Analgesic

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An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). This derives from Greek an-, "without", and -algia, "pain". Analgesic drugs act in various ways on the peripheral and central nervous system; they include paracetamol (acetaminophen), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, narcotic drugs such as morphine, synthetic drugs with narcotic properties such as tramadol, and various others. Some other classes of drugs not normally considered analgesics are used to treat neuropathic pain syndromes; these include tricyclic antidepressants and anticonvulsants.

Contents 1 The major classes 1.1 Paracetamol and NSAIDs 1.2 COX-2 inhibitors 1.3 Opiates and morphinomimetics 1.4 Specific agents 2 Specific forms and uses 2.1 Combinations 2.2 Topical or systemic 2.3 Psychotropic agents 2.4 Atypical and/or Adjuvant Analgesics 3 Addiction 4 See also 5 References 6 External link

The major classes

Paracetamol and NSAIDs

The exact mechanism of action of paracetamol is uncertain, but it appears to be acting centrally. Aspirin and the NSAIDs inhibit cyclooxygenase, leading to a decrease in prostaglandin production; this reduces pain and also inflammation (in contrast to paracetamol and the opioids).^{[citation needed]}

Paracetamol has few side effects, but dosing is limited by possible hepatotoxicity (potential for liver damage). NSAIDs may predispose to peptic ulcers, renal failure, allergic reactions, and hearing loss.^{[citation needed]} They may also increase the risk of hemorrhage by affecting platelet function. The use of certain NSAIDs in children under 16 suffering from viral illness may contribute to Reye's syndrome.

COX-2 inhibitors

Main article: COX-2 inhibitor

These drugs have been derived from NSAIDs. The cyclooxygenase enzyme inhibited by NSAIDs was discovered to have at least 2 different versions: COX1 and COX2. Research suggested that most of the adverse effects of NSAIDs were mediated by blocking the COX1 (constitutive) enzyme, with the analgesic effects being mediated by the COX2 (inducible) enzyme. The COX2 inhibitors were thus developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). These drugs (such as rofecoxib and celecoxib) are equally effective analgesics when compared with NSAIDs, but cause less gastrointestinal hemorrhage in particular. However post-launch data indicated increased risk of cardiac and cerebrovascular events with these drugs, and rofecoxib was subsequently withdrawn from the market. The role for this class of drug is currently hotly debated.

Opiates and morphinomimetics

Morphine, the archetypal opioid, and various other substances (e.g. codeine, oxycodone, hydrocodone, diamorphine, pethidine) all exert a similar influence on the cerebral opioid receptor system. Tramadol and buprenorphine are thought to be partial agonists of the opioid receptors. Dosing of all opioids may be limited by opioid toxicity (confusion, myoclonic jerks and pinpoint pupils), but there is no dose ceiling in patients who tolerate this.

Opioids, while very effective analgesics, may have some unpleasant side-effects. Up to 1 in 3 patients starting morphine may experience nausea and vomiting (generally relieved by a short course of antiemetics). 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.

When used appropriately, opioids and similar narcotic analgesics are safe and effective, carrying relatively little risk of addiction. Occasionally, gradual tapering of the dose is required to avoid withdrawal symptoms.

Specific agents

In patients with chronic or neuropathic pain, various other substances may have analgesic properties. Tricyclic antidepressants, especially amitriptyline, have been shown to improve pain in what appears to be a central manner. The exact mechanism of carbamazepine, gabapentin and pregabalin is similarly unclear, but these anticonvulsants are used to treat neuropathic pain with modest success.

Specific forms and uses

Combinations

Analgesics are frequently used in combination, such as the paracetamol and codeine preparations found in many non-prescription pain relievers. They can also be found in combination with vasoconstrictor drugs such as pseudoephedrine for sinus-related preparations, or with antihistamine drugs for allergy sufferers.

The use of paracetamol, as well as aspirin, ibuprofen, naproxen, and other NSAIDS concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been shown to have beneficial synergistic effects by combating pain at multiple sites of action--NSAIDs reduce inflammation which, in some cases, is the cause of the pain itself while opiates dull the perception of pain--thus, in cases of mild to moderate pain caused in part by inflammation, it is generally recommended that the two are prescribed together.[1]

Topical or systemic

Topical analgesia is generally recommended to avoid systemic side-effects. Painful joints, for example, may be treated with an ibuprofen- or diclofenac-containing gel; capsaicin also is used topically. Lidocaine and steroids may be injected into painful joints for longer-term pain relief. Lidocaine is also used for painful mouth sores and to numb areas for dental work and minor medical procedures.

Psychotropic agents

Tetrahydrocannabinol and some other cannabinoids, either from the Cannabis sativa plant or synthetic, have analgesic properties, although the use of cannabis derivatives is illegal in many countries. Other psychotropic analgesic agents include ketamine (an NMDA receptor antagonist), clonidine and other α₂-adrenoreceptor agonists, and mexiletine and other local anaesthetic analogues.

