Therapeutic Agents for the Gastrointestinal System

Transcription

1 Therapeutic Agents for the Gastrointestinal System Chapter 20 1 Form and Function of the Gastrointestinal System There are three main functions of the gastrointestinal (GI) system: Digestion Absorption Metabolism It is controlled by parasympathetic system (peripheral nervous system) Each organ completes a specific task Do you remember what the parasympathetic nervous system is? (The parasympathetic nervous system is part of the autonomic [involuntary] nervous system. It controls the normal functions of the body at rest, such as digestion.) The GI system has four main functions in the body: digestion, absorption, metabolism, and excretion. The organs of the GI system include the mouth, salivary glands, pharynx, and esophagus (ingestion and digestion), followed by the stomach and small intestine (nutrient absorption), the large intestine (resorption of water and electrolytes and storage of feces), and finally the anus (elimination). 2 Anatomy of the Gastrointestinal System Main organs: Mouth, salivary glands, pharynx, and esophagus (ingestion) Stomach, small intestine, and large intestine (absorption) Rectal area (excretion) How is the large intestine different from the small intestine? (The large intestine has a larger circumference than the small intestine, but the small intestine is longer. Although absorption takes place in both the small intestine and the large intestine, the large intestine primarily absorbs water and electrolytes, whereas the small intestine absorbs most of the nutrients from food.) Auxiliary organs that are important within the GI system include the tongue, salivary glands, liver, pancreas, and gallbladder. The appendix has no function in digestion. Fats begin their process of digestion in the duodenum where they encounter bile, which is produced by the liver and stored in the gallbladder. 3

2 Gastrointestinal System Anatomy Figure 20-1 shows the anatomy of the GI system (including the mouth, pharynx, esophagus, stomach, and intestines). From Potter PA, Perry AG: Fundamentals of nursing, ed 8, St Louis, 2013, Mosby. 4 Ingestion Mouth is the first apparatus, where food is broken into smaller pieces Teeth chew food; salivary glands secrete enzyme amylase for chemical breakdown Three pairs of salivary glands: Sublingual, submandibular, and parotid Saliva moistens esophagus for easy swallowing (with help from tongue) Pharynx connects mouth to esophagus, contains epiglottis Epiglottis closes off trachea to prevent food entry Esophagus performs peristalsis to propel food What is the function of the enzyme amylase? (Amylase is an enzyme that breaks starch down into simpler sugars.) Peristalsis is the process by which waves of involuntary muscle contractions push food through the esophagus into the stomach. Peristalsis is the contraction and relaxation of the tubular muscles of the esophagus, stomach, and intestines that moves substances from the mouth to the anus. 5 Major Glands of the Mouth Sublingual means under the tongue, and submandibular means under the mandible (or jawbone). Parotid comes from the Greek prefix para- and root word otid, meaning near the ear. 6

3 Ingestion In the stomach, food enters acidic environment, chemical breakdown takes place Food activates gastric juices secreted in the stomach Gastric juice consists of intrinsic factor enzymes and hydrochloric acid (HCl); ph 2 Inner mucosal lining is alkaline for protection Protective mucosal lining prevents acid from eating through stomach wall Extremely acidic environment kills bacteria; activates enzymes to break down food Gastric juices are acidic. Do acidic solutions have high or low ph values? (Acidic solutions have ph values below seven [low], and basic solutions have ph values above seven [high]. A ph of seven indicates a neutral [neither acidic nor basic] solution.) The ph scale ranges from 0 to 14. How does the alkaline inner mucosal lining of the stomach provide protection? (The interior of the stomach is very acidic [low ph], so the alkaline [basic, high ph] lining protects the rest of the body because it neutralizes acid from the stomach. Adding an acid to a base results in a neutral solution.) 7 Ingestion (Cont.) Pepsin is a stomach enzyme that breaks down proteins. Amino acids are the building blocks of proteins. In an important chemical reaction, pepsinogen becomes pepsin (active enzyme) After breakdown, acidic mixture becomes chyme, passes through pyloric sphincter to small intestine 8 Absorption Patients who have had gastric bypass surgery usually need to take supplemental vitamins to replace those that are poorly absorbed through the shortened digestive tract. Vitamins and minerals move through lining of gut Molecules of glucose, amino acids, and fatty acids circulate into body fluids Blood is where nutrients travel to reach cells Metabolism is the overall process 9

