. | Bioavailability = 100%; protein binding = 91.4%; volume of distribution = 120 L; half-life = 22 hours; hepatic metabolism; excretion = urine (70%), faeces (20%).[84] | Acute pain; gout; osteoarthritis. | As per diclofenac. |
Lumiracoxib† | Comes in free form; acetic acid derivative. | As per celecoxib. | PO. | Bioavailability = 74%; protein binding > 98%; extensive hepatic metabolism, mostly via CYP2C9; half-life = 3–6 hours; excretion = Urine (50%), faeces (50%).[85] | Osteoarthritis. | As above, plus hepatotoxicity. |
| Meloxicam | Comes in free form; fairly insoluble in water and in most organic solvents; oxicam derivative. | As per celecoxib. | PO, rectal. | Bioavailability = 89%; protein binding > 99%; volume of distribution = 0.1–0.2 L/kg; half-life = 22–24 hours; extensive hepatic metabolism; excretion = urine (45%), faeces (47%).[86] | Osteoarthritis; rheumatoid arthritis. | As per diclofenac. |
| Nimesulide | Comes in free and betadex form; practically insoluble in water and ethanol, soluble in acetone. | As per celecoxib. | PO, rectal, topical. | Unavailable. | Acute pain; dysmenorrhoea; sprains (topical); tendinitis. | As per diclofenac. |
| Parecoxib | Comes in sodium salt form; sulfonamide. | As per celecoxib. | IM, IV. | Plasma binding = 98%; volume of distribution = 55 L; hepatic metabolism, mostly via CYP2C9, CYP3A4; half-life = 8 hours; excretion = urine (70%).[87] | Postoperative pain. | As per diclofenac. |
Rofecoxib† | Comes in free form; sulfonamide. | As per celecoxib. | PO. | Bioavailability = 93%; protein binding = 87%; hepatic metabolism; half-life = 17 hours.[88][89] | Acute pain; osteoarthritis; rheumatoid arthritis. | As per diclofenac. |
Valdecoxib† | Comes in free form; sulfonamide. | As per celecoxib. | PO. | Bioavailability = 83%; protein binding = 98%; hepatic metabolism, mostly via CYP3A4 and CYP2C9; half-life = 8.11 hours; excretion = urine (90%).[90] | Pain from dysmenorrhoea; rheumatoid arthritis; osteoarthritis. | As above and also potentially fatal skin reactions (e.g. toxic epidermal necrolysis). |
Opioids | ||||||
Those with a morphine skeleton | ||||||
| Buprenorphine | Comes in free and hydrochloride salt forms; fairly insoluble in water, soluble in ethanol, methanol and acetone; degrades upon contact with light. | Partial agonist at the mu opioid receptor; agonist at delta opioid receptor; antagonist at kappa opioid receptor. | Sublingual, transdermal, IM, IV, intranasal, epidural, SC. | Bioavailability = 79% (sublingual); protein binding = 96%: volume of distribution = 97–187 L/kg; half-life = 20–36 hours; excretion = urine, faeces.[91] | Opioid dependence, moderate-severe pain. | As per codeine, respiratory effects are subject to a ceiling effect. |
| Codeine | Comes in free form, hydrochloride salt, sulfate salt and phosphate salts; soluble in boiling water (free form), freely soluble in ethanol (free form), soluble/freely soluble in water (salt forms); sensitive to degradation by light. Methoxy analogue of morphine. | Metabolised to morphine, which activates the opioid receptors. | PO, IM, IV. | Extensive hepatic metabolism, mostly via CYP2D6, to morphine; half-life = 3–4 hours; excretion = urine (86%).[92] | Mild-moderate pain, often in combination with paracetamol or ibuprofen. | Constipation, dependence, sedation, itching, nausea, vomiting and respiratory depression. |
| Diamorphine | Comes in hydrochloride salt form; freely soluble in water, soluble in alcohol; degrades upon contact with light. Diacetyl derivative of morphine. | Rapidly hydrolysed to 6-acetylmorphine and then to morphine after crossing the blood-brain barrier which in turn activates the opioid receptors in the CNS. | IM, intrathecal, intranasal, PO, IV, SC. | Extensively metabolised to morphine with 6-acetylmorphine as a possible intermediate. Mostly excreted in urine. | Severe pain (including labour pain); cough due to terminal lung cancer; angina; left ventricular failure. | As per codeine. Higher potential for abuse compared to other opioids due to its rapid penetration of the blood-brain barrier. |
