出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/05/27 06:11:47」(JST)
非ステロイド性抗炎症薬(ひステロイドせいこうえんしょうやく、NSAIDs:Non-Steroidal Anti-Inflammatory Drugs)とは、抗炎症作用(Anti-inflammatory)、鎮痛作用(Pain reliever)、解熱作用(Antipyretic)を有する薬剤の総称。
ステロイドではない抗炎症薬すべてを含む。疼痛、発熱、炎症の治療に用いられる。NSAIDs(非ステロイド消炎物質:エヌセイド)とも呼ばれる。非ステロイド性抗炎症薬には選択性のものと非選択性のものがある。非選択性のNSAIDsの例としては、アスピリンなどのサリチル酸、ジクロフェナク(ボルタレン®)、インドメタシン(インダシン®)、イブプロフェン、ケトプロフェン、ナプロキセン、ピロキシカムなどである。
様々なNSAIDsは医学的作用には大差がなく、異なるのは用量、服用方法である。NSAIDsの胃粘膜保護に関する試みで最も成功したのは、アセチル化とpHの調整、また、胃粘膜保護作用を持つ薬剤との併用である。胃酸分泌抑制効果のあるH2ブロッカー(例:ラフチジン(プロテカジン®)、ラニチジン(ザンタック®)や、ミソプロストール(サイトテック®)が、(アメリカでは)最も成功した薬剤である。例えば、ジクロフェナクとミソプロストールを合剤にしたオルソテックなどもあり、非常に効果的だが、高価である。日本では、バファリン®等の合剤がある。
一般医を受診する患者の25%は変形性関節症で、その半数から全ての例がNSAIDsを処方される。65歳以上の人口の80%にX線上有意な変形性関節症が存在するとされており、そのうち60%が疼痛などの症状を訴える。2001年には、アメリカでは7000万錠のNSAIDsが処方され、300億錠が薬局で販売された。
最も一般的な非ステロイド性抗炎症薬の多くは、すべてのシクロオキシゲナーゼ(COX-1、COX-2)活性を可逆的に競合阻害する。アラキドン酸が結合するシクロオキシゲナーゼの疎水性チャネルを封鎖することでアラキドン酸が酵素活性部位に結合することを防いでいる。例外は、アスピリンで、これはシクロオキシゲナーゼ(COX-1,2両方とも)をアセチル化することで阻害する。これは不可逆的な反応であり、核を持たず蛋白合成ができない血小板にとっては不可逆的な作用をもつ。この特性からアスピリンは冠動脈疾患や脳梗塞の既往のある者に対して投与される抗血小板薬として用いられる。アスピリンの抗血小板作用は退薬後、血小板の寿命である約10日間持続する。シクロオキシゲナーゼ1(COX-1)は恒常的に発現しており、胃壁の防御作用に関与している。胃壁が自ら分泌する、胃液に含まれる胃酸(塩酸)により溶かされないよう防ぐのに必要である。COX-1が阻害されると、胃潰瘍や消化管出血の原因となる。一方COX-2は炎症時に誘導されるプロスタグランジン合成酵素であり、NSAIDsの抗炎症作用はCOX-2阻害に基づくと近年考えられ、COX-2を選択的に阻害する新しいNSAIDsが創製されている。特に酸性NSAIDsは強いシクロオキシゲナーゼ活性阻害を有しており、COXによりアラキドン酸からプロスタグランジンが合成されるのを阻害する(最近では、COX-1、COX-2共に抑制された場合のみ消化管障害が発現し、いずれかが阻害されずに残っている場合には消化管障害は起きにくいことがCOX-1あるいはCOX-2、もしくはCOX-1とCOX-2を遺伝的に欠損させたマウスの実験から明らかとなっている)。
プロスタグランジンには、炎症、発熱作用があるため結果的にNSAIDsは抗炎症作用、鎮痛作用、解熱作用を持つ。パラセタモール(アセトアミノフェン)もシクロオキシゲナーゼ活性阻害作用を持つため、NSAIDsに分類されることがあるが、明らかな抗炎症作用は持たず、真の意味でのNSAIDsではない。近年まではっきり解明されていなかったがこの抗炎症作用の欠落は、アセトアミノフェンのシクロオキシゲナーゼ阻害作用が中枢神経系に主に作用するからと考えられている。この中枢神経に存在するシクロオキシゲナーゼは、COX-3と呼ばれる。
1829年初頭に、鎮痛効果があるとして民間療法で用いられていたヤナギの樹皮から初めてサリチル酸が分離された。非ステロイド性抗炎症薬は、意識抑制、呼吸抑制、依存などの容認できない副作用があるにもかかわらず、少量で鎮痛効果、大量投与で抗炎症効果がある薬物として重要なものとなった。以前は処方箋が必要であったが、現在では、イブプロフェンなどは薬局で販売される様になっている。古くはリウマチなどの重篤な疾患にのみ処方されていたが、スポーツや事故による怪我の鎮痛、腰痛や手術後の鎮痛にも処方される様になって久しい。癌や、冠動脈疾患など他の適応についての研究も続けられている。
