salicylates and Osteoarthritis

To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA).. PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies.. 43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=-0.30, 95% CI -0.40 to -0.20) and improving function (SMD=-0.35, 95% CI -0.45 to -0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=-0.81, 95% CI -1.12 to -0.52) and piroxicam was most effective for functional improvement (SMD=-1.04, 95% CI -1.60 to -0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs.. Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study.

Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Bayes Theorem; Humans; Network Meta-Analysis; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Salicylates; Transdermal Patch

This review discusses the pharmacology, analgesic efficacy, safety and tolerability of topical NSAIDs, salicylates and capsaicin for the management of osteoarthritis (OA) pain. Topical therapies present a valuable therapeutic option for OA pain management, with substantial evidence supporting the efficacy and safety of topical NSAIDs, but less robust support for capsaicin and salicylates. We define topical therapies as those intended to act locally, in contrast to transdermal therapies intended to act systemically. Oral therapies for patients with mild to moderate OA pain include paracetamol (acetaminophen) and NSAIDs. Paracetamol has only weak efficacy at therapeutic doses and is hepatotoxic at doses >3.25 g/day. NSAIDs have demonstrated efficacy in patients with OA, but are associated with dose-, duration- and age-dependent risks of gastrointestinal, cardiovascular, renal, haematological and hepatic adverse events (AEs), as well as clinically meaningful drug interactions. To minimize AE risks, treatment guidelines for OA suggest minimizing NSAID exposure by prescribing the lowest effective dose for the shortest duration of time. Systemic NSAID exposure may also be limited by prescribing topical NSAIDs, particularly in patients with OA pain limited to a few superficial joints. Topical NSAIDs have been available in Europe for decades and were introduced to provide localized analgesia with minimal systemic NSAID exposure. Guidelines of the American Academy of Orthopaedic Surgeons, European League Against Rheumatism (EULAR), Osteoarthritis Research Society International, and National Institute for Health and Clinical Excellence (NICE) state that topical NSAIDs may be considered for patients with mild to moderate OA of the knee or hand, particularly in patients with few affected joints and/or a history of sensitivity to oral NSAIDs. In fact, the EULAR and NICE guidelines state that topical NSAIDs should be considered before oral therapies. Clinical trials of topical NSAIDs, most notably formulations of diclofenac and ketoprofen, have shown efficacy significantly superior to placebo and similar to oral NSAIDs. Most topical NSAIDs (piroxicam being the exception) have shown improved safety and tolerability compared with oral NSAIDs. Topical salicylates and capsaicin are available in the US without a prescription, but neither has shown substantial efficacy in clinical trials, and both have potential to cause serious AEs. Accidental poisonings have been reported

Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Dose-Response Relationship, Drug; Humans; Osteoarthritis; Practice Guidelines as Topic; Salicylates; Sensory System Agents

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown efficacy in patients with osteoarthritis (OA) pain but are also associated with a dose-dependent risk of gastrointestinal, cardiovascular, hematologic, hepatic, and renal adverse events (AEs). Topical NSAIDs were developed to provide analgesia similar to their oral counterparts with less systemic exposure and fewer serious AEs. Topical NSAIDs have long been available in Europe for the management of OA, and guidelines of the European League Against Rheumatism and the Osteoarthritis Research Society International specify that topical NSAIDs are preferred over oral NSAIDs for patients with knee or hand OA of mild-to-moderate severity, few affected joints, and/or a history of sensitivity to oral NSAIDs. In contrast, the guidelines of the American Pain Society and American College of Rheumatology have in the past recommended topical methyl salicylate and topical capsaicin, but not topical NSAIDs. This reflects the fact that the American guidelines were written several years before the first topical NSAID was approved for use in the United States. Neither salicylates nor capsaicin have shown significant efficacy in the treatment of OA. In October 2007, diclofenac sodium 1% gel (Voltaren Gel) became the first topical NSAID for OA therapy approved in the United States following a long history of use internationally. Topical diclofenac sodium 1% gel delivers effective diclofenac concentrations in the affected joint with limited systemic exposure. Clinical trial data suggest that diclofenac sodium 1% gel provides clinically meaningful analgesia in OA patients with a low incidence of systemic AEs. This review discusses the pharmacology, clinical efficacy, and safety profiles of diclofenac sodium 1% gel, salicylates, and capsaicin for the management of hand and knee OA.

Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Diclofenac; Drug-Related Side Effects and Adverse Reactions; Hand; Humans; Osteoarthritis; Osteoarthritis, Knee; Salicylates; Sensory System Agents

Topics: Acetaminophen; Administration, Topical; Analgesics; Anesthetics, Local; Capsaicin; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Injections, Intra-Articular; Lidocaine; Osteoarthritis; Salicylates; Tramadol

Topics: Acetylation; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Humans; Osteoarthritis; Patient Compliance; Salicylates; Stereoisomerism

Study of the early stages of osteoarthritis (OA) in humans presents numerous difficulties, since the patient commonly does not seek medical attention until pathologic changes are far advanced and articular cartilage has already been extensively lost. Investigators have, therefore, used animal models to obtain information about the early changes in articular cartilage, bone, and synovium. Among the most widely studied of these models is the cruciate-deficient dog. This report validates the cruciate-deficient dog as a model of progressive OA and emphasizes that, before full-thickness loss of articular cartilage, OA is marked by a phase of cartilage hypertrophy associated with a striking increase in synthesis of matrix macromolecules by the chondrocyte (compensatory repair). It reviews evidence that some nonsteroidal antiinflammatory drugs (NSAIDs) and deafferentation of the unstable limb may accelerate cartilage loss in OA, and examines the relationship of synovitis and of changes in subchondral bone to the changes in articular cartilage.

Topics: Animals; Anterior Cruciate Ligament; Anti-Inflammatory Agents, Non-Steroidal; Bone and Bones; Denervation; Disease Models, Animal; Dogs; Hindlimb; Osteoarthritis; Radiography; Salicylates; Synovitis; Wound Healing

The pharmacologic properties, clinical efficacy and tolerability of the newer non-steroidal anti-rheumatic drugs are compared. Guidelines for a prescribing policy are given in which a safety-first approach is adopted. Propionic acid derivatives or newer drugs with similar properties are proposed as initial therapy to control symptoms of rheumatoid arthritis or osteoarthrosis. Special problems such as compliance in chronic disease, treatment of ulcer patients with anti-rheumatic drugs, therapy in the elderly, treatment for juvenile rheumatoid arthritis and treatment during pregnancy are considered.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Carbazoles; Chronic Disease; Diclofenac; Diflunisal; Humans; Indomethacin; ortho-Aminobenzoates; Osteoarthritis; Phenylbutazone; Piroxicam; Rheumatic Diseases; Salicylates; Thiazines; Tolmetin

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty; Humans; Osteoarthritis; Physical Therapy Modalities; Salicylates

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It has been studied in osteoarthritis, pain resulting from musculoskeketal sprains and strains and from minor surgery and cancer. The duration of its analgesic effect is longer than that of aspirin and diflunisal is effective when given twice daily. Diflunisal is not metabolised to salicylic acid and has a lesser effect than aspirin on platelet function in vivo. In osteoarthritis, diflunisal appears comparable in efficacy to moderate doses of aspirin (2 to 3g daily), but is better tolerated. It has not been compared with the most active phenylalkanoic acid derivatives such as naproxen in adequate numbers of patients. Diflunisal is comparable with glafenine in pain and with propoxyphene/paracetamol combinations and oxyphenbutazone in pain and in musculoskeletal strains and sprains. As with other non-steroidal agents, gastrointestinal complaints are the most frequently reported side effects.