4 Absorption (Cont.) Nutrients used for energy and as building blocks for larger complex chemicals Anabolism: Act of building molecules Catabolism: Act of breaking down molecules to release energy Metabolism = Anabolism + Catabolism Small intestines: Responsible for final steps of digestion Absorb nutrients Send remains to large intestines The adjective form of anabolism is anabolic, hence the term anabolic steroids, which refers to steroids that promote tissue growth and muscle mass. Food and drug absorption takes place in the small intestines. Chyme (acidic blend of juices in the stomach) is produced to breakdown food and drugs prior to their entry here. The level of acidity is important in the absorption of many drugs and minerals. A variety of drug interactions can occur between acid-lowering medications, such as proton pump inhibitors (PPIs), and medications that require an acidic environment within the stomach for proper absorption. The acidic environment of the stomach can also destroy many medications that enter into it, which is the reason why several medications need special coating for protection. Alternatively, some medications (e.g., parenteral medications such as insulin) need to be administered in a totally different form to bypass the stomach and its acidic environment. 10 The Small Intestine Small intestines are three sections: Duodenum: 25 cm long Connected to liver and pancreas Receives secretions to mix with chyme Jejunum: 2.5 m long Ileum: 3.5 m long What is the inside surface area of the small intestine? (The inside surface area of the small intestine is estimated to be 200 to 500 square meters.) Why does the small intestine have such a large internal surface area? (The small intestine has a large internal surface area because to efficiently absorb nutrients from food, it must make contact with as much of the food as possible for as long as possible.) 11 Process of Absorption Intestinal secretions: Alkaline ph Enzymes break down sugar, protein, and fat Acidic environment destroys medications (special coatings needed or use parenteral medications) Gallbladder releases bile to disperse and absorb fats Patients who have had their gallbladders removed can usually live with no problems. In such patients, bile is still produced by the liver, but it enters the small intestine continuously rather than being released in response to a fatcontaining meal. The gallbladder releases bile to help in the dispersion of fats. 12

5 Excretion Substances moving through here are turned into fecal matter as water and electrolytes are absorbed. Large intestine main sections: Cecum, colon, rectum, and anus Absorption limited to water and electrolytes Substances transformed into solid fecal matter 13 Excretion (Cont.) What are hemorrhoids? (Hemorrhoids are swollen veins within the lower rectum or anus. They can make defecation painful.) How is a hemorrhoid different from an inguinal hernia? (Both conditions involve protruding tissue in the digestive tract, but an inguinal hernia is the protrusion of the intestine through the abdominal wall.) Rectum: Shortest section Connects to anal canal Empty except during defecation Time for normal passage of fecal material: 3 to 5 days Anal canal Internal sphincter involuntary External sphincter voluntary 14 Auxiliary Organ Functions Carbohydrates must be broken down to simple molecules. They arrive in the stomach as large sugar molecules. What is involved in the process of emulsification? (Emulsification is the process by which an insoluble liquid, such as oil or fat, is broken into drops small enough to be suspended in another liquid, such as water.) Pancreas, liver, and gallbladder all have ducts leading to duodenum They break down proteins, carbohydrates, and fats Proteins are broken down into peptides first by pepsin, then by trypsin and chymotrypsin from pancreas Carbohydrates: Large sugar molecules, broken down to disaccharides, then to monosaccharides; absorbed and used for energy Fats: Broken down by bile (emulsification), then by lipases (enzymes) 15

