PHARMACOLO NURS 251 MODULE 7

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Module 7 7.1: Introduction to Gastroenterology The organs of the upper gastrointestinal tract (mouth, pharynx, esophagus, stomach, and duodenum) work in conjunction to first digest food and then ab ... sorb the nutrients obtained from the digested food. Both the stomach and the upper part of the small intestines (duodenum) release hormones and enzymes that help in this process. When food enters the body, the stomach is triggered to begin releasing gastric juices such as hydrochloric acid (HCl) and an enzyme called pepsin. HCl is released by parietal cells located in the stomach. Due to its acidic nature, HCl aids in the breakdown of food entering the stomach. Pepsin is the primary digestive enzyme found in the stomach. Pepsin is responsible for the catabolism (breaking down) of proteins into polypeptides. There are three major stimulators that affect the release of gastric juices: Acetylcholine (ACh), gastrin, and histamine. First, the ingestion of food stimulates ACh to bind to its target receptors, stimulating the release of pepsin, gastrin, histamine, and HCl from chief cells, G cells, enterochromaffin like (ECL) cells, and parietal cells respectively. Gastrin then binds to its target receptors on ECL and parietal cells which stimulates the release of more histamine and more HCl. The histamine then binds to the H2 receptors on the parietal cells which, in turn, increases the amount of HCl or gastric acid released. Figure 7.1 Stimulation of Gastric Juices. The figure above depicts the different cells involved in the release of the different gastric juices. The process is started by ACH being released when food is ingested. The release of the initial gastrin and histamine go on to stimulate the release of more histamine and HCL. Peptic Ulcers and Gastrointestinal Esophageal Reflux Disease (GERD) Peptic ulcers are defined as open sores in the mucous membranes of the mucosal lining of the stomach or duodenum. Pathophysiology: The cause of peptic ulcers is not always the same. The majority of GI ulcers are caused by the bacterium Helicobacter Pylori (H. Pylori). The bacterium is believed to enter the body through contaminated food or water. Reacting to the bacteria, an inflammatory response is initiated, which is often associated with an increase in stomach acid secretions. The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is also closely related to the incidence of peptic ulcers. NSAIDs block prostaglandins which play a role in inhibiting gastric acid secretion. In both cases, the resulting increase in stomach acid secretions places a strain on the inner lining of the stomach until an ulcer (break or tear) appears. Symptoms of a peptic ulcer include pain, nausea, and loss of appetite. The pain is typically described as a dull, gnawing, burning sensation similar to heartburn. Interestingly, if the ulcer is in the duodenum, food often relieves the pain, whereas if the ulcer is in the stomach, food often worsens the pain. GERD stands for gastrointestinal esophageal reflux disease and is characterized primarily by the presence of heartburn. Heartburn (acid indigestion) is defined as a painful burning feeling behind the sternum that occurs when stomach acid backs up into the esophagus. Pathophysiology of GERD involves the lower esophageal sphincter (LES) or valve at the bottom of the esophagus going into the stomach. This valve loosens such that the gastric acid is able to go back up (reflux) into the esophagus. Symptoms of GERD go beyond occasional heartburn. In GERD, heartburn is part of an ongoing problem, often occurring after meals and upon lying down. In severe cases, there can even be blood loss from chronic injury to the esophagus. Treatment Overview Peptic Ulcers If the patient has a peptic ulcer that is caused by H. Pylori, they will need to be treated with antibiotics. It is generally recommended to use at least two antibiotics in combination with bismuth salts (Pepto-Bismol or Kaopectate), a regimen referred to as “triple therapy.” When a proton pump inhibitor (PPI) is added to the regimen it is then referred to as “quadruple therapy.” PPIs will be discussed further below. The recommended antibiotics to treat H. pylori include amoxicillin, tetracycline, metronidazole, and clarithromycin. The purpose of the Pepto-Bismol is that bismuth is thought to disrupt the bacterial cell wall