Topics: Diflunisal; Drug Interactions; Humans; Kinetics; Osteoarthritis; Pain; Salicylates; Sprains and Strains

Topics: Allopurinol; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Gold; Gout; Humans; Lupus Erythematosus, Systemic; Osteoarthritis; Penicillamine; Rheumatic Diseases; Salicylates; Spondylitis, Ankylosing; Vasculitis

Topics: Arthroplasty; Aspirin; Cathepsins; Debridement; Humans; Joint Dislocations; Joint Prosthesis; Knee; Osteoarthritis; Patella; Salicylates; Synovitis

Topics: Analgesics; Anti-Inflammatory Agents; Arthrodesis; Bone Marrow; Cartilage; Debridement; Diet, Reducing; Glycosaminoglycans; Humans; Joint Prosthesis; Lysosomes; Muscle Relaxants, Central; Osteoarthritis; Osteomalacia; Osteotomy; Physical Therapy Modalities; Protease Inhibitors; Rest; Salicylates; Silicones; Tissue Extracts

Topics: Adrenocorticotropic Hormone; Aged; Aminopyrine; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Dogs; Drug Hypersensitivity; Duodenal Ulcer; Esophageal Diseases; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Glucocorticoids; Humans; Hydrocortisone; Indomethacin; Intestinal Mucosa; Osteoarthritis; Penicillins; Phenylbutazone; Prednisolone; Rats; Rheumatic Diseases; Salicylates; Sodium Salicylate; Stomach Diseases; Stomach Ulcer; Streptomycin

Topics: Adrenal Cortex Hormones; Cartilage Diseases; Exercise Therapy; Humans; Indomethacin; Injections, Intra-Articular; Osteoarthritis; Phenylbutazone; Physical Therapy Modalities; Radiography; Rest; Salicylates; Spinal Diseases; Synovial Fluid; United States

Topics: Activities of Daily Living; Arthritis, Rheumatoid; Bursitis; Chloroquine; Diagnosis, Differential; Finger Joint; Gold; Gout; Hot Temperature; Humans; Hydroxychloroquine; Methylprednisolone; Neuralgia; Osteoarthritis; Pain; Physical Examination; Physical Exertion; Physical Therapy Modalities; Prednisolone; Rest; Salicylates; Synovectomy; Triamcinolone; Wrist Joint

Topics: Animals; Cartilage, Articular; Humans; Hydrocortisone; Indomethacin; Lidocaine; Osteoarthritis; Pyrazoles; Rabbits; Rats; Salicylates; Sulfur Isotopes

To assess the efficacy and safety of a copper-salicylate gel in osteoarthritis of the hip and knee.. Randomised, double-blind, placebo-controlled study.. Rheumatology Clinic of St Vincent's Hospital, Sydney, New South Wales (a tertiary referral hospital), June 1993 to October 1994.. 116 patients with pain associated with osteoarthritis of the hip and/or knee (diagnosed by criteria of the European League against Rheumatism), drawn from patients attending the Clinic or self-referred after newspaper advertisements.. Copper-salicylate or placebo gel (1.5 g) applied twice daily to the forearm for four weeks.. Self-assessment of pain before the trial and after two and four weeks of treatment; patient and investigator assessments of efficacy; additional analgesia required; adverse reactions; and withdrawal rates.. Pain scores at rest and on movement decreased in both the copper-salicylate and placebo groups by 13%-20%. There was no significant difference between the two groups for decrease in pain score, patient and investigator efficacy ratings, number of patients requiring paracetamol for extra analgesia (active, 77%; placebo, 71%) and average dose of paracetamol (active, 555 mg/day; placebo, 600 mg/day). Significantly more patients in the copper-salicylate group reported adverse reactions (83% versus 52% of the placebo group), most commonly skin reactions, and withdrew from the trial because of these reactions (17% versus 1.7% of the placebo group).. Copper-salicylate gel applied to the forearm was no better than placebo gel as pain relief for patients with osteoarthritis of the hip or knee, but produced significantly more skin rashes.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Copper; Double-Blind Method; Female; Gels; Humans; Knee Joint; Male; Middle Aged; Organometallic Compounds; Osteoarthritis; Osteoarthritis, Hip; Pain Measurement; Salicylates

Imidazole salicylate (750 mg t.i.d.) was compared with ibuprofen (400 mg t.i.d.) in a 60-day double-blind parallel group clinical trial in 31 patients with osteoarthritis. Both drugs were effective in relieving joint pain and in reducing the duration of morning stiffness. A statistically significant reduction of the severity of these symptoms was observed already one week after the start of treatment, lasting until the end of the study. No significant differences in efficacy were demonstrated between the two drugs throughout the trial. The systemic tolerability, assessed by changes in tests of hematological, liver and kidney function, urinalysis and faecal occult blood was excellent with both treatments. The incidence of side effects (mostly gastrointestinal complaints) was fairly low in both groups, and less severe in the group treated with imidazole salicylate.

Topics: Adult; Aged; Double-Blind Method; Female; Humans; Ibuprofen; Imidazoles; Knee Joint; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Hip; Salicylates

The clinical efficacy and gastroduodenal tolerability of imidazole salicylate (imidazole 2-hydroxybenzoate, ITF 182), a new synthetic drug with an anti-inflammatory action, was evaluated endoscopically in comparison with those of piroxicam in elderly patients suffering from osteoarthrosis. Of the 41 patients entering the trial, only 38 completed the protocol (6 men and 32 women; mean age, 71; range, 65-80 years). After upper gastrointestinal endoscopy for the purpose of excluding gastric and duodenal mucosal lesions, the patients were allocated at random, according to a double-blind, double-dummy protocol, to treatment either with imidazole salicylate 750 mg three times daily or with piroxicam 20 mg once daily for a period of 4 weeks. Imidazole salicylate proved active in controlling a number of the pain symptoms caused by arthrosis, although its efficacy was inferior to that of piroxicam. Grade 2 gastric mucosal lesions were detected in 1 of 20 patients (5%) treated with imidazole salicylate; lesions corresponding to grades 2, 3, and 4 were found in 6 of 18 (33%) of those treated with piroxicam (P = .034). Painful dyspepsia was reported by 15% of the patients in the imidazole salicylate group and by 28% of those in the piroxicam group. On the basis of these results and under the experimental conditions adopted in this trial, the authors concluded that imidazole salicylate is characterized by good gastric tolerability and can thus be used in the treatment of rheumatic diseases in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Activities of Daily Living; Aged; Anti-Inflammatory Agents, Non-Steroidal; Consumer Behavior; Double-Blind Method; Endoscopy; Female; Humans; Imidazoles; Male; Osteoarthritis; Peptic Ulcer; Piroxicam; Salicylates

Imidazole salicylate (750 mg t.i.d.) was compared with ibuprofen (400 mg t.i.d.) in a 30-day multicenter double-blind clinical trial in patients with osteoarthrosis. Both drugs were effective in relieving joint pain and in reducing the duration of morning stiffness. A statistically significant reduction of the severity of these symptoms was observed already one week after the start of treatment, lasting until the end of the study. No significant differences in efficacy were demonstrated between the two drugs throughout the trial. The systemic tolerability, assessed by changes in tests of hematological, liver and kidney function, was excellent with both treatments. The incidence of side effects (mostly gastrointestinal complaints) was fairly low in both groups, and lower in the group treated with imidazole salicylate.

Topics: Adult; Aged; Anti-Inflammatory Agents; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Ibuprofen; Imidazoles; Male; Middle Aged; Osteoarthritis; Random Allocation; Salicylates

Fifty patients with osteoarthritis were studied in a double-blind, crossover trial of diflunisal (1000 mg daily) and naproxen (750 mg daily). In the 45 patients who completed the study, no significant difference was noted between the drugs in most of the parameters studied, including evening pain intensity and effectiveness rating by patient and investigator. There was a trend towards greater patient preference for diflunisal, although this trend did not reach statistical significance. Naproxen produced significantly fewer side-effects, although side-effects with both drugs were mild.

