Analgesic

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Analgesic
Drug class
Opium pod cut to demonstrate fluid extraction1.jpg
Opium poppies such as this one provide ingredients for the class of analgesics called opiates. Also visible is the plant's latex, from which numerous opiate compounds have been isolated.
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ATC code N02A
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An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

Contents

Analgesic choice is also determined by the type of pain: For neuropathic pain, recent research has suggested that classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and anticonvulsants may be considered as an alternative. [1]

Various analgesics, such as many NSAIDs, are available over the counter in most countries, whereas various others are prescription drugs owing to the substantial risks and high chances of overdose, misuse, and addiction in the absence of medical supervision.

Etymology

The word analgesic derives from Greek an- (ἀν-, "without"), álgos (ἄλγος, "pain"), [2] and -ikos (-ικος, forming adjectives). Such drugs were usually known as "anodynes" before the 20th century. [3] [4]

Classification

Analgesics are typically classified based on their mechanism of action. [5]

A bottle of acetaminophen Tylenol.jpg
A bottle of acetaminophen

Paracetamol (acetaminophen)

Paracetamol, also known as acetaminophen or APAP, is a medication used to treat pain and fever. [6] It is typically used for mild to moderate pain. [6] In combination with opioid pain medication, paracetamol is now used for more severe pain such as cancer pain and after surgery. [7] It is typically used either by mouth or rectally but is also available intravenously. [6] [8] Effects last between two and four hours. [8] Paracetamol is classified as a mild analgesic. [8] Paracetamol is generally safe at recommended doses. [9]

NSAIDs

Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a drug class that groups together drugs that decrease pain [10] and lower fever, and, in higher doses, decrease inflammation. [11] The most prominent members of this group of drugs, aspirin, ibuprofen and naproxen, Diclofenac are all available over the counter in most countries. [12]

COX-2 inhibitors

These drugs have been derived from NSAIDs. The cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least two 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. [13]

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. [13]

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. [14] 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. [15] [16] [17] [18] 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. [19] 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. [20]

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 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). [21]

Alcohol

Alcohol has biological, mental, and social effects which influence the consequences of using alcohol for pain. [22] Moderate use of alcohol can lessen certain types of pain in certain circumstances. [22]

The majority of its analgesic effects come from antagonizing NMDA receptors, similarly to ketamine, thus decreasing the activity of the primary excitatory (signal boosting) neurotransmitter, glutamate. It also functions as an analgesic to a lesser degree by increasing the activity of the primary inhibitory (signal reducing) neurotransmitter, GABA. [23]

Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and alcohol use disorder. [22]

Cannabis

Medical cannabis, or medical marijuana, refers to cannabis or its cannabinoids used to treat disease or improve symptoms. [24] [25] 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. [26] [27] [28]

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 people with allergies.

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 combating pain at multiple sites of action, [29] [30] 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. [31]

Alternative medicine

There is some evidence that some treatments using alternative medicine can relieve some types of pain more effectively than placebo. [32] The available research concludes that more research would be necessary to better understand the use of alternative medicine. [32]

Other drugs

Nefopam—a monoamine reuptake inhibitor, and calcium and sodium channel modulator—is also approved for the treatment of moderate to severe pain in some countries. [33]

Flupirtine is a centrally acting K+ channel opener with weak NMDA antagonist properties. [34] It was used in Europe for moderate to strong pain, as well as its migraine-treating and muscle-relaxant properties. It has no significant 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. [35] However, tolerance may develop in some cases. [36]

Ziconotide, a blocker of potent N-type voltage-gated calcium channels, is administered intrathecally for the relief of severe, usually cancer-related pain. [37]

Adjuvants

Certain drugs that have been introduced for uses other than analgesics are also used in pain management. Both first-generation (such as amitriptyline) and newer antidepressants (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 orphenadrine, mexiletine, pregabalin, gabapentin, cyclobenzaprine, hyoscine (scopolamine), and other drugs possessing anticonvulsant, anticholinergic, and/or antispasmodic properties, as well as many other drugs with CNS actions. These drugs are used along with analgesics to modulate and/or modify the action of opioids when used against pain, especially of neuropathic origin.

