Antiinflamatory Agents Less Dangerous for Gastrointestinal Tract

Abstract

NSAIDs represent one of the most commonly used therapeutic drug groups world wide. 1.5% of the world's population is estimated as taking NSAIDs. However, their use is not risk free and gastrointestinal (GI) lesions do appear, which is indeed the main reason for their toxicity. Frequently (50%) NSAID-induced GI lesions are asymptomatic, and perforations or hemorrhages could occur without any previous symptoms. 71% of GI perforations and 50% of upper gastric hemorrhages (UGH) are associated with taking NSAIDs. How frequent GI lesions appear is directly related to whether the patient is in a risk group or not. Factors increasing the risk of GI lesions occurring are the following: being older than 60, using corticoids or other NSAIDs concomitantly, having a history of duodenal ulcer, alcohol consumption, smoking or taking oral anticoagulants. As the toxicity and how frequent the lesions appear depend on which drug is used, there is a need for research into new drugs which are both clinically effective and safer to use. GI toxicity of NSAIDs is mediated by two mechanisms, direct toxicity and prostaglandin synthesis inhibition or sistemic mechanism. Due to the relatively recent discoveries concerning the physiopathology of inflammation and gastric physiology, research into new NSAID derivatives is taking place. Such derivatives are prodrugs, galenic buffer forms, selective COX-2 inhibitors, isomeric compounds, NO-donors, and as a future possibility, phosphodiesterase inhibitors.

Multicentre, controlled, randomised and blinded field study comparing efficacy of suxibuzone and phenylbutazone in lame horses

“…This may be caused by the direct local damage of the superficial epithelial cells of the gastric mucosa additionally to the systemic effect mediated by unspecific cyclooxygenase inhibition (Scheiman 1994). To avoid this local effect and minimise the risk of side effects, the use of both specific enteric forms and prodrugs with lower direct toxicity than the parent compound has been proposed (Rodríguez-Téllez et al 2001).…”

“…In horses, SBZ is converted to PBZ and oxyphenbutazone immediately after its absorption from the GI tract (Mayós 2002). The direct epithelial cell damage attributable to PBZ's gastric mucosal irritation potential is therefore avoided, as described for other prodrugs (Sheiman 1994;Rodríguez-Téllez et al 2001).…”

31P Magnetic Resonance Spectroscopy of Endothelial Cells Grown in Three-Dimensional Matrigel Constructs as an Enabling Platform Technology: II. The Effect of Anti-Inflammatory Drugs on Phosphometabolite Levels

“…Such effects may be also encountered upon implantation of a tissueengineered construct containing a NSAID. One approach to reduce the adverse effects of NSAIDs is the use of a prodrug strategy (Rodriguez-Tellez et al 2001). We took advantage of a newly developed indomethacin prodrug (DP-155; Dvir et al 2006) to study its effects on the 31 P MRS phospholipid profile of ECs grown in 3D Matrigel threads.…”

Antiinflamatórios não esteróides inibidores da ciclooxigenase-2 (COX-2): aspectos atuais

“…Estas são responsáveis pela manutenção da integridade da mucosa gástrica, reduzem a secreção de ácido, aumentam a secreção de bicarbonato e melhoram o fluxo sangüíneo na microcirculação da mucosa 36,38 . O sangramento No entanto, ainda existem pontos a serem esclarecidos, pois a probabilidade de desenvolvimento de lesões gástricas em paciente em uso de AINES depende de fatores de risco preexistentes (ex: fumantes, indivíduos em uso de anticoagulante, corticosteróides, pacientes que necessitam de altas doses de AINES, em uso de aspirina, alcoólatras, idosos, histó-ria de úlcera péptica e/ou dispepsia prévia) 41 . Indivíduos com historia de úlcera péptica e sangramento gastrointestinal em uso de AINE têm risco de complicações gastrointestinais em torno de 5% ao ano, em contraste com uma incidência de 0,4% de chance em pacientes sem história prévia 12 .…”

“…However, there are still questions to be answered because the probability of developing gastric injuries in patients using NSAIDs depends on preexisting risk factors (e.g. : smokers, users of anticoagulants, steroids, patients needing high NSAID doses, using aspirin, alcohol abusers, elderly, peptic ulcer and/or dyspepsia history) 41 . Individuals with a previous history of peptic ulcer and GI bleeding and using NSAIDs have an approximately 5% risk a year for developing GI complications, as compared to 0.4% in patients without previous history 12 .…”