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mail.newcastle.edu.au
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and effective treatments for pain and inflammation. They have a substantial toxicity profile with side effects mainly affecting the gastrointestinal tract, heart and kidneys. Although they comprise a chemically diverse group of drugs, NSAIDs are unified by a common mode of action the ability to inhibit the enzyme cyclo-oxygenase (COX). This also accounts for much of their toxicity. The enzyme exists in at least 2 isoforms. COX-1 generates prostaglandins with physiological functions, COX-2 is induced by inflammation and its physiologic functions are unclear at present. Conventional NSAIDs, like diclofenac, ibuprofen, and naproxen, are non-selective COX inhibitors, blocking the production of both physiologic and inflammatory prostaglandins. In this chapter, we describe the main predictable gastrointestinal, cardiac and renal toxicities that can be explained by such blockade and review the supporting clinical and epidemiological evidence. In the gastrointestinal tract, the side effects associated with conventional NSAIDs are both local and systemic, and include ulceration, bleeding, perforation, and obstruction. The upper gastrointestinal tract is more commonly affected than the lower. The cardiac and renal side effects are most likely to occur in patients with existing heart or kidney disease, where prostaglandins play an essential role in maintaining the vasoconstrictor/dilator balance necessary for homeostasis. The patients at highest risk of toxicity are the elderly, those with a prior history of ulceration or bleeding, and those with a history of cardiac disease. Among such patients, the decision to prescribe NSAIDs requires careful consideration of the potential benefits and harms.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11102559&dopt=Abstract
nottingham.ac.uk
AIM: To investigate the pharmacoepidemiology of NSAID usage in Nottingham general practices. DESIGN: Questionnaire sent to 1137 consecutive recipients of an NSAID prescription from 21 doctors in six general practices with computerized records. Patient responses were subsequently linked to data held on the practice records. SETTING: General practices in and around Nottingham, selected to reflect local variations in number of partners, list size, geographical location, deprivation, prescribing burden and prescribing rate. SUBJECTS: Unselected patients receiving NSAIDs prescribed for all indications. MAIN OUTCOME MEASURES: Indication for treatment, differences in prescribing to different age groups, compliance and overall scheme drug exposure, drug effectiveness and tolerability, possible drug-related adverse events, patients' overall satisfaction with treatment and estimated costs of care. RESULTS: NSAIDs were used for a wide range of conditions and only a small number of patients had rheumatoid arthritis. The main drugs used were ibuprofen, diclofenac and naproxen. Patients making short-term use of NSAIDs had low compliance if they experienced adverse drug effects, whilst conversely in long-term users, those with high compliance reported more adverse drug effects. Calculated compliance did not vary with age although older patients (over 65 years) claimed in their questionnaires to be more compliant than younger patients. Half the patients reported good or complete symptom relief. Half of those questions (and two thirds of those with good or complete symptom relief) rated their NSAID as the best treatment they had received for their current condition. The frequency of gastrointestinal adverse events was higher in the young and the old, which correlated with the use of anti-ulcer drugs, and increased with the total number of medications used. CONCLUSIONS: NSAIDs are used for a wide-range of conditions. They give symptom relief to, and are perceived as effective by, most patients taking them.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10651658&dopt=Abstract
Gastroenterology. 1990 May;98(5 Pt 1):1245-9.
Rectal administration of nonsteroidal antiinflammatory drugs. Effect on rat gastric ulcerogenicity and prostaglandin E2 synthesis.
Ligumsky M, Sestieri M, Karmeli F, Zimmerman J, Okon E, Rachmilewitz D.
Department of Gastroenterology, Hadassah University Hospital, Jerusalem, Israel.
Oral administration of nonsteroidal antiinflammatory drugs induces gastroduodenal mucosal damage in experimental animals as well as in humans. The aim of the present study was to evaluate the effect of rectally administered nonsteroidal antiinflammatory drugs on gastric mucosal damage, as well as on mucosal prostaglandin E2 synthesis. Fasting male rats were treated intrarectally with 0.5 ml 1% NaHCO3 solution containing several concentrations of either indomethacin, aspirin, ibuprofen, diclofenac, ketoprofen, or sulindac and concomitantly received 1 ml of 150 mM HCL intragastrically. Control rats received intrarectally the vehicle only. After 4 h, lesions in the secretory part of the stomach were scored and mucosal prostaglandin E2 synthesis was determined by the ex vivo prostaglandin generation technique. Dose-dependent mucosal damage was observed in indomethacin- and diclofenac-treated rats. Ketoprofen damage did not show dose dependency. In sulindac- and aspirin-treated rats, as well as in controls, no damage was detected. All drugs induced a significant and comparable degree of inhibition of prostaglandin E2 synthesis. There was no correlation between the severity of the mucosal damage and the inhibition of prostaglandin E2 synthesis. The ulcerogenicity of rectally administered nonsteroidal antiinflammatory drugs is therefore not directly related to the degree of inhibition of prostaglandin E2 synthesis and is probably related to the specific chemical and pharmacokinetic properties of each individual drug.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2323517&dopt=Abstract
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