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1.
The elderly (age > 65 years) are more vulnerable to side-effects induced by non-steroidal anti-inflammatory drugs (NSAIDs). We therefore performed a double-blind comparative study of ketoprofen SR and sulindac in patients with active rheumatoid arthritis, 65 years of age or older. Sulindac was chosen because of its possible renal sparing effects, and ketoprofen SR because of its short half life and sustained release delivery system. Eighty patients were entered. More patients withdrew from the study due to side-effects in the sulindac group; both treatment groups had a high incidence of side-effects during this study and during previous exposure to other NSAIDs, demonstrating that the elderly are susceptible to side-effects from NSAIDs.  相似文献   

2.
The disposition and effect on hemostasis of a single 150 mg dose of sulindac was studied in young healthy subjects and in older patients with arthritis. Older patients were restudied after 2 weeks of sulindac, 150 mg b.i.d. The only difference in disposition of the first dose was a reduced plasma sulfone metabolite concentration in the elderly patients with arthritis. Chronic sulindac dosing resulted in accumulation of the drug and its sulfone and sulfide metabolites in plasma to a greater extent than previously reported for young subjects. No differences in renal clearance of sulindac and its sulfone metabolite related to age or chronic drug dosing were observed. No renal excretion of the active sulfide metabolite was detected. Bleeding time in the elderly patients was shorter than in the young healthy subjects before sulindac dosing, but was prolonged in the elderly patients after 2 weeks of dosing to values similar to control data from the young healthy subjects. This change correlated weakly with plasma sulfide metabolite concentrations. Differences in bleeding time were not reflected in changes in platelet aggregation induced by adenosine diphosphate either with respect to age or chronic drug dosing. Our data provide no justification for lowering the recommended dose of sulindac for patients older than 65 years of age.  相似文献   

3.
CONTEXT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs for patients 65 years of age or older, primarily for musculoskeletal symptoms of osteoarthritis. Because NSAIDs frequently cause serious gastrointestinal (GI) and other complications among elderly patients, expert guidelines for osteoarthritis recommend acetaminophen-based regimens, which are safer and often as effective as NSAIDs. OBJECTIVE: Evaluate a physician education program that communicated guidelines for management of osteoarthritis in elderly patients that emphasized avoidance of NSAIDs when possible. The program reviewed NSAID risks and benefits and recommended: re-evaluating continuous NSAID users, considering substitution of up to 4 g/d of acetaminophen for the NSAID, and trying topical agents and nonpharmacologic measures. DESIGN AND SETTING: Randomized controlled trial among community-dwelling Tennessee Medicaid enrollees. SUBJECTS: Study physicians had 5 or more patients who: were community-dwelling Medicaid enrollees 65 years of age or older; had used NSAIDs regularly for at least 180 days; had had no medical care encounters during this period suggesting an indication other than osteoarthritis; and had 1 year of baseline and follow-up data. The study thus included 209 physicians (103 intervention/106 control) with 1,566 qualifying regular NSAID users (768/798). INTERVENTIONS: Face-to-face visit to study physicians by another physician, and reminder placements in the charts of patients eligible to have NSAID use reevaluated. OUTCOMES: Change between baseline and follow-up years in: days of prescribed NSAIDs, acetaminophen, other drugs for musculoskeletal disorders, and GI drugs; outpatient visits and inpatient days of stay; SF36 measures of general health, physical function, and bodily pain (from 40% random patient sample); and over-the-counter NSAIDs (from the sample). RESULTS: Intervention-attributable reduction of 7% (95% CI, 3% to 11%) in days of prescribed NSAIDs use with concomitant increase in acetaminophen use. No significant changes in other study endpoints. The intervention effect was greater among 75 physicians with a completed study visit, whose 564 patients had a 10% (95% CI, 6% to 14%) attributable reduction in NSAID use. CONCLUSIONS: The educational program modestly reduced NSAID exposure in community-dwelling elderly patients without undesirable substitution of other medications or detectable worsening of musculoskeletal symptoms.  相似文献   

