Nonsteroidal anti-inflammatory drugs as potential ecto-nucleotide phosphodiesterase inhibitors

Phosphodiesterases (PDE) are group of enzymes which catalyze the hydrolysis of cAMP and cGMP. Since these cyclic phosphate moieties worked as intracellular second messengers in numerous physiological processes, their inhibition can affect normal physiology of living system. NSAIDs are among the frequently prescribed medications, because of their efficacy as analgesic, antipyretic and anti-inflammatory agents. They are known to block cyclooxygenase pathway. In limited data NSAIDs has been shown anti-tumor potential, and phosphodiesterase inhibition has assumed to be one of the mechanism. To date no further evaluation being done. Further, NSAIDs are classified as cyclooxygenase inhibitors and phosphodiesterase inhibition can imprint its side effects. This study first time investigates the effects of NSAIDs on phosphodiesterase 1 inhibition. The activity against snake venom phosphodiesterase 1 was assayed on a microtitre plate reader spectrophotometer. Selective COX-2 inhibitor, celecoxib, exhibited a potent PDE1 inhibitory activity, at therapeutic doses, with an IC50 value of 29.4 µM. The findings of our study are indicative of new pharmacological actions of cyclooxygenase inhibitors. This article presents the PDE inhibitory properties as a new effects of already existing drugs. These additional effects could be potentially helpful for researchers to assess other physiological and pathological states.

Respondiendo a la interrogante: ¿el metamizol es o no un antiinflamatorio no esteroideo? / Answering the question: is metamizole a non-steroidal anti-inflammatory or not?

Resumen: El objetivo de este artículo es determinar la importancia del metamizol como analgésico en México, al conocer la frecuencia de su uso y los mecanismos de acción y así clasificar adecuadamente al medicamento dentro de la farmacopea de analgésicos. Pocos fármacos generan discusión sobre su filiación, pero el metamizol, desde que salió al mercado en 1922 hasta el día de hoy, se mantiene sin definirse claramente. Comúnmente cuando se busca una clasificación de los antiinflamatorios no esteroideos (AINE), se clasifica al metamizol dentro de los mismos como derivados de la pirazolona. Se debe comenzar entonces con los aspectos farmacológicos para relacionar las semejanzas y diferencias con otros AINEs y poder sacar conclusiones adecuadas. Aun así, el medicamento es de los más utilizados por los médicos en los hospitales de segundo y tercer nivel (82%), aunque la mayoría no sabe en realidad cuál es su mecanismo de acción (91%), por ello, la importancia de conocer el mecanismo de acción de este fármaco.

Abstract: The aim of this article is to know the importance of metamizol as analgesic in Mexico, knowing the frequency of their use and the mechanisms of action and to adequately classify the drug in the pharmacopoeia of painkillers. Few drugs generate discussion about their parentage but metamizol from that hits the market in 1922 until today, it has no clearly defined. Commonly when NSAIDs rated seeks to metamizol is classified within the same as pyrazolone derivatives. We then start with the pharmacological aspects and later to know the similarities and differences with other NSAIDs and can draw appropriate conclusions. Even so, the medicine is one of the most used by physicians in second and third level hospitals (82%), although most do not really know what their mechanism of action is (91%), so the importance of knowing the mechanism of action of this drug.

Effect of premedication with aceclofenac and ibuprofen on the success rate of two different local anesthetic agents in irreversible pulpitis cases of maxillary posterior teeth (a prospective randomized double-blind clinical trial)

A double blind, randomized controlled clinical trial was done to investigate the effect of analgesics aceclofenac and ibuprofen in reducing pre-operative pain following local anesthesia with lidocaine and articaine. One hundred and twenty patients with irreversible pulpitis of the maxillary premolars and first molar region were randomly divided into 2 groups with group 1, 2% lidocaine with 1:200000 epinephrine and group 2, 4% articaine with 1:100000 epinephrine. The two groups were again subdivided into 3 subgroups in which patients were given identical capsules containing ibuprofen 600 mg, aceclofenac 100 mg, placebo (vitamin tablets), half an hour before the administration of buccal infiltration anesthesia. Patients indicated their pain scores on a Heft Parker Visual analog scale (VAS). Infiltration anaesthesia was given under sterile condition.1 min after the injection, electric Imrana Tasneem, B.R. Bharat, Murari Uday Kumar, Srirekha A. Effect of premedication with aceclofenac and ibuprofen on the success rate of two different local anesthetic agents in irreversible pulpitis cases of maxillary posterior teeth (a prospective randomized double-blind clinical trial). IAIM, 2019; 6(5): 40-45. Page 41 pulp test and cold test were done and testing was repeated after every 2 minutes for a total of 10 minutes. Premedication with ibuprofen (600 mg) and aceclofenac (100 mg) resulted in statistically significant increase in onset of action for both the anesthetic agents. There was no significant difference in the time of onset of anesthesia between the two local anesthetic solution (chi-square test/ One way ANOVA).

