Chapter 9 Gastrointestinal System PDF

DRUGS USED TO TREAT ULCER DISEASE § The H2 antagonists selectively block H2 receptors located on the parietal cells. § Blocking these receptors prevents the release of gastrin, a hormone that causes local release of histamine (due to stimulation of histamine receptors), ultimately bloc...

DRUGS USED TO TREAT ULCER DISEASE § The H2 antagonists selectively block H2 receptors located on the parietal cells. § Blocking these receptors prevents the release of gastrin, a hormone that causes local release of histamine (due to stimulation of histamine receptors), ultimately blocking the production of hydrochloric acid. This action also decreases pepsin production by the chief cells. § H2 receptor sites are also found in the heart, and high levels of these drugs can produce cardiac arrhythmias. Pharmacokinetics § Cimetidine, ranitidine, and famotidine are available in oral and parenteral forms. Nizatidine is available only in oral form. § Cimetidine was the first drug in this class to be developed (prototype). It has been associated with antiandrogenic effects, including gynecomastia and galactorrhea. It is metabolized mainly in the liver; it can slow the metabolism of many other drugs that use the same metabolizing enzyme system. It is excreted in urine. § Ranitidine and Famotidine, which are longer acting and more potent than cimetidine, are not associated with the antiandrogenic adverse effects or the marked slowing of metabolism in the liver as cimetidine is. They are metabolized in the liver and excreted in urine. § Famotidine is approved for use in children ages 1 to 16 years old. § Nizatidine, the newest drug in this class, is similar to ranitidine in its effectiveness and adverse effects. It differs from the other three drugs in that it is eliminated by the kidneys, with no first-pass metabolism in the liver. It is the drug of choice for patients with liver dysfunction. Contraindications and Cautions § Caution should be used during pregnancy or lactation because of the potential for adverse effects on the fetus or nursing baby and with hepatic or renal dysfunction, which could interfere with drug metabolism and excretion. Adverse Effects § GI effects of diarrhea or constipation § CNS effects of dizziness, headache, somnolence, confusion, or even hallucinations. § Cardiac arrhythmias and hypotension more commonly seen with intravenous (IV) or intramuscular (IM). § Gynecomastia with long-term use of cimetidine and impotence. § The gastric acid pump or proton pump inhibitors suppress gastric acid secretion by specifically inhibiting the hydrogen–potassium adenosine triphosphatase (H+, K+-ATPase) enzyme system on the secretory surface of the gastric parietal cells. § This action blocks the final step of acid production, lowering the acid levels in the stomach. § They are recommended for the short-term treatment of active duodenal ulcers, GERD, erosive esophagitis, and benign active gastric ulcer; for the long-term treatment of pathological hypersecretory conditions; as maintenance therapy for healing of erosive esophagitis and ulcers; and in combination with amoxicillin and clarithromycin for the treatment of H. pylori infection. Pharmacokinetics § These drugs are acid labile and are rapidly absorbed from the GI tract, reaching