Dextromethorphan has been noted to slow the development of and reverse tolerance to opioids, as well as to exert additional analgesia by acting upon NMDA receptors, as does ketamine. [38] Some analgesics such as methadone and ketobemidone and perhaps piritramide have intrinsic NMDA action. [39]

The anticonvulsant carbamazepine is used to treat neuropathic pain. Similarly, the gabapentinoids gabapentin and pregabalin are prescribed for neuropathic pain, and phenibut is available without prescription. Gabapentinoids work as α2δ-subunit blockers of voltage-gated calcium channels, and tend to have other mechanisms of action as well. Gabapentinoids are all anticonvulsants, which are most commonly used for neuropathic pain, as their mechanism of action tends to inhibit pain sensation originating from the nervous system. [40]

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. [41] ); capsaicin also is used topically. Lidocaine, an anesthetic, and steroids may be injected into 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. [42]

Uses

Topical nonsteroidal anti-inflammatory drugs provide 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. [43]

List of drugs with comparison

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. [128]

See also

Related Research Articles

<span class="mw-page-title-main">Hydrocodone</span> Opioid drug used in pain relief

Hydrocodone, also known as dihydrocodeinone, is a semi-synthetic opioid used to treat pain and as a cough suppressant. It is taken by mouth. Typically, it is dispensed as the combination acetaminophen/hydrocodone or ibuprofen/hydrocodone for pain severe enough to require an opioid and in combination with homatropine methylbromide to relieve cough. It is also available by itself in a long-acting form sold under the brand name Zohydro ER, among others, to treat severe pain of a prolonged duration. Hydrocodone is a controlled drug: in the United States, it is classified as a Schedule II Controlled Substance.

<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

<span class="mw-page-title-main">Ibuprofen</span> Medication treating pain, fever, and inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be taken orally or intravenously. It typically begins working within an hour.

<span class="mw-page-title-main">Tramadol</span> Opioid pain medication

Tramadol, sold under the brand name Ultram among others, is an opioid pain medication and a serotonin–norepinephrine reuptake inhibitor (SNRI) used to treat moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It is available in combination with paracetamol (acetaminophen).

<span class="mw-page-title-main">Opioid</span> Psychoactive chemical

Opioids are a class of drugs that derive from, or mimic, natural substances found in the opium poppy plant. Opioids work in the brain to produce a variety of effects, including pain relief. As a class of substances, they act on opioid receptors to produce morphine-like effects.

<span class="mw-page-title-main">Pethidine</span> Opioid analgesic

Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a fully synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Otto Eisleb, its analgesic properties were first recognized by Otto Schaumann while working for IG Farben, in Germany. Pethidine is the prototype of a large family of analgesics including the pethidine 4-phenylpiperidines, the prodines, bemidones, and others more distant, including diphenoxylate and analogues.

<span class="mw-page-title-main">Remifentanil</span> Synthetic opioid analgesic

Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.

<span class="mw-page-title-main">Ketorolac</span> Nonsteroidal anti-inflammatory drug (NSAID; analgesic)

Ketorolac, sold under the brand name Toradol among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain. Specifically it is recommended for moderate to severe pain. Recommended duration of treatment is less than six days, and in Switzerland not more than seven days. It is used by mouth, by nose, by injection into a vein or muscle, and as eye drops. Effects begin within an hour and last for up to eight hours. Ketorolac also has antipyretic (fever-reducing) properties.

<span class="mw-page-title-main">Zomepirac</span> Withdrawn non-steroidal anti-inflammatory drug

Zomepirac is an orally effective nonsteroidal anti-inflammatory drug (NSAID) that has antipyretic actions. It was developed by McNeil Pharmaceutical, approved by the FDA in 1980, and sold as the sodium salt zomepirac sodium, under the brand name Zomax. Due to its clinical effectiveness, it was preferred by doctors in many situations and obtained a large share of the analgesics market; however, it was subsequently withdrawn in March 1983 due to its tendency to cause serious anaphylaxis in a small, but unpredictable, subset of the patient population.

<span class="mw-page-title-main">Dezocine</span> Opioid analgesic

Dezocine, sold under the brand name Dalgan, is an atypical opioid analgesic which is used in the treatment of pain. It is used by intravenous infusion and intramuscular injection.

<span class="mw-page-title-main">Propiram</span> Opioid analgesic drug

Propiram is a partial μ-opioid receptor agonist and weak μ antagonist analgesic from the ampromide family of drugs related to other drugs such as phenampromide and diampromide. It was invented in 1963 in the United Kingdom by Bayer but was not widely marketed, although it saw some limited clinical use, especially in dentistry. Propiram reached Phase III clinical trials in the United States and Canada.