分娩直前(妊娠末期)では、胎児の動脈管の閉鎖を引き起こすため、絶対に服用してはならない。又、手や指で部位を塗布した場合、犬や猫などの所謂、愛玩動物が何らかの経緯で中毒を起こし健康を害したり死亡させる事例が確認されている。
大量に消費されているため、副作用も多く出現する。最も多いのは胃腸炎で、軽い胃部不快感から、治療に長期間を要する、重篤な出血を伴う潰瘍までが起こりうる。
NSAIDsの注意点としては、消化管潰瘍の副作用、喘息患者に合併するアスピリン喘息、また各種アレルギー反応、腎障害というものがあげられる。ニューキノロン薬との併用、妊婦への投与は製剤を選べば副作用回避が可能ともいわれているが、用いない方が無難とされている。
他の副作用としては骨折の治癒を阻害する、心血管系では血小板機能を阻害し出血を止まりにくくする。また、腎機能障害や、腎のプロスタグランジンを阻害し、血圧調整機能を障害する。以上の理由で、慢性心疾患、腎機能障害、血圧異常の患者にNSAIDsは慎重に使用する必要がある。NSAIDsは、身体の障害によって産生されるプロスタグランジンの合成を阻害することにより効果を発揮するが、プロスタグランジンは、炎症と疼痛をもたらすだけではなく、胃内膜などの再生に関わるなど、必要な役割もある。
NSAIDsの胃腸障害作用は用量依存性であり、多くの場合致命的となる胃穿孔や、上部消化管出血を起こす。概ねNSAIDsを処方された患者の10~20%に消化器症状が現れ、アメリカでは年間に10万人以上が入院し、1万6500人が死亡している。また、薬剤が原因の救急患者の43%をNSAIDsが占めている。このような事態の多くは本当は避けられたとする研究結果もある。ある研究によると、NSAIDsを処方された患者の42%は、実際は不必要な処方であった[2]。
NSAIDsによるプロスタグランジン産生抑制
→腎血管収縮による腎血流量減少+ヘンレループでのナトリウム再吸収増加+抗利尿ホルモン作用亢進 →尿量減少
となり、腎血流量低下と尿量減少から腎機能低下例では腎不全に至ることがある。
連用した場合は薬物乱用頭痛を引き起こす。英国国立医療技術評価機構は、アセトアミノフェン・アスピリン・NSAIDsを単独または併用の服用が月に15日以上ある状態が3ヶ月以上続く場合、薬物乱用性頭痛の可能性が疑われるとしている[3]
NSAIDsは様々な種類が知られている。NSAIDsの選択において重要なのは、その使い分けが治療に本質的な差を生むことはなく、副作用のコントロールのためと考えて行うことである。患者のQOLを考慮した技術にすぎない。
前述のようにCOX-1/2をともに阻害すると消化管の障害が出現するため、COX-2選択性の高い薬剤が開発された。しかし、血小板凝集抑制作用のあるプロスタサイクリンがCOX-2阻害により減り、相対的にトロンボキサンA2の働きが強まり、血栓傾向が高まり心血管事故が増えることがわかり、全米で3万件近い訴訟が起こるなど一大問題となった。メルクが開発した、rofecoxib(商品名:バイオックス®)は自主回収になった。
2002年にシモンズらがアセトアミノフェン(パラセタモール、タイレノール®)に関連する新たなアイソザイムを発見したと発表した。COX-3は、主に中枢神経系に存在するCOX-1の変種(スプライシングバリアント)で、アセトアミノフェンなどの鎮痛消炎剤によって阻害されるとされ、チャンドラセクハランらにより構造が決定、発表された。
ただしその後、COX-3の存在を疑問視する研究結果も発表されている[要出典]。
この項目は、薬学に関連した書きかけの項目です。この項目を加筆・訂正などしてくださる協力者を求めています(プロジェクト:薬学/Portal:医学と医療)。 |
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Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs /ˈɛnsɛd/ EN-sed), also called nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal anti-inflammatory medicines (NSAIMs), are a class of drugs that provides analgesic (pain-killing) and antipyretic (fever-reducing) effects, and, in higher doses, anti-inflammatory effects.