4.
Lornoxicam (xefocam) as an agent of perioperative antinociceptive defense was studied and compared with other nonsteroidal anti-inflammatory drugs (NSAIDs) (ketorolac, ketoprofen). A comparative study was performed in 140 cancer surgical patients who were mainly middle-aged and elderly (51 +/- 10.9 years) and who had various concomitant diseases (ASA II-III). Extensive oncological operations under multicomponent general anesthesia were performed in these patients on the abdomen (n=60), small pelvis (n=46), and head and neck (n=34). All NSAIDs were used on the principle of preemptive analgesia, by intramuscularly injecting the therapeutic dose of an analgesic 40-60 min before surgery and by further continuing this basic therapy in combination with an opioid after surgery. Thirty patients received lornoxicam (xefocam, 16 mg/day), 30 had ketorolac (ketanov, 60-90 mg/day), 30, ketoprofen/ketonal (200 mg/day), and 20 patients, ketoprofen/artrozilene (320 mg/day). A control group comprised 30 patients who did not receive NSAIDs. In the patients of all the groups, the anesthesia scheme included one more antinociceptive agent--the kininogenesis inhibitor contrical (the total dose was 50,000-60,000 ATrU) (beginning from the stage of induction) and its administration (30,000 ATrU/day) was continued within 2 days after surgery. The studies performed have established that lornoxicam (xefocam) used in therapeutic doses shows a 50% reduction (versus 30% when ketorolac or ketoprofen is used) in a need for the potent opioid bepronorfine after extensive operations for cancer is one of the most effective NSAIDs. It has been noted that a short-term course of perioperative therapy with NDAIDs does not cause complications or side effects if individual contraindications to and limitations on their use are followed.  相似文献   

5.
Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been withdrawn from the market because of hepatic adverse drug reactions (ADRs). Moreover, some cases of liver diseases have been reported in patients taking NSAIDs (arylcarboxylic NSAIDs, piroxicam, sulindac, nimesulide, etc.). Pharmacoepidemiological studies have shown a risk of hepatic ADRs with NSAIDs used in association with other hepatotoxic drugs. In contrast, other studies performed in hospitalized patients did not found any association. The aim of this study was to assess the hepatic risk associated with the use of NSAID in the setting of primary care. The study design was a case-control study where cases and controls were all recruited among patients seen in the context of medical community care. Eighty-eight cases and 178 controls were included between January 1998 and December 2000. Cases used more drugs than controls in the 15 days before index day (2.9 +/- 2.2 vs. 1.8 +/- 1.8 different consumed drugs; P < 10(-4)). After adjustment, we found a significant association between liver injury and NSAID exposure in women [odds ratio (OR) = 6.49 (1.67-25.16)] but not in men [OR = 1.06 (0.36-3.12)]. A total of 22 cases were exposed to NSAIDs. Of them, seven patients were exposed to salicylates, five to diclofenac, four to ibuprofen, four to ketoprofen, two to niflumic acid, one to flurbiprofen and one to meloxicam (two patients were simultaneously exposed to two different NSAIDs: salicylate + niflumic acid and salicylate + diclofenac). These patients suffered from hepatocellular (53.3%), cholestatic (20%) or mixed (26.7%) injury. In 18 cases, liver enzymes returned to normal values after discontinuation of drug. No case had a fatal outcome. This study shows the existence of a significant association between liver disturbances and NSAID use in women.  相似文献   

6.
The Pharmacoepidemiologic Service of the Second University of Naples analyzed the use and tolerability of over-the-counter (OTC) oral nonsteroidal antiinflammatory drugs (NSAIDs) purchased in Campania, a region of southern Italy. Forty private pharmacies uniformly distributed throughout the region were recruited. The study was conducted by means of a questionnaire completed by purchasers and lasted from December 1, 1999 to March 31, 2000; 2053 questionnaires were collected. The age of respondents averaged 45.3 ± 3.49 years (range, 17–85 years). The NSAIDs analyzed were acetylsalicylic acid, paracetamol, ibuprofen, ketoprofen, diclofenac, and piroxicam. Adverse effects, mainly gastrointestinal symptoms, were reported by 5.5% of the users and occurred primarily with diclofenac, piroxicam, ibuprofen, and ketoprofen. Because the use and availability of OTC NSAIDs are increasing, further studies of the tolerability of this important drug class are warranted.  相似文献   

