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The Use And Misuse Of Nonsteroidal Anti-inflammatory Drugs (nsaids)
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4. SYSTEMIC MYCOSIS.
Systemic mastocytosis is a condition in which there are excessive mast cells in the bone marrow, reticuloendothelial system, gastrointestinal system, bones, and skin. In patients with systemic mastocytosis, prostaglandin D2, released from mast cells in large amounts, has been found to be the major mediator of severe episodes of vasodilation and hypotension; this PGD2 effect is resistant to antihistamines. The addition of aspirin or ketoprofen has provided relief (Worobec, 2000). However, aspirin and NSAIDs can cause degranulation of mast cells, so blockade with H1 and H2 histamine receptor antagonists should be established before NSAIDs are initiated.
5. BARTER’S SYNDROME. Bartter's syndrome includes a series of rare disorders (1-0.1/100,000) characterized by hypokalemic, hypochloremic metabolic alkalosis with normal blood pressure and hyperplasia of the juxtaglomerular apparatus. Fatigue, muscle weakness, diarrhea, and dehydration are the main symptoms. Distinct variants are caused by mutations in a Na+:K+:2Cl- cotransporter, an apical ATP-regulated K+ channel, a basolateral Cl- channel, a protein (barttin) involved in cotransporter trafficking, and the extracellular calcium-sensing receptor. Renal COX-2 is induced and biosynthesis of PGE2 is increased. Treatment with indomethacin, combined with potassium repletion and spironolactone, is associated with improvement in the biochemical derangements and symptoms. Selective COX-2 inhibitors also have been used (Guay-Woodford, 1998).
6. Cancer Chemoprevention. Chemoprevention of cancer is an area where the potential use of aspirin and/or NSAIDs is under active investigation. Epidemiological studies suggested that frequent use of aspirin is associated with as much as a 50% decrease in the risk of colon cancer (Kune et al., 1998) and similar observations have been made with other cancers (Jacobs et al., 2004). NSAIDs have been used in patients with familial adenomatous polyposis (FAP), an inherited disorder characterized by multiple adenomatous colon polyps developing during adolescence and the inevitable occurrence of colon cancer by the sixth decade.
7. NIACIN TOLERABILITY
Large doses of niacin (nicotinic acid) effectively lower serum cholesterol levels, reduce LDL, and raise HDL. However, niacin is tolerated poorly because it induces intense flushing. This flushing is mediated by a release of prostaglandin D2 from the skin, which can be inhibited by treatment with aspirin (Jungnickel et al., 1997) and would be susceptible to inhibition of PGD synthesis or antagonism of its DP receptors.
ADVERSE EFFECTS OF NSAIDS THERAPY
Age generally is correlated with an increased probability of developing serious adverse reactions to NSAIDs, and caution is warranted in choosing a lower starting dose for elderly patients.
Gastrointestinal. The most common symptoms associated with these drugs are gastrointestinal, including anorexia, nausea, dyspepsia, abdominal pain, and diarrhea. These symptoms may be related to the induction of gastric or intestinal ulcers, which is estimated to occur in 15% to 30% of regular users. Ulceration may range from small superficial erosions to full-thickness perforation of the muscularis mucosa. There may be single or multiple ulcers, and ulceration can be accompanied by gradual blood loss leading to anemia or by life-threatening hemorrhage. The risk is further increased in those with Helicobacter pylori infection, heavy alcohol consumption, or other risk factors for mucosal injury, including the concurrent use of glucocorticoids. Although there is a perception that NSAIDs vary considerably in their tendency to cause such erosions and ulcers, this is based on overview analyses of small and heterogeneous studies, often at single doses of individual NSAIDs. Large-scale comparative studies of NSAIDs have not been performed, and there is no reliable information on which to assess the comparative likelihood of GI ulceration on antiinflammatory doses of aspirin versus NSAIDs. Thus, most information is derived from the use of surrogate markers or from epidemiological datasets and suggests that the relative risk for serious adverse gastrointestinal events is elevated about threefold in NSAID users compared to nonusers. Epidemiological studies suggest that combining low-dose aspirin (for cardioprotection) with other NSAIDs synergistically increases the likelihood of gastrointestinal adverse events.
All of the selective COX-2 inhibitors have been shown to be less prone than equally efficacious doses of tNSAIDs to induce endoscopically visualized gastric ulcers (Deeks et al., 2002), and this has provided the basis of FDA approval of valdecoxib and celecoxib. To date, three comparative studies of clinical outcome have been published, two of which reported a significant difference in serious gastrointestinal events. The VIGOR study showed that important gastrointestinal events¾mainly bleeds¾were reduced from 4% to 2% in subjects treated with rofecoxib (now withdrawn from the market worldwide), and the TARGET trial (which actually was two distinct comparative studies with naproxen and ibuprofen, respectively) showed a reduction in ulcer complications in patients taking lumiracoxib (Schnitzer et al., 2004). In contrast, adverse events with celecoxib were not significantly decreased in the CLASS study (Silverstein et al., 2000). While the outcome of the VIGOR study was consistent with the hypothesis that COX-2-selective inhibitors are associated with a decreased incidence of gastrointestinal adverse events, the results were tempered by a fivefold increase in the incidence of myocardial infarction, probably reflecting a cardiovascular hazard in predisposed individuals treated with selective COX-2 inhibitors together with a modest cardioprotective effect of naproxen.
Gastric damage by NSAIDs can be brought about by at least two distinct mechanisms. Inhibition of COX-1 in gastric epithelial cells depresses mucosal cytoprotective prostaglandins, especially PGI2 and PGE2. These eicosanoids inhibit acid secretion by the stomach, enhance mucosal blood flow, and promote the secretion of cytoprotective mucus in the intestine. Inhibition of PGI2 and PGE2 synthesis may render the stomach more susceptible to damage and can occur with oral, parenteral, or transdermal administration of aspirin or NSAIDs. Another mechanism by which NSAIDs or aspirin may cause ulceration is by local irritation from contact of orally administered drug with the gastric mucosa. Local irritation allows backdiffusion of acid into the gastric mucosa and induces tissue damage. It also is possible that enhanced generation of lipoxygenase products (e.g., LTs) contributes to ulcerogenicity in patients treated with NSAIDs.
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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---
