Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed group of drugs in the world. They are used primarily for pain relief in chronic inflammatory joint disease and act by inhibiting enzymes COX1 and COX2 and ultimately preventing the production of active prostanoids which are required for the innate inflammatory pathway. The use of NSAIDs have been associated with the development of gastrointestinal (GI) symptoms ranging from simple dyspepsia to life threatening GI bleeds and perforations. The definition of dyspepsia has evolved over the years and this has hampered accurate studies on the prevalence of dyspepsia as different studies used varying criteria to define dyspepsia. It is now known that NSAIDs significantly increase the risk of dyspepsia.The risk of developing peptic ulcer disease vary with specific NSAIDs and dosages but there is no correlation between the symptoms of dyspepsia and underlying peptic ulcers. The pathogenesis of dyspepsia with NSAIDs is not completely understood. Peptic ulceration alone is not able to account for the majority of dyspepsia symptoms encountered by NSAIDs users. Erosive oesophagitis secondary to NSAIDs may be contributing factor to the prevalence of dyspepsia in NSAIDs users. Altered gut permeability and changes in gastric mechanosensory function due to NSAIDs may also be a contributory factor. Management of NSAID induced dyspepsia is involves a multipronged approach. Drug avoidance if possible would be ideal. Other options include using the lowest effective dose, changing to an NSAIDs with a safer GI risk profile, avoiding concurrent use with other NSAIDs or if the patient has a previous history of peptic ulcer disease, and co-prescribing with anti-secretory medications such as proton pump inhibitors. Eradication of Helicobacter pylori has a protective role against developing peptic ulcers and may also improve symptoms of NSAIDs induced dyspepsia.
The objectives of the study were first, to determine if gastric emptying was altered in patients with functional dyspepsia with and without Helicobacter pylori infection compared with normal healthy volunteers; and second, to determine if there were further alterations in gastric emptying when the infection was eradicated. Gastric emptying was measured using a 99mtechnetium radiolabelled solid meal and gastric emptying time was measured as t1/2, viz. time taken for half the radiolabelled meal to be emptied from the stomach. The mean gastric emptying time for H. pylori-positive patients (n=20) was 56.4+/-24.8 min; H. pylori-negative patients (n=19) 67.8+/-31.8 min; and normal controls (n=20) 58.8+/-18.8min. No significant difference was obtained between the groups (ANOVA; P=0.348). Thirteen of 18 H. pylori-positive patients successfully eradicated the infection following treatment with omeprazole 40 mg o.m. and amoxycillin 500 mg t.d.s. for 2 weeks. The mean difference in the gastric emptying time before and after H. pylori eradication was 23.9+/-13.2 min (P= 0.556). There was no significant difference in the frequency of specific dyspeptic symptoms as well as the overall mean symptom score between the H. pylori-positive and -negative patients. Gastric emptying was not different between patients with functional dyspepsia and normal controls. Helicobacter pylori infection does not appear to affect gastric emptying in patients with functional dyspepsia.
Functional dyspepsia (FD) is a common disorder of yet uncertain etiology. Dyspeptic symptoms are usually meal related and suggest an association to gastrointestinal (GI) sensorimotor dysfunction. Cholecystokinin (CCK) is an established brain-gut peptide that plays an important regulatory role in gastrointestinal function. It inhibits gastric motility and emptying via a capsaicin sensitive vagal pathway. The effects on emptying are via its action on the proximal stomach and pylorus. CCK is also involved in the regulation of food intake. It is released in the gut in response to a meal and acts via vagal afferents to induce satiety. Furthermore CCK has also been shown to be involved in the pathogenesis of panic disorder, anxiety and pain. Other neurotransmitters such as serotonin and noradrenaline may be implicated with CCK in the coordination of GI activity. In addition, intravenous administration of CCK has been observed to reproduce the symptoms in FD and this effect can be blocked both by atropine and loxiglumide (CCK-A antagonist). It is possible that an altered response to CCK may be responsible for the commonly observed gastric sensorimotor dysfunction, which may then be associated with the genesis of dyspeptic symptoms.
Dyspepsia itself is not a diagnosis but stands for a constellation of symptoms referable to the upper gastrointestinal tract. It consists of a variable combination of symptoms including abdominal pain or discomfort, postprandial fullness, abdominal bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation. Patients with heartburn and acid regurgitation invariably have gastroesophageal reflux disease and should be distinguished from those with dyspepsia. There is a substantial group of patients who do not have a definite structural or biochemical cause for their symptoms and are considered to be suffering from functional dyspepsia (FD). Gastrointestinal motor abnormalities, altered visceral sensation, dysfunctional central nervous system-enteral nervous system (CNS-ENS) integration and psychosocial factors have all being identified as important pathophysiological correlates. It can be considered as a biopsychosocial disorder with dysregulation of the brain-gut axis being central in origin of disease. FD can be categorized into different subgroups based on the predominant single symptom identified by the patient. This subgroup classification can assist us in deciding the appropriate symptomatic treatment for the patient.