Drugs for Gastrointestinal System Disorders Prepared by I Gede Purnawinadi, S.Kep.,M.Kes. Preview Very little of the food we eat is directly available to body cells. Food must be broken down, absorbed, and chemically modified before it is in
a useful form. The digestive system performs these functions, and more. Some disorders of the digestive system are mechanical in nature, providing for the transit of substances through the gastrointestinal tract. Others are metabolic, involving the secretion of digestive enzymes and fluids or the absorption of essential nutrients. Many signs and symptoms of digestive disorders are nonspecific and may be caused by any number of different pathologies. This chapter examines the pharmacotherapy of two common disorders
of the upper digestive system: peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). Nutrient Food Non Nutrient
Assimilated Digestive system Eliminated Normal Digestive Processes
The digestive system consists of two basic anatomic divisions: the alimentary canal and the accessory organs. The alimentary canal, or gastrointestinal (GI) tract, is a long, continuous, hollow tube that extends from the mouth to the anus. The accessory organs of digestion include the salivary glands, liver, gallbladder, and pancreas. The digestive system is responsible for breaking down food, absorbing nutrients, and eliminating wastes.
Overview of GI tract PROSES PENCERNAAN : Masuknya makanan mel. Sal. Cerna/GIT (Ingestion) Pergerakan makanan mel. Sal. Cerna (Motility) Sekresi getah pencernaan (Secretion) Pencernaan makanan (Digestion)
Penyerapan hasil pencernaan, Air & berbagai Elektrolit (Absorption) Sirkulasi darah melalui Organ GIT membawa hasil Absorpsi. Pengaturan: Sistem Saraf & Sistem Hormonal Pembuangan bahan yg tidak dibutuhkan tubuh (eliminasi) Overview of GI Processes Food
Digestion Secretion Absorption Blood Vessels
Motility The inner lining of the alimentary canal is the mucosa layer, which provides a surface area for the various acids, bases, mucus, and enzymes to break down food. Substances are propelled along the GI tract by peristalsis, which are rhythmic contractions of layers of smooth muscle.
The speed at which substances move through the GI tract is critical to the absorption of nutrients and water and for the removal of wastes. If peristalsis is too fast, nutrients and drugs will not have sufficient contact with the mucosa to be absorbed. In addition, the large intestine will not have enough time to absorb water, and diarrhea may result. Abnormally slow transit may result in constipation or even obstructions in the small or large intestine.
To chemically break down ingested food, a large number of enzymes and other substances are required. Digestive enzymes are secreted by the salivary glands, stomach, small intestine, and pancreas. The liver makes bile, which is stored in the gallbladder until needed for lipid digestion. Food passes from the esophagus to the stomach by traveling through the lower esophageal (cardiac) sphincter. This ring of
smooth muscle usually prevents the stomach contents from moving backward, a condition known as esophageal reflux. A second ring of smooth muscle, the pyloric sphincter, is located at the entrance to the small intestine. This sphincter regulates the flow of substances leaving the stomach. The stomach thoroughly mixes ingested food and secretes substances that promote the processes of chemical digestion. Gastric glands extending deep into the mucosa of the stomach
contain several cell types critical to digestion and important to the pharmacotherapy of digestive disorders. Chief cells secrete pepsinogen, an inactive form of the enzyme pepsin that chemically breaks down proteins. Parietal cells secrete 1 to 3 L of hydrochloric acid each day. This strong acid helps break down food, activates pepsinogen, and kills microbes that may have been ingested.