The term nonsteroidal distinguishes these drugs from steroids, which, among a broad range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. As analgesics, NSAIDs are unusual in that they are non-narcotic and thus are used as a non-addictive alternative to narcotics.
The most prominent members of this group of drugs, aspirin, ibuprofen and naproxen, are all available over the counter in most countries.[1] Paracetamol (acetaminophen) is generally not considered an NSAID because it has only little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body.[2]
NSAIDs inhibit the activity of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby, the synthesis of prostaglandins and thromboxanes. It is thought that inhibiting COX-2 leads to the anti-inflammatory, analgesic and antipyretic effects and that those NSAIDs also inhibiting COX-1, particularly aspirin, may cause gastrointestinal bleeding and ulcers.[3]
NSAIDs are usually used for the treatment of acute or chronic conditions where pain and inflammation are present. Research continues into their potential for prevention of colorectal cancer.
NSAIDs are generally used for the symptomatic relief of the following conditions:[4][5]
Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation. This is useful in the management of arterial thrombosis and prevention of adverse cardiovascular events. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A2.
NSAIDs may be used with caution by people with the following conditions:[5]
NSAIDs should usually be avoided by people with the following conditions:[5]
The widespread use of NSAIDs has meant that the adverse effects of these drugs have become increasingly prevalent. Use of NSAIDs increases risk of having a range of gastrointestinal (GI) problems.[10] When NSAIDs are used for pain management after surgery they cause increased risk of kidney problems.[11]
An estimated 10-20% of NSAID patients experience dyspepsia. In the 1990s high doses of prescription NSAIDs were associated with serious upper gastrointestinal adverse events, including bleeding.[12] Over the past decade, deaths associated with gastric bleeding have declined.
NSAIDs, like all drugs, may interact with other medications. For example, concurrent use of NSAIDs and quinolones may increase the risk of quinolones' adverse central nervous system effects, including seizure.[13][14]
If a COX-2 inhibitor is taken, a traditional NSAID (prescription or over-the-counter) should not be taken at the same time.[15][not in citation given] In addition, people on daily aspirin therapy (e.g., for reducing cardiovascular risk) must be careful if they also use other NSAIDs, as these may inhibit the cardioprotective effects of aspirin.
Rofecoxib (Vioxx) was shown to produce significantly fewer gastrointestinal ADRs compared with naproxen.[16] This study, the VIGOR trial, raised the issue of the cardiovascular safety of the coxibs. A statistically insignificant increase in the incidence of myocardial infarctions was observed in patients on rofecoxib. Further data, from the APPROVe trial, showed a statistically significant relative risk of cardiovascular events of 1.97 versus placebo[17]—which caused a worldwide withdrawal of rofecoxib in October 2004.
Use of methotrexate together with NSAIDS in rheumatoid arthritis is safe, if adequate monitoring is done.[18]
NSAIDs aside from aspirin, both newer selective COX-2 inhibitors and traditional anti-inflammatories, increase the risk of myocardial infarction and stroke.[19][20] They are not recommended in those who have had a previous heart attack as they increase the risk of death and / or recurrent MI.[21] Evidence indicates that naproxen may be the least harmful out of these.[20][22]
NSAIDs aside from (low-dose) aspirin are associated with a doubled risk of heart failure in people without a history of cardiac disease.[22] In people with such a history, use of NSAIDs (aside from low-dose aspirin) was associated with a more than 10-fold increase in heart failure.[23] If this link is proven causal, researchers estimate that NSAIDs would be responsible for up to 20 percent of hospital admissions for congestive heart failure. In people with heart failure, NSAIDs increase mortality risk (hazard ratio) by approximately 1.2-1.3 for naproxen and ibuprofen, 1.7 for rofecoxib and celecoxib, and 2.1 for diclofenac.[24]
A 2005 Finnish study linked long term (over 3 months) use of NSAIDs with an increased risk of erectile dysfunction.[25] This study was correlational only, and depended solely on self-reports (questionnaires).