<span class="mw-page-title-main">Antifolate</span> Class of antimetabolite medications

Antifolates are a class of antimetabolite medications that antagonise (that is, block) the actions of folic acid (vitamin B9). Folic acid's primary function in the body is as a cofactor to various methyltransferases involved in serine, methionine, thymidine and purine biosynthesis. Consequently, antifolates inhibit cell division, DNA/RNA synthesis and repair and protein synthesis. Some such as proguanil, pyrimethamine and trimethoprim selectively inhibit folate's actions in microbial organisms such as bacteria, protozoa and fungi. The majority of antifolates work by inhibiting dihydrofolate reductase (DHFR).

<span class="mw-page-title-main">Nefopam</span> Analgesic medication

Nefopam, sold under the brand name Acupan among others, is a centrally acting, non-opioid painkilling medication, with central stimulant and sympathomimetic properties that is primarily used to treat moderate to severe pain.

An equianalgesic chart is a conversion chart that lists equivalent doses of analgesics. Equianalgesic charts are used for calculation of an equivalent dose between different analgesics. Tables of this general type are also available for NSAIDs, benzodiazepines, depressants, stimulants, anticholinergics and others.

<span class="mw-page-title-main">Norpropoxyphene</span> Chemical compound

Norpropoxyphene is a major metabolite of the opioid analgesic drug dextropropoxyphene, and is responsible for many of the side effects associated with use of this drug, especially the unusual toxicity seen during dextropropoxyphene overdose. It has weaker analgesic effects than dextropropoxyphene itself, but is a relatively potent pro-convulsant and blocker of sodium and potassium channels, particularly in heart tissue, which produces prolonged intracardiac conduction time and can lead to heart failure following even relatively minor overdoses. The toxicity of this metabolite makes dextropropoxyphene up to 10 times more likely to cause death following overdose compared to other similar mild opioid analgesics, and has led to dextropropoxyphene being withdrawn from the market in some countries.

<span class="mw-page-title-main">Opiate</span> Substance derived from opium

An opiate is an alkaloid substance derived from opium. It differs from the similar term opioid in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain. Opiates are alkaloid compounds naturally found in the opium poppy plant Papaver somniferum. The psychoactive compounds found in the opium plant include morphine, codeine, and thebaine. Opiates have long been used for a variety of medical conditions, with evidence of opiate trade and use for pain relief as early as the eighth century AD. Most opiates are considered drugs with moderate to high abuse potential and are listed on various "Substance-Control Schedules" under the Uniform Controlled Substances Act of the United States of America.

<span class="mw-page-title-main">Pain management in children</span> Medical condition

Pain management in children is the assessment and treatment of pain in infants and children.

<span class="mw-page-title-main">Mitragynine</span> Opioid analgesic compound

Mitragynine is an indole-based alkaloid and is one of the main psychoactive constituents in the Southeast Asian plant Mitragyna speciosa, commonly known as kratom. It is an opioid that is typically consumed as a part of kratom for its pain-relieving and euphoric effects. It has also been researched for its use to potentially manage symptoms of opioid withdrawal.

Total intravenous anesthesia (TIVA) refers to the intravenous administration of anesthetic agents to induce a temporary loss of sensation or awareness. The first study of TIVA was done in 1872 using chloral hydrate, and the common anesthetic agent propofol was licensed in 1986. TIVA is currently employed in various procedures as an alternative technique of general anesthesia in order to improve post-operative recovery.