Prescription pattern of analgesics in orthopedics outpatient department at a tertiary care hospital.

Background: Analgesics are the most common class of drugs prescribed for various conditions in the orthopedics outpatient department (OPD). This study is performed for a better understanding of analgesics prescribing pattern in orthopedics and to correlate the use of selective cyclooxygenase-2 (COX-2) inhibitors, conventional non-steroidal anti-infl ammatory drugs (NSAIDs), and opioid analgesics in practice in the present scenario. Methods: The prescriptions from the OPD of Orthopedics at Dr. B. R. Ambedkar Medical College was reviewed between June 2013 and November 2013, entered in a pre-designed proforma. Pain was quantifi ed using numeric rating scale. The type of analgesics administered, whether monotherapy or combined therapy and the duration of therapy, was analyzed to obtain an overview of the current prescribing pattern. Results: A total of 300 prescriptions were analyzed. 800 drugs were prescribed with an average of 2.6 drugs per prescription. Of these, 62.3% were NSAIDs, 15.4% were opioid analgesics and 22.3% were gastroprotective agents. 61% of the NSAIDs were prescribed as monotherapy and 39% were prescribed as fi xed drug combination (FDC). The ratio of selective to non-selective NSAIDs is 1.3:1. Conclusions: The results of the present study show frequent use of selective COX-2 inhibitors, although non-selective NSAIDs topped the list of various selective NSAIDs, non-selective NSAIDs, and opioid analgesics. This suggests that gastrointestinal safety was an important concern while prescribing these drugs. Many FDCs were found to be irrational.

Ciprofloxacin induced fixed drug eruption.

Fixed drug eruption (FDE) is a clinical entity occurring in the same site or sites each time the drug is administered. Acute lesions appear as sharply marginated erythematous plaques, which are usually found on lips, genitalia, abdomen, and legs. The eruptions usually occur within hours of administration of the offending agent and resolves spontaneously without scarring after few weeks of onset. Most common drugs causing FDE are sulfonamides, tetracyclines, salicylates, barbiturates, doxycycline, fluconazole, clarithromycin, etc. Ciprofloxacin, a widely used fluoroquinolone antimicrobial, induces cutaneous adverse drug reactions (ADRs) in about 1-2% of treated patients. Urticaria, angioedema, maculopapular exanthems, and photosensitivity are the most frequently documented cutaneous adverse reactions. In this case report, the patient soon after taking ciprofloxacin tablets, developed itching in the lips, palms and in scrotal region. On continuing the treatment, the next day he developed fluid filled lesions over palm, knuckle, and hyperpigmentation. He gives a history of severe itching and rashes in scrotal region. He gives a history of similar complaints in the previous month after taking ciprofloxacin medication. There was no history of intake of any other medication. On examination, bullous lesions and pustules in finger webs, hyperpigmentation on knuckles, and scrotal erosions were seen. In the present case report, the patient presented with FDE immediately after oral administration of ciprofloxacin and got completely cured after stopping the drug and taking adequate treatment. According to the Naranjo’s ADR probability scale (score=8), this ADR is categorized as a “probable” reaction to the drug.

Efficacy of Topical NSAIDs and Anesthetic Drug in Reducing Post-PRK Pain: Comparative Study

To evaluate the efficacy and safety of topical NSAIDs and topical anesthetics on post-PRK pain control, we performed a prospective, randomized, paralle group, placebe-controlled study of 105 consecutive eyes having excimer laser PRK, that were divided into 7 pain management groups. The groups were arranged in order, Group 1: Suprofen(Profenal), Group 2: Diclofenac I(Naclof), Group 3: Diclofenac II (Decrol), Group 4: diluted proparacaine, Group 5: Diclofenac I(Naclof)+diluted proparacaine, Group 6: Fluorometholone, Group 7(conrol): Tears Naturale. Results were evaluated by several types of questionnaires and pain score was recorded using visual analogue scale. Corneal epithelial defect area was measured on post-operative day 1, 2, 3, 4 and 1 week. Diclofenac-treated groups showed the best analgesic effect and the least discomfort at instillation. Diclofenac, used with diluted proparacaine, had some additive effect on pain control, but not statistically significant. Full epithelial closure occurred in all eyes within 4 days without any clinically significant complications. Topical diclofenac and combinatin with diluted proparacaine can be used in post-PRK pain management effectively and safely.