Diclofenac Sodium In Treatment Research Articles

Effect of prenatal exposure to diclofenac sodium on the male rat arteries: a stereological and histopathological study

In this study, we investigated the morphometric and histological alterations of the aorta, brachial, and femoral arteries in 4- and 20-week-old rats that were prenatally exposed to diclofenac sodium (DS). For this purpose, pregnant rats were divided into three groups: control, saline injected, and drug treated. Beginning from day 5 after mating through day 15 of pregnancy, saline or DS (1 mg/kg daily) was intraperitoneally injected into groups 2 and 3. No injection was given to the rats in the control group. After spontaneous delivery, male offspring were obtained. At the end of weeks 4 and 20, vessel samples were removed. After dissection and routine histological preparation, histopathological and stereological investigations were made. Our results indicate that both saline and DS application lead to a decrease in the mean volume fraction of tunica media in all vessel walls, but result in an increase of the same fraction of lumen to the whole vessel wall, especially in 4-week-old rats. Elastic fibers of the vessel wall were affected by DS treatment, because a decrease of the elastic fiber was observed in this group. Finally, in light of our findings, we suggest that DS or saline may lead to vascular changes (i.e., vasodilatation or vasoconstriction) in rats that are prenatally subjected to increased volume of maternal blood resulting from injection.

Intramuscular Drotaverine and Diclofenac in Acute Renal Colic: A Comparative Study of Analgesic Efficacy and Safety

To evaluate the analgesic efficacy and safety of intramuscular drotaverine hydrochloride vs diclofenac sodium in treatment of acute renal colic. We conducted a randomized, single-blind study comparing single intramuscular doses of drotaverine hydrochloride (80 mg) vs diclofenac sodium (75 mg) on 100 patients (50 in each arm) presenting to the emergency department (ED) with renal colic. Subjects with inadequate pain relief at 30 minutes received rescue intramuscular tramadol (100 mg). Pain intensity was recorded using a visual analog scale (VAS), which is the primary outcome measure of this study, before drug administration and 30 and 60 minutes afterwards. The drug effectiveness was defined as ≥50% decrease in pain intensity 60 minutes after intramuscular administration, without exacerbation during the following 2 hours. The need for rescue medication and the presence of adverse effects were considered as secondary outcome of the study. VAS decreased significantly (P < 0.001) with both drotaverine (52.4%) and diclofenac (49%) at 30 minutes. Reduction of VAS at 60 minutes was 61.3% with drotaverine in comparison to 60.4% with diclofenac. Forty-five patients (90%) in the drotaverine group and 44 (88%) in the diclofenac group found the therapy effective. The need for rescue medication was in five patients of the drotaverine group and six patients in the diclofenac group. There was no significant difference in safety profile in the study groups. The efficacy and safety of drotaverine as analgesic in renal colic is noninferior to diclofenac and may be used as an alternative or add-on therapy to currently available options.

Diacerein as adjuvant to diclofenac sodium in osteoarthritis knee

To evaluate clinical effectiveness of diacerein as an adjuvant to diclofenac sodium in treatment of Indian patients with symptomatic osteoarthritis (OA) knee. This is a prospective, double-blind, placebo-controlled and intention-to-treat study. An initial washout period of 1 week, was followed by 3 months treatment period during which patients were randomly divided to receive either capsule diacerein 50 mg or matched placebo once daily for the first month and twice daily for the next 2 months with diclofenac sodium 75 mg sustained release tablet once daily given to both groups. Patients were observed for one more month, using paracetamol as rescue therapy. Treatment efficacy was assessed by a visual analogue scale (VAS) and the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, patient and physician global assessment of OA, daily paracetamol intake. Of 84 patients screened, 74 patients formed the intent-to-treat population (37 patients in each group). At baseline, both groups were comparable and at the third month functional index and pain intensity were better in the diacerein group (VAS 15.33 ± 5.07; WOMAC 15.9 ± 2.40) as compared to the placebo group (VAS 22.83 ± 6.90;WOMAC 36.8 ± 2.92; P < 0.05). When analyzed at the fourth month, improvement persisted in the iacerein group (VAS 14.83 ± 5.16; WOMAC 16 ± 2.5) as compared to placebo group (VAS 33 ± 7.72; WOMAC 48.26 ± 3.5; P < 0.05), demonstrating the carry-over effect of diacerein, which was confirmed by lesser paracetamol consumption in the diacerein group (5.967 ± 0.8087) as compared to the placebo group (12.433 ± 2.128; P < 0.05). Use of diacerein and diclofenac sodium together decreases pain and improves joint function significantly more than diclofenac alone in OA knee.