| Dihydrocodeine | Comes in freebase, hydrochloride, phosphate, polistirex, thiocyanate, tartrate, bitartrate and hydrogen tartrate salt forms; freely soluble in water, practically insoluble in organic solvents (hydrogen tartrate salt); degrades upon contact with air and light. | Opioid receptor agonist. | IM, IV, PO, SC. | Bioavailability = 20%; extensive hepatic metabolism, partly via CYP2D6 to dihydromorphine and CYP3A4 to nordihydrocodeine; half-life = 3.5 –5 hours; excretion = urine. | Moderate-severe pain; usually in combination with paracetamol and/or aspirin. | As per codeine. |
| Ethylmorphine | Comes in freebase, hydrochloride, camphorate and camsilate salt forms; soluble in water and alcohol; degrades upon contact with light. | Opioid receptor ligand. | PO. | No data. | Cough suppressant. | As per codeine. |
| 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.[93] | Chronic pain. | As per codeine. |
| Hydromorphone | Comes in hydrochloride salt form; freely soluble in water, fairly insoluble in organic solvents; degrades upon contact with light or temperatures outside 15 °C and 35 °C. | Opioid receptor agonist. | IM, IV, PO, SC. | Bioavailability = 50–62% (oral); protein binding = 8–19%; extensively hepatically metabolised; half-life = 2–3 hours; excretion = urine.[94] | Moderate-severe pain; cough. | As per codeine. |
| 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. |
| Nicomorphine | Dinicotinic acid ester derivative of morphine. | As per morphine. | IM, IV, PO, rectal, SC. | No available data. | Moderate-severe pain. | As per codeine. |
| Oxycodone | Comes in freebase, hydrochloride and terephthalate salt forms; freely soluble in water and practically insoluble in organic solvents; degrades upon contact with air. | Opioid receptor agonist. | PO. | Bioavailability = 60–87%; protein binding = 45%; volume of distribution = 2.6 L/kg; extensively metabolised in the liver via CYP3A4 and to a lesser extent via CYP2D6 to oxymorphone; half-life = 2–4 hours; excretion = urine (83%).[95] | Moderate-severe pain. | As per codeine. |
| Oxymorphone | Comes in hydrochloride salt form; fairly soluble in water (1 in 4), practically insoluble in most organic solvents; degrades upon contact with air, light and temperatures outside 15 °C to 30 °C. | As per morphine. | PO, IM, SC. | Bioavailability = 10% (oral); protein binding = 10–12%; volume of distribution = 1.94–4.22 L/kg; hepatic metabolism; half-life = 7–9 hours, 9–11 hours (XR); excretion = urine, faeces.[96] | Postoperative analgesia/anaesthesia; moderate-severe pain. | As per codeine. |
Morphinans | ||||||
| Butorphanol | Comes in tartrate salt form; sparingly soluble in water, insoluble in most organic solvents; degrades upon contact with air and at temperatures outside the range of 15 °C and 30 °C. | Kappa opioid receptor agonist; mu opioid receptor partial agonist. | IM, IV, intranasal. | Bioavailability = 60–70% (intranasal); protein binding = 80%; volume of distribution = 487 L; hepatic metabolism, mostly via hydroxylation; excretion = urine (mostly); half-life = 4.6 hours.[97] | Moderate-severe pain, including labour pain. | As above, but with a higher propensity for causing hallucinations and delusions. Respiratory depression is subject to ceiling effect. |