7.
The purpose of this study was to elucidate the interactions of human organic anion transporters (hOATs) and human organic cation transporters (hOCTs) with nonsteroidal anti-inflammatory drugs (NSAIDs) using cells stably expressing hOATs and hOCTs. NSAIDs tested were acetaminophen, acetylsalicylate, salicylate, diclofenac, ibuprofen, indomethacin, ketoprofen, mefenamic acid, naproxen, piroxicam, phenacetin, and sulindac. These NSAIDs inhibited organic anion uptake mediated by hOAT1, hOAT2, hOAT3, and hOAT4. By comparing the IC(50) values of NSAIDs for hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions with NSAIDs than did hOAT2 and hOAT4. HOAT1, hOAT2, hOAT3, and hOAT4 mediated the uptake of either ibuprofen, indomethacin, ketoprofen, or salicylate, but not acetylsalicylate. Although organic cation uptake mediated by hOCT1 and hOCT2 was also inhibited by some NSAIDs, hOCT1 and hOCT2 did not mediate the uptake of NSAIDs. In conclusion, hOATs and hOCTs interacted with various NSAIDs, whereas hOATs but not hOCTs mediated the transport of some of these NSAIDs. Considering the localization of hOATs, it was suggested that the interactions of hOATs with NSAIDs are associated with the pharmacokinetics and the induction of adverse reactions of NSAIDs.  相似文献   

8.
BACKGROUND: Tramadol is widely prescribed, even to the eldest patients. Although age-related differences in pharmacologic responsiveness are to be expected, the pharmacodynamic and pharmacokinetic (PK) properties of tramadol have not been systematically compared between patients of various ages. OBJECTIVE: The aim of this study was to explore the effectiveness, PK properties, and safety profile of 2 galenic tramadol formulations in 3 similarly sized age groups with malignant and nonmalignant pain of moderate to severe intensity. METHODS: This prospective, age-group-controlled study was conducted at the ambulatory pain clinic of the Landeskrankenhaus K?rnten, Klagenfurt, Austria. Male and female adults with malignant and nonmalignant pain of moderate to severe intensity were eligible. Patients were stratified into similarly sized age groups, as follows: >or=75, 65-<75, and <65 years. Patients first received the immediate-release galenic formulation of tramadol (tramadol IR) until steady state was achieved, followed by the sustained-release formulation (tramadol SR) until steady state. Serum concentrations of tramadol and its active metabolite (O-desmethyl-tramadol [M1]) were measured using gas chromatography to estimate the age-related PK handling of the analgesic drug. Three validated scales were used to measure pain intensity during the study: a 100-mm visual analog scale (VAS), an 11-point numeric analog scale (NAS), and a 4-point verbal rating scale (VRS). Tolerability was assessed by evaluating daily answers about the potential occurrence of adverse events (and respective details such as type and severity) from baseline until the end of the observation period. RESULTS: A total of 100 patients were enrolled (58 women, 42 men; mean [SD] age, 65.2 [15.0] years; >or=75, 30 patients; 65-<75, 31 patients; and <65 years, 39 patients). Predominant causes of pain were neoplasms (27.4% of causes) and injury and other external causes (20.8%), and diseases of the musculoskeletal and connective-tissues systems (19.8%). Fifty-five patients completed the study and provided all data as planned. Mean (SEM) steady-state tramadol IR doses were 250 (20.2), 277 (39.8), and 325 (33.1) mg/d in patients aged >or=75, 65-<75, and 65 years, respectively (P = NS); tramadol SR, 278 (27.5), 306 (39.7), and 340 (35.1) mg/d (P = NS). Serum concentrations of tramadol and M1 were statistically similar across all 3 age groups. Overall, mean pain intensity scores, as measured using the VAS and NAS, were decreased from baseline (62.4 [2.0] mm and 6.22 [0.22] points, respectively) to steady state with tramadol IR (23.6 [2.9] mm and 2.65 [0.30] points) and tramadol SR (16.9 [2.5] mm and 1.91 [0.26] points) (all, P < 0.001). Pain intensity before and improvements during both treatment phases were similar across all 3 age groups. RESULTS: for pain intensity on the VRS also did not find age-related differences. The predominant adverse effects were nausea (27.0% of patients), dizziness and giddiness (18.0%), and malaise and fatigue (15.0%); no significant differences in adverse events were found between age groups. CONCLUSIONS: The fate of tramadol and its active metabolite, and their clinical effects, have been examined here for the first time in a prospective cohort study, which compared patients aged <65 years, 65-<75 years, and >or=75 years. In contrast to expectations, it was concluded that tramadol IR and tramadol SR were both generally well tolerated and effective in the treatment of moderate to severe pain in any of the 3 age groups in these patients. Although the eldest group of patients consumed, on average, 20% less tramadol (P = NS) than the youngest group, the PK properties of both drugs were not changed when given to elderly patients.  相似文献   