Stomach lower esophageal (cardiac) sphincter Control of Acid Secretion
May be considered as three separate phases. 1. Cephalic phase. 2. Gastric phase. 3. Intestinal phase. 1. CEPHALIC PHASE
Vagus nerve Sight, smell or thought of food Parasympathetic activation of gastric motility & gastric juice secretion
2. GASTRIC PHASE Food arrival causes muscular reflexes & gastrin secretion by G cells. Gastrin
FOOD Gastrin stimulates secretion from both chief & parietal cells. GO 3. INTESTINAL PHASE
Arrival of food in duodenum triggers release of hormones that inhibit gastric motility & secretions. Secretin & Cholecystokinin (CCK)
Circulation Pathogenesis of Peptic Ulcer Disease An ulcer is an erosion of the mucosa layer of the GI tract, usually associated with acute inflammation. Although ulcers may occur in any portion of the alimentary canal, the duodenum is the most common site. The term peptic ulcer refers to a lesion located in either the stomach (gastric) or small intestine
(duodenal). Peptic ulcer disease is associated with the following risk factors: Close family history of PUD. Blood group O. Smoking tobacco (increases gastric acid secretion). Consumption of beverages and food that contain caffeine. Drugs, particularly corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDS), and platelet
inhibitors such as aspirin and clopidogrel. Excessive psychological stress. Infection with Helicobacter pylori Pathogenesis of Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) is a common condition in which the acidic contents of the stomach move upward into the esophagus.
This causes an intense burning (heartburn) sometimes accompanied by belching. In severe cases, untreated GERD can lead to complications such as esophagitis, or esophageal ulcers or strictures. Although most often thought a disease of people older than age 40, GERD also occurs in a significant percentage of infants. The cause of GERD is usually a weakening of the lower esophageal sphincter. The sphincter may no longer close tightly, allowing the contents of the stomach to move upward when the stomach contracts.
Pharmacotherapy of Peptic Ulcer Disease Before initiating pharmacotherapy, patients are usually advised to change lifestyle factors contributing to the severity of PUD or GERD. For example, eliminating tobacco and alcohol use and reducing stress often allow healing of the ulcer and cause it to go into remission. Avoiding certain foods and beverages can lessen the severity of
symptoms. For patients who are taking NSAIDs, the initial approach to PUD is to switch the patient to an alternative medication. For patients with PUD who are infected with H. pylori, elimination of the bacteria using anti-infective therapy is the primary goal of pharmacotherapy. The goals of PUD pharmacotherapy are to provide immediate relief
from symptoms, promote healing of the ulcer, and prevent future recurrence of the disease. The mechanisms of action of the primary drug classes for PUD are shown in Pharmacotherapy Illustrated 40.1: Proton pump inhibitors, H2-receptor antagonists, Antacids, Antibiotics, Miscellaneous drugs.
Histamine has two types of receptors: H1 and H2. Activation of H1 receptors produces the classic symptoms of inflammation and allergy, whereas the H2 receptors are responsible for increasing acid secretion in the stomach. Proton pump inhibitors act by blocking the enzyme responsible for secreting hydrochloric acid in the stomach. They are drugs of choice for the short-term therapy of PUD and GERD.
Proton pump inhibitors (PPIs) reduce acid secretion in the stomach by binding irreversibly to H+, K+-ATPase, the enzyme that acts as a pump to release acid (also called H+, or protons) onto the surface of the GI mucosa. PPIs reduce acid secretion to a greater extent than the H2-receptor antagonists and have a longer duration of action. PPIs heal more than 90% of duodenal ulcers
within 4 weeks and about 90% of gastric ulcers in 6 to 8 weeks. Prior to the development of H2-receptor antagonists and PPIs, antacids were the mainstays of peptic ulcer and GERD pharmacotherapy. Although antacids may provide temporary relief from heartburn or indigestion, they are no longer recommended as the primary drug class for PUD. This is because antacids do not promote healing of the ulcer,
nor do they help to eradicate H. pylori. Antibiotics for H. Pylori The gram-negative bacterium H. pylori is associated with 80% of patients with duodenal ulcers and 70% of those with gastric ulcers. It is also strongly associated with gastric cancer. To more rapidly and completely heal peptic ulcers, combination therapy with several antibiotics is used to eradicate this bacterium.