Topics: Adult; Aged; Aged, 80 and over; Diflunisal; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Naproxen; Osteoarthritis; Random Allocation; Salicylates

Topics: Clinical Trials as Topic; Diflunisal; Female; Humans; Knee; Male; Middle Aged; Osteoarthritis; Salicylates

A single blind randomized endoscopic study comparing the effects of diflunisal and naproxen on the gastric and duodenal mucosa of 34 patients with osteoarthritis was performed over a 2-week period. At the dosages utilized in the study, diflunisal produced significantly less gastric injury than naproxen, as assessed by mean gastric injury scores (p = 0.0002). Sixty-five percent of the diflunisal treated group had no evidence of gastric mucosal injury compared with 13% in the naproxen group. Moreover, treatment with diflunisal resulted in a significantly lower incidence of severe gastric injury than naproxen (p less than 0.01).

Topics: Adult; Aged; Clinical Trials as Topic; Diflunisal; Digestive System; Drug Tolerance; Endoscopy; Gastric Mucosa; Humans; Intestinal Mucosa; Middle Aged; Naproxen; Osteoarthritis; Random Allocation; Salicylates

Thirty-one patients with osteoarthritis of the knee were treated with either diflunisal (n = 17) or naproxen (n = 14) in a 12-week open-label study. Treatment was begun with 500 mg BID of diflunisal or 375 mg BID of naproxen. Patients not showing an adequate response to these dosages were given increases to 750 mg BID of diflunisal (n = 7) or 500 mg BID of naproxen (n = 8). Both drugs achieved statistically significant improvements in pain indices, tenderness, swelling, morning stiffness, functional capacity, knee flexion, and 50-foot walking time, and no significant difference was found between the two drugs. At the end of the study, all patients taking diflunisal and 11/14 patients taking naproxen felt that they had improved with treatment. Drug safety and tolerability were assessed in 21 patients given diflunisal and 16 given naproxen (including patients not part of the efficacy evaluation). Six (29%) patients in the diflunisal group and four (25%) in the naproxen group experienced side effects; three were withdrawn from the diflunisal group and one from the naproxen group because of adverse effects. In general, both drugs were well tolerated.

Topics: Adult; Aged; Clinical Trials as Topic; Diflunisal; Drug Tolerance; Female; Humans; Knee Joint; Male; Middle Aged; Naproxen; Osteoarthritis; Salicylates

An open-label comparison of diflunisal, a nonacetylated salicylate nonsteroidal anti-inflammatory drug (NSAID), and piroxicam, an NSAID belonging to the oxicam family, was conducted in patients with osteoarthritis. Efficacy assessments were made biweekly by the physician and patients during a 12-week treatment and observation period. The physician's evaluations showed that both drugs resulted in significant reductions in knee pain, tenderness, swelling, stiffness, and difficulty walking. A greater number of statistically significant differences were noted with diflunisal than with piroxicam, but there were no statistically significant differences between the two treatment groups. Patients' efficacy ratings tended to favor diflunisal, and diflunisal was significantly more effective than piroxicam in relieving night pain. Seventy-five percent of patients receiving diflunisal and 40% of those receiving piroxicam considered their condition improved after treatment; however, the proportion of good to excellent drug ratings was similar for the two drugs. Both drugs were generally well tolerated. Adverse effects were encountered in five (28%) of 18 patients given diflunisal and in four (33%) of 12 patients given piroxicam. Six patients were withdrawn from the study because of side effects, four from the piroxicam group and two from the diflunisal group. In this study, diflunisal was found to be an effective and well tolerated drug for use in the management of osteoarthritis.

Topics: Clinical Trials as Topic; Diflunisal; Drug Tolerance; Hip Joint; Humans; Knee Joint; Osteoarthritis; Piroxicam; Prospective Studies; Salicylates

A 12-week, double blind study was conducted in 140 patients with osteoarthritis to compare the efficacy and toleration of piroxicam 10-20 mg once daily to indomethacin 75-125 mg in divided doses. Seventy-seven percent of piroxicam and 63% of indomethacin patients completed the study. The number of drop-outs due to side effects in the indomethacin group was twice that in the piroxicam group (p less than 0.05). The frequency of GI side effects was similar in both groups. There were more CNS side effects with indomethacin (headache), and more skin side effects with piroxicam. Piroxicam was comparable to indomethacin with respect to efficacy and offered better toleration and a simplified dosage regimen.

Topics: Clinical Trials as Topic; Female; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Patient Compliance; Piroxicam; Salicylates; Salicylic Acid; Thiazines

Diflunisal, a long acting antiinflammatory analgesic was compared in high (1000 mg daily) and low (750 mg daily) doses with placebo in a randomized, double blind study of 6 weeks' duration in patients with osteoarthritis of the knee. Two hundred twenty-seven patients from 47 centers completed the study--high dose 69, low dose 88 and placebo 70. Pain relief was significantly greater with both doses of diflunisal than with placebo. Both patient and investigator global opinions reflected significantly greater efficacy with diflunisal. Although there was a trend in favour of the higher dose, no statistically significant differences in efficacy were found between the 2 doses of diflunisal studied. Overall adverse reactions with diflunisal were no more frequent than with placebo, but gastrointestinal side effects were significantly greater with the higher dose.

Topics: Adult; Aged; Clinical Trials as Topic; Diflunisal; Digestive System; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain; Random Allocation; Salicylates

Topics: Aged; Anti-Inflammatory Agents; Clinical Trials as Topic; Diclofenac; Double-Blind Method; Female; Humans; Imidazoles; Male; Osteoarthritis; Random Allocation; Salicylates

In an open-label trial, 182 patients with common forms of arthritis were treated with 3 gm of salsalate daily (two 750-mg tablets twice daily) for 15 days. Before entering the study, these patients had received a wide variety of antiarthritic medications. Five indices of disease severity (pain, stiffness, joint swelling, limitation of motion, and disability) were evaluated before and after salsalate therapy, the incidence of side effects was tabulated before and after treatment, and patient compliance with the salsalate regimen was assessed. A reduction in disease symptoms was noted in 79% of the treated patients. Median improvement, measured on a summary index, was 47%. The incidence of side effects experienced with previous therapy was reduced by 65% during salsalate administration. Patient compliance with the regimen was greater than 95%. The findings show salsalate to be effective and safe in ameliorating the symptoms of arthritic disease. The convenient twice-daily dosage regimen makes this drug particularly suitable for chronic use.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Osteoarthritis; Salicylates

A double-blind, crossover study was carried out in 44 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerability of treatment with a new slow-release formulation of indomethacin (50 mg) with that of diflunisal (250 mg). After a 1-week wash-out period, patients were allocated at random to receive 2 tablets daily of one or other preparation for 6 weeks before being crossed over to the alternative drug for a further 6 weeks. Aspirin was allowed as a rescue analgesic throughout the study. Subjective assessments of pain and objective assessments of joint mobility were made before the start of treatment and at the end of each period, and details were recorded of rescue analgesic usage and any side-effects. Analysis of the results from 42 patients showed that whilst both treatments helped to alleviate pain, patients' overall evaluation of efficacy at the end of the study indicated that indomethacin was slightly more effective than diflunisal and there was a significant preference for indomethacin. Both drugs were well tolerated and none of the side-effects, reported in about 15% of patients on each drug, resulted in any withdrawals.