9.
Effect of non-steroidal anti-inflammatory drug (NSAID) on blood pressure (BP) control was evaluated in elderly hypertensive patients treated with calcium antagonist. The study was based on a randomized, crossover design to compare the effect of an NSAID, sulindac, with that of another NSAID, diclofenac sodium, in the hypertension treatment. The study was completed in six elderly female subjects (the average age: 66 +/- 3 year) whose systolic BP and diastolic BP were more than 160 mmHg and more than 95 mmHg, respectively. When BP was controlled by nifedipine (20 mg x 2 per day in slow releasing form) within normal limits, sulindac (100 mg x 3 per day) or diclofenac sodium (25 mg x 3 per day) was administered for a week. After one week-washout period, the other NSAID was substituted. Plasma and urinary variables were measured on the final day of each study period. The average systolic BP and diastolic BP and the entry of study were 167 +/- 5 mmHg and 93 +/- 5 mmHg, respectively. Nifedipine significantly decreased the systolic BP to 140 +/- 4 mmHg (p less than 0.02) and the diastolic BP to 84 +/- 4 mmHg (p less than 0.05). Addition of either sulindac or diclofenac sodium did not affect BP, whereas urinary PGE2 excretion and plasma renin activity were significantly inhibited. Plasma creatinine and electrolyte concentration were not changed by the NSAIDs. The results indicate that either sulindac or diclofenac sodium does not interfere with control of hypertension by a calcium antagonist, nifedipine in in elderly hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
The prevention of colorectal cancer by aspirin use.   总被引:5,自引:0,他引:5  
Epidemiologic studies indicate strongly that aspirin use reduces the risk of colorectal cancer and adenoma by approximately 40 to 50%. Perhaps up to ten years of use may be required before a benefit is apparent in colorectal cancer. The chemo-preventive actions of aspirin and other non-steroidal anti-inflammatory agents (NSAIDs) in colorectal carcinogenesis are also supported by animal studies, and by intervention studies that demonstrate that the anti-inflammatory agent sulindac causes regression of adenomas in familial adenomatous polyposis. Despite this evidence, the clinical implications are not clear because of increased gastro-intestinal irritation and bleeding episodes related to chronic aspirin use. Emerging evidence suggests that the anti-tumor properties of NSAIDs may be related primarily to the inhibition of cyclooxygenase-2 (COX-2), one of the two isoenzymes of the COX enzyme family. If confirmed, a new generation of selective COX-2 inhibitors may retain some of the chemo-preventive properties of NSAIDs with fewer side-effects. Firm recommendations regarding the use of aspirin or other NSAIDs to prevent colorectal cancer must await further research. For now, the decision must lie with the patient, in consultation with his or her healthcare provider, after a careful weighing of all potential risks and benefits.  相似文献   

11.
Age is not as important in predisposing to infections as are the associated problems peculiar to certain age groups. Factors such as the advanced age of the patients combined with the presence of chronic disease reduce their resistance to infection. This study comprises 212 elderly patients (aged 65-98 years) who were treated with 500-1000 mg/day ciprofloxacin for 1-18 days. Despite the high incidence of associated chronic diseases, microbiology showed that infections were eradicated in 88.5%. Clinical resolution occurred in 75.5% of patients and clinical failure occurred in 6.1%. Treatment was well tolerated, with clinical side-effects reported in only seven patients. Ciprofloxacin may be considered an effective and safe antimicrobial agent for the treatment of infections in the elderly.  相似文献   