Perubahan kadar hemoglobin akibat terapi kurkuminoid ekstrak rimpang kunyit dibandingkan natrium diklofenak pada penderita osteoartritis

Background: In general, patients with osteoarthritis require long live treatments, especially anti-infammatory drugs. Non steroidal anti infammatory drugs are mostly follow by some side effects such as dyspepsia and gastrointestinal bleeding. The use of natural medicine for rheumatic diseases have commonly been practiced worldwide.Objectives: To learn the changes of hemoglobin level due to treatment with curcuminoid from Curcuma domestica Val. rhizome extract compared to diclofenac sodium as anti-infammatory agent for the treatment of osteoarthritis.Methods: This research is a prospective randomized open end blinded evaluations (PROBE). Patients treated with 30 mg curcuminoid from Curcuma domestica Val. rhizome extract or 25 mg diclofenac sodium three times daily for 4 weeks respectively.The hemoglobin level was checked before and after treatment. Results: A total of 80 patients with knee osteoarthritis participated in this study. There was no signifcant difference in the frequency of sex, educational level, duration of suffering, percentage of co-morbidities in both groups. There was no signifcant different of hemoglobin level before treatment between both treatment group. The hemoglobin level was increase signifcantly in curcuminoid treatment groups while no signifcant change in diclofenac group. Treatment with curcuminoid increasing the hemoglobin level signifcantly compare to diclofenac sodium (p=0.03).Conclusion: Treatment with curcuminoid from Curcuma domestica Val. rhizome increasing the hemoglobin level signifcantly compare to diclofenac sodium treatment for osteoarthritis.

A histological investigation concerning the effects of diclofenac sodium to the lung in 4- and 20-week-old rats treated prenatally

Objective. We aimed to investigate the possible postnatal effects on the lung tissues of the rat offspring treated with diclofenac sodium (DS) during pregnancy.Methods. After mating, pregnant female rats were separated into the control (n = 10) and DS (n = 10) groups. DS (1 mg/kg) was injected intraperitoneally (i.p) to the drug-treated group for the period of gestational days 5–19. Physiological saline (1 ml, i.p.) was given to the control groups. After birth, pups were separated into DS treatment groups (n = 24) and control group (n = 24). The DS and control group animals were anaesthetised with i.p. injection of urethane and their lungs were removed to prepare for histopathological evaluation.Results. Histological examination of the lung tissues of the 4- and 20-week-old rats revealed no significant differences between males and females in both the control and DS treated rats.Conclusion. Because of the use of DS in the pregnant women further studies are needed in this field.

Diclofenac Sodium, a Nonselective Nonsteroidal Anti-Inflammatory Drug Aggravates Doxorubicin-Induced Cardiomyopathy in Rats

The cardiotoxic effects of selective cyclo-oxygenase-2 inhibitors are well documented. Recently, concerns have been raised over the cardiovascular safety of nonselective nonsteroidal antiinflammatory drugs. The aim of this study was to assess the cardiac effects of diclofenac sodium on doxorubicin-induced cardiomyopathy in rats. Male Wistar rats were treated with doxorubicin (15 mg/kg intraperitoneally, single dose), diclofenac sodium (2.5 and 10 mg/kg/day, respectively, by gavage for 5 days) alone and doxorubicin + diclofenac sodium treatment, 24 hours after doxorubicin administration. Doxorubicin-induced a significant (P < 0.001) increase in the serum lactate dehydrogenase, cardiac thiobarbituric acid-reactive substance and catalase levels and a significant (P < 0.001) decrease in the cardiac glutathione and superoxide dismutase levels, which were significantly (P < 0.001) aggravated by diclofenac sodium treatment. Diclofenac sodium alone also showed a significant change in these parameters compared with the control. Ultrastructural studies showed that doxorubicin causes apoptosis in myocardium, which was characterized by condensation of chromatin network at the margins of nuclear membrane. Apoptosis induced by doxorubicin was exacerbated by diclofenac sodium treatment. Thus, our study indicates that diclofenac sodium, a nonaspirin nonsteroidal anti-inflammatory drug, is not free from cardiotoxicity and aggravates doxorubicin-induced cardiomyopathy in rats.