Topics: Adult; Aged; Delayed-Action Preparations; Diflunisal; Female; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Adult; Aged; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Naproxen; Osteoarthritis; Random Allocation; Salicylates

A report is given about a multicentric double-blind test for proof of effectiveness of two new suppository preparations with and without codeine against comparable remedies. Dolo Visano Supp. sine codeino showed a slight superiority over the reference preparation. This was proved above all for the influence upon pain and muscular overstrain. The better tolerability was marked. Dolo Visano Supp. (with codeine) showed advantages against the reference preparation. It was used in cases of severe pain, and in 88% it had a very good effect, whereas for the reference preparation this applied only in 67,9%. The assessments of physician and patients were almost alike. The myotonolytic effect has been proved equally for both of the new suppository preparations.

Topics: Arthritis; Aspirin; Clinical Trials as Topic; Codeine; Diphenhydramine; Double-Blind Method; Drug Combinations; Humans; Meprobamate; Muscle Rigidity; Nerve Compression Syndromes; Nicotinic Acids; Osteoarthritis; Pain; Plant Extracts; Salicylamides; Salicylates; Spinal Nerve Roots; Suppositories

Topics: Adult; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Female; Humans; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Adult; Aged; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Naproxen; Osteoarthritis; Random Allocation; Salicylates

Twenty-five patients with symptomatic osteoarthritis (OA) of the knee were treated topically for one week with either 10% trolamine salicylate cream or placebo cream in a randomized double-blind crossover study. No significant difference was found in subjective or objective measures of pain relief between the treatment and control groups. Eight patients preferred "active" test cream, six preferred placebo, and 11 had no preference. No side effects were reported. Topically applied 10% trolamine salicylate cream did not relieve the pain of OA of the knee any more than did placebo.

Topics: Administration, Topical; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Knee Joint; Male; Ointments; Osteoarthritis; Random Allocation; Salicylates

Sixty-two patients with osteoarthrosis entered a 10-week double-blind cross-over trial of diflunisal and naproxen. Eight patients withdrew for drug-related reason, and seven for other reasons. There was no statistically significant difference in parameters of disease activity on each treatment period, but naproxen produced fewer withdrawals due to drug-related side-effects.

Topics: Aged; Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Humans; Male; Naproxen; Osteoarthritis; Salicylates

Topics: Administration, Topical; Clinical Trials as Topic; Double-Blind Method; Humans; Ointments; Osteoarthritis; Salicylates

A total of 30 patients participated in a double-blind crossover trial to compare the efficacy and safety of benoxaprofen with naproxen in the treatment of osteoarthritis. Benoxaprofen, 600 mg administered once daily, was as effective as naproxen, 250 mg administered twice daily. Adverse reactions were mostly mild to moderate in severity and the incidence of the reactions was similar for the 2 study drugs. The advantage of the once-a-day dose regimen of benoxaprofen is discussed.

Topics: Adult; Aged; Analysis of Variance; Anti-Inflammatory Agents; Benzoxazoles; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Naproxen; Osteoarthritis; Patient Compliance; Propionates; Salicylates; Time Factors

A double-blind study comparing the efficacy and safety of diflunisal (Unisal), a new derivative of salicylic acid, and acetylsalicylic acid (Aspirin) was conducted in the rheumatology clinics of the Cantonal Hospital Beau-Séjour, Geneva, and the Triemli City Hospital, Zurich. A total of 38 patients with established osteoarthritis of the hip and/or knee were studied for 12 weeks. The daily dose of diflunisal was 500-750 mg and that of acetylsalicylic acid 2000-3000 mg. After 12 weeks diflunisal was judged superior to Aspirin by both patients and investigators. Among the most important clinical symptoms evaluated were pain and limitation of motion. Side effects, particularly gastro-intestinal symptoms, of sufficient severity to cause discontinuation of therapy were more frequent in the acetylsalicylic acid-treated patients than in the group receiving diflunisal.

Topics: Adult; Aged; Aspirin; Diflunisal; Double-Blind Method; Drug Evaluation; Female; Hip; Humans; Knee; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Male; Osteoarthritis; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Kidney Diseases; Male; Middle Aged; Osteoarthritis; Salicylates

A randomized double-blind study in ambulatory patients with osteoarthritis of hip and/or knee was conducted, comparing the efficacy and safety of diflunisal 500 mg daily with ibuprofen 1200 mg daily, and a period of 8 weeks. Thirty-five patients participated in the study. The results revealed no significant differences between the treatment groups with regard to the efficacy parameters.

Topics: Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Hip Joint; Humans; Ibuprofen; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain; Salicylates

A single-blind two-week comparison of benorylate and naproxen tablets was carried out in 85 patients with painful osteoarthritis. The degree of discomfort, pain at rest and on movement, joint stiffness and difficulty using affected joints all improved during the study with no significant difference between the treatments. Both patients' and observers' assessment of overall improvement favoured benorylate although the difference was not statistically significant. The majority had disease of weight-bearing joints for which Benoral was significantly more effective. Both drugs were well tolerated.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Naproxen; Osteoarthritis; Salicylates

A short-term, double-blind controlled crossover study was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the effectiveness and tolerance of salsalate and aspirin. After a 1-week placebo washout period, patients received either 3 g salsalate per day or 3.6 g soluble aspirin per day for 2 weeks before being crossed over to the alternative treatment. Paracetamol was used as a rescue analgesic. The results of clinical assessments of pain, stiffness and sleep disturbance, using visual analogue scales, showed that salsalate produced a comparable clinical improvement to that with aspirin, and similar serum salicylate levels. Salsalate, however, was significantly superior to aspirin with regard to side-effects and faecal occult blood loss.

Topics: Acetaminophen; Adult; Aged; Aspirin; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Occult Blood; Osteoarthritis; Salicylates

In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250 mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects.

Topics: Analgesics; Aspirin; Biphenyl Compounds; Clinical Trials as Topic; Humans; Occult Blood; Osteoarthritis; Pain; Salicylates; Time Factors

Thirty patients with osteoarthritis of knees or hips took part in a double-blind randomized 12-week inter-group clinical trial of diflunisal 250 mg to 375 mg twice daily against aspirin 500 mg to 750 mg four times daily using the double-placebo technique. Changes were assessed in weight-bearing pain and night pain, stiffness after rest, a specified activity, and overall judgements by patient and physician, all graded on a five-point scale. Intermalleolar distance or knee flexion were measured. Side-effects and safety tests were monitored. Diflunisal produced statistically significant responses for all the criteria, when numbers of patients better or worse after 12 weeks were compared using the sign test. Neither the figures for aspirin alone, nor a comparison between the two treatment groups, reached statistical significance. Side-effects and especially dropouts were less on diflunisal. Nine patients on diflunisal but only two on aspirin wanted to continue treatment beyond 12 weeks, though still 'blind' when deciding this. Diflunisal may be a useful, less toxic and longer acting alternative to aspirin in the management of osteoarthritis.

Topics: Abdomen; Aspirin; Clinical Trials as Topic; Dizziness; Double-Blind Method; Drug Administration Schedule; Edema; Humans; Osteoarthritis; Pain; Salicylates; Time Factors

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Clinical Trials as Topic; Drug Evaluation; Fluorobenzenes; Humans; Ibuprofen; Osteoarthritis; Patient Dropouts; Salicylates; Time Factors

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Drug Combinations; Female; Gels; Heparin; Humans; Hyperemia; Male; Middle Aged; Nicotinic Acids; Osteoarthritis; Pain; Regional Blood Flow; Salicylates

This study compared benorylate suspension and placebo in a double-blind randomised cross-over design to investigate their analgesic effect in osteoarthritis of the hip and the knee. Benorylate and placebo were each given for 7 days. Assessment of efficacy and tolerance was carried out on the 7th day of each period. The results were subjected to sequential analysis and the analgesic effect of benorylate suspension was significantly demonstrated after 8 case reports. Mild digestive side effects appeared in 30% of patients. In addition, benorylate suspension was well tolerated in an open trial carried on for 30 to 90 days in 7 patients.