References

Citations

  1. Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, et al. (November 2003). "Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations". Archives of Neurology. 60 (11): 1524–34. doi: 10.1001/archneur.60.11.1524 . PMID   14623723.
  2. Harper D (2001). "Online Etymology Dictionary: Analgesia". Archived from the original on March 3, 2014. Retrieved December 3, 2012.
  3. EB (1878).
  4. EB (1911).
  5. "British National Formulary: Analgesics". BNF online. Retrieved 8 June 2017.
  6. 1 2 3 "Acetaminophen". The American Society of Health-System Pharmacists. Archived from the original on 2016-06-05.
  7. Scottish Intercollegiate Guidelines Network (SIGN) (2008). "6.1 and 7.1.1" (PDF). Guideline 106: Control of pain in adults with cancer. Scotland: National Health Service (NHS). ISBN   9781905813384. Archived (PDF) from the original on 2010-12-20.
  8. 1 2 3 Hochhauser D (2014). Cancer and its Management. John Wiley & Sons. p. 119. ISBN   9781118468715. Archived from the original on 2017-09-10.
  9. 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.
  10. Mallinson T (2017). "A review of ketorolac as a prehospital analgesic". Journal of Paramedic Practice. 9 (12): 522–526. doi: 10.12968/jpar.2017.9.12.522 . Retrieved 2 June 2018.
  11. Mallinson T (2017). "A review of ketorolac as a prehospital analgesic". Journal of Paramedic Practice. 9 (12). London: MA Healthcare: 522–526. doi: 10.12968/jpar.2017.9.12.522 . Archived from the original on 5 June 2018. Retrieved 2 June 2018.
  12. Warden SJ (April 2010). "Prophylactic use of NSAIDs by athletes: a risk/benefit assessment". The Physician and Sportsmedicine. 38 (1): 132–8. doi:10.3810/psm.2010.04.1770. PMID   20424410. S2CID   44567896. Archived from the original on 2010-11-26.
  13. 1 2 Conaghan PG (June 2012). "A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity". Rheumatology International. 32 (6): 1491–502. doi:10.1007/s00296-011-2263-6. PMC   3364420 . PMID   22193214.
  14. Smith HS, Raffa RB, Pergolizzi JV, Taylor R, Tallarida RJ (July 2014). "Combining opioid and adrenergic mechanisms for chronic pain". Postgraduate Medicine. 126 (4): 98–114. doi:10.3810/pgm.2014.07.2788. PMID   25141248. S2CID   19782818.
  15. 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.
  16. 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.
  17. 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.
  18. 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. hdl: 10533/173421 . PMID   12354291. S2CID   13397864.
  19. Tozer A. "Replacing Opioids: Developing drugs to treat pain". Analytical Cannabis. Archived from the original on 22 August 2017. Retrieved 22 August 2017.
  20. Oxford Textbook of Palliative Medicine, 3rd ed. (Doyle D, Hanks G, Cherney I and Calman K, eds. Oxford University Press, 2004).
  21. Bannister K (June 2015). "Opioid-induced hyperalgesia: where are we now?". Current Opinion in Supportive and Palliative Care. 9 (2): 116–21. doi:10.1097/SPC.0000000000000137. PMID   25872113. S2CID   13922218.
  22. 1 2 3 Zale EL, Maisto SA, Ditre JW (April 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.
  23. Nagy J (March 2008). "Alcohol related changes in regulation of NMDA receptor functions". Current Neuropharmacology. 6 (1): 39–54. doi:10.2174/157015908783769662. PMC   2645546 . PMID   19305787.
  24. Murnion B (December 2015). "Medicinal cannabis". Australian Prescriber. 38 (6): 212–5. doi:10.18773/austprescr.2015.072. PMC   4674028 . PMID   26843715.
  25. "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.
  26. 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. S2CID   8503107.
  27. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. (23 June 2015). "Cannabinoids for Medical Use: A Systematic Review and Meta-analysis" (PDF). JAMA. 313 (24): 2456–73. doi: 10.1001/jama.2015.6358 . hdl:10757/558499. PMID   26103030. Archived (PDF) from the original on 21 September 2017.
  28. Jensen B, Chen J, Furnish T, Wallace M (October 2015). "Medical Marijuana and Chronic Pain: a Review of Basic Science and Clinical Evidence". Current Pain and Headache Reports. 19 (10): 50. doi:10.1007/s11916-015-0524-x. PMID   26325482. S2CID   9110606.
  29. Patel R, Dickenson AH (October 2021). "Neuropharmacological basis for multimodal analgesia in chronic pain". Postgraduate Medicine. 134 (3): 245–259. doi:10.1080/00325481.2021.1985351. PMID   34636261. S2CID   238635838.
  30. Mehlisch DR (July 2002). "The efficacy of combination analgesic therapy in relieving dental pain". Journal of the American Dental Association. 133 (7): 861–71. doi:10.14219/jada.archive.2002.0300. PMID   12148679.
  31. Murnion B. "Combination analgesics in adults". Australian Prescriber (33): 113–5. Archived from the original on 25 March 2012. Retrieved 12 August 2010.
  32. 1 2
  33. Girard P, Chauvin M, Verleye M (January 2016). "Nefopam analgesia and its role in multimodal analgesia: A review of preclinical and clinical studies". Clinical and Experimental Pharmacology & Physiology. 43 (1): 3–12. doi: 10.1111/1440-1681.12506 . PMID   26475417.
