Analgesic

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"Painkiller" redirects here. For other uses, see Painkiller (disambiguation).
Opium poppies such as this one provide ingredients for the class of analgesics called opiates

An analgesic or painkiller is any member of the group of drugs used to achieve analgesia, relief from pain.

Analgesic drugs act in various ways on the peripheral and central nervous systems. They are distinct from anesthetics, which temporarily affect, and in some instances completely eliminate, sensation. Analgesics include paracetamol (known in North America as acetaminophen or simply APAP), the non-steroidal anti-inflammatory drugs (NSAIDs) such as the salicylates, and opioid drugs such as morphine and oxycodone.

In choosing analgesics, the severity and response to other medication determines the choice of agent; the World Health Organization (WHO) pain ladder[1] specifies mild analgesics as its first step.

Analgesic choice is also determined by the type of pain: For neuropathic pain, traditional analgesics are less effective, and there is often benefit from classes of drugs that are not normally considered analgesics, such as tricyclic antidepressants and anticonvulsants.[2]

Uses[edit]

These drugs provide pain management.[citation needed]

Contraindications[edit]

There are several classes of analgesic drugs.[citation needed] Each class has a different history of use for treating different sorts of pain and in different sorts of people.[citation needed] It is difficult to make a statement about when such drugs should be avoided.[citation needed]

In general, pain medication should not be used when there is another, less risky alternative.[citation needed] At the same time, people in pain should not experience undertreatment of pain.[citation needed] When a treatment is available to address the pain, a health care provider should recommend that correct treatment and not a lessor treatment which leaves too much pain.[citation needed]

Classification[edit]

Tilidine, a type of painkiller

Drugs for pain are typically classified by chemical structure.[citation needed]

They may also be classified in other ways. Sometimes they are classified by use for various classes of medical condition.[citation needed] Other times they are sorted by the needs of special populations who would use them.[citation needed] They might be listed by availability in a geographical area, perhaps to prevent recommending a drug which is illegal in one place even if it is easily available elsewhere.[citation needed]

Paracetamol/acetaminophen[edit]

Main article: Paracetamol

Paracetamol, also known as acetaminophen or APAP, is a medication used to treat pain and fever.[3] It is typically used for mild to moderate pain.[3] In combination with opioid pain medication, paracetamol is used for more severe pain such as cancer pain and after surgery.[4] It is typically used either by mouth or rectally but is also available intravenously.[3][5] Effects last between two and four hours.[5] Paracetamol is classified as a mild analgesic.[5] Paracetamol is generally safe at recommended doses.[6]

NSAIDs[edit]

Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs), are a drug class that groups together drugs that provide analgesic (pain-killing) and antipyretic (fever-reducing) effects, and, in higher doses, anti-inflammatory effects. The most prominent members of this group of drugs, aspirin, ibuprofen and naproxen, are all available over the counter in most countries.[7] As analgesics, NSAIDs are unusual in that they are non-narcotic and thus are used as a non-addictive alternative to narcotics.[citation needed]

COX-2 inhibitors[edit]

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 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.[8]

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.[8]

Opioids[edit]

Main article: Opioid

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.[9] 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.[10][11][12][13] 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 a 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.[citation needed]

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.[14]

When used appropriately, opioids and other central analgesics are otherwise 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 so, when safe to do so, the dosage may need to be increased to maintain effectiveness. This may be of particular concern regarding patients suffering with chronic pain.[citation needed] 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.

Alcohol[edit]

See also: Ethanol

Describing the effects of using alcohol to treat pain is difficult.[15] Alcohol has biological, mental, and social effects which influence the consequences of using alcohol for pain.[15] Moderate use of alcohol can lessen certain types of pain in certain circumstances.[15] Attempting to use alcohol to treat pain has also been observed to lead to negative outcomes including excessive drinking and alcohol use disorder.[15]

Medical cannabis[edit]

Main article: Medical cannabis

Medical cannabis or medical marijuana, can refer to the use of cannabis and its cannabinoids to treat disease or improve symptoms.[16][17] There is limited evidence suggesting cannabis can be used to treat chronic pain and muscle spasms.[18][19][20]

Other agents[edit]