12.
13.
The pharmacokinetics of nonsteroidal anti-inflammatory drugs (NSAIDs) in the cerebrospinal fluid (CSF) is of clinical interest as it may be related to some of their properties and side-effects. Two types of NSAIDs can be described with respect to their concentration and time course in CSF: in the first type, the transfer across the blood-brain barrier seems to be controlled by simple physico-chemical factors. These drugs (oxyphenbutazone, indomethacin, ketoprofen) are characterized by a high lipophilicity. At steady state, their free plasma concentrations correspond to their CSF concentrations. The second group consists of more hydrophilic compounds (salicylates); there is no correlation between plasma concentrations and CSF concentration. Further investigation needs to be carried out on CNS side-effects and the antialgesic activity of salicylates in relation on their CSF distribution.  相似文献   

14.
The reciprocal effects on pharmacokinetic parameters after a single oral dose of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and sulindac and repeated oral doses of the H2-receptor antagonists cimetidine and ranitidine were determined in two groups of nine healthy subjects each (indomethacin and sulindac groups). Administration of NSAIDs increased the AUC and decreased the oral clearance and apparent volume of distribution of the H2-receptor antagonists without modifying their t1/2. Urinary data and observed modifications in ranitidine and cimetidine metabolites seem to justify a greater increase of H2-receptor antagonist bioavailability with indomethacin (p less than 0.05) than with sulindac (NS). The administration of ranitidine significantly reduced the sulindac volume of distribution without modifying its clearance, which caused an increase in the maximum concentration and a decrease in the t1/2 (p less than 0.05). The effects of cimetidine on the two NSAIDs were more intense than the effect of ranitidine: the decrease in sulindac volume of distribution (p less than 0.02) was accompanied by a significant reduction in sulindac clearance (p less than 0.05). AUC and urinary amounts of sulindac's sulfone metabolite were decreased. These results show that NSAIDs increased the bioavailability of H2-receptor antagonists, and that the latter drugs decrease the volume of distribution of NSAIDs. Furthermore, cimetidine modifies the oxidation metabolism of sulindac.  相似文献   

15.
To evaluate and compare the outcome of open-heart surgery in elderly patients with a concurrent group of younger patients in a developing country, data of all adult patients who underwent open-heart surgery during the period of 3 years from January 1999 to December 2001 were collected prospectively. Demographic data such as age and gender, other data such as preoperative diagnoses, comorbid illnesses, type of surgery, time of cardio-pulmonary bypass, length of stay and hospital outcome were recorded. The characteristics of patients above the age of 65 years were compared with a concurrent cohort of patients aged less than 65 years. One hundred and forty-five adult patients underwent open-heart surgeries in 3 years, and the overall mortality rate was 4.8%. The much common surgeries were coronary artery bypass grafting, valve repair/replacement surgery and surgery for adult congenital heart diseases. Forty-five (31%) patients were above the age of 65 years. The mortality rate was 2.2% for patients who were aged 65 years and above, in comparison with that of the concurrent cohort of younger patients (6%). This was probably because of more number of surgeries for congenital heart diseases in the latter group. However, even with other surgeries such as coronary artery bypass grafting, the elderly group of patients did equally well as the younger group. Elderly patients tolerate cardiac surgery well, and age should not be an exclusive criterion to decide against open-heart surgery.  相似文献   

16.
Objective : To characterize the ED utilization patterns of the elderly population using nationally representative data.
Methods : A secondary analysis was performed using the National Hospital Ambulatory Medical Care Survey (NHAMCS), a nationwide, stratified probability sample of ED encounters. Using these physician-reported data, the demographics, patient complaints, physician diagnoses, and dispositions were compared by age group, i.e., young-old (age 65–84 years) vs old-old (age ±85 years).
Results : The elderly (age ±65 years) represented 5,038 (19.6%) of 25,646 ED encounters for all adults (age ±18 years). The geriatric age groups (ages 65–74, 75–84, and ±85 years) accounted for 45.3%, 37.4%, and 17.2% of all the encounters by the elderly. The proportions of female patients and white patients were higher with increasing age. The proportion of elderly patients hospitalized was 4 times that of younger adults and reflected monotonic increase with increasing age among elders. Patient complaints and physician diagnoses were generally similar for the young-old (65–84 years) and the old-old (±85 years).
Conclusions : These findings are consistent with previous single-center studies of geriatric ED patients. This data source may be useful for investigation of clinical issues related to the care of elderly ED patients.  相似文献   

