Current approaches to prevent NSAID‐induced gastropathy – COX selectivity and beyond

Abstract

Gastrointestinal (GI) toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is still an important medical and socio-economic problem -despite recent pharmaceutical advances. To prevent NSAID-induced gastropathy, three strategies are followed in clinical routine: (i) coprescription of a gastroprotective drug, (ii) use of selective COX-2 inhibitors, and (iii) eradication of Helicobacter pylori . Proton pump inhibitors are the comedication of choice as they effectively reduce gastrointestinal adverse events of NSAIDs and are safe even in long-term use. Co-medication with vitamin C has only been little studied in the prevention of N SAID-induced gastropathy. Apart from scavenging free radicals it is able to induce haeme-oxgenase 1 in gastric cells, a protective enzyme with antioxidant and vasodilative proper ties. Final results of the celecoxib outcome study (CLASS study) attenuated the initial enthusiasm about the GI safety of selective COX-2 inhibitors, especially in patients concomitantly taking aspirin for cardiovascular prophylaxis. Helicobacter pylori increases the risk for ulcers particularly in NSAID-naive patients and therefore eradication is recommended prior to long-term NSAID therapy at least in patients at high risk. New classes of COXinhibitors are currently evaluated in clinical studies with very promising results: N SAIDs combined with a nitric oxide releasing moiety (NO -NSAID) and dual inhibitors of COX and 5-LOX. These drugs offer extended anti-inflammatory potency while sparing gastric mucosa.

Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

“…Approximately 30 million patients consume NSAIDs on a daily basis (1). However, NSAIDs have limitations; they induces gastropathy, and ϳ107,000 patients are hospitalized every year due to NSAIDrelated gastrointestinal complications (3). Extensive studies have established that besides acid secretion, there are other important factors, such as gastric mucosal blood flow, mucusbicarbonate secretion, antioxidant level, reactive oxygen species (ROS), mitochondrial oxidative stress (MOS), apoptosis, and mucosal cell renewal, involved in the pathogenesis of gastroduodenal injury (4 -11).…”

“…was given to the fasted animals to induce gastric injury. In the drug-pretreated groups, the animals were given SEGA (3a) (50,20,10,5,3, and 1 mg⅐kg Ϫ1 b.w. ), intraperitoneally 30 min prior indomethacin treatment.…”

The Incidence of Upper Gastrointestinal Complications of Non-Steroidal Anti-Inflammatory Drugs in Elderly Patients

“…On comparing Celecoxib group and Ibuprofen group, our results were in accordance with two studies paying the attention to the absence of statistically significant difference between the two drugs regarding the percent of incidence of ulcer [26,33].…”

“…Although, Becker JC et al [26] paid the attention to the fact that overall gastrointestinal toxicity seems to be reduced with Meloxicam as selective cox-2 inhibitor when compared with unselective NSAIDs. A study found that after having Meloxicam, 40% of the included patients had more severe impairment of gastric mucosa [27].…”

Rebamipide and Pantoprazole Combination in NSAIDs-Gastropathy Treatment

“…The main mechanism of the NSAIDs damaging effect on stomach and duodenum mucosa is the COX (enzyme cyclooxygenase blockade), which has two structural isomers (constructive): COX-1 and COX-2 induced. NSAIDs interrupt the cyclooxygenase pathway of arachidonic acid metabolism by inhibiting the synthesis of PG (prostaglandine), prostacyclin and thromboxane [2]. NSAIDs, as weak organic acids, easily penetrate the phospholipid membrane in the cell cytoplasm, causing local damage to the stomach and duodenum mucosa as erosions and ulcers [3].…”