| Levorphanol | Comes in tartrate salt form; fairly insoluble in water (1 in 50) and fairly insoluble in ethanol, chloroform and ether; unstable outside of 15 °C and 30 °C; phenanthrene derivative. | Mu opioid; NMDA antagonist; SNRI.[98] | PO, IM, IV, SC. | Protein binding = 40%; extensive first-pass metabolism; half-life = 12–16 hours, 30 hours (repeated dosing).[98][99] | Acute/chronic pain. | As per codeine. |
| Nalbuphine | Comes primarily as its hydrochloride salt. | Full agonist at kappa opioid receptors, partial agonist/antagonist at the mu opioid receptors.[38] | IM, IV, SC. | Protein binding = not significant; hepatic metabolism; half-life = 5 hours; excretion = urine, faeces.[100][101] | Pain; anaesthesia supplement; opioid-induced pruritus. | As per codeine. Respiratory depression is subject to ceiling effect. |
Benzomorphans | ||||||
| Dezocine | No data available. | Mixed opioid agonist-antagonist. | IM, IV. | Volume of distribution = 9–12 L/kg; half-life = 2.2–2.7 hours. | Moderate-severe pain. | As per codeine. |
| Eptazocine | Comes as hydrobromide salt. | As per morphine. | IM, SC. | No data. | Moderate-severe pain. | As per codeine. |
| Pentazocine | Comes in free, hydrochloride and lactate salt forms; fairly insoluble in water (1:30 or less), more soluble in ethanol and chloroform; degrades upon contact with air and light. | Kappa opioid receptor agonist; mu opioid receptor antagonist/partial agonist. | IM, IV, SC. | Bioavailability = 60–70%; protein binding = 60%; hepatic metabolism; half-life = 2–3 hours; excretion = urine (primary), faeces.[102][103] | Moderate-severe pain. | As per codeine. Respiratory effects are subject to a ceiling effect. |
Phenylpiperidines | ||||||
| Anileridine | Comes in free, hydrochloride and phosphate forms; fairly insoluble in water, soluble in ethanol, ether and chloroform; degrades upon contact with air and light. | Mu opioid receptor agonist. | IM, IV. | No data. | 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.[104] | Moderate-severe pain. | As per other opioids. |
| Pethidine | Comes in hydrochloride form; very soluble in water, sparingly soluble in ether, soluble in ethanol; degrades upon contact with air and light. | Mu opioid receptor agonist with some serotonergic effects. | IM, IV, PO, SC. | Bioavailability = 50–60%; protein binding = 65–75%; hepatic metabolism; half-life = 2.5–4 hours; excretion = urine (primarily).[105][106][107][108][109] | Moderate-severe pain. | As per other opioids; and seizures, anxiety, mood changes and serotonin syndrome. |
Open-chain opioids | ||||||
| Dextromoramide | Comes in tartrate salt and free forms; soluble in water (tartrate salt). | IM, IV, PO, rectal. | No data available. | Severe pain. | As per other opioids. | As per other 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. |
| Dipipanone | Comes in hydrochloride salt form; practically insoluble in water and ether, soluble in acetone and ethanol. | Mu opioid. | PO, often in combination with cyclizine. | Half-life = 20 hours.[110] | Moderate-severe pain. | Less sedating than morphine, otherwise as per morphine. |
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. |
| Levomethadone | Comes in hydrochloride salt form; soluble in water and alcohol; degrades upon contact with light. | Mu opioid; NMDA antagonist. | PO. | No data. | As per methadone. | As per methadone. |
| Meptazinol | Comes in hydrochloride salt form; soluble in water, ethanol and methanol, fairly insoluble in acetone; unstable at temperatures greater than 25 °C. | Mixed opioid agonist-antagonist, partial agonist at mu-1 receptor; cholinergic actions exist. | IM, IV, PO. | Bioavailability = 8.69% (oral); protein binding = 27.1%; half-life = 2 hours; excretion = urine.[111] | Moderate-severe pain; perioperative analgesia; renal colic. | As per pentazocine. |