  34. 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". Journal of Neural Transmission. 106 (9–10): 857–67. doi:10.1007/s007020050206. PMID   10599868. S2CID   11636934.
  35. Klawe C, Maschke M (June 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. S2CID   11597721.
  36. Stoessel C, Heberlein A, Hillemacher T, Bleich S, Kornhuber J (August 2010). "Positive reinforcing effects of flupirtine--two case reports". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 34 (6): 1120–1. doi:10.1016/j.pnpbp.2010.03.031. PMID   20362025. S2CID   19710997.
  37. Bäckryd E (August 2018). "Do the potential benefits outweigh the risks? An update on the use of ziconotide in clinical practice". European Journal of Pain. 22 (7): 1193–1202. doi:10.1002/ejp.1229. PMID   29635804. S2CID   4710528.
  38. Hewitt DJ (June 2000). "The use of NMDA-receptor antagonists in the treatment of chronic pain". The Clinical Journal of Pain. 16 (2 Suppl): S73-9. doi:10.1097/00002508-200006001-00013. PMID   10870744. S2CID   40067641.
  39. Elliott KJ, Brodsky M, Hyanansky A, Foley KM, Inturrisi CE (December 1995). "Dextromethorphan shows efficacy in experimental pain (nociception) and opioid tolerance". Neurology. 45 (12 Suppl 8). NEUROLOGY, 2005: S66-8. doi:10.1212/WNL.45.12_Suppl_8.S66. PMID   8545027. S2CID   46279174.
  40. Eardley I, Whelan P, Kirby R, Schaeffer A. "Drugs Used In The Treatment Of Interstitial Cystitis". Drug Treatment in Urology. John Wiley & Sons, 2008. p. 65.
  41. Voltaren Gel (diclofenac sodium topical gel) 1% – Hepatic Effects Labeling Changes Archived 2014-01-08 at the Wayback Machine
  42. Archived October 19, 2010, at the Wayback Machine
  43. Derry S, Moore RA, Gaskell H, McIntyre M, Wiffen PJ (June 2015). "Topical NSAIDs for acute musculoskeletal pain in adults". The Cochrane Database of Systematic Reviews. 6 (6): CD007402. doi:10.1002/14651858.CD007402.pub3. PMC   6426435 . PMID   26068955.
  44. 1 2 3 4 5 Brayfield, A (ed.). "Martindale: The Complete Drug Reference". Medicines Complete. Pharmaceutical Press. Retrieved 9 April 2014.
  45. 1 2 3 4 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.
  46. 1 2 3 4 5 6 7 8 9 Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN   978-0-9805790-9-3.
  47. 1 2 3 Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN   978-0-85711-084-8.
  48. "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.
  49. "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.
  50. 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.
  51. 1 2 "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.
  52. "(diflunisal) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
  53. "Nalfon (fenoprofen) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
  54. 1 2 Abdel-Aziz AA, Al-Badr AA, Hafez GA (2012). Flurbiprofen (PDF). Profiles of Drug Substances, Excipients and Related Methodology. Vol. 37. pp. 113–81. doi:10.1016/B978-0-12-397220-0.00004-0. ISBN   9780123972200. PMID   22469318.{{cite book}}: |journal= ignored (help)
  55. 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. S2CID   207301513.
  56. 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. S2CID   40750585.
  57. 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.
  58. "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.
  59. Coaccioli S (August 2011). "Ketoprofen 2.5% gel: a clinical overview". European Review for Medical and Pharmacological Sciences. 15 (8): 943–9. PMID   21845805.
  60. 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.
  61. 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. S2CID   207298956.
  62. Shohin IE, Kulinich JI, Ramenskaya GV, Abrahamsson B, Kopp S, Langguth P, 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. S2CID   31263593.
  63. 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 . hdl: 2434/667356 . PMID   21052564.
  64. "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.
  65. McCormack PL (July 2011). "Ketorolac 0.45% ophthalmic solution". Drugs & Aging. 28 (7): 583–9. doi:10.2165/11207450-000000000-00000. PMID   21721602. S2CID   36573017.
  66. 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. S2CID   25006837.
  67. 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. S2CID   21022357.
  68. 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. S2CID   41818971.
  69. 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. S2CID   25001604.
  70. 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. S2CID   12843704.
  71. 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.
  72. 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. S2CID   265522598.
  73. 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. S2CID   46662001.
  74. "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.
  75. "Relafen (nabumetone) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
  76. 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. S2CID   195692083.
  77. "Daypro (oxaprozin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
