The symptomatology of the gastroesophageal reflux disease and the first line therapy

Statistically, gastroesophageal reflux disease (GERD) or gastroesophageal reflux (GER) has a prevalence that varies between regions and countries from 8.8% to 28% of the respective population [1]. GERD is a digestive disorder that affects the lower esophageal sphincter (LES), being one of the most common diagnosis managed in the gastroentherology clinics [2]. LES protects the esophagus from stomach acid and if it relaxes, the gastric content can flow back and cause acid reflux. The symptomatology of the gastroesophageal reflux disease and the first line therapy


rISK FActorS In GErd
Multiple mechanisms are involved in GERD pathogenesis. First of them are motor abnormalities, like damaged LES resting tone with spontaneous and transient LES relaxation (TLESRs) of 10-60s duration and damaged esophageal acid clearance. Anatomical risk factors include hiatal hernia (prevalance of 43%) [8] and obesity (prevalance of 35.8%) [5]. Hiatal hernia is considered to be a significant anatomical factor, because it increases the frequency of TLESRs and decreases esophageal clearance [6]. A possible mechanism through which obesity aggravates GERD consists in increasing abdominal pressure, delaying gastric emptying, increasing frequency of TLESRs and reducing LES resting pressure. For the patients with moderate obesity, with body mass index (BMI) >40, some bariatric procedures like ballons or bands can aggravate the reflux [7]. The incidence of reflux symptoms rises progressively with increasing BMI [6]. Metabolic syndrome and especially hypertriglyceridemia have been common associated with erosive esophagitis or reflux symptoms [8].
GERD risk factors include also a considerable number of genetic factors. Numerous single-nucleotide polymorphisms (SNPs) have been proposed as potential factors in the appearance of reflux disease [6]. Physiological conditions, such as pregnancy, are another factor associated with reflux disease, which can cause GERD, especially in the second or third trimester of pregnancy [1].
Some commonly used groups of drugs can cause GERD through various mechanisms and can also lead to an increase in the existing symptoms of GERD. The mechanism that causes reflux includes the potential for drugs to cause damage and inflammation to the esophageal mucosa [9]. The use of non-steroidal anti-inflammatory drugs (NSAIDs) aggravates GERD symptoms. Acetylsalicylic acid may slightly increase the risk of developing GERD, which increases with the combination of nonsteroidal anti-inflammatory drugs. The use of calcium channel blockers can lead to GERD and exacerbate existing reflux symptoms. Theophylline, an antiasthmatic drug, can increase the number of GERD episodes in asthma patients and can also exacerbate existing reflux symptoms. Anticholinergic drugs can also increase the number of episodes of reflux [10] GErd trEAtMEnt The treatment for GERD aims to prevent and to relieve symptoms, to heal the damage caused by the acid and to stop the development of the disease, thus avoiding further complications. Although GERD symptoms vary from patient to patient, the treatment can be addressed from two perspectives: nonpharmacological and pharmacological approach.

Nonpharmacological approach
Both lifestyle changes and eating habits are the first line of treatment in reducing the symptoms of GERD. The elevation of the head of the bed is a proven lifestyle modification which decreases esophageal acid exposure and esophageal clearance time, thus reducing the GERD symptoms [11]. Several changes in lifestyle can prevent from developing symptoms: eating smaller servings, eating slowly and at least 2 to 3 hours before bedtime. Foods that may cause acid reflux are presented in Table 1. Persons with GERD should avoid this type of foods because they can irritate the esophagus and can relax LES [11]. Stopping daily habits like smoking, alcohol and caffeine intake is important to reduce GERD symptoms [6].
Also, those aliments that have a low pH, are acidic and thus they are more likely to cause reflux. Contrariwise alkaline foods can help offset strong stomach acid and watery foods can dilute it. These are presented in Table 2. New studies highlight the protective effect of curcumin in esophageal diseases, including gastroesophageal reflux, reflux esophagitis,