| Methadone | Comes in hydrochloride salt form; soluble in water and ethanol; degrades upon contact with air and light and outside the temperature range of 15 °C and 30 °C. | Mu opioid; NMDA antagonist. | IM, IV, PO, SC. | Bioavailability = 36–100% (mean: 70–80%); protein binding = 81–97% (mean: 87%); volume of distribution = 1.9-8 L/kg (mean: 4 L/kg); hepatic metabolism, mostly via CYP3A4, CYP2B6 and to a lesser extent: CYP2C9, CYP2C19, CYP2D6 & CYP2C8; half-life = 5–130 hours (mean: 20–35 hours); excretion = urine (20–50%), faeces.[112] | Opioid addiction; chronic pain. | As per other opioids, plus QT interval prolongation. |
| Piritramide | Comes in free or tartrate salt forms. | Mu opioid. | IM, IV, SC. | No data available. | Severe pain. | As per other opioids. |
| Tapentadol | Comes in free and hydrochloride salt forms. | Mu opioid and norepinephrine reuptake inhibitor. | PO. | Bioavailability = 32%; protein binding = 20%; hepatic metabolism, mostly via CYP2C9, CYP2C19, CYP2D6; excretion = urine (70%), faeces; half-life = 4 hours. | Moderate-severe pain. | As per other opioids; less likely to cause nausea, vomiting and constipation. |
| Tilidine | Comes in hydrochloride salt form; soluble in water, ethanol and dichloromethane; degrades upon contact with light. | Mu opioid metabolite, nortilidine. | PO. | No data. | Moderate-severe pain. | As per other opioids. |
| Tramadol | Comes in hydrochloride salt form; freely soluble in water and methanol, insoluble in acetone; degrades at temperatures less than 15 °C and 30 °C and upon contact with light. | Mu opioid (mostly via its active metabolite, O-desmethyltramadol) and SNRI. | IM, IV, PO, rectal. | Bioavailability = 70–75% (oral), 100% (IM); protein binding = 20%; hepatic metabolism, via CYP3A4 and CYP2D6; half-life = 6 hours; excretion = urine, faeces. | Moderate-severe pain. | 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 | ||||||
| Alfentanil | Comes in hydrochloride salt form; freely soluble in ethanol, water, methanol; degrades upon contact with air and light. | Mu opioid. | Epidural, IM, IV, intrathecally. | Protein binding = 90%; volume of distribution = small; half-life = 1–2 hours; hepatic metabolism, mostly via CYP3A4; excretion = urine. | Procedural anaesthesia. | As per other opioids. Very sedating. |
| Fentanyl | Comes in free, hydrochloride salt, citrate salt forms; practically insoluble in water (free form), soluble in water (citrate salt form), freely soluble in ethanol and methanol; degrades outside the temperature range of 15 °C and 30 °C and upon contact with light. | Mu opioid. | Buccal, epidermal, IM, IV, intrathecal, intranasal, SC, sublingual. | Bioavailability = 50% (buccal), 89% (intranasal); protein binding = 80%; hepatic metabolism, mostly via CYP3A4; half-life = 219 min; excretion = urine (primary), faeces. | Moderate-severe pain (including labour pain); adjunct to anaesthesia. | As with other opioids, with less nausea, vomiting, constipation and itching and more sedation. |
| Remifentanil | Comes in hydrochloride salt. | Mu opioid. | IV. | Protein binding = 70%; hydrolysed by blood and tissue esterases; half-life = 20 min; excretion = urine (95%). | Anaesthesia maintenance. | As with fentanyl. |
| Sufentanil | Comes in free and citrate salt forms; soluble in water, ethanol and methanol; degrades upon contact with light and temperatures outside 15 °C and 30 °C. | Mu opioid. | Epidural, IV, intrathecal, transdermal. | Protein binding = 90%; half-life = 2.5 hours; excretion = urine (80%). | Adjunct to anaesthesia and moderate-severe pain. | As with fentanyl. |
Other analgesics | ||||||
| Acetanilide | No data. | Paracetamol prodrug. | PO. | No data. | Pain; fever. | Cancer; AEs of paracetamol. |