6 Conditions Affecting the Gastrointestinal System Occurring and reoccurring conditions: Heartburn, upset stomach, GERD, constipation, and diarrhea Severe illnesses: Crohn s disease, ulcers Bacterial infections, food allergies, and tumors Genetic defects: Lack of chemicals GERD stands for gastroesophageal reflux disease. Many women experience heartburn during pregnancy. Why would relaxed sphincters of the GI system cause heartburn? (Heartburn is actually a condition of the GI system and does not actually directly involve the heart. Heartburn occurs when small amounts of acid rise up into the esophagus [which does not have a protective lining]. When the esophagus is exposed to the acid, it can become inflamed and painful. The sphincters of the GI system prevent acid from the stomach from escaping into the esophagus, so if one of the sphincters has relaxed, then some of the acid from the stomach can get to the esophagus, causing heartburn.) 16 Stomach Conditions Stomach conditions caused by high acid content Upset stomach, heartburn, and indigestion Two main conditions: GERD Peptic ulcers (Helicobacter pylori bacterium) What is a hiatal hernia? How does the presence of a hiatal hernia contribute to GERD? (A hiatal hernia is a condition in which the stomach bulges up slightly through the diaphragm at the point where the stomach is connected to the esophagus. This condition might contribute to GERD because it makes the diaphragm less able to help prevent acid from entering the esophagus.) Ulcers attributable to drugs, such as nonsteroidal antiinflammatory drugs (NSAIDs) and infections with bacteria (H. pylori) are the leading causes of peptic ulcer disease (PUD). 17 Gastroesophageal Reflux Disease GERD occurs when the cardiac sphincter relaxes Acidic contents back up into esophagus; causes burning sensations in chest and throat Changing eating habits may help Despite its heart-sounding name, the cardiac sphincter is part of the stomach, not the heart. Acid causes or worsens ulcers and GERD. Constipation is a condition in which the feces are hard and dry and bowel movements are infrequent or irregular. Risk factors for GERD include obesity, smoking, and pregnancy. H 2 -receptor blockers reduce acid production. PPIs inhibit gastric acid production within the stomach lining by blocking the final enzymatic reaction before acid secretion. Antacids neutralize acid. 18

7 Drug Treatments for Gastroesophageal Reflux Disease Patients who are taking certain antibiotics, such as tetracycline and ciprofloxacin, should not take antacids that contain magnesium or aluminum because these chemicals can reduce the absorption of the antibiotics. Ion additives used: Aluminum carbonate, sodium bicarbonate, calcium carbonate, magnesium hydroxide, and aluminum hydroxide Aluminum causes constipation Magnesium causes diarrhea Buffers decrease acidity within stomach 19 Drug Treatments for Gastroesophageal Reflux Disease (Cont.) The histamine that causes gastric acid secretion is the same chemical that causes allergic reactions; it is the receptor type (histamine-1 versus histamine-2) that determines the effect of the histamine. Histamine-2 (H 2 ) antagonists: Action bind to H 2 -receptor sites, lowering acid secretions Side effects: GI upset, drowsiness Proton pump inhibitors: Block gastric acid secretions in the stomach Available only by prescription Delayed-release form taken once daily 20 Peptic Ulcer Disease H. pylori (gram-negative bacillus) embeds itself in mucosal lining of stomach, duodenum, and rectum Cause of inflammation, peptic ulcers; linked to stomach cancer Wash hands to reduce spread of bacteria Although H. pylori are known to cause ulcers, some researchers believe it might confer protection against GERD and esophageal cancer. H. pylori is commonly treated with a combination of two antibiotics and a PPI. NSAIDs can cause ulcers by interfering with the protective prostaglandins in the stomach. Alcohol also increases the chance of ulcers but is not considered a medication. 21