A 2011 publication[26] in the Journal of Urology received widespread publicity.[27] According to this study, men who used NSAIDs regularly were at significantly increased risk of erectile dysfunction. A link between NSAID use and erectile dysfunction still existed after controlling for several conditions. However, the study was observational and not controlled, with low original participation rate, potential participation bias, and other uncontrolled factors. The authors warned against drawing any conclusion regarding cause.[28]
The main adverse drug reactions (ADRs) associated with NSAID use relate to direct and indirect irritation of the gastrointestinal (GI) tract. NSAIDs cause a dual assault on the GI tract: the acidic molecules directly irritate the gastric mucosa, and inhibition of COX-1 and COX-2 reduces the levels of protective prostaglandins. Inhibition of prostaglandin synthesis in the GI tract causes increased gastric acid secretion, diminished bicarbonate secretion, diminished mucus secretion and diminished trophic[clarification needed] effects on epithelial mucosa.
Common gastrointestinal ADRs include:[4]
Clinical NSAID ulcers are related to the systemic effects of NSAID administration. Such damage occurs irrespective of the route of administration of the NSAID (e.g., oral, rectal, or parenteral) and can occur even in patients with achlorhydria.[30]
Ulceration risk increases with therapy duration, and with higher doses. To minimise GI ADRs, it is prudent to use the lowest effective dose for the shortest period of time—a practice that studies show is often not followed. Recent studies show that over 50% of patients who take NSAIDs have sustained some mucosal damage to their small intestine.[31]
There are also some differences in the propensity of individual agents to cause gastrointestinal ADRs. Indomethacin, ketoprofen and piroxicam appear to have the highest prevalence of gastric ADRs, while ibuprofen (lower doses) and diclofenac appear to have lower rates.[4]
Certain NSAIDs, such as aspirin, have been marketed in enteric-coated formulations that manufacturers claim reduce the incidence of gastrointestinal ADRs. Similarly, some believe that rectal formulations may reduce gastrointestinal ADRs. However, considering the mechanism of such ADRs, and in clinical practice, these formulations have not demonstrated a reduced risk of GI ulceration.[4]
Commonly, gastric (but not necessarily intestinal) adverse effects can be reduced through suppressing acid production, by concomitant use of a proton pump inhibitor, e.g., omeprazole, esomeprazole; or the prostaglandin analogue misoprostol. Misoprostol is itself associated with a high incidence of gastrointestinal ADRs (diarrhea). While these techniques may be effective, they are expensive for maintenance therapy.
NSAIDs should be used with caution in individuals with inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) due to their tendency to cause gastric bleeding and form ulceration in the gastric lining. Pain relievers such as paracetamol (also known as acetaminophen) or drugs containing codeine (which slows down bowel activity) are safer medications for pain relief in IBD.[citation needed]
NSAIDs are also associated with a relatively high incidence of renal adverse drug reactions (ADRs). The mechanism of these renal ADRs is due to changes in renal haemodynamics (kidney blood flow), ordinarily mediated by prostaglandins, which are affected by NSAIDs. Prostaglandins normally cause vasodilation of the afferent arterioles of the glomeruli. This helps maintain normal glomerular perfusion and glomerular filtration rate (GFR), an indicator of renal function. This is particularly important in renal failure where the kidney is trying to maintain renal perfusion pressure by elevated angiotensin II levels. At these elevated levels, angiotensin II also constricts the afferent arteriole into the glomerulus in addition to the efferent arteriole it normally constricts. Prostaglandins serve to dilate the afferent arteriole; by blocking this prostaglandin-mediated effect, particularly in renal failure, NSAIDs cause unopposed constriction of the afferent arteriole and decreased RPF (renal perfusion pressure).
Common ADRs associated with altered renal function include:[4]
These agents may also cause renal impairment, especially in combination with other nephrotoxic agents. Renal failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor (which removes angiotensin II's vasoconstriction of the efferent arteriole) and a diuretic (which drops plasma volume, and thereby RPF)—the so-called "triple whammy" effect.[32]
In rarer instances NSAIDs may also cause more severe renal conditions:[4]
NSAIDs in combination with excessive use of phenacetin and/or paracetamol (acetaminophen) may lead to analgesic nephropathy.[33]
Photosensitivity is a commonly overlooked adverse effect of many of the NSAIDs.[34] The 2-arylpropionic acids are the most likely to produce photosensitivity reactions, but other NSAIDs have also been implicated including piroxicam, diclofenac and benzydamine.