tHE roLE oF tHE PHArMAcISt In GErd MAnAGEMEnt
Often times, pharmacists are the first healthcare professionals that patients come in contact with to ask for advice concerning their health. It is important for the pharmacists to have a proper knowledge of basic GERD symptoms in order to determine the right approach for this ailment. Since patients with GERD have varied symptomatology, which sometimes interferes with other pathology, the pharmacist plays a very important role in recognizing symptoms and advising the patient about the diet and treatment.
For the proper management of GERD treatment it is important that the patient answer a few questions like: "When did the symptoms start?", "(Do you) have acidic taste in the mouth?", "(Do you) experience heartburns? Are they connected to food intake or not?", "When does the symptoms appear more frequently?", "Is the heartburn linked with regurgitation?", "(Do you) find it hard to swallow?", "(Do you) feel pain in the chest?", "(Do you) take any other medication?", "Are you pregnant?", "Do you have a family history of gastric and/or esophageal reflux?, "How frequently are the symptoms occurring?", "Have you tried any lifestyle changes or medications that have made your symptoms better or worse?". Usually, heartburn and acid regurgitations are sufficient to suspect GERD [1,11,12].
Also, the pharmacist should be aware that the medication presented in the previous chapter can predispose patients to reflux and potentially exacerbate the symptomatology.
It is the duty of the pharmacist to ask basic questions in order to identify the severity of the ailment and then to choose and present treatment options. Also it is important to give clear information about the duration and proper administration of the selected medication. A notable role that the pharmacist plays Barett's esophagus and last but not least esophageal carcinoma [13].

Pharmacological approach
Where necessary, therapeutic strategies should be focused on the GERD phenotype and revolve around the severity of the symptoms reported by the patients [12]. We can look at managing the GERD from two perspectives. First is to progressively introduce the use of antacids followed by/or together with H2 blockers and in case of persisting symptoms, switching to PPIS [1]. Second perspective is to start with the most effective approach and then gradually reduce the intensity of the treatment to the use of antacids and even give up treatment [1].
Antacids have the role of neutralizing the pH level in the stomach, providing relief from the burning sensation caused by the acidity. The most common antacids contain aluminum hydroxide, magnesium hydroxide, calcium carbonate, sodium bicarbonate [1]. The role of H2 blockers is to inhibit histamine stimulation of the parietal cell, thus decreasing gastric acid secretion. Among H2 blockers, more used are famotidine, ranitidine and cimetidine. PPIS therapy decrease the acid secreted from parietal cells into the gastric lumen. The most potent class used in GERD therapy are PPIS, prodrugs that are converted into active compounds in the acidic environment of the gastric lumen [10,11]. PPIS needed to be administered once daily, at the same time every day [10]. Statistically, 10% of patients who administrate full-dose PPIS still suffer from heartburn and regurgitation [7]. Overmore, some patients report refractory symptoms when the PPIS therapy is finished. So, what's to be done for these patients?
If the patiens cannot tolerate antacid treatment because of the side effects (usually diarrhea and hypomagnesemia), or the symptoms persist in spite of optimized PPIS therapy, the antireflux surgery is required. These patients are named partial responders or nonresponders, depending on the degree of symptom alleviation [7]. If it is necessary to do an endoscopy, it is not recommended for patients with typical symptomatology unless they don't respond to PPIS treatment [10].
is to also educate the patients about the potentially adverse effects as well as of the consequences of long-term use of the medication.
Not to be neglected is the involvement of the pharmacist in the follow-up of the treatment adopted by the patients. This way, if GERD symptoms persist or worsen, the patient could be guided to seek medical attention and benefit from advanced investigations.

concLuSIonS
In conclusion, the treatment of gastroesophageal reflux can be successful, only if the non-pharmaceuti-cal aspects of the therapy like lifestyle changes are complementary to the pharmaceutical treatments.
Because frequent reflux symptoms are not optimaly treated with alginates or antacids, a short-term treatment with PPIs is required in patients without alarm symptoms. The importance of pharmacists in ameliorating reflux disease cannot be forgotten because, by customizing the treatment scheme, the fastest and best results can be obtained. Also, as they are able to guide the treatment, it is essential to stay up to date with the available products, both medications and over-the-counter products.

Conflict of interest: none declared
Financial support: none declared