8 Drug Treatment for Peptic Ulcer Disease Many times treatment for peptic ulcers requires a regimen of several classes of drugs together. H packs are one way these are provided. Refer to Table 20-4 (p. 514). Antibiotics: May consist of two, three, or four agents given simultaneously Protein pump inhibitors (PPIs) Antacids 22 Intestinal Conditions Most common symptoms: Diarrhea and constipation Causes: Various infections, bacteria, viruses, and parasites (diarrhea) Tumors and obstructions (constipation) Medications are a common cause Stool softeners alleviate problems What is diverticulosis? (Diverticulosis is an intestinal condition marked by the presence of small pouches [diverticula] in the large intestine. Diverticulosis might be caused in part by a diet lacking enough fiber. If one or more of the diverticula become plugged and infected, the condition is called diverticulitis.) 23 Crohn's Disease Causes ulcerations in the small and large intestinal lining; can effect anywhere from mouth to anus Direct cause unknown: Autoimmune and genetic factors play role Can cause fistulae in the bowel Treatment: Lifestyle changes, avoid trigger foods, vitamin injections, and avoid dairy Drug treatment: 5-aminosalicylates (5-ASA), sulfasalazine (Azulfidine), mesalamine (Asacol), corticosteroids, and biological agents As mentioned previously, Crohn s disease is closely related to ulcerative colitis, and together they constitute inflammatory bowel disease. Symptoms include cramping, tenderness, flatulence, nausea, fever, and diarrhea. In debilitated patients, parenteral nutrition may be necessary to maintain nutritional status while resting the bowels. 5-Aminosalicylates to control inflammation are approved by the U.S. Food and Drug Administration (FDA) for the treatment of ulcerative colitis. Many of the medications used for ulcerative colitis are the same as those used for Crohn disease, including 5-aminosalicylates. IBS, constipation, and diarrhea do not involve inflammation. 24

9 Ulcerative Colitis Inflammation/sores in large intestine and colon Affects only colon and rectum Symptoms: Stomach pain, cramps, bloody diarrhea, and rectal bleeding Treatment: Lifestyle changes, stress reduction techniques, and surgery (severe cases) Drug treatment: Antidiarrheals, corticosteroids, 5-ASA, and aminosalicylates Because the symptoms associated with ulcerative colitis are often seen with other, related conditions, it is important to rule out an infectious cause. Many of the medications used for ulcerative colitis are the same as those used for Crohn's disease. Diphenoxylate/atropine (Lomotil) slows intestinal motility to treat diarrhea. 25 Irritable Bowel Syndrome Characterized by chronic abdominal pain and altered bowel habits Abdominal pain ranges from mild to debilitating Treatment: Avoid any triggers/irritants Drug treatments: Antispasmodics (dependence if long-term use), antidiarrheals, and bile acid sequestrants Irritable bowel syndrome (IBS) is the most commonly diagnosed GI condition and affects men, women, young patients, and the elderly. Altered bowel habits can include episodic diarrhea, constipation, and alternating diarrhea and constipation. Lotronex is to be used by women suffering from IBS who have had diarrhea for at least 6 months. Lotronex has not shown to be effective in men with IBS. The common adult dosage is 0.5 mg twice daily for 4 weeks. Infrequent but serious adverse effects have occurred with the use of Lotronex, including ischemic colitis and severe constipation that may result in hospitalization and, in rare cases, blood transfusion, surgery, and death. Crohn disease and ulcerative colitis are the two major types of IBD. Ulcerative colitis affects only the colon and rectum, whereas Crohn disease can affect the entire GI system. Symptoms of both disorders include abdominal cramping and diarrhea. A nondrug approach to both diseases involve some dietary changes and restrictions. 26 Diarrhea Two types: Acute and chronic Symptoms (bacteria): Watery stools, abdominal cramping, and general discomfort Vital fluids and electrolytes lost: If not replaced, death occurs in a few days Susceptible persons: Older adults and children Some children develop chronic diarrhea from drinking too much apple or pear juice. As diarrhea continues, vital fluids and electrolytes are lost through the intestines. Death can occur if fluids and electrolytes are not replaced. Diarrhea is a significant cause of death worldwide. 27