| Amitriptyline | Comes in free form and in hydrochloride and embonate salt forms; practically insoluble in water (embonate salt), freely soluble in water (HCl); degrades upon contact with light. | SNRI. | PO. | Hepatic metabolism, via CYP2C19, CYP3A4; active metabolite, nortriptyline; half-life = 9–27 hours; excretion = urine (18%), faeces. | Neuropathic pain; nocturnal enuresis; major depression; migraine prophylaxis; urinary urge incontinence. | Sedation, anticholinergic effects, weight gain, orthostatic hypotension, sinus tachycardia, sexual dysfunction, tremor, dizziness, sweating, agitation, insomnia, anxiety, confusion. |
| Dronabinol | Comes in free form; degrades upon contact with light. | Cannabinoid receptor partial agonist. | PO. | Bioavailability = 10–20%; protein binding = 90–99%; volume of distribution = 10 L/kg; hepatic metabolism; half-life = 25–36 hours, 44–59 hours (metabolites); excretion = faeces (50%), urine (15%).[113] | Refractory chemotherapy-induced nausea and vomiting; anorexia; neuropathic pain. | Dizziness, euphoria, paranoia, somnolence, abnormal thinking, abdominal pain, nausea, vomiting, depression, hallucinations, hypotension, special difficulties, emotional lability, tremors, flushing, etc. |
| Duloxetine | Comes in hydrochloride salt form; slightly soluble in water, freely soluble in methanol; degrades upon contact with light. | SNRI. | PO. | Protein binding > 90%; volume of distribution = 3.4 L/kg; hepatic metabolism, via CYP2D6, CYP1A2; half-life = 12 hours; excretion = urine (70%), faeces (20%).[114] | Major depression; generalised anxiety disorder; neuropathic pain. | Anticholinergic effects, GI effects, yawning, sweating, dizziness, weakness, sexual dysfunction, somnolence, insomnia, headache, tremor, decreased appetite. |
| Flupirtine | Comes as maleate salt. Chemically related to retigabine. | Potassium channel (Kv7) opener.[115] | PO, rectal. | Bioavailability = 90% (oral), 72.5% (rectal); protein binding = 80%; volume of distribution = 154 L; hepatic metabolism; half-life = 6.5 hours; excretion = urine (72%). | Pain; fibromyalgia; Creutzfeldt–Jakob disease. | Drowsiness, dizziness, heartburn, dry mouth, fatigue and nausea.[116] |
| Gabapentin | Comes in free and enacarbil salt forms; fairly insoluble in ethanol, dichoromethane, fairly soluble in water. | Binds to the α2δ-1 subunit of voltage gated calcium ion channels in the spinal cord. May also modulate NMDA receptors and protein kinase C. | PO. | Half-life = 5–7 hours. | Neuropathic pain; epilepsy. | Fatigue, sedation, dizziness, ataxia, tremor, diplopia, nystagmus, amblyopia, amnesia, abnormal thinking, hypertension, vasodilation, peripheral oedema, dry mouth, weight gain and rash. |
| Milnacipran | No data. | SNRI. | PO. | Bioavailability = 85–90%; protein binding = 13%: volume of distribution = 400 L; hepatic metabolism; half-life = 6–8 hours (L-isomer), 8–10 hours (D-isomer); excretion = urine (55%).[117] | Fibromyalgia. | As per duloxetine, plus hypertension. |
| Nabiximols | Contains cannabidiol and dronabinol in roughly equal concentrations. | As per dronabinol. | Buccal spray. | Not available. | Neuropathic pain and spasticity as part of MS. | As per dronabinol. |
| Nefopam | Comes in a hydrochloride salt form. Chemically related to orphenadrine. | Unknown; serotonin-norepinephrine-dopamine reuptake inhibitor. | PO, IM. | Protein binding = 73%; half-life = 4 hours; excretion = urine, faeces (8%). | Analgesia, especially postoperative; hiccups. | Has antimuscarinic and sympathomimetic effects.[118] |
| Paracetamol | Comes in free form; practically insoluble in water, freely soluble in ethanol; degrades upon contact with moisture, air and light. | Multiple; inhibits prostaglandin synthesis in the CNS, an active metabolite, AM404, is an anandamide reuptake inhibitor. | PO, IV, IM, rectal. | Protein binding = 10–25%; volume of distribution = 1 L/kg; hepatic metabolism; half-life = 1–3 hours; excretion = urine.[119] | Analgesia and fever reduction. | Hepatotoxicity; hypersensitivity reactions (rare), including Stevens-Johnson syndrome; hypotension (rare; IV). |