Topics: Adult; Aged; Clinical Trials as Topic; Digestion; Drug Evaluation; Drug Hypersensitivity; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Clinical Trials as Topic; Female; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Diet, Reducing; Drug Interactions; Female; Humans; Imidazoles; Indoles; Indomethacin; Male; Middle Aged; Obesity; Osteoarthritis; Placebos; Salicylates; Time Factors

Topics: Arthritis, Rheumatoid; Benzoates; Brachial Plexus Neuritis; Clinical Trials as Topic; Drug Combinations; Glycols; Humans; Nicotinic Acids; Ointments; Osteoarthritis; Rheumatic Diseases; Salicylates; Skin Temperature; Thermography

Topics: Action Potentials; Adult; Aged; Analgesics; Arthritis, Rheumatoid; Audiometry; Clinical Trials as Topic; Electromyography; Female; Humans; Irritants; Male; Methane; Middle Aged; Muscle Cramp; Osteoarthritis; Pain; Placebos; Salicylates; Sensation

Topics: Acute Disease; Arthritis, Rheumatoid; Bone Diseases; Clinical Trials as Topic; Drug Synergism; Humans; Osteoarthritis; Osteochondritis; Osteoporosis; Pain; Penicillins; Placebos; Pleurisy; Prednisolone; Rheumatic Diseases; Rheumatic Fever; Salicylates; Spondylitis

To examine trends in the initial prescription of commonly-prescribed analgesics and patient- as well as practice-level factors related to their selection in incident OA.. Patients consulting with incident clinical OA between 2000-2016 were identified within The Health Improvement Network in the United Kingdom (UK) general practice. Excluded were patients who had history of cancer or were prescribed the analgesics of interest within 6 months before diagnosis of OA. Initial analgesic prescription included oral non-selective NSAID, oral selective cyclooxygenase-2 inhibitor, topical NSAID, paracetamol, topical salicylate or oral/transdermal opioid within 1 month after OA diagnosis.. ∼44% of patients with incident OA (n = 125 696) were prescribed one of these analgesics. Incidence of oral NSAID prescriptions decreased whereas other analgesic prescriptions, including oral opioid prescriptions, increased (all P-for-trend < 0.001). Patients with a history of gastrointestinal disease were more likely to receive topical NSAIDs, paracetamol or oral/transdermal opioids. Only 38% of patients with history of gastrointestinal disease and 21% of patients without it had co-prescription of gastroprotective agent with oral NSAIDs. Oral/transdermal opioid prescription was higher among the elderly (≥65 years), women, obesity, current smoker, and patients with gastrointestinal, cardiovascular or chronic kidney disease. Prescription of oral opioids increased with social deprivation (P-for-trend < 0.05) and was highest in Scotland, whereas transdermal opioid prescription was highest in Northern Ireland (all P-for-homogeneity-test < 0.05).. The initial prescription pattern of analgesics for OA has changed over time in the UK. Co-prescription of gastroprotective agents with oral NSAIDs remains suboptimal, even among those with prior gastrointestinal disease.

Topics: Acetaminophen; Administration, Cutaneous; Administration, Oral; Aged; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Female; Gastrointestinal Agents; Gastrointestinal Diseases; Humans; Incidence; Male; Middle Aged; Osteoarthritis; Salicylates; Socioeconomic Factors; Time Factors; United Kingdom

Although during treatment of arthrosis with meloxicam the level of thromboxan A2 decreases, thrombocyte functions are not affected. Meloxicam in therapeutic doses doesn't increase the risk of haemorrhage. Previously it was suspected that co-administration of salicylates with certain other non-steroid antiinflammatory drugs (NSAIDs) will suppress the effect of salicylate. Van Ryn et al have proved that this is not the case with salicylate plus meloxicam therapy. It is hypothesized that meloxicam loosely binds to the cyclooxygenase-1 (COX-1) enzyme and salicylate can easily replace it.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Hemorrhage; Humans; Meloxicam; Osteoarthritis; Salicylates; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondrocytes; Humans; Inflammation; Osteoarthritis; Proteoglycans; Salicylates

Topics: Administration, Cutaneous; Analgesics; Copper; Gels; Hip Joint; Humans; Knee Joint; Osteoarthritis; Osteoarthritis, Hip; Pain; Salicylates

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the activity of glycosyltransferases required for the synthesis of the polysaccharide chains of proteoglycans, was studied in human osteoarthritic cartilage in vitro. Using exogenous acceptors, salicylate and indomethacin suppressed the activity of glucuronyl- and xylosyltransferases in a concentration-dependent manner, but had little effect on N-acetylgalactosaminyl- and galactosyltransferases. When used at a concentration derived from the values found in the synovial fluid, salicylate, indomethacin and chloroquine significantly suppressed the activity of glucuronyl- and xylosyltransferases, while tiaprofenic acid, paracetamol (acetaminophen), floctafenine, ketoprofen, ibuprofen and tenoxicam had no effect on the enzymes. An alteration of some glycosyltransferases could explain the reported suppressive effect of some NSAIDs on cartilage proteoglycan synthesis.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chloroquine; Depression, Chemical; Female; Glucuronosyltransferase; Glycosyltransferases; Humans; Indomethacin; Male; Middle Aged; Osteoarthritis; Pentosyltransferases; Propionates; Proteoglycans; Salicylates; UDP Xylose-Protein Xylosyltransferase

Choline magnesium trisalicylate is a non-acetylated salicylate used widely as a nonsteroidal anti-inflammatory drug. Although mild transient hepatotoxicity associated with aspirin and other salicylates has been well documented, most commonly with high-dose treatment for rheumatologic disorders 112), we report a case of severe hypersensitivity hepatitis with striking tissue and peripheral eosinophilia after ingestion of choline magnesium trisalicylate.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Choline; Eosinophilia; Female; Humans; Osteoarthritis; Salicylates

Topics: Administration, Topical; Aerosols; Drug Combinations; Humans; Linseed Oil; Osteoarthritis; Plant Oils; Salicylates; Tea

A three phase study was designed to define further the sensitivity and specificity of symptomatic salicylate ototoxicity (primarily tinnitus) for serum salicylate concentrations. In phase one 260 patients with osteoarthritis and 112 with rheumatoid arthritis, none taking salicylates, were interviewed about their ear symptoms. Their responses were not significantly different from those of 134 salicylate treated patients with rheumatoid arthritis previously reported. In the second phase 56 patients who were taking salicylates, and who volunteered the complaint of tinnitus, had serum salicylate concentrations measured while symptomatic, and 30 (54%) had concentrations less than 1.3 mmol/l. Few tolerated an upward salicylate dose adjustment. For phase three, 94 patients were found to have a salicylate concentration above 2.2 mmol/l on one or more occasion, and these subjects were interviewed. Fifty two patients (55%) had no tinnitus, and tinnitus correlated with the blood salicylate concentration in only 28 (30%). Audiological evaluation of most of the symptomatic patients was carried out, and results were abnormal in the majority, even in those patients not reporting tinnitus. Symptomatic salicylate ototoxicity is too nonspecific and too insensitive to be a useful indicator of serum salicylate concentration.