and prevent further binding to the mucosa. Treatment typically lasts for 8 weeks leading to the eradication of the bacteria. If the ulcer was not caused by H. Pylori, treatment does not involve antibiotics but rather anti-secretory drugs. Antisecretory drugs are defined as drugs that inhibit the secretion of digestive enzymes, hormones, or acids. Such drugs include H2 receptor antagonists, prostaglandins, and proton pump inhibitors. Treatment should last 4-8 weeks. Prostaglandins are only useful in the treatment or prevention of NSAID-induced ulcers. Prostaglandins inhibit histamine which counteracts the NSAIDs inhibition of prostaglandin synthesis. There is only one synthetic prostaglandin available, misoprostol. It is limited in its use, primarily being used for patients at high risk of developing an ulcer that must be on an NSAID for a limited time. Misoprostol has not been shown to be effective at preventing ulcers in patients on chronic NSAID therapy. Misoprostol is also known to cause uterine contractions and is, therefore, contraindicated in pregnancy due to the risk of miscarriage. GERD Depending on the severity of the disease, the recommended treatment may differ. In mild-moderate GERD, the H2 antagonists are a great option. They have a longer duration of action than alternatives such as an OTC antacid and provide good relief. However, in severe GERD or in cases where there is ulcerative damage, PPIs are considered first line therapy. Lifestyle modifications are a critical part of the management of peptic ulcers and GERD. Recommendations include smoking cessation, avoiding caffeine and alcohol, as well as reducing stress. If possible, NSAIDs should be avoided. If the patient is overweight, weight loss can help. If the patient has symptoms at night, it is recommended to elevate their bed. Drug Therapy H2 receptor antagonists were introduced in Module 2. We will go into more detail in this module. Mechanism of action: Work by competitively inhibiting the interaction of histamine with H2 receptors within the GI mucosa. This blockade significantly reduces the secretion of acid and pepsin from the stomach. Uses: Recommended for the short-term use (up to 8 weeks) of benign gastric ulcers and duodenal ulcers, GERD, stress ulcers and gastric irritation in patients that need to remain on NSAIDs. Adverse Events: Headache or constipation. Cimetidine specifically has been associated with reversible CNS effects such as confusion and disorientation, usually in critically ill patients. Drug Interactions: Cimetidine has been reported to increase the drug levels of many medications by altering metabolism. Select examples include calcium channel blockers, beta blockers, sulfonylureas, and theophylline. Famotidine and nizatidine have no effect on the metabolic pathway and are therefore preferred. They do not appear to interact with food and therefore can be taken at mealtime. Example Drugs: Cimetidine, ranitidine, famotidine, and nizatidine PPIs are superior in their effectiveness in acid reduction and ulcer healing compared to H2 receptor antagonists. Mechanism of action: The exchange of hydrogen and potassium via the ATPase exchange is essential to the production of HCl. PPIs work by inhibiting this exchange, therefore, preventing the formation of acid. Uses: First line along with antibiotics to treat H. Pylori related ulcers, benign gastric ulcers, active duodenal ulcers, and GERD. They promote better healing over H2 blockers and therefore are the drug of choice for healing ulcers. Adverse Events: Headache, abdominal pain, diarrhea, nausea, and constipation. New concerns have arisen that longterm use could lead to the development of osteoporosis. Overprescription of PPIs could lead to an increase in GI infections because of the reduction of normal acid-mediated microbial protection. Drug Interactions: Omeprazole can increase levels of warfarin and some seizure medications (diazepam, phenytoin). It can also affect the absorption of drugs that require an acidic environment such as iron. Omeprazole has also been shown to decrease the antiplatelet effects of clopidogrel. Lansoprazole, pantoprazole, and rabeprazole have no clinically relevant drug interactions. Example Drugs: Omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole. See Table 7.1 below for a summary chart of the H2 receptor antagonists and the PPIs. [Show More]

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