| Phenacetin | No data. | Prodrug to paracetamol. | PO. | No data. | Analgesia and fever reduction. | Haematologic, nephrotoxicity, cancer and paracetamol AEs. |
| Pregabalin | Comes in free form. | As per gabapentin. | PO. | Bioavailability = 90%; half-life = 6.3 hours; hepatic metabolism; excretion = urine (90%).[120] | Neuropathic pain; anxiety; epilepsy. | As per gabapentin. |
| Propacetamol | Freely soluble in water; degrades upon contact with moisture. | Prodrug to paracetamol. | IM, IV. | No data available. | Analgesia and fever reduction. | As per paracetamol. |
| Ziconotide | Peptide. | N-type calcium-channel blocker. | Intrathecal. | Protein binding = 50%; half-life = 2.9–6.5 hours; excretion = urine (<1%).[121] | Chronic pain. | CNS toxicity (abnormal gait, abnormal vision, memory problems, etc.); GI effects.[121] |
| Where † indicates products that are no longer marketed. | ||||||
Etymology
The word analgesic derives from Greek an- (ἀν-, "without"), álgos (ἄλγος, "pain"),[122] and -ikos (-ικος, forming adjectives). Such drugs were usually known as anodynes before the 20th century.[123][124]
Research
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
- Audioanalgesia
- Pain management
- Patient-controlled analgesia
- Pain in babies
Congenital analgesia (insensitivity to pain)
Notes
^ 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..mw-parser-output cite.citationfont-style:inherit.mw-parser-output qquotes:"""""""'""'".mw-parser-output code.cs1-codecolor:inherit;background:inherit;border:inherit;padding:inherit.mw-parser-output .cs1-lock-free abackground:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration abackground:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center.mw-parser-output .cs1-lock-subscription abackground:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registrationcolor:#555.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration spanborder-bottom:1px dotted;cursor:help.mw-parser-output .cs1-hidden-errordisplay:none;font-size:100%.mw-parser-output .cs1-visible-errorfont-size:100%.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-formatfont-size:95%.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-leftpadding-left:0.2em.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-rightpadding-right:0.2em
^ 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.
^ 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.
^ "British National Formulary: Analgesics". BNF online. Retrieved 8 June 2017.
^ abc "Acetaminophen". The American Society of Health-System Pharmacists. Archived from the original on 2016-06-05.
^ 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. Archived (PDF) from the original on 2010-12-20.
^ abc Hochhauser, Daniel (2014). Cancer and its Management. John Wiley & Sons. p. 119. ISBN 9781118468715. Archived from the original on 2017-09-10.
^ 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 2572451. PMID 12856055.
^ Mallinson, Tom (2017). "A review of ketorolac as a prehospital analgesic". Journal of Paramedic Practice. London: MA Healthcare. 9 (12): 522–526. Archived from the original on 5 June 2018. Retrieved 2 June 2018.
^ 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. Archived from the original on 2010-11-26.
^ ab 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 3364420. PMID 22193214.
^ 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.
^ 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 1908625. PMID 1596676.
^ 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.
^ 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.
^ 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.