Topics: Adult; Aged; Arthritis, Rheumatoid; Hearing Disorders; Humans; Middle Aged; Osteoarthritis; Salicylates; Sensitivity and Specificity; Tinnitus

Salicylates suppress net glycosaminoglycan synthesis in articular cartilage. The inhibitory effect is greater in osteoarthritic (OA) cartilage than in normal cartilage. Whether the isolated OA chondrocyte is inherently more susceptible to the effects of salicylate on glycosaminoglycan metabolism has not been determined. The results of this study show that, after isolation from the extracellular matrix, normal and OA chondrocytes in suspension culture are similarly susceptible to the metabolic effects of salicylate. However, chondrocytes from the contralateral knees of dogs with unilateral OA were notably resistant to the effects of salicylate.

Topics: Animals; Body Water; Cartilage; Cartilage, Articular; Cells, Cultured; Dogs; Glycosaminoglycans; Knee Joint; Osteoarthritis; Salicylates; Uronic Acids

Topics: Drug Synergism; Female; Humans; Middle Aged; Ointments; Osteoarthritis; Salicylates; Warfarin

Topics: Aged; Female; Humans; Osteoarthritis; Salicylates; Thyroid Function Tests; Thyrotropin; Thyroxine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Humans; Hydrocortisone; Microbial Collagenase; Osteoarthritis; Propionates; Salicylates; Synovial Fluid

A postmarketing survey was conducted by 37 orthopedists and traumatologists among 700 patients of both sexes, aged 7 to 87 years, to evaluate the efficacy and tolerability of imidazole salicylate. The 467 patients with osteoarthrosis received 750-mg tablets (TID) for up to one month and 233 patients with traumatic pathologies received imidazole salicylate gel (BID-TID) for ten days, or tablets (BID-TID), or both gel and tablets combined. The treatment was satisfactory in both patient groups, significantly reducing the intensity of pain and swelling and improving articular function. No adverse experiences that had not been reported previously were recorded; only some gastrointestinal side effects exceeded an incidence of 1%.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Bone and Bones; Child; Female; Humans; Imidazoles; Male; Middle Aged; Muscles; Osteoarthritis; Product Surveillance, Postmarketing; Salicylates

Salicylates and several other nonsteroidal anti-inflammatory drugs (NSAIDs) that are commonly employed in the treatment of osteoarthritis effectively decrease joint pain and increase mobility. Results from in vitro studies indicate that, in addition, some of these compounds affect proteoglycan metabolism of articular cartilage. Data from in vivo studies suggest that salicylate administration may accelerate articular cartilage damage in several animal models of osteoarthritis. At in vitro concentrations comparable to those that are achieved in the synovial fluid of patients treated with the drug, several NSAIDs suppress proteoglycan synthesis by the chondrocyte. Salicylate has been shown to inhibit the enzymes involved in the early stages of chondroitin sulfate biosynthesis. These NSAID-related effects on chondrocyte metabolism appear unrelated to inhibition of prostaglandin synthetase, and are much more profound in osteoarthritic cartilage than in normal cartilage, due to enhanced uptake of NSAIDs by the osteoarthritic cartilage. Depletion of matrix proteoglycans appears to be a major factor in the increased vulnerability of chondrocytes in degenerating cartilage to effects of NSAIDs. Some NSAIDs may be bound to matrix components. If similar changes occur in the cartilage of patients with arthritis treated with NSAIDs, despite the symptomatic improvement that these drugs produce, cartilage degeneration could be accelerated.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondroitin Sulfates; Culture Techniques; Dogs; Humans; Osteoarthritis; Proteoglycans; Salicylates

Topics: Adrenal Cortex Hormones; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Chondrocalcinosis; Female; Giant Cell Arteritis; Gout; Humans; Male; Middle Aged; Osteoarthritis; Osteoporosis; Rheumatic Diseases; Salicylates

Topics: Animals; Anti-Inflammatory Agents; Dogs; Glycosaminoglycans; Humans; Indomethacin; Osteoarthritis; Salicylates

The effects of salicylate and indomethacin on glycosaminoglycan (GAG) synthesis by atrophic and osteoarthritic (OA) canine cartilage were examined in vitro by transecting distal femora at the metaphysis and incubating the knuckle, with its overlying cap of articular cartilage, in medium containing sodium salicylate or indomethacin, and 35SO4. Atrophic cartilage had an intact articular surface, but its uronic acid content averaged 65% of the control level, and GAG synthesis was decreased to 50% of control values. Both salicylate and indomethacin decreased net GAG synthesis in the atrophic cartilage by an additional 10%. OA cartilage showed surface disruption, a uronic acid content 49% of the control value, and a 49% increase in net GAG synthesis. Salicylate and indomethacin profoundly decreased GAG synthesis in the OA cartilage. However, GAG synthesis and uronic acid content of cartilage which had been lacerated in vitro immediately prior to culture (to stimulate fibrillation) were normal and not affected by either drug. The data emphasize the importance of matrix proteoglycan content in protecting the chondrocyte from the suppressive effects of salicylate and indomethacin on GAG metabolism, and suggest that the lower proteoglycan content of OA cartilage may be more important than fibrillation in rendering it vulnerable to the metabolic effects of these drugs.

Topics: Animals; Atrophy; Cartilage, Articular; Culture Techniques; Dogs; Glycosaminoglycans; Indomethacin; Osteoarthritis; Salicylates; Staining and Labeling; Uronic Acids

Topics: Anti-Inflammatory Agents; Antigen-Antibody Complex; Arthritis, Rheumatoid; Cartilage; Collagen; Humans; Immune Complex Diseases; Immunity; Inflammation; Osteoarthritis; Proteoglycans; Salicylates; Steroids; Water

Topics: Adult; Aged; Anti-Inflammatory Agents; Female; Humans; Imidazoles; Male; Middle Aged; Osteoarthritis; Pain; Salicylates

Ulcers of the small bowel are documented in a patient after intake of salsalate. Rapid clinical and endoscopic improvement occurred on discontinuation of administration of the drug. Endoscopic features suggested the direct effect of a tablet dissolving in the proximal part of the small bowel. To my knowledge, this is the first report of small-bowel ulcerations associated with the newer form of salicylates that bypass the stomach for their absorption.

Topics: Female; Humans; Intestinal Diseases; Intestine, Small; Middle Aged; Osteoarthritis; Peptic Ulcer; Salicylates; Ulcer

A high unit dose (15 grain/975 mg) enteric coated aspirin preparation was studied in normal individuals and patients with arthritis to determine how readily well tolerated, therapeutic (150-300 micrograms/ml) salicylate (SA) levels could be achieved using a twice daily dosing regimen. Of 36 participants enrolled, 33 (92%) achieved this goal (mean SA = 224 micrograms/ml), while in the remaining 3 an initially toxic level fell below the therapeutic range after reducing the dose by one tablet/day. Although the relationship between dose (mg/kg) and steady state SA levels was roughly linear (r = 0.74), in some subjects there was a striking incremental change in the SA level when the dose was adjusted. Over 90% of subjects taking a starting dose between 45-60 mg/kg/day achieved a therapeutic level. Thus, antiinflammatory therapy using 15 grain/975 mg enteric coated aspirin given twice daily appears to be feasible.