In patients with chronic or neuropathic pain, various other substances may have analgesic properties. Tricyclic antidepressants, especially clomipramine and amitriptyline, have been shown to improve pain in what appears to be a central manner.[citation needed] Nefopam is used in Europe for pain relief with concurrent opioids. The exact mechanism of carbamazepine, gabapentin, and pregabalin is similarly unclear, but these anticonvulsants are used to treat neuropathic pain with differing degrees of success. Anticonvulsants are most commonly used for neuropathic pain as their mechanism of action tends to inhibit pain sensation.[21]

Flupirtine is a centrally acting K+ channel opener with weak NMDA antagonist properties.[22] It is used in Europe for moderate to strong pain and migraine and its muscle-relaxant properties. It has no anticholinergic properties and is believed to be devoid of any activity on dopamine, serotonin, or histamine receptors. It is not addictive, and tolerance usually does not develop.[23] However, tolerance may develop in single cases.[24]

Combinations[edit]

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

While the use of paracetamol, aspirin, ibuprofen, naproxen, and other NSAIDS concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been said to show beneficial synergistic effects by combatting pain at multiple sites of action,[25] 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.[26]

Psychotropic agents[edit]

Other psychotropic analgesic agents include ketamine (an NMDA receptor antagonist), clonidine and other α2-adrenoreceptor agonists, and mexiletine and other local anaesthetic analogues.

Atypical, adjuvant analgesics & potentiators[edit]

Drugs that have been introduced for uses other than analgesics are also used in pain management. Both first-generation (such as amitriptyline) and newer anti-depressants (such as duloxetine) are used alongside NSAIDs and opioids for pain involving nerve damage and similar problems. Other agents directly potentiate the effects of analgesics, such as using hydroxyzine, promethazine, carisoprodol, or tripelennamine to increase the pain-killing ability of a given dose of opioid analgesic.

Adjuvant analgesics, also called atypical analgesics, include nefopam, orphenadrine, pregabalin, gabapentin, cyclobenzaprine, scopolamine, and other drugs possessing anticonvulsant, anticholinergic, and/or antispasmodic properties, as well as many other drugs with CNS actions. These drugs are used along with analgesics to modulate and/or modify the action of opioids when used against pain, especially of neuropathic origin.

Dextromethorphan has been noted to slow the development of tolerance to opioids and exert additional analgesia by acting upon the NMDA receptors;[citation needed] some analgesics such as methadone and ketobemidone and perhaps piritramide have intrinsic NMDA action.[citation needed]

High-alcohol liquor, two forms of which found in the US Pharmacopoeia up until 1916 and in common use by physicians well into the 1930s, has been used in the past as an agent for dulling pain, due to the CNS depressant effects of ethyl alcohol, a notable example being the American Civil War.[citation needed] However, the ability of alcohol to relieve severe pain is likely inferior to many analgesics used today (e.g., morphine, codeine). As such, in general, the idea of alcohol for analgesia is considered a primitive practice in virtually all industrialized countries today.

The use of adjuvant analgesics is an important and growing part of the pain-control field and new discoveries are made practically every year. Many of these drugs combat the side-effects of opioid analgesics, an added bonus. For example, antihistamines including orphenadrine combat the release of histamine caused by many opioids. Stimulants such as methylphenidate, caffeine, ephedrine, dextroamphetamine, methamphetamine, and cocaine work against heavy sedation and may elevate mood in distressed patients as do the antidepressants.[citation needed] The use of medicinal cannabis remains a debated issue.

Other classification systems[edit]

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.[27]); capsaicin also is used topically. Lidocaine, an anesthetic, and steroids may be injected into painful joints for longer-term pain relief. Lidocaine is also used for painful mouth sores and to numb areas for dental work and minor medical procedures. In February 2007 the FDA notified consumers and healthcare professionals of the potential hazards of topical anesthetics entering the blood stream 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.[28]

List of drugs with comparison[edit]

Society and culture[edit]

Term[edit]

The word analgesic derives from Greek an- (ἀν-, "without"), álgos (ἄλγος, "pain"),[113] and -ikos (-ικος, forming adjectives). Such drugs were usually known as anodynes before the 20th century.[114][115]

Research[edit]

Some novel and investigational analgesics include subtype-selective voltage-gated sodium channel blockers such as funapide and raxatrigine, as well as multimodal agents such as ralfinamide.[citation needed]

See also[edit]

References[edit]

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