Atypical and/or Adjuvant Analgesics

Orphenadrine, cyclobenzaprine, scopolamine, atropine, gabapentin, first-generation antidepressants and other drugs possessing anticholinergic and/or antispasmodic properties are used in many cases along with analgesics to potentiate centrally acting analgesics such as opioids when used against pain especially of neuropathic origin and to and modulate the effects of many other types of analgesics by action in the parasympathetic nervous system. Dextromethorphan has been noted to slow the development of tolerance to opioids and exert additional analgesia by acting upon the NMDA receptors -- some analgesics such as methadone and ketobemidone and perhaps piritramide have intrinsic NMDA action.

The use of adjuvant analgesics is an important and growing part of the pain-control field and new discoveries are made practically every year. Many of the drugs also combat the side effects of opioid analgesics, an added bonus. For example, antihistamines including orphenadrine combat the release of histamine caused by many opioids, methylphenidate, caffeine, ephedrine, dextroamphetamine, and cocaine work against heavy sedation and may elevate mood in distressed patients as do the antidepressants. The one indisputably true benefit of THC to chronic pain patients on opioids may be its superior anti-nauseant action, though it would make more sense to go the route of the Marinol capsule, or oral, rectal, or vapour administration of hash oil rather than smoking cannabis for the same reasons most doctors advise against smoking tobacco.

Addiction

In the United States in recent years, there has been a wave of new addictions to prescription narcotics such as oxycodone (OxyContin) and hydrocodone (Vicodin, Lortab etc.) when available in pure formulations as opposed to combined with other medications (as in Percocet which contains both oxycodone and acetaminophen/paracetamol). Hydrocodone is only available in pure form in some European countries as the original hydrocodone pharmaceutical, Dicodid tablets. Far from reducing addiction liability, the paracetamol content of many codeine, dihydrocodeine, hydrocodone, and oxycodone pharmaceuticals in the United States only saddles users with the high risk of severe liver damage, and extraction of the opioids with cold water or solvents reduces this problem for the sophisticated abuser, self-medicator, and legitimate prescription holder alike [2]. Most hydrocodone, codeine, and dihydrocodeine cough syrups available in the United States also contain active ingredients such as acetaminophen which are dangerous in overdose.

See also

• Patient-controlled analgesia

References

• Cancer pain relief and palliative care. Report of a WHO expert committee [World Health Organization Technical Report Series, 804] . Geneva, Switzerland: World Health Organization; 1990. pp. 1-75. ISBN 92-4-120804-X.
• Bandolier pain site (Oxford pain group)

External link

• FDA proposes new pain reliever warnings

v • d • e Analgesics (N02A, N02B)
Opioids	Bezitramide, Buprenorphine, Butorphanol, Dextromoramide, Dextropropoxyphene, Diamorphine, Dihydrocodeine, Fentanyl, Hydromorphone, Ketobemidone, Methadone, Morphine, Nalbufine, Nicomorphine, Opium, Oxycodone, Papaveretum, Pethidine, Piritramide, Tramadol (see also longer list)
Salicylic acid and derivatives	Aspirin (Acetylsalicylic Acid), Diflunisal, Ethenzamide -- See also: NSAIDs
Pyrazolones	Aminophenazone, Metamizole, Phenazone
Anilides	Paracetamol (acetaminophen), Phenacetin
Others	Ziconotide, Tetrahydrocannabinol, Ibuprofen, Ketoprofen, Mefenamic Acid, Naproxen, Diclofenac, Flurbiprofen, Diflunisal, Fenoprofen, Indomethacin, Ketorolac, Meclofenamate, Meloxicam, Piroxicam, Tolmetin

v • d • e Major Drug Groups
Brain and Nervous system	Analgesics, Anesthetics, Anxiolytics, Antidepressants, Antipsychotics, Anticonvulsants, Nervous system stimulants, Antiemetics, Hallucinogens, Mood stabilizers
Respiratory system	Bronchodilators, Decongestants
Heart and Circulation	Angiotensin converting enzyme inhibitors, Antiarrhythmics, Antianginals, Antihypertensives, Antihyperlipidemics, Anticoagulants, Antiplatelets, Beta blockers, Diuretics, Thrombolytics, Vasodilators
Gastrointestinal tract	Antacids, Antidiarrhoeals, H2-receptor antagonists, Proton pump inhibitors, Laxatives
Muscles, Bones, and Joints	Anti-inflammatories, Antirheumatics, Corticosteroids, Muscle relaxants
Allergy	Antihistamines
Infections and Infestations	Antibiotics, Antivirals, Vaccines, Antiprotozoals, Antifungals, Anthelmintics
Endocrine system	Corticosteroids, Anti-diabetics
Malignant and Immune disease	Anticancer agents, Immunosuppressants
Reproductive system	Hormonal contraception, Fertility agents, Selective estrogen receptor modulators
Skin	Antipruritics

ar:مسكن ألم

ca:Analgèsic cs:Analgetikum da:Analgesia de:Analgetikum es:Analgésico fr:Analgésique it:Analgesia he:שיכוך כאב ms:Analgesik nl:Pijnstiller ja:鎮痛剤 pl:Analgezja pt:Analgésico sl:Analgetik fi:Analgeetti sv:Analgetika th:ยาบรรเทาปวด tr:Analjezik uk:Анальгетики

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