Benoxaprofen, since withdrawn due to its hepatotoxicity, was the most photoactive NSAID observed. The mechanism of photosensitivity, responsible for the high photoactivity of the 2-arylpropionic acids, is the ready decarboxylation of the carboxylic acid moiety. The specific absorbance characteristics of the different chromophoric 2-aryl substituents, affects the decarboxylation mechanism. While ibuprofen has weak absorption, it has been reported as a weak photosensitising agent.[citation needed]
NSAIDs are not recommended during pregnancy, particularly during the third trimester. While NSAIDs as a class are not direct teratogens, they may cause premature closure of the fetal ductus arteriosus and renal ADRs in the fetus. Additionally, they are linked with premature birth[35] and miscarriage.[36][37] Aspirin, however, is used together with heparin in pregnant women with antiphospholipid antibodies.[38] Additionally, Indomethacin is used in pregnancy to treat polyhydramnios by reducing fetal urine production via inhibiting fetal renal blood flow.
In contrast, paracetamol (acetaminophen) is regarded as being safe and well-tolerated during pregnancy, but Leffers et al. released a study in 2010 indicating that there may be associated male infertility in the unborn.[39][40] Doses should be taken as prescribed, due to risk of hepatotoxicity with overdoses.[41]
In France, the country's health agency contraindicates the use of NSAIDs, including aspirin, after the sixth month of pregnancy.[42]
Common adverse drug reactions (ADR), other than listed above, include: raised liver enzymes, headache, dizziness.[4] Uncommon ADRs include: hyperkalaemia, confusion, bronchospasm, rash.[4] Rapid and severe swelling of the face and/or body. Ibuprofen may also rarely cause irritable bowel syndrome symptoms. NSAIDs are also implicated in some cases of Stevens–Johnson syndrome.
Most NSAIDs penetrate poorly into the central nervous system (CNS). However, the COX enzymes are expressed constitutively in some areas of the CNS, meaning that even limited penetration may cause adverse effects such as somnolence and dizziness.
In very rare cases, ibuprofen can cause aseptic meningitis.[43]
As with other drugs, allergies to NSAIDs might exist. While many allergies are specific to one NSAID, up to 1 in 5 people may have unpredictable cross-reactive allergic responses to other NSAIDs as well.[44]
NSAIDs reduce renal blood flow and thereby decrease the efficacy of diuretics, and inhibit the elimination of lithium and methotrexate.[45]
NSAIDs cause hypocoagulability, which may be serious when combined with other drugs that also decrease blood clotting, such as warfarin.[45]
NSAIDs may aggravate hypertension (high blood pressure) and thereby antagonize the effect of antihypertensives,[45] such as ACE Inhibitors.[46]
NSAIDs may interfere and reduce efficiency of SSRI antidepressants[47][48]
Various widely used nonsteroidal anti-inflammatory drugs (NSAIDs) enhance endocannabinoid signaling by blocking the anandamide-degrading membrane enzyme fatty acid amide hydrolase (FAAH).[49]
Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes. This inhibition is competitively reversible (albeit at varying degrees of reversibility), as opposed to the mechanism of aspirin, which is irreversible inhibition.[50] COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of inflammation. This mechanism of action was elucidated by John Vane (1927–2004), who received a Nobel Prize for his work (see Mechanism of action of aspirin).
COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes. One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid. COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.
When nonselective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, ulcers of the stomach or duodenum internal bleeding can result.
NSAIDs have been studied in various assays to understand how they affect each of these enzymes. While the assays reveal differences, unfortunately different assays provide differing ratios.[51]
The discovery of COX-2 led to research to development of selective COX-2 inhibiting drugs that do not cause gastric problems characteristic of older NSAIDs.
Paracetamol (acetaminophen) is not considered an NSAID because it has little anti-inflammatory activity. It treats pain mainly by blocking COX-2 mostly in the central nervous system, but not much in the rest of the body.[2]
However, many aspects of the mechanism of action of NSAIDs remain unexplained, and for this reason further COX pathways are hypothesized. The COX-3 pathway was believed to fill some of this gap but recent findings make it appear unlikely that it plays any significant role in humans and alternative explanation models are proposed.[2]
NSAIDs are also used in the acute pain caused by gout because they inhibit urate crystal phagocytosis besides inhibition of prostaglandin synthase.[52]
NSAIDS have antipyretic activity and can be used to treat fever.[53][54] Fever is caused by elevated levels of prostaglandin E2, which alters the firing rate of neurons within the hypothalamus that control thermoregulation.[53][55] Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis (PGE2) within the hypothalamus.[53][54] PGE2 signals to the hypothalamus to increase the body's thermal set point.[54][56] Ibuprofen has been shown more effective as an antipyretic than paracetamol (acetaminophen).[55][57] Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D & E.
NSAIDs can be classified based on their chemical structure or mechanism of action. Older NSAIDs were known long before their mechanism of action was elucidated and were for this reason classified by chemical structure or origin. Newer substances are more often classified by mechanism of action.
Most NSAIDs are chiral molecules (diclofenac is a notable exception). However, the majority are prepared in a racemic mixture. Typically, only a single enantiomer is pharmacologically active. For some drugs (typically profens), an isomerase enzyme in vivo converts the inactive enantiomer into the active form, although its activity varies widely in individuals. This phenomenon is likely responsible for the poor correlation between NSAID efficacy and plasma concentration observed in older studies, when specific analysis of the active enantiomer was not performed.
Ibuprofen and ketoprofen are now available in single, active enantiomer preparations (dexibuprofen and dexketoprofen), which purport to offer quicker onset and an improved side-effect profile. Naproxen has always been marketed as the single active enantiomer.
NSAIDs within a group tend to have similar characteristics and tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses.[64] Rather, differences among compounds usually relate to dosing regimens (related to the compound's elimination half-life), route of administration, and tolerability profile.
Regarding adverse effects, selective COX-2 inhibitors have lower risk of gastrointestinal bleeding, but a substantially more increased risk of myocardial infarction than the increased risk from nonselective inhibitors.[64] Some data also supports that the partially selective nabumetone is less likely to cause gastrointestinal events.[64] The nonselective naproxen appears risk-neutral with regard to cardiovascular events.[64]
A consumer report noted that ibuprofen, naproxen, and salsalate are less expensive than other NSAIDs, and essentially as effective and safe when used appropriately to treat osteoarthritis and pain.[65]
Most nonsteroidal anti-inflammatory drugs are weak acids, with a pKa of 3-5. They are absorbed well from the stomach and intestinal mucosa. They are highly protein-bound in plasma (typically >95%), usually to albumin, so that their volume of distribution typically approximates to plasma volume. Most NSAIDs are metabolised in the liver by oxidation and conjugation to inactive metabolites that typically are excreted in the urine, though some drugs are partially excreted in bile. Metabolism may be abnormal in certain disease states, and accumulation may occur even with normal dosage.
Ibuprofen and diclofenac have short half-lives (2–3 hours). Some NSAIDs (typically oxicams) have very long half-lives (e.g. 20–60 hours).
From the era of Greek medicine to the mid-19th century, the discovery of medicinal agents was classed as an empirical art; folklore and mythological guidance were combined in deploying the vegetable and mineral products that made up the expansive pharmacopoeia of the time. Myrtle leaves were in use by 1500 BCE. Hippocrates (460 – 377 BCE) first reported using willow bark[66] and in 30 BCE Celsus described the signs of inflammation and also used willow bark to mitigate them. On April 25, 1763, Edward Stone wrote to the Royal Society describing his observations on the use of willow bark-based medicines in febrile patients.[67] The active ingredient of willow bark, a glycoside called salicin, was first isolated by Johann Andreas Buchner in 1827. By 1829, French chemist Henri Leroux had improved the extraction process to obtain about 30g of purified salicin from 1.5 kg of bark.[67]
By hydrolysis, salicin releases glucose and salicylic alcohol which can be converted into salicylic acid, both in vivo and through chemical methods.[66] The acid is more effective than salicin and, in addition to its fever-reducing properties, is anti-inflammatory and analgesic. In 1869, Hermann Kolbe synthesised salicylate, although it was too acidic for the gastric mucosa.[66] The reaction used to synthesise aromatic acid from a phenol in the presence of CO2 is known as the Kolbe-Schmitt reaction.[68][69][70]
By 1897 the German chemist Felix Hoffmann and the Bayer company prompted a new age of pharmacology by converting salicylic acid into acetylsalicylic acid—named aspirin by Heinrich Dreser. Other NSAIDs were developed from the 1950s forward.[67]
In 2001, NSAIDs accounted for 70,000,000 prescriptions and 30 billion over-the-counter doses sold annually in the United States.[12]
Research supports the use of NSAIDs for the control of pain associated with veterinary procedures such as dehorning and castration of calves. The best effect is obtained by combining a short-term local anesthetic such as lidocaine with an NSAID acting as a longer term analgesic. However, as different species have varying reactions to different medications in the NSAID family, little of the existing research data can be extrapolated to animal species other than those specifically studied, and the relevant government agency in one area sometimes prohibits uses approved in other jurisdictions.
For example, ketoprofen's effects have been studied in horses more than in ruminants but, due to controversy over its use in racehorses, veterinarians who treat livestock in the United States more commonly prescribe flunixin meglumine, which, while labeled for use in such animals, is not indicated for post-operative pain.
In the United States, meloxicam is approved for use only in canines, whereas (due to concerns about liver damage) it carries warnings against its use in cats[71][72] except for one-time use during surgery.[73] In spite of these warnings, meloxicam is frequently prescribed "off-label" for non-canine animals including cats and livestock species.[74] In other countries, for example The European Union (EU), there is a label claim for use in cats.[citation needed]
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ignored (help)Summaries of key questions from the Drug Effectiveness Review Project (DERP), Oregon Health & Science University
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国試過去問 | 「112F082」「106B054」「108B061」「106C031」「106C030」「109G063」「110E042」「109D038」「108I071」「110F027」「113C052」「113D075」「113A043」「108D037」「112A047」「111A038」「106G050」「106D032」「107A033」「108B046」 |
リンク元 | 「100Cases 27」「ライ症候群」「スティーブンス・ジョンソン症候群」「アスピリン」「WHO方式癌疼痛治療」 |
ABC
※国試ナビ4※ [112F081]←[国試_112]→[112F083]
D
※国試ナビ4※ [106B053]←[国試_106]→[106B055]
AD
※国試ナビ4※ [108B060]←[国試_108]→[108B062]
次の文を読み、 30、 31の問いに答えよ。
C
※国試ナビ4※ [106C030]←[国試_106]→[106D001]
D
※国試ナビ4※ [106C029]←[国試_106]→[106C031]
CE
※国試ナビ4※ [109G062]←[国試_109]→[109G064]
A
※国試ナビ4※ [110E041]←[国試_110]→[110E043]
C
※国試ナビ4※ [109D037]←[国試_109]→[109D039]
C
※国試ナビ4※ [108I070]←[国試_108]→[108I072]
E
※国試ナビ4※ [110F026]←[国試_110]→[110F028]
C
※国試ナビ4※ [113C051]←[国試_113]→[113C053]
ABE
※国試ナビ4※ [113D074]←[国試_113]→[113E001]
A
※国試ナビ4※ [113A042]←[国試_113]→[113A044]
C
※国試ナビ4※ [108D036]←[国試_108]→[108D038]
B
※国試ナビ4※ [112A046]←[国試_112]→[112A048]
C
※国試ナビ4※ [111A037]←[国試_111]→[111A039]
E
※国試ナビ4※ [106G049]←[国試_106]→[106G051]
E
※国試ナビ4※ [106D031]←[国試_106]→[106D033]
D
※国試ナビ4※ [107A032]←[国試_107]→[107A034]
D
※国試ナビ4※ [108B045]←[国試_108]→[108B047]
薬剤群 | 代表薬 | 代替薬 |
非オピオイド鎮痛薬 | アスピリン | コリン・マグネシウム・トリサルチレート) |
アセトアミノフェン | ジフルニサルa) | |
イブプロフェン | ナプロキセン | |
インドメタシン | ジクロフェナク | |
フルルビプロフェン※1 | ||
弱オピオイド (軽度から中等度の強さの痛みに用いる) |
コデイン | デキストロプロポキシフェンa) |
ジヒドロコデイン | ||
アヘン末 | ||
トラマドールb) | ||
強オピオイド (中等度から高度の強さの痛みに用いる) |
モルヒネ | メサドンa) |
ヒドロモルフォンa) | ||
オキシコドン | ||
レボルファノールa) | ||
ペチジンc) | ||
ブプレノルフィンa) | ||
フェンタニル※2 |
.