Diclofenac induced toxic manifestations on adjuvant induced arthritic rats pheripheral and reproductive organ of male wistar rats rattus norvegicus

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are the most frequently prescribed therapeutic agents, used for the treatment of rheumatic diseases, because they have analgesic, antipyretic and anti- inflammatory actions. Diclofenac (Voltaren) is a well-known member of the acetic acid family of NSAIDs, used to reduce inflammation and pain associated with arthritis osteoarthritis, and ankylosing spondylitis. There is considerable interest in the toxicity of diclofenac because of its clinical use and for the study of the mechanisms of nephrotoxicity, renal dysfunction, hematotoxicity and hypersensitivity reactions. In the present study we have reported the basic metabolites and activities of enzymes were studied in different tissues against adjuvant and diclofenac sodium treatment. The change due to the adjuvant treatment was attributed to the inflammation associated changes and the further alteration in diclofenac sodium was implicated to its toxic manifestation, besides the drug side effect is caused by metabolic idiosyncrasy. Key words: Inflammation, adjuvant arthritis, metabolites, enzymes.

Development of a novel floating pulsatile system for chronotherapeutic release of diclofenac sodium

The main objective of the present study was to develop a multiple-unit, floating-pulsatile drug delivery system for obtaining no drug release during floating and in the proximal small intestine followed by pulsed, rapid drug release in distal small intestine to achieve chronotherapeutic release of diclofenac sodium for treatment of rheumatoid arthritis. The system developed consists of drug containing core pellets prepared by extrusion-spheronization process, which were coated with an inner pH-dependent layer of Eudragit S100 and outer effervescent layer of sodium bicarbonate and HPMC K100M (Hydroxypropyl methylcellulose- K100M; HPMC; Methocel K100M premium, Colorcon Asia Pvt. Ltd., India). Developed formulations were evaluated for particle size analysis, friability, scanning electron microscopy, in vitro buoyancy studies and in vitro drug release studies. Outer effervescent layer prolongs the gastric residence time and inner layer prevents the drug release in acidic medium. Pellets showed instantaneous floating with no drug release in acidic medium followed by pulsed drug release in basic medium. Concentration of HPMC K100M and layering level of effervescent agent significantly affected performance of pellets. The system showed excellent lag phase followed by burst release in the distal small intestine which gives site and time specific delivery of diclofenac sodium which could serve in the chronotherapy of rheumatoid arthritis Keywords : Floating-pulsatile drug delivery; Chronotherapy; Diclofenac sodium; Rheumatoid arthritis Journal of Pharmacy and Bioresources Vol. 4 (2) 2007: pp. 32-38

Morphological Studies on Crushed Sciatic Nerve of Rabbits with Electroacupuncture or Diclofenac Sodium Treatment

Sciatic nerves of 15 rabbits were crushed by Halsted straight mosquito hemostat with 8-11 Newton force for 60 seconds on a point 5 mm above the knee joint, and then the rabbits were equally divided into three groups. The acupuncture group was treated by electroacupuncture on Huan Tiao and Wei Zhong points (25 minutes/day) for 7 days. The medicine group was treated with intramuscular administration of dicofenac sodium (15 mg) daily for 7 days. The control group was not treated. After treatment, the distal parts of crushed nerve were examined under light microscope, the densities of normal myelinated fibers in 0.126 mm2 were counted, and the diameters of 20 normal myelinated fibers were measured for each animal. The results showed that the mean densities were 176.2 +/- 5.953 in the acupuncture group, 118.2 +/- 10.878 in the medicine group and 101.4 +/- 8.548 in the control group. The mean values were significantly different between the acupuncture and medicine groups (p < 0.01) and highly significant difference between the acupuncture and control groups (p < 0.001); but there was no significant difference between the medicine and control groups (p > 0.05). There are more small myelinated fibers (0-9 microm) in the acupuncture group than in the medicine and control groups (p = 0.0028). The results revealed and confirmed that acupuncture promotes nerve regeneration; diclofenac sodium did not show such an effect. The present study demonstrates the positive effect of acupuncture on regeneration of a crushed sciatic nerve in the rabbits. And acupuncture is a better treatment for regeneration of crushed nerve than diclofenac sodium.