10 Drug Treatment for Diarrhea Treatments are agents with adsorbent and/or protectant quality Agents: OTC and prescription OTC: Kaopectate, FiberCon, and Pepto-Bismol Potent/controlled substances: Diphenoxylate/ atropine (Lomotil) and paregoric (short-term use) Most OTC diarrhea medications are not recommended for children, and some can be dangerous. A pediatrician should be called if a child with diarrhea shows any signs of dehydration. Lomotil is a C-V medication that can be purchased from the pharmacist without a prescription. 28 Constipation Symptoms: Lack of defecation, dry and hard stools Cause: Lack of fiber in diet Treatment: Laxatives (bulk-forming agents, stool softeners, hyperosmotic agents, and powerful stimulants) Stool softeners pull water and fatty compounds into intestines to aid elimination Hyperosmotic agents increase pressure within bowels by drawing in water Dietary fiber comes in two forms: soluble and insoluble. Both types provide health benefits for humans. Insoluble fiber provides bulk for the stools, helping them to move through the intestines. Common sources of soluble fiber are vegetables, whole grains, and wheat bran. Soluble fiber is thought to help lower LDL ("bad") cholesterol levels, regulate blood sugar levels, and bulk up stools. Common sources of soluble fiber are beans, nuts, oat bran, citrus fruits, apples, and strawberries. A positive aspect of bulk-forming laxatives is that they can be taken over long periods and can be used for both constipation and diarrhea. Stimulant laxatives work by increasing peristalsis within the intestines (specifically the colon), which forces the contents to be expelled. Persons who constantly take stimulant laxatives eventually may become dependent on them; therefore stimulant laxatives are recommended for use on a shortterm basis. 29 Flatulence Caused by by-products of microbial breakdown of certain foods Lactose-intolerant people cannot metabolize lactose Cause: Poor absorption of food in small intestine Treatment: Soy products, lactose supplements, and eliminating trigger foods Drug treatment: Simethicone Sugars (lactose, sorbitol, and fructose) and starches (rice, wheat, and certain vegetables) may pose a problem because they may be difficult to digest. This enzyme is located in the lining of the intestines, and without it the person cannot metabolize the carbohydrate lactose; this results in poor digestion of milk products. Symptoms are discomfort (bloating) and pain in the abdominal cavity. This medication is available in tablets, chewable tablets, and liquid for children. OTC medications used for the treatment of flatulence typically contain simethicone as the primary ingredient. 30

11 Emesis Extreme nausea and vomiting caused by chemotherapy treatments Medulla oblongata is the control center Chemoreceptor trigger zone (CTZ) or nausea center activated by smell, pain, medication, motion sickness, and emotions CTZ activated, chemical signals sent via nervous system to emetic center, relays message to stomach, and muscles work together to cause vomiting Antiemetics: Drugs used require prescription because of effect on the CTZ How can chemotherapy treatments cause emesis? (Some chemotherapy drugs cause nausea and vomiting because they affect the parts of the brain that control vomiting and/or they irritate the stomach lining.) Why do antiemetics require a prescription? (Antiemetics require a prescription because they affect the CTZ, which is located near the respiratory center of the brain. When the CTZ is inhibited, it can also inhibit the respiratory center of the brain, leading to a decrease in respiration.) Agents that do not affect the chemoreceptor trigger zone (CTZ) can be purchased OTC and are usually used to treat the symptoms of motion sickness. The CTZ or nausea zone, a small area of the brainstem, can be activated by smell, pain, medication, motion sickness (originating in the inner ear), and even emotions. Other causes of emesis include food or drug poisoning, overconsumption of alcohol, or a postsurgical reaction to anesthesia. Chemotherapeutic agents activate the CTZ, causing emesis as a common side effect. Because metoclopramide blocks dopamine receptors in the brain, it should not be used in patients with Parkinson disease. It actually has a boxed warning for the possibility of tardive dyskinesias attributable to its effects on dopamine receptors. 31 Drug Treatments for Emesis A signal is sent to the CTZ that triggers vomiting. The nervous system responds and relays the message to the stomach. Anticholinergics Antidopaminergics: Lessen vomiting H 1 -antihistamines Cannabinoids (dronabinol) Corticosteroids (dexamethasone, methylprednisolone) Benzodiazepines (lorazepam) 32 Colorectal Cancer Although the mortality rate has been decreasing by about 3% per year since 1990, colorectal cancer (CRC) is still the second most common cause of cancer-related death in the United States. Symptoms: Abdominal pain, changing bowel habits, blood in stool, weakness, anemia, and weight loss Treatment: Surgery is only curative treatment Drug treatment: Chemotherapeutic agents 33