^ Tozer, Adam. "Replacing Opioids: Developing drugs to treat pain". Analytical Cannabis. Analytical Cannabis. Archived from the original on 22 August 2017. Retrieved 22 August 2017.
^ Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
^ Bannister, Kirsty (June 2015). "Opioid-induced hyperalgesia". Current Opinion in Supportive and Palliative Care. 9 (2): 116–121. doi:10.1097/SPC.0000000000000137. PMID 25872113.
^ abcd 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 4385458. PMID 25766100.
^ Murnion, B (December 2015). "Medicinal cannabis". Australian prescriber. 38 (6): 212–5. doi:10.18773/austprescr.2015.072. PMC 4674028. PMID 26843715.
^ "What is medical marijuana?". National Institute of Drug Abuse. July 2015. Archived from the original on 17 April 2016. 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.
^ 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.
^ 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" (PDF). JAMA. 313 (24): 2456–2473. doi:10.1001/jama.2015.6358. hdl:10757/558499. PMID 26103030. Archived (PDF) from the original on 21 September 2017.
^ 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.
^ 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.
^ Murnion B. "Combination analgesics in adults". Australian Prescriber (33): 113–5. Archived from the original on 25 March 2012. Retrieved 12 August 2010.
^ 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.
^ ab
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.
^ 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.
^ Willian, Ronald S. (1 May 2015). "NDMA on Lower Back Pain". The Gold Rush. CCXXIX (Cincinnati): 38. Archived from the original on 26 April 2018. Retrieved 12 December 2015.
^ 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.
^ 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.
^ 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.
^ 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.
^ Voltaren Gel (diclofenac sodium topical gel) 1% – Hepatic Effects Labeling Changes Archived 2014-01-08 at the Wayback Machine.
^ [1] Archived October 19, 2010, at the Wayback Machine.
^ abcde Brayfield, A (ed.). "Martindale: The Complete Drug Reference". Medicines Complete. Pharmaceutical Press. Retrieved 9 April 2014.
^ abcd 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.
^ abcdefghi Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
^ abc Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
^ "Zorprin, Bayer Buffered Aspirin (aspirin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 7 April 2014. Retrieved 6 April 2014.
^ "Seractil 300mg Film-Coated Tablets – Summary of Product Characteristics". electronic Medicines Compendium. Genus Pharmaceuticals. 30 September 2005. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
^ 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. PMC 4170892. PMID 24151035.
^ ab "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.
^ "(diflunisal) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
^ "Nalfon (fenoprofen) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
^ ab 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.
^ 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.
^ 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.
^ 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 3598606. PMID 22341541.
^ "Arthrexin Indomethacin PRODUCT INFORMATION" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 14 October 2011. Archived from the original on 15 October 2015. Retrieved 7 April 2014.
^ Coaccioli S (August 2011). "Ketoprofen 2.5% gel: a clinical overview". European Review for Medical and Pharmacological Sciences. 15 (8): 943–9. PMID 21845805.
^ 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.
^ 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.
^ 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.
^ 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.
^ "NAME OF THE MEDICINE TORADOL (ketorolac trometamol)" (PDF). TGA eBusiness Services. ROCHE PRODUCTS PTY LIMITED. 3 February 2012. Archived from the original on 15 October 2015. Retrieved 7 April 2014.
^ McCormack PL (July 2011). "Ketorolac 0.45% ophthalmic solution". Drugs & Aging. 28 (7): 583–9. doi:10.2165/11207450-000000000-00000. PMID 21721602.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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 3272202. PMID 22094296.
^ 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.
^ 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.
^ "PRODUCT INFORMATION PONSTAN CAPSULES (mefenamic acid)" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 12 October 2012. Archived from the original on 15 October 2015. Retrieved 7 April 2014.
^ "Relafen (nabumetone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
^ 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.
^ "Daypro (oxaprozin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
^ 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.
^ "CHEMMART PIROXICAM CAPSULES" (PDF). TGA eBusiness Services. Apotex Pty Ltd. 18 December 2013. Archived from the original on 15 October 2015. Retrieved 7 April 2014.
