Pathophysiology and First-Line Treatment of Osteoarthritis

2002 ◽  
Vol 36 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Jesse H Hogue ◽  
Tracey L Mersfelder

OBJECTIVE: To review the pathophysiology of osteoarthritis (OA) and the various treatment modalities, focusing specifically on acetaminophen (APAP), nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors as the primary treatment options. DATA SOURCES: Primary literature and tertiary references were identified by a MEDLINE search (1966–March 2001) and through other secondary sources. STUDY SELECTION AND DATA EXTRACTION: After evaluating the articles and references identified from the data sources, all the information that was judged relevant by the reviewers was included in the review article. DATA SYNTHESIS: OA is the most common joint disorder worldwide. Current research suggests that factors such as inflammation and changes in subchondral bone may play a larger role in the pathophysiology than previously thought. With this research and the development of COX-2 inhibitors, selecting the medication of choice for OA has become difficult. CONCLUSIONS: More research needs to be done before the pathophysiology of OA can be clearly determined. In the meantime, treatment should be based on clinical data and patient response. Studies have shown that APAP and NSAIDs have comparable efficacy, as do traditional NSAIDs and COX-2 inhibitors. APAP is associated with fewer toxicities than are the traditional NSAIDs. Due to their mechanism of action, the new COX-2 inhibitors should result in fewer adverse effects compared with traditional NSAIDs, but evidence from clinical trials has not been conclusive. Therefore, APAP should still be considered the drug of choice for OA.

2000 ◽  
Vol 34 (6) ◽  
pp. 743-760 ◽  
Author(s):  
Brigitte T Luong ◽  
Barbara S Chong ◽  
Dionne M Lowder

OBJECTIVE: To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). DATA SOURCES: A MEDLINE search (1966–January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. DATA SYNTHESIS: Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. CONCLUSIONS: Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.


2003 ◽  
Vol 37 (4) ◽  
pp. 546-555 ◽  
Author(s):  
Kelly R Ragucci ◽  
Nicole S Culhane

OBJECTIVE: To review the pathophysiology and psychology of female sexual dysfunction (FSD) and describe potential prevention and treatment strategies for the disorder. DATA SOURCES: Articles identified from a MEDLINE search (1966–June 2002) using the term female sexual dysfunction. Additional references were obtained from cross referencing retrieved articles. STUDY SELECTION AND DATA EXTRACTION: After evaluating various review articles, clinical trials, and investigational studies, all information that was deemed relevant by the reviewers was included. DATA SYNTHESIS: FSD is a multicausal and multidimensional problem combining biological, psychological, and interpersonal factors. The American Foundation for Urological Disease classifies FSD into 4 broad categories: sexual desire disorders, arousal disorder, orgasmic disorder, and sexual pain disorders. Depending on specific individual characteristics and category of disorder, a variety of potential treatments are available. Pharmacists can play a role in identifying and managing medication-related adverse effects that may be exacerbating FSD and educating women on treatment modalities. CONCLUSIONS: FSD is a complicated disorder that is often difficult to identify, classify, and treat appropriately. Pharmacists should have an understanding of the potential causes of FSD and the treatment options available so that they may make appropriate recommendations and counsel women effectively.


2005 ◽  
Vol 39 (9) ◽  
pp. 1511-1516 ◽  
Author(s):  
Sarah P Shrader ◽  
Kelly R Ragucci

OBJECTIVE: To present the chemistry, pharmacology, and pharmacokinetics of parathyroid hormone (PTH) (1-84%) and review the available clinical trials that evaluate its efficacy and safety; clinical applicability of this agent and its relationship to other Food and Drug Administration (FDA)–approved medications for treatment of osteoporosis are also discussed. DATA SOURCES: A MEDLINE search (1996–December 2004%) was completed, along with a review of information obtained from the manufacturer, NPS Pharmaceuticals. Key search terms included parathyroid hormone, PTH (1–84%), and ALX 111. STUDY SELECTION AND DATA EXTRACTION: Studies were selected based on their relevance and availability. Pertinent information, including objectives, design, demographics, outcomes, adverse events, dosing strategies, and therapeutic controversies, was extracted. DATA SYNTHESIS: PTH (1-84%) is being developed for treatment of osteoporosis. Recent studies have shown that, when administered intermittently as a subcutaneous injection, PTH (1-84%) produces an increase in bone mineral density and prevents vertebral fractures. The fact that this agent contains the C-terminal region of PTH may differentiate it from PTH (1-34%), teriparatide, which is approved by the FDA for treatment of osteoporosis. Further trials are necessary to determine the role of PTH (1-84%) in combination with other treatments for osteoporosis and/or the order in which PTH (1-84%) is given with these other agents. There are currently no comparative trials with other osteoporosis treatment modalities. CONCLUSIONS: PTH (1-84%), when given intermittently as a subcutaneous injection, appears to be a safe and efficacious treatment option for osteoporosis. Further trials are needed to determine its specific place in therapy compared with other treatment options.