Two or more antibiotics are given concurrently to increase the effectiveness of therapy and to lower the potential for bacterial resistance. The antibiotics are also combined with a PPI or an H2receptor antagonist. Miscellaneous Drugs for Peptic Ulcer Disease Several additional drugs are beneficial in treating PUD. Sucralfate (Carafate) consists of sucrose (a sugar) plus aluminum hydroxide (an
antacid). The drug produces a thick, gel-like substance that coats the ulcer, protecting it against further erosion and promoting healing. It does not affect the secretion of gastric acid. Misoprostol (Cytotec) inhibits gastric acid secretion and stimulates the production of protective mucus. Its primary use is for the prevention of peptic ulcers in patients who are taking high doses of NSAIDS or corticosteroids
Drugs for Bowel Disorders and Other Gastrointestinal Conditions The lower portion of the GI tract consists of the small and large intestines. The first 10 inches of the small intestine, the duodenum, is the site where partially digested food from the stomach, known as
chyme, mixes with bile from the gallbladder and digestive enzymes from the pancreas. The remainder of the small intestine consists of the jejunum and ileum. The jejunum is the site where most nutrient absorption occurs. The ileum empties its contents into the large intestine through the ileocecal valve. The large intestine, or colon,
receives chyme from the ileum in a fluid state. The major functions of the colon are to reabsorb water from the waste material and to excrete the remaining fecal material from the body.
Pathophysiology of Constipation Constipation is a decrease in the frequency of bowel movements. Stools may become dry, hard, and difficult to evacuate from the rectum without straining. As waste material travels through the large intestine, water is reabsorbed. Reabsorption of the proper amount of water results in stools of a normal, softformed consistency. If the waste material remains in the colon for an extended period, however, too much water will be reabsorbed, leading to small, hard stools.
Constipation may cause abdominal distention and discomfort and flatulence. Constipation is not a disease but a symptom of an underlying disorder. The etiology of constipation may be related to lack of exercise; insufficient food intake, especially insoluble dietary fiber; diminished fluid intake; or a medication regimen that includes drugs that reduce intestinal motility. Pharmacotherapy with Laxatives Laxatives promote the evacuation of the bowel, or
defecation, and are widely used to prevent and treat constipation. Laxatives are drugs given to promote emptying of the large intestine by stimulating peristalsis, lubricating the fecal mass, or adding more bulk or water to the colon contents. Pathophysiology of Diarrhea
When the large intestine does not reabsorb enough water from the fecal mass, stools become watery. Diarrhea is an increase in the frequency and fluidity of bowel movements. Diarrhea is not a disease but a symptom of an underlying disorder. Indeed, diarrhea may be considered a type of body defense, rapidly and completely eliminating the body of toxins and pathogens. When prolonged or severe, especially in children, diarrhea can result in
significant loss of body fluids, and pharmacotherapy is indicated. Prolonged diarrhea may lead to fluid, acidbase, or electrolyte disorders. Pharmacotherapy with Antidiarrheals Pharmacotherapy related to diarrhea depends on the severity of the condition and any identifiable etiologic factors. If the cause is an infectious disease, then an antibiotic or antiparasitic
drug is indicated. If the cause is inflammatory in nature, antiinflammatory drugs are warranted. When the diarrhea appears to be an adverse effect of pharmacotherapy, the health care provider may discontinue the offending medication, lower the dose, or substitute an alternative drug. Pathophysiology of Nausea and Vomiting
Vomiting is a defense mechanism used by the body to rid itself of toxic substances. Vomiting is a reflex primarily controlled by the vomiting center of the medulla of the brain, which receives sensory signals from the digestive tract, the inner ear, and the chemoreceptor trigger zone (CtZ) in the cerebral cortex. Interestingly, the CTZ is not protected by the bloodbrain barrier, as is the vast majority of the brain; thus, these neurons can directly sense the presence of toxic substances in the blood. Once the vomiting reflex is triggered,
wavelike contractions of the stomach quickly propel its contents upward and out of the body. A large number of antiemetics are available to treat nausea and vomiting. Selection of a particular agent depends on the experience of the health care provider and the cause of the nausea and vomiting.
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