  78. 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. S2CID   195692751.
  79. "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.
  80. 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. S2CID   209070732.
  81. "(salsalate) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 7 April 2014.
  82. "Aclin Sulindac" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 8 November 2011. Archived from the original on 15 October 2015. Retrieved 7 April 2014.
  83. 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. S2CID   195698431.
  84. 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. S2CID   25446820.
  85. 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. S2CID   33403236.
  86. 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. S2CID   71357689.
  87. 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. S2CID   195692567.
  88. 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. S2CID   195693229.
  89. Brocks DR, Jamali F (April 1994). "Etodolac clinical pharmacokinetics". Clinical Pharmacokinetics. 26 (4): 259–74. doi:10.2165/00003088-199426040-00003. PMID   8013160. S2CID   43007023.
  90. 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. S2CID   11718396.
  91. 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. S2CID   22656859.
  92. 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. S2CID   9873285.
  93. "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.
  94. Scott LJ, Lamb HM (September 1999). "Rofecoxib". Drugs. 58 (3): 499–505, discussion 506–7. doi:10.2165/00003495-199958030-00016. PMID   10493277. S2CID   219216087.
  95. Hillson JL, Furst DE (July 2000). "Rofecoxib". Expert Opinion on Pharmacotherapy. 1 (5): 1053–66. doi:10.1517/14656566.1.5.1053. PMID   11249495. S2CID   219291177.
  96. Ormrod D, Wellington K, Wagstaff AJ (2002). "Valdecoxib". Drugs. 62 (14): 2059–71, discussion 2072–3. doi:10.2165/00003495-200262140-00005. PMID   12269850. S2CID   250308600.
  97. "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.
  98. "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.
  99. "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.
  100. "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.
  101. "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.
  102. "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.
  103. "Stadol (butorphanol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 8 April 2014.
  104. 1 2 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. S2CID   10916508.
  105. "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.
  106. "Nubain (nalbuphine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
  107. 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. S2CID   196363445.
  108. 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. S2CID   28014084.
  109. "Talwin (pentazocine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
  110. 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. doi:10.1111/j.1399-6576.1982.tb01848.x. PMID   6124079. S2CID   35733660.
  111. "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.
  112. 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.
  113. 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. S2CID   23410891.
  114. MacPherson RD, Duguid MD (2008). "Strategy to Eliminate Pethidine Use in Hospitals". Journal of Pharmacy Practice and Research. 38 (2): 88–89. doi: 10.1002/j.2055-2335.2008.tb00807.x . S2CID   71812645.
  115. 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. S2CID   35402662.
  116. "Dipipanone 10mg + Cyclizine 30mg Tablets – Summary of Product Characteristics". 22 August 2012. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
  117. 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. S2CID   208818234.
  118. 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. S2CID   29509469.
  119. "Marinol (dronabinol) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
  120. "Cymbalta (duloxetine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
  121. 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. S2CID   16535456.
  122. 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. S2CID   22053483.
  123. "Savella (milnacipran) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 9 April 2014.
  124. Evans MS, Lysakowski C, Tramèr MR (November 2008). "Nefopam for the prevention of postoperative pain: quantitative systematic review". British Journal of Anaesthesia. 101 (5): 610–7. doi: 10.1093/bja/aen267 . PMID   18796441.
  125. "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.
  126. 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. S2CID   39007929.
  127. 1 2 "Prialt (ziconotide) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 13 April 2014. Retrieved 8 April 2014.
  128. Yekkirala AS, Roberson DP, Bean BP, Woolf CJ (August 2017). "Breaking barriers to novel analgesic drug development". Nature Reviews. Drug Discovery. 16 (8): 545–564. doi:10.1038/nrd.2017.87. PMC   5675565 . PMID   28596533.

Sources