2005 ◽  
Vol 39 (7-8) ◽  
pp. 1249-1259 ◽  
Author(s):  
S Christopher Jones

OBJECTIVE To evaluate the clinical literature on cyclooxygenase-2 (COX-2) inhibitors to determine whether a greater incidence of thromboembolic events is universal within the drug class. DATA SOURCES A MEDLINE search was conducted (1996–March 2005) for key articles in the English language assessing the efficacy or safety of these agents. STUDY SELECTION AND DATA EXTRACTION Randomized, double-blind, and controlled trials, as well as case–control and retrospective cohort studies, that assessed the cardiovascular safety of COX-2 inhibitors were reviewed. DATA SYNTHESIS Seventeen published studies were reviewed, and the cardiovascular safety data were extracted from each trial. The mechanism by which COX-2 inhibitors may induce a thromboembolic event is likely multifactorial involving (1) COX-2–specific isoform binding affinity, (2) drug dose, (3) duration of therapy, and (4) cardiovascular risk profile of the patient. Evidence supports an association between cardiovascular adverse events and the use of rofecoxib, valdecoxib, and celecoxib. However, this risk is not equally distributed among the drugs. Given the relative paucity of data, lumiracoxib and etoricoxib cardiovascular effects remain uncertain. CONCLUSIONS Each COX-2 inhibitor has a unique cardiovascular risk profile. Based on the current evidence, celecoxib is the safest COX-2 inhibitor when prescribed appropriately in the lowest possible dose for the shortest duration in the ideal target population.


2021 ◽  
pp. 1-10
Author(s):  
Sherif M.H. Sanad ◽  
Ahmed E.M. Mekky

In the current study, we reported the tandem synthesis of two series of arene-linked pyrimidinone hybrids with related fused thieno[2,3-b]pyridine moiety. The target hybrids were prepared, in moderate to excellent yields, by the reaction of a ternary mixture of the appropriate of 3-aminothieno[2,3-b]pyridine-2-carboxylate, DMF-DMA, and a series of aryl amines in dioxane at 110 °C for 8 h. The antibacterial activity of the new hybrids was estimated against six susceptible ATCC strains. Hybrids 5g and 7g, linked to a sulfonamide unit, showed the best efficacy against S. aureus and E. faecalis strains with minimum inhibitory concentration (MIC) values of 1.7–1.8 μM, which exceed ciprofloxacin. Furthermore, some of new hybrids were examined as potential inhibitors of four different MRSA and VRE strains. Hybrids 5g and 7g demonstrated more potent efficacy than linezolid against MRSA strains with MIC values of 3.6/3.4 and 1.8/1.7 μM against ATCC:33591 and ATCC:43300 strains, respectively. The prior hybrids displayed a comparable efficacy with linezolid against VRE strains with MIC values of 7.3/6.9 and 3.6/3.4 μM against ATCC:51299 and ATCC:51575 strains, respectively. Additionally, some of the new hybrids were examined as potential COX-2 inhibitors using the reference celecoxib (IC50 of 0.117 µM). Hybrid 7g revealed more potent inhibitory efficacy than celecoxib with IC50 of 0.112 µM, whereas hybrid 5g showed almost inhibitory activity equivalent to celecoxib with IC50 of 0.121 µM. Molecular docking was performed to predict the possible binding interactions between hybrids 5g and 7g with the target COX-2 enzyme.


