+ Comparison of different analgesics Generic name (INN) Physicochemistry Mechanism of action Routes of administration Pharmacokinetics Indications Major safety concerns 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. Oral (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%. 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%). Osteoarthritis; mild-moderate pain and menstrual pain. 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. 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%). 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. 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%). Ophthalmologic: Vernal keratoconjunctivitis; postoperative ocular swelling; herpetic stromal keratitis, excimer laser photorefractive keratectomy; ocular gingivitis. Systemic use: rheumatoid arthritis; osteoarthritis. 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, potassium 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. Pain; fever; inflammatory illness; rheumatoid arthritis; osteoarthritis; heavy menstrual bleeding; patent ductus arteriosus. 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%). Rheumatoid arthritis; osteoarthritis; gout; ankylosing spondylitis; period pain; patent ductus arteriosus. 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. 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). Rheumatoid arthritis, osteoarthritis and superficial sporting injuries (topical use). 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%). 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. 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%). 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%). 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%). Inflammatory pain and heavy menstrual bleeding. 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%). 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%). 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. 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%). 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. Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and sports injuries (topical use). 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. 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%). Rheumatoid arthritis; osteoarthritis; gout; ankylosing spondylitis; inflammatory pain. 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%). 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. 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%). 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%). 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%). 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%). 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%). 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%). 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%). 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. 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%). 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. 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%). 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. 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. 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%). 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. 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. 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. PO, IM, IV, SC. Protein binding = 40%; extensive first-pass metabolism; half-life = 12–16 hours, 30 hours (repeated dosing). 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. IM, IV, SC. Protein binding = not significant; hepatic metabolism; half-life = 5 hours; excretion = urine, faeces. 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. 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. 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). 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). Mu opioid. IM, IV, PO, rectal. No data available. Severe pain. 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. 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. 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. 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%). 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%). 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. 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. 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%). 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. 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. 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%). 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%). Chronic pain. CNS toxicity (abnormal gait, abnormal vision, memory problems, etc.); GI effects. Where † indicates products that are no longer marketed.
+ Comparison of different analgesics Generic name (INN) Physicochemistry Mechanism of action Routes of administration Pharmacokinetics Indications Major safety concerns 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. Oral (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%. 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 aci,d 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%). Osteoarthritis; mild-moderate pain and menstrual pain. 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. 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%). 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 = ?; prote,in binding = 99%; hepatic metabolism; excretion = urine, faeces. 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%). Ophthalmologic: Vernal keratoconjunctivitis; postoperative ocular swelling; herpetic stromal keratitis excimer laser photorefractive keratectomy; ocular gingivitis. Systemic use: rheumatoid arthritis; osteoarthritis. 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, potassium 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. Pain; fever; inflammatory illness; rheumatoid arthritis; osteoarthritis; heavy menstrual bleeding; patent ductus arteriosus. 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%). Rheumatoid arthritis; osteoarthritis; gout; ankylosing spondylitis; period pain; patent ductus arteriosus. 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. 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). Rheumatoid arthritis, osteoarthritis and superficial sporting injuries (topical use). 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%). 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. 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%). 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%). 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%). Inflammatory pain and heavy menstrual bleeding. 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%). 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%). 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. 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%). 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. Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and sports injuries (topical use). 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. 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%). Rheumatoid arthritis; osteoarthritis; gout; ankylosing spondylitis; inflammatory pain. 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%). 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. 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%). 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%). 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%). 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%). 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%). 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%). 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%). 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. 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%). 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. 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%). 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. 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. 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%). 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. 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. 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. PO, IM, IV, SC. Protein binding = 40%; extensive first-pass metabolism; half-life = 12–16 hours, 30 hours (repeated dosing). 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. IM, IV, SC. Protein binding = not significant; hepatic metabolism; half-life = 5 hours; excretion = urine, faeces. 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. 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. 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). 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). Mu opioid. IM, IV, PO, rectal. No data available. Severe pain. 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. 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. 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. 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%). 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%). 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. 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. 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%). 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. 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. 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%). 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%). Chronic pain. CNS toxicity (abnormal gait, abnormal vision, memory problems, etc.); GI effects. Where † indicates products that are no longer marketed.