Topics: Adult; Aged; Arthritis, Rheumatoid; Aspirin; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Osteoarthritis; Salicylates; Salicylic Acid; Tablets, Enteric-Coated; Tinnitus

Topics: Aged; Female; Humans; Osteoarthritis; Salicylates; Salicylic Acid

According to in vivo experimental data, salicylates and several other nonsteroidal anti-inflammatory agents suppress proteoglycan biosynthesis in normal and degenerating articular cartilage. Therapeutic levels of aspirin in vivo had a similar adverse effect on degenerating cartilage, as noted in two canine models of osteoarthritis and cartilage atrophy. Because the effective daily antirheumatic dose of nonsteroidal anti-inflammatory drugs is lower than that of salicylates, these drugs may have less negative effects on degenerating articular cartilage. However, clinical significance cannot be extrapolated from these experimental data.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Atrophy; Cartilage, Articular; Dogs; Extracellular Matrix; Glycosaminoglycans; Indomethacin; Osteoarthritis; Prostaglandin Antagonists; Proteoglycans; Salicylates; Sulfur Radioisotopes; Sulindac; Uronic Acids

Topics: Adult; Aged; Diflunisal; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Salicylates

The disposition of diflunisal was studied at daily doses of 250, 500, 750, 1000 mg/day in 24 male patients (mean age 65 yr and mean creatinine clearance 72 ml/min). Each dose was given for 14 days and diflunisal apparent oral clearance and serum urate was measured on the last day of each dosing regimen. There was a dose-dependent decrease in mean diflunisal apparent oral clearance with dose from 628 ml/hr at 250 mg/day to 426 ml/hr at 1000 mg/day, with most of the decrease occurring at the lower doses and becoming less pronounced at doses of 750 and 1000 mg/day. There was a strong positive correlation between diflunisal apparent oral clearance and creatinine clearance. Diflunisal induced a hypouricemic effect at all doses, but the responses at doses of 750 and 1000 mg/day did not differ.

Topics: Aged; Chromatography, High Pressure Liquid; Creatinine; Diflunisal; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Osteoarthritis; Salicylates; Uric Acid

In clinical rheumatology, the hazardousness of mixed preparations containing cortisone is being stressed even more, their use is only recommended in very special cases and only for short periods. Dolo Visano Supp. sine codeino and Dolo Visano Supp. are remedies which are indicated, like other mixed preparations not containing steroids, in cases of painful muscular overstrain and psychomuscular kinesalgia (symptom range of non-articular rheumatism). In our study, they were used in acute and severe pain conditions in intermediate or short-term therapy until complaints improved. Dolo Visano Supp. sine codeino and Dolo Visano Supp. (with codeine) can contribute in limiting the use of the risky preparations containing cortisone, which have hitherto been applied so frequently.

Topics: Aspirin; Codeine; Diphenhydramine; Drug Combinations; Female; Gout; Humans; Male; Meprobamate; Middle Aged; Muscle Rigidity; Nerve Compression Syndromes; Nicotinic Acids; Osteoarthritis; Pain; Plant Extracts; Salicylamides; Salicylates; Spinal Nerve Roots; Suppositories

The relative risks associated with anti-inflammatory drug prescription for patients with an earlier history of drug-associated gastro-intestinal disturbance have been investigated in a retrospective study. Under these circumstances ibuprofen was well tolerated. The risks associated with modified salicylates (principally aspirin in enteric-coated form) and indomethacin suppositories also appeared to be relatively slight. Retreatment with phenylbutazone, oral indomethacin, naproxen and combination therapy was hazardous.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents; Arthritis; Duodenal Ulcer; Female; Gastrointestinal Hemorrhage; Humans; Ibuprofen; Indomethacin; Male; Middle Aged; Osteoarthritis; Peptic Ulcer; Peptic Ulcer Hemorrhage; Recurrence; Retrospective Studies; Salicylates; Suppositories; Time Factors

Topics: Anti-Inflammatory Agents; Arthritis; Arthritis, Rheumatoid; Aspirin; Bursitis; Humans; Osteoarthritis; Salicylates; Spondylitis; Tendinopathy

Twenty-eight medical specialists (internists, rheumatologists) selected 102 primarily arthritic patients for a two-week efficacy and safety field study of salicylsalicylic acid. Data were gathered on pain, morning stiffness, range of motion, serum salicylate concentration, erythrocyte sedimentation rate (ESR) and gastro-intestinal bleeding before and after a 15-day drug trial. Results showed a 67% favourable clinical response in the physician's global evaluation and a 60% improvement in pain; the drug itself was well tolerated by 96% of patients. Response correlations with morning stiffness and range of motion were equivocal. Of fifty-four patients examined before and after treatment for intestinal bleeding, only two (3.7%) had detectable faecal blood loss. Good clinical response had a statistically significant association with serum drug concentrations of 13.6 to 13.8 mg%; unsatisfactory response was noted in those patients with mean serum salicylate levels of 8.6 mg%. ESR decreased or was unchanged in thirty-five patients with satisfactory clinical response and in fourteen patients with unsatisfactory response.

Topics: Adult; Aged; Analgesics; Arthritis; Arthritis, Rheumatoid; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Osteoarthritis; Salicylates

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Humans; Osteoarthritis; Salicylates

Topics: Consumer Behavior; Female; Humans; Ibuprofen; Male; Osteoarthritis; Salicylates

The effectiveness of Benoral Tablets in controlling joint pain and stiffness in osteoarthritis was assessed over a two-week period in a multicentre general practice open study. In this trial it has been demonstrated that a correlation exists between pain relief from stiffness for patients suffering from osteoarthritis taking Benoral Tablets over this period. It was also found that patients with initially mild to moderate pain benefited most from their treatment.

Topics: Adult; Drug Evaluation; Female; Humans; Male; Osteoarthritis; Salicylates; Tablets; Time Factors

A two-week assessment of Benoral tablets was carried out in general practice in 171 patients with degenerative joint disease to see how symptomatic response related to selected presenting features of the disease. A short history, less severe initial state and multiple joint involvement were each associated with a better response. Overall 84-4% of patients reported Benoral tablets to have helped relieve their symptoms and a high proportion preferred Benoral to their previous anti-arthritic medication.

Topics: Adolescent; Female; Humans; Male; Osteoarthritis; Salicylates; Tablets

Surgical inducement of medial instability in the right knee of rabbits was used to produce joint changes which resemble those observed in human osteoarthritis. Ordinary tap water was supplied to half of the rabbits and tap water plus sodium salicylate to the others. Determinations of prostaglandin were made on the synovial fluid and cartilage from all rabbits five months after surgery. In both groups, the concentration of prostaglandin in synovial fluid was lower in the operated knees, but the total amount of prostaglandin was found to be approximately equal to that in the unoperated knees. The development of degenerative joint changes therefore was not accompanied by increases in prostaglandin content. Salicylate treatment did not alter this observation, however, it did reduce overall prostaglandin levels. These results suggest that prostaglandin interaction is not involved in osteoarthritic joint degeneration.

Topics: Animals; Cartilage, Articular; Joints; Knee Joint; Osteoarthritis; Prostaglandins; Rabbits; Salicylates; Synovial Fluid

Degenerative joint changes were produced in one knee of each of fourteen rabbits by surgical induction of instability. The involved knee in rabbits with and without systemic salicylate treatment was compared with the knee not operated on. Salicylate did not significantly change the activities of lysosomal enzymes in cartilage or synovial fluid, the uptake of tritiated thymidine, glycine, or 35S-inorganic sulphate by cartilage, or the histological manifestations of cartilage degeneration.

Topics: Animals; Cartilage, Articular; Glycine; Joint Diseases; Knee Joint; Lysosomes; Osteoarthritis; Rabbits; Salicylates; Sulfur Radioisotopes; Surgical Procedures, Operative; Synovial Fluid; Thymidine; Tritium

52 outpatients with rheumatoid arthritis or osteoarthritis were given benorylate (as the 40% suspension) in doses of up to 8 g daily. Peroids of medication were varied but some patients were given the drug for nearly 2 years. Assessments of clinical progress were made at regular intervals by recording both subjective and objective measurements including duration of morning stiffness, grip strength, joint size. Laboratory investigations include renal function tests, liver function tests, blood picture and occult blood. No serious side effect, attributable to benorylate was reported and it was concluded that the drug is satisfactory for the long term treatment of rheumatic diseases.

Topics: Arthritis, Rheumatoid; Blood Sedimentation; Drug Evaluation; Dyspepsia; Humans; Nausea; Osteoarthritis; Rheumatic Diseases; Salicylates; Urea; Vomiting

Benorylate is obtained by esterification of acetylsalicylic acid and N-acetyl p-aminophenol (4-acetamidophenyl 2-acetoxybenzoate). Experimentally, this new product has been shown to be a good analgesic and anti-inflammatory agent. A clinical trial was carried out in order to study the efficacy, side effects and tolerance of this new product. In a group of 49 hospitalised patients aged from 20 to 70 years who were treated with this new product, 15 had ankylosing spondylitis, 11 had chronic progressive rheumatoid arthritis, 4 had Reiter's syndrome, 4 had psoriatic arthropathy, 8 had osteoarthrosis of the hip and 7 had various forms of rheumatism. The drug was administered orally in suspension form, initially three times per day, then twice, the total daily doses being 15 ml (6 g) or 20 ml (8 g). Treatment was regarded as effective in 62% of the cases, and of these 62%, 46% good and very good results were obtained. In 88% of the patients, tolerance was satisfactory and of these, it was excellent in 80%. Only in 2 cases did treatment have to be discontinued on account of side effects. From the biological point of view, uricaemia was significantly reduced in 7 patients, and in 6 patients uricuria increased. With regard to the level of salicylate in the blood assays showed that it is the same for 6 g benorylate and for 4 g aspirin. Benorylate has been shown to be an effective treatment for both inflammatory and degenerative rheumatic disorders. The results of its use can be compared with those obtained by acetylsalicylic acid, but is better tolerated. In addition, in chronic disorders it is better to have to take the product only twice per day.

Topics: Administration, Oral; Adult; Aged; Arthritis; Arthritis, Rheumatoid; Drug Evaluation; Female; Humans; Male; Middle Aged; Osteoarthritis; Rheumatic Diseases; Salicylates

Topics: Arthritis, Juvenile; Arthritis, Reactive; Arthritis, Rheumatoid; Chemotaxis; Exudates and Transudates; Humans; Joint Diseases; Leukocytes; Osteoarthritis; Phenylbutazone; Rheumatoid Factor; Salicylates; Synovial Fluid

Topics: Aged; Ankle Joint; Arthritis; Arthritis, Rheumatoid; Arthroplasty; Bursitis; Gout; Hip Joint; Humans; Indomethacin; Knee Joint; Laminectomy; Middle Aged; Osteoarthritis; Osteotomy; Phenylbutazone; Physical Therapy Modalities; Radiography; Salicylates; Shoulder Joint; Spinal Diseases; Tarsal Joints; Wrist Joint

A survey of 763 patients with rheumatoid arthritis and 145 with osteoarthritis in six clinics in New Zealand showed no association between aspirin intake and a score designed to detect analgesic nephropathy. Analgesic nephropathy was diagnosed clinically in three patients taking APC (aspirin, phenacetin, and caffeine or codeine or both) and in one who took aspirin and phenylbutazone and was suspected in one who took aspirin and paracetamol. Isolated aspirin was not implicated. The study showed that most people can take large quantities of salicylates without renal injury.The findings are, however, consistent with the view that there is a risk from APC compounds taken in large quantity, but the numbers at risk in this study were small. Aspirin may have an additive effect with other analgesics in causing renal damage. An increased frequency of urinary tract symptoms in those taking analgesics requires further investigation.

Topics: Acetaminophen; Adult; Arthritis, Rheumatoid; Aspirin; Caffeine; Codeine; Drug Synergism; Female; Humans; Kidney Diseases; Male; Middle Aged; New Zealand; Osteoarthritis; Phenacetin; Phenylbutazone; Salicylates; Urinary Tract Infections

Topics: Aged; Bursitis; Calcinosis; Cartilage, Articular; Diagnosis, Differential; Female; Humans; Knee; Ligaments, Articular; Male; Middle Aged; Nerve Compression Syndromes; Osteoarthritis; Osteotomy; Postoperative Complications; Radiography; Salicylates

Topics: Adrenal Cortex Hormones; Chronic Disease; Humans; Indomethacin; Osteoarthritis; Phenylbutazone; Salicylates; Spondylitis, Ankylosing

Topics: Administration, Oral; Adult; Arthritis; Arthritis, Rheumatoid; Aspirin; Bursitis; Humans; Middle Aged; Osteoarthritis; Psoriasis; Salicylates; Synovial Fluid; Synovitis; Time Factors

Topics: Administration, Oral; Back Pain; Drug Tolerance; Humans; Injections, Intramuscular; Injections, Intravenous; Osteoarthritis; Rheumatic Diseases; Salicylates; Sciatica

Topics: Adult; Alkaptonuria; Ascorbic Acid; Humans; Male; Methylthiouracil; Middle Aged; Osteoarthritis; Radiography; Salicylates

Topics: Adrenal Cortex Hormones; Analgesics; Anti-Inflammatory Agents; Antidepressive Agents; Arthritis, Reactive; Arthritis, Rheumatoid; Drug Synergism; Humans; Osteoarthritis; Rheumatic Diseases; Salicylates; Spondylitis, Ankylosing

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Emulsions; Female; Heparinoids; Humans; Male; Middle Aged; Nicotinic Acids; Osteoarthritis; Salicylates; Spinal Diseases

Topics: Adult; Anti-Inflammatory Agents; Bone Transplantation; Exercise Therapy; Female; Humans; Intervertebral Disc; Lumbar Vertebrae; Male; Middle Aged; Myelography; Osteoarthritis; Salicylates; Spinal Cord Compression; Spinal Diseases; Spinal Fusion; Transplantation, Autologous

Topics: Adrenal Cortex Hormones; Aged; Analgesics; Balneology; Female; Humans; Male; Middle Aged; Osteoarthritis; Physical Therapy Modalities; Salicylates; Shoulder

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Chloroquine; Gold; Humans; Hyaluronic Acid; Hydrocortisone; Joints; Osteoarthritis; Salicylates; Synovial Fluid

Topics: Adrenal Cortex Hormones; Arthritis, Rheumatoid; Exercise Therapy; Gold; Hot Temperature; Osteoarthritis; Salicylates; Temporomandibular Joint

Topics: Camphor; Drug Therapy; Humans; Injections; Injections, Intra-Articular; Knee Joint; Oils; Osteoarthritis; Salicylates

Topics: Administration, Oral; Aspirin; Blood; Blood Chemical Analysis; Drug Therapy; Geriatrics; Humans; Osteoarthritis; Salicylates; Salicylic Acid

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Hypoparathyroidism; Osteoarthritis; Pantothenic Acid; Phenylbutyrates; Salicylates

Topics: Adrenal Cortex Hormones; Antimalarials; Arthritis; Arthritis, Rheumatoid; Gold; Humans; Osteoarthritis; Phenylbutazone; Physical Therapy Modalities; Salicylates

Topics: Acetaminophen; Analgesics; Analgesics, Non-Narcotic; Antipyretics; Aspirin; Diagnosis, Differential; Humans; Osteoarthritis; Oxyphenbutazone; Phenacetin; Phenylbutazone; Physical Therapy Modalities; Salicylates

Topics: Disease; Knee; Knee Joint; Osteoarthritis; Salicylanilides; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Humans; Osteoarthritis; Rheumatic Diseases; Salicylates

Topics: Arthritis; Arthritis, Rheumatoid; Aspirin; Humans; Osteoarthritis; Salicylates; Succinates; Succinic Acid