Author(s):  
Amit Kumar Jha ◽  
Amit Kumar Jha

Various exogenous and endogenous stimuli incite a complex reaction in vascularized connective tissue called inflammation. Non sterodial antiinflammatory drugs are used to reduce inflammation Preferential COX-2 inhibitors namely diclofenac and aceclofenac was taken for my present work and anti inflammatory effect was compared with control and with each other. Student-t-test-was done to compare result. It was found that inflammation varied significantly across the three groups (P=000) compared to control, in~lammation was less in both diclofenac and aceclofenac (P=00). Reduction of inflammation with diclofenac was less, in comparision to aceclofenac at end. Aceclofenac is more efficacious than diclofenac. Keywords: Aceclofenac, diclofenac, Anti inflammatory effect


2017 ◽  
Author(s):  
Maricela Schnur ◽  
Michael Fitzsimons ◽  
Fangfang Xing

Chronic pain impacts the lives of millions of people in significant medical and psychosocial ways. Pharmacologic treatments are steering away from chronic opioid therapy due to serious side effects, an epidemic of prescription opioid abuse, and a lack of clear long-term benefit.  Therefore, nonopioid medications such as nonsteroidal antiinflammatory drugs, acetaminophen, tricyclic antidepressants, lidocaine patch, and anticonvulsants are important opioid-sparing or primary treatment options. Agents such as capsaicin, cannabis, botulinum toxin, and ketamine are less frequently prescribed adjuncts that are under active investigation to determine their roles in chronic pain therapy. Understanding the research can help the clinician determine the risks and benefits of these medications for their patients. In the future, dose and delivery optimization, combination therapy, elucidating the biology of pain, and developing novel agents will improve pharmacologic approaches to treatment.          


2006 ◽  
Vol 96 (10) ◽  
pp. 413-416 ◽  
Author(s):  
Thomas Hohlfeld ◽  
Sebastian Harder ◽  
Artur-Aron Weber

SummaryThe issue of the risk-benefit assessment of cyclooxygenase-2 (COX-2) inhibitors, as compared to traditional non-steroidal anti-inflammatory drugs (tNSAIDs), is far from being resolved. These compounds need to be carefully re-evaluated in order to avoid hasty conclusions, as it happened when COX-2 inhibitors were introduced into clinical practice. Several arguments support the concept, that COX-2 inhibitors remain a valuable therapeutic option at least for selected patients.


1993 ◽  
Vol 27 (2) ◽  
pp. 167-170 ◽  
Author(s):  
Karen A. Pallone ◽  
Morton P. Goldman ◽  
Matthew A. Fuller

Objective To describe a case of isoniazid-associated psychosis and review the incidence of this adverse effect. Data Sources Information about the patient was obtained from the medical chart. A MEDLINE search of the English-language literature published from 1950 to 1992 was conducted and Index Medicus was manually searched for current information. Study Selection All case reports describing isoniazid-associated psychosis were reviewed. Data Extraction Studies were evaluated for the use of isoniazid, symptoms of psychosis, onset of symptoms, and dosage of isoniazid. Data Synthesis The case report is compared with others reported in the literature. The incidence of isoniazid-associated psychosis is rare. Conclusions The mechanism of isoniazid-associated psychosis is uncertain. It appears that isoniazid was associated with the psychosis evident in our patient and in the cases reviewed.


2005 ◽  
Vol 39 (5) ◽  
pp. 944-948 ◽  
Author(s):  
Leisa L Marshall

OBJECTIVE: To report the probable association of angioedema with aspirin therapy and the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib. CASE SUMMARY: A 44-year-old white woman, previously tolerant to aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs), developed angioedema of the lips after ingesting two 325-mg aspirin tablets during one day. The reaction occurred 3 hours after taking the second aspirin and resolved within 3 hours. Two weeks later, the patient took a 25-mg rofecoxib tablet for a sore throat, and she developed angioedema 51/2 hours later. Although the woman took 50 mg of diphenhydramine, the swelling did not subside. She repeated the diphenhydramine dose in the evening and, by noon the next day, 261/2 hours after the angioedema began, it was resolved. The patient's internist prescribed an epinephrine auto-injector and advised her to consult an allergist. With skin testing and oral rechallenge with aspirin, but not rofecoxib, the allergist determined the cause of the reactions to be aspirin-induced angioedema and selective COX-2 inhibitor intolerance. The Naranjo probability scale indicated that aspirin was a highly probable cause and rofecoxib was a probable cause of this patient's angioedema. DISCUSSION: Aspirin-induced angioedema and NSAID intolerance have been well documented. There are reports of both tolerance and intolerance to selective COX-2 inhibitors in patients with documented allergy-like reactions to aspirin and NSAIDs. CONCLUSIONS: Patients with aspirin and NSAID intolerance may develop intolerance to COX-2 inhibitors, especially with repeated exposure.


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