17.
The kinetic of sulindac and its two metabolites (sulfide and sulfone) was investigated in twelve elderly patients, following multiple oral dose administration of 400 mg/d. Data were compared to those obtained previously in ten healthy volunteers who received the same dosage regimen. Following multiple dose administration, accumulation ratios indicate that sulindac do not accumulate either in elderly patients (R = 1.35; R = AUC0-24 J8/AUC0-24 J1) or in healthy young subjects (R = 1.38; R = U0-24 J1). No significant modification of sulindac and sulfide kinetic parameters was observed. The apparent bioavailability of the inactive metabolite, sulfone, was found to be doubled in elderly patients (p less than 0.05). We conclude that there is no need to modify the dosage regimen of Arthrocine (400 mg once a day) in elderly patients.  相似文献   

18.
19.
PurposeDrowning is one of the major causes of traumatic death. The impact of drowning in the elderly and patients who were not elderly will be different because of physiological differences. We wanted to analyze the clinical differences such as mortality, incidence rate of complications, degree of hypothermia and rate of cardiac arrest between elderly and adult drowning patients.MethodsThis study included drowning patients over 18 years old who came to an emergency department (ED) located on a riverside from September 1997 to July 2016. Patients over the age of 65 years were classified as elderly, while those under the age of 65 years were classified as adults. Demographic data and clinical outcomes were surveyed.ResultsA total of 611 patients were included in this study. Sixty-one patients (9.9%) were elderly, and 550 patients (90.1%) were adults. There were 17 elderly patients (15.8%) and 87 adult patients (27.9%) who had cardiac arrest at the time of ED arrival (p = 0.017). The rate of body temperatures < 34 °C was higher in elderly patients than that in adult patients (27.9% vs 17.5%, respectively, p = 0.025). The rates of hospitalization in the intensive care unit (ICU) and mortality were higher in elderly group (23% vs. 15.1%, respectively, p = 0.01; 37.7% vs 21.8%, respectively, p = 0.01). There was no significant difference in suicidal intent between the elderly and adult patient groups (82.0% vs 78.9%, respectively, p = 0.421).ConclusionsElderly drowning patients accounted for approximately 1/10 of all drowning cases and were more likely to experience a cardiac arrest, hypothermia, mortality, and ICU admission.  相似文献   

20.
The prohypertensive effect of non-steroidal anti-inflammatory drugs (NSAIDs) can be manifested by the decreased efficiency of antihypertensive therapy. The tactics of their differential use in relation to the its effect on blood pressure (BP) in patients with osteoarthrosis (OA) and arterial hypertension (AH) has not been developed for the most effective and safe therapy. In this connection, it is extremely urgent to study the comparative safety of used NSAIDs as to their prohypertensive effect and to work out the management of patients with AH and OA. Ninety-eight patients with second-third degree OA of the knee and hip joints concurrent with the pain syndrome and first-second grade AH were followed up. Diclofenac, ketoprofen, arthrotec, nimesulide, and meloxicam were used. In a control group, the analgesic tramadol was supplemented to the therapy. AH was controlled by enalapril monotherapy. In groups of patients receiving diclofenac, arthrotec, meloxicam, and ketoprofen, there was a trend for the number of cases of an adequate nocturnal BP lowering (Dipper) to reduce and for those of an inadequate nocturnal BP decrease (Non-dipper), which may be accounted for by the prohypertensive effect of these drugs; this trend was most pronounced in the diclofenac and arthrotec groups. Despite its marked prohypertensive effect, nimesulide did not impair circadian BP variations. The central-acting analgesic tramadol exerted no prohypertensive effect and it did not increase BP values. The prohypertensive effect of the tested NSAIDs and tramadol increases in the following order: tramadol, ketoprofen, meloxicam, nimesulide, arthrotec, diclofenac.  相似文献   

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