^ 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.
^ "(salsalate) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
^ "Aclin Sulindac" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 8 November 2011. Archived from the original on 15 October 2015. Retrieved 7 April 2014.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ Brocks DR, Jamali F (April 1994). "Etodolac clinical pharmacokinetics". Clinical Pharmacokinetics. 26 (4): 259–74. doi:10.2165/00003088-199426040-00003. PMID 8013160.
^ 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.
^ 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.
^ 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.
^ "PRODUCT INFORMATION DYNASTAT parecoxib (as sodium)" (PDF). TGA eBusiness Services. Pfizer Australia Pty Ltd. 6 February 2013. Archived from the original on 15 October 2015. Retrieved 7 April 2014.
^ Scott LJ, Lamb HM (September 1999). "Rofecoxib". Drugs. 58 (3): 499–505, discussion 506–7. doi:10.2165/00003495-199958030-00016. PMID 10493277.
^ Hillson JL, Furst DE (July 2000). "Rofecoxib". Expert Opinion on Pharmacotherapy. 1 (5): 1053–66. doi:10.1517/14656566.1.5.1053. PMID 11249495.
^ Ormrod D, Wellington K, Wagstaff AJ (2002). "Valdecoxib". Drugs. 62 (14): 2059–71, discussion 2072–3. doi:10.2165/00003495-200262140-00005. PMID 12269850.
^ "Buprenex, Subutex (buprenorphine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
^ "PRODUCT INFORMATION ACTACODE" (PDF). TGA eBusiness Services. Aspen Pharma Pty Ltd. 19 September 2006. Archived from the original on 15 October 2015. Retrieved 8 April 2014.
^ "Zohydro ER (hydrocodone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 8 April 2014.
^ "Dilaudid, Dilaudid HP (hydromorphone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 8 April 2014.
^ "Roxicodone, OxyContin (oxycodone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 8 April 2014.
^ "Opana, Opana ER (oxymorphone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 8 April 2014.
^ "Stadol (butorphanol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 8 April 2014.
^ ab 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.
^ "Levo Dromoran (levorphanol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
^ "Nubain (nalbuphine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
^ 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.
^ 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.
^ "Talwin (pentazocine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
^ 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.
^ "Demerol, Pethidine (meperidine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 8 April 2014. Retrieved 9 April 2014.
^ 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.
^ 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.
^ MacPherson, RD; Duguid, MD (2008). "Strategy to Eliminate Pethidine Use in Hospitals" (PDF). Journal of Pharmacy Practice and Research. 38 (2): 88–89. Archived from the original (PDF) on 2014-02-15.
^ 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.
^ "Dipipanone 10mg + Cyclizine 30mg Tablets – Summary of Product Characteristics". 22 August 2012. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
^ 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.
^ 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.
^ "Marinol (dronabinol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
^ "Cymbalta (duloxetine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
^ 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.
^ 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.
^ "Savella (milnacipran) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
^ 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. Archived (PDF) from the original on 2015-10-15.
^ "Tylenol, Tylenol Infants' Drops (acetaminophen) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 14 April 2014. Retrieved 8 April 2014.
^ 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.
^ ab "Prialt (ziconotide) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 8 April 2014.
^ Harper, D. (2001). "Online Etymology Dictionary: Analgesia". Archived from the original on March 3, 2014. Retrieved December 3, 2012.
^ EB (1878).
^ EB (1911).
References
Baynes, T.S., ed. (1878), "Anodyne", Encyclopædia Britannica, 2 (9th ed.), New York: Charles Scribner's Sons, p. 90.- Chisholm, Hugh, ed. (1911), "Anodyne", Encyclopædia Britannica, 2 (11th ed.), Cambridge University Press, p. 79.
Baynes, T.S., ed. (1878), "Anodyne", Encyclopædia Britannica, 2 (9th ed.), New York: Charles Scribner's Sons, p. 90.Authority control  |
|
|---|