Drugs and Wells' syndrome: a possible causal relationship?

In April 1997, a 28‐year‐old woman presented with a 3‐day history of multiple papules and vesicles on the fingers and wrist of her right hand. She reported that she had been taking nonsteroidal anti‐inflammatory drugs containing tenoxicam and diclofenac sodium, and had no history of an insect bite. The medical history also included pruritic erythema on her trunk 1 month before her initial visit, and oral tenoxicam and diclofenac sodium treatment for ankle arthralgia 2 days before the skin lesions appeared. At that time, her dermatologist had told her that the skin lesions might be due to an insect bite and were secondarily infected. She took amoxicillin for the lesions, and during the following days developed bullous lesions on her hands and feet. The patient was diagnosed with ‘‘drug reaction’' at another hospital based on a histopathologic examination of the affected skin. Treatment with topical corticosteroids and oral antihistamines was ineffective.Physical examination revealed a few crusted, erythematous, papular lesions on the dorsal aspects of the patient's feet, bullous lesions on her right wrist, and vesiculopapules on her fingers. She had no fever or other abnormal clinical findings.Laboratory studies showed a white blood cell count of 6000/mL with 16.5% eosinophils. A bacterial culture of the content of one of the bullous lesions was negative. The results of stool tests for parasites and ova were negative. Clinical and laboratory findings were in line with the diagnosis of drug reaction. The patient was advised not to take nonsteroidal anti‐inflammatory drugs. The skin lesions resolved rapidly on treatment with wet compresses of Burow's solution and oral prednisolone (40 mg/day). The dose of prednisolone was gradually reduced, and was discontinued after 3 weeks. The patient was readmitted in July 1997 for an indurated, erythematous plaque on her left foot, a lesion that resembled cellulitis. Her history at that time included the initiation of amoxicillin treatment for a gingival abscess 2 days before the skin lesion appeared. The lesion regressed after amoxicillin was discontinued and the patient received an intramuscular injection of triamcinolone acetonide.Several months later, in October 1997, she developed a similar cellulitis‐like lesion on her right ankle. This time there was no history of drug intake. We obtained a skin biopsy from the lesion, and histopathology revealed an intense eosinophilic infiltrate in the dermis and extending into the subcutaneous tissue. Flame figures were abundant (Fig. 1). We also observed edema and erythrocyte extravasation in the dermis. Based on these features and her history, a diagnosis of Wells' syndrome was made. The skin lesion resolved spontaneously, and she has experienced no lesion recurrence since.A characteristic ‘‘flame figure’' (hematoxylin and eosin stain; original magnification, × 230)image

Arachidonic Acid Metabolites After Excimer Laser Corneal Surgery

We investigated early mediators of inflammation following excimer laser ablation in a rabbit cornea model. The ability of topical anti-inflammatory agents to influence these responses was also examined. Adult New Zealand white rabbits were subjected to photorefractive keratectomy with a 193-nm argon fluoride excimer laser. Prostaglandin E2 and leukotriene B4 levels were measured using an enzyme immunoassay, and leukocyte infiltration was determined histologically. Prostaglandin E2 production was rapid and sustained, but we were unable to detect the presence of leukotriene B4. Relative to control, postoperative topical diclofenac sodium treatment caused a significant decrease in prostaglandin E2 levels and a significant increase in corneal leukocytes at 10 hours. Fluorometholone treatment did not significantly alter prostaglandin E2 levels but markedly depressed leukocyte ingress. Diclofenac reduces prostaglandin E2 levels but not leukocyte infiltration in the cornea following photorefractive keratectomy and thus may be useful clinically to reduce postsurgical pain.