I- Non-steroidal anti-inflammatory drugs (NSAIDs)  NSAIDs cause damage at all levels of the gastro-intestinal tract.  Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recognized for their ability to cause gastro-duodenal ulceration.  Erosions, superficial and deep ulcerations and strictures have been identified as complications of chronic use of NSAIDs, particularly the slow release forms.

Mechanisms of NSAIDs-induced GIT ulcerations  What causes ulceration is precisely not known. It is believed to occur as the result of a complex interplay of aggravating factors and protective factors.  Prostaglandins(PGs) have long been known to be mucoprotective and ulcer healing agents. Prostaglandins protect GI mucosa by forming a cytoprotective layer and increasing the secretion of bicarbonate ions that neutralize the gastric acidity.

 All therapeutically useful NSAIDs act by inhibiting the synthesis of PGs through inhibiting Cyclooxygenase enzyme (COX).  COX has two isoforms, one constitutive (COX-1) and another inducible (COX-2),, up-regulated by several proinflammatory cytokines.  Conventional NSAIDs cause non-selective inhibition of COX, which leads to reduction in PGs Coupled with vasoconstriction that occurs due to NSAIDs, which causes hypoxia and consequent formation of ulcer.

Risk factors of ulcer development  Previous history or active peptic ulceration  Female gender or advanced age (> 65)  Smoking, alcoholism or heavy coffee consumption  Prolonged use of heavy doses of NSAIDs  Use of multiple NSAIDs; concomitant administration of anticoagulant or GI toxic drugs  Hepatic-renal dysfunction or Serious systemic illness

Possible treatments of the GI T ulceration  Attempt should be made to prevent it from developing.  Drug discontinuation is the most obvious option however drug discontinuation may not be feasible in all patients as the dangers of drug discontinuation can be considerable like pain and stiffness.  Recent evidence suggests that drugs with less potential for GI irritation like paracetamol should be introduced early in the course of the disease.

 Individual NSAIDs also differ in their propensity to cause ulceration but none is free from causing the risk of ulcer when taken on a long- term basis.  Newer NSAIDs like celecoxib (COX-2 selective) have shown to have a four fold lesser potential for causing ulceration but it is quite expensive.

 Ulcer formation can be reduced by the use of famotidine or ranitidine (H 2 receptor blocker) or omiprazole (proton pump inhibitors).  Misoprostol, a prostaglandin E1 analogue is also effective

Contraindications during NSAID treatment  Smoking, drinking alcohol, Heavy coffee consumption,  Concomitant ingestion of GI toxic drugs  Adjustment of the dose and not using multiple NSAIDs  Concomitant administration of anticoagulant.

The interaction between NSAIDs and anticoagulats is due to: 1- irreversible acetylation of cyclo- oxygenase in platelets, which results in a prolongation of the bleeding time. 2- the severity of gastrointestinal bleeding induced by NSAIDs could be increased by the concomitant use of anticoagulants.

II-Doxycycline  Doxycycline is in a tetracycline antibiotics.  It is used as antibacterial in respiratory tract, skin, genital, and urinary systems infections. As well as in Lyme disease and acne.

Doxycycline-induced Oesophageal ulcer  Doxycycline-induced esophageal ulcer patients are mostly young persons with no history of esophageal dysfunction.  Heartburn, pain and dysphagia are the most common symptoms.  Extensive ulcerations, mimicking esophageal cancer were also reported in rare cases.

Doxycycline-induced oesophageal ulceration  Drug-induced oesophagitis is more frequent with capsule than with tablet, because of its easier adhesion to the oesophageal surface.  Taking the medication with a small amount of water immediately before sleeping, increases transit time and incidence of ulceration.

 As an acidic drug, doxycycline accumulation in the epithelial cells subsequent local cytochemical effects.  Doxycycline can cause ulceration and friability of the adjacent oesophageal mucosa.  In addition, doxycycline can also inhibit protein synthesis functions in the oesophagus.

Prevention of Doxycycline-induced oesophageal ulceration The could be achieved by  Not taking it before sleep  Swallowing the drug with at least 100 ml of water  After swallowing the medication remain in the upright position thereafter.

Treatment 1-Sucralfate: It is a locally acting substance that in an acidic environment reacts with hydrochloric acid in the stomach to form a cross-linking, viscous, paste-like material capable of acting as an acid buffer. It also attaches to proteins on the surface of ulcers, such as albumin and fibrinogen, to form stable insoluble complexes. These complexes serve as protective barriers at the ulcer surface, preventing further damage from acid, pepsin, and bile

2- Omeprazole: It is a selective and irreversible proton pump inhibitor. It suppresses stomach acid secretion by specific inhibition of the H + /K + ATPase system found at the secretory surface of gastric parietal cells. Omeprazole also inhibits both basal and stimulated acid secretion irrespective of the stimulus.