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The Use And Misuse Of Nonsteroidal Anti-inflammatory Drugs (nsaids)
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Aspirin covalently modifies COX-1 and COX-2, irreversibly inhibiting
cyclooxygenase activity. This is an important distinction from all the
NSAIDs because the duration of aspirin's effects is related to the
turnover rate of cyclooxygenases in different target tissues. The
duration of effect of nonaspirin NSAIDs, which competitively inhibit the
active sites of the COX enzymes, relates more directly to the time
course of drug disposition. The importance of enzyme turnover in relief
from aspirin action is most notable in platelets, which, being
anucleate, have a markedly limited capacity for protein synthesis. Thus,
the consequences of inhibition of platelet COX-1 (COX-2 is expressed
only in megakaryocytes) last for the lifetime of the platelet.
Inhibition of platelet COX-1-dependent TXA2 formation therefore is
cumulative with repeated doses of aspirin (at least as low as 30 mg/day)
and takes roughly 8 to 12 days three quarter of the platelet turnover
time three quarter to recover once therapy has been stopped.
COXs are configured such that the active site is accessed by the AA substrate via a hydrophobic channel. Aspirin acetylates serine 530 of COX-1, located high up in the hydrophobic channel. Interposition of the bulky acetyl residue prevents the binding of AA to the active site of the enzyme and thus impedes the ability of the enzyme to make prostaglandins. Aspirin acetylates a homologous serine at position 516 in COX-2. Although covalent modification of COX-2 by aspirin also blocks the cyclooxygenase activity of this isoform, an interesting property not shared by COX-1 is that acetylated COX-2 synthesizes 15(R)-hydroxyeicosatetraenoic acid [15(R)-HETE]. This may be metabolized, at least in vitro, by 5-lipoxygenase to yield 15-epilipoxin A4, which has potent antiinflammatory properties (Serhan and Oliw, 2001). Due to these features, repeated doses of aspirin that acutely do not completely inhibit platelet COX-1-derived TXA2 can exert a cumulative effect with complete blockade. This has been shown in randomized trials for doses as low as 30 mg per day. However, most of the clinical trials demonstrating cardioprotection from low-dose aspirin have used doses in the range of 75 to 81 mg/day.
The unique sensitivity of platelets to inhibition by such low doses of aspirin is related to their presystemic inhibition in the portal circulation before aspirin is deacetylated to salicylate on first pass through the liver (Pederson and FitzGerald, 1984). In contrast to aspirin, salicylic acid has no acetylating capacity. It is a weak, reversible competitive inhibitor of cyclooxygenase.
The vast majority of NSAIDs listed are organic acids, and in contrast to aspirin, act as reversible, competitive inhibitors of cyclooxygenase activity. Even the nonacidic parent drug nabumetone is converted to an active acetic acid derivative in vivo. As organic acids, the compounds generally are well absorbed orally, highly bound to plasma proteins, and excreted either by glomerular filtration or by tubular secretion. They also accumulate in sites of inflammation, potentially confounding the relationship between plasma concentrations and duration of drug effect. The NSAIDs include those with shorter (less than 6 hours) or longer (greater than 10 hours) half-lives.
Most NSAIDs inhibit both COX-1 and COX-2 with little selectivity, although some, conventionally thought of as NSAIDs diclofenac, meloxicam, and nimesulide¾exhibit selectivity for COX-2 that is close to that of celecoxib in vitro. Indeed, meloxicam achieved approval in some countries as a selective inhibitor of COX-2. The hypothesis that the antiinflammatory effects of NSAIDs would be accompanied by a lower ulcerogenic potential propelled efforts to design drugs with greater selectivity for COX-2 versus COX-1 (FitzGerald and Patrono, 2001). These efforts led to the approval and marketing of rofecoxib, celecoxib, and valdecoxib as selective COX-2 inhibitors, known as the coxibs, and the development of others (e.g., etoricoxib and lumiracoxib). Based on whole blood assays, several previously marketed NSAIDs also have selectivity ratios comparable to those of the least-selective of the novel COX-2 inhibitors, celecoxib. These include meloxicam, nimesulide, and diclofenac (Warner et al., 1999; FitzGerald and Patrono, 2001).
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ABSRACT - [ Total Page(s): 1 ]ABSTRACT COMING SOON ... Continue reading---
CHAPTER TWO - [ Total Page(s): 3 ]EXCLUSION CRITERIAAll pharmacists not practicing as community pharmacistsAll patent medicine vendors and outlets2.4 SAMPLE SIZE DETERMINATIONa. Retrospective review of prescriptions: All prescriptions from November 2013 and April 2014 were obtained from the Outpatient Pharmacy Department prescription bank. The prescriptions containing NSAIDs were separated from those without NSAIDs.b. Ilorin metropolis is made up of three local government areas: Ilorin West, Ilori ... Continue reading---
CHAPTER THREE - [ Total Page(s): 8 ]CHAPTER THREE RESULTS3.1 RESULTS OF ANALYSIS OF PRESCRIPTIONS/TREATMENT SHEETSOut of 1497 prescription sheets 1297 prescriptions contained NSAIDs with total of 1392 NSAIDs. The prescribing rate was hence found to be 86.6%. 7.3% of prescriptions contained more than one NSAIDs. ... Continue reading---
CHAPTER FOUR - [ Total Page(s): 2 ]CHAPTER FOURDISCUSSIONStudy of the Prescribing pattern of Nonsteroidal Antiinflammatory Drugs indicated more number of females assess health care for pain and related conditions than their male counterpart (Table 3.1), although there is widespread assumption that women will consult more readily for all symptoms or conditions and that men will be more reluctant or will delay consulting may result in health care providers assuming that women have a lower level of symptom severity before deciding ... Continue reading---
CHAPTER FIVE - [ Total Page(s): 1 ]CHAPTER FIVE CONCLUSIONThe prescribing rate of NSAIDs was high. The prevalence of NSAIDs misuse by residents was high Ibuprofen was the most highly misused among the residents. Dispensing pattern of NSAIDs by Pharmacists appeared to agree with the choice of medication use among residents. Educational status, occupation, prior knowledge of medication use and dispensing pattern of Pharmacists are factors that can influence public choice of NSAIDs use. ... Continue reading---
REFRENCES - [ Total Page(s): 5 ]Slater DM, Zervou S, Thornton S. (2002). Prostaglandins and prostanoid receptors in human pregnancy and parturition. J. Soc. Gynecol. Investig. 9:118-124.Soleymani F, Ahmadizar A and Abdollahi MA(2013). Survey on the factors influencing the pattern of medicine's use: Concerns on irrational use of drugs. J Res Pharm Pract. 2(2), 59–63.Solomon SD, McMurray JJ, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E, Bertagnolli M (2005). Cardiovascular risk associated with c ... Continue reading---
