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The Use And Misuse Of Nonsteroidal Anti-inflammatory Drugs (nsaids)
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TNF, originally termed "cachectin" because of its ability to produce a wasting syndrome, is composed of two closely related proteins: mature TNF (TNF-a) and lymphotoxin (TNF-b), both of which are recognized by the same cell-surface receptors. There are two types of TNF receptors, a 75-kd type 1 receptor and a 55-kd type 2 receptor. IL-1 and TNF produce many of the same proinflammatory responses.
A naturally occurring IL-1 receptor antagonist (IL-1ra), competes with IL-1 for receptor binding, blocks IL-1 activity in vitro and in vivo, and in experimental animals can prevent death induced by administration of bacteria or LPS. IL-1ra often is found in high levels in patients with various infections or inflammatory conditions. Thus, the balance between IL-1 and IL-1ra may contribute to the extent of an inflammatory response. Preliminary studies suggest that the administration of IL-1ra (designated anakinra)¾by blocking IL-1 action on its receptor¾may be beneficial in rheumatoid arthritis and other inflammatory conditions(Louie et al., 2003; Olson and Stein, 2004).
Other cytokines and growth factors [e.g., IL-2, IL-6, IL-8, and granulocyte/macrophage colony stimulating factor (GM-CSF)] contribute to manifestations of the inflammatory response. The concentrations of many of these factors are increased in the synovia of patients with inflammatory arthritis. Certain relevant peptides, such as substance P, which promotes firing of pain fibers, also are elevated and act in concert with cytokines at the site of inflammation. Other cytokines and growth factors counter the effects and initiate resolution of inflammation. These include transforming growth factor-b1 (TGF-b1), which increases extracellular matrix formation and acts as an immunosuppressant, IL-10, which decreases cytokine and prostaglandin E2 formation by inhibiting monocytes, and interferon gamma, IFN-g, which possesses myelosuppressive activity and inhibits collagen synthesis and collagenase production by macrophages.
Histamine was one of the first identified mediators of the inflammatory process. Although several H1 histamine-receptor antagonists are available, they are useful only for the treatment of vascular events in the early transient phase of inflammation. Bradykinin and 5-hydroxytryptamine (serotonin, 5-HT) also may play a role in mediating inflammation, but their antagonists ameliorate only certain types of inflammatory response. Leukotriene (LT)-receptor antagonists (montelukast and zafirlukast) exert antiinflammatory actions and have been approved for the treatment of asthma. Another lipid autacoid, platelet-activating factor (PAF), has been implicated as an important mediator of inflammation; however, inhibitors of PAF synthesis and PAF-receptor antagonists have proven disappointing in the treatment of inflammation.
Intradermal, intravenous, or intra-arterial injections of small amounts of prostaglandins mimic many components of inflammation. Administration of prostaglandin E2 (PGE2) or prostacyclin (PGI2) causes erythema and an increase in local blood flow. Such effects may persist for up to 10 hours with PGE2 and include the capacity to counteract the vasoconstrictor effects of substances such as norepinephrine and angiotensin II, properties not generally shared by other inflammatory mediators. In contrast to their long-lasting effects on cutaneous vessels and superficial veins, prostaglandin-induced vasodilation in other vascular beds vanishes within a few minutes.
Although PGE1 and PGE2 (but not PGF2a) cause edema when injected into the hind paw of rats, it is not clear if they can increase vascular permeability in the postcapillary and collecting venules without the participation of other inflammatory mediators (e.g., bradykinin, histamine, and leukotriene C4 [LTC4]). Furthermore, PGE1 is not produced in significant quantities in humans in vivo, except under rare circumstances such as essential fatty acid deficiency. Unlike LTs, prostaglandins are unlikely to be involved in chemotactic responses, even though they may promote the migration of leukocytes into an inflamed area by increasing blood flow.
Rheumatoid Arthritis. Although the detailed pathogenesis of rheumatoid arthritis is largely unknown, it appears to be an autoimmune disease driven primarily by activated T cells, giving rise to T cell-derived cytokines, such as IL-1 and TNF-a. Activation of B cells and the humoral response also are evident, although most of the antibodies generated are IgGs of unknown specificity, apparently elicited by polyclonal activation of B cells rather than from a response to a specific antigen.
Many cytokines, including IL-1 and TNF-a, have been found in the rheumatoid synovium. Glucocorticoids interfere with the synthesis and actions of cytokines, such as IL-1 or TNF-a . Although some of the actions of these cytokines are accompanied by the release of prostaglandins and thromboxane A2 (TXA2), COX inhibitors appear to block only their pyrogenic effects. In addition, many of the actions of the prostaglandins are inhibitory to the immune response, including suppression of the function of helper T cells and B cells and inhibition of the production of IL-1. Thus, it has been suggested that COX-independent effects may contribute to the efficacy of NSAIDs in this setting. Besides an impact on adhesive interactions, salicylate and certain NSAIDs can directly inhibit the activation and function of neutrophils, perhaps by blockade of integrin-mediated neutrophil responses by inhibiting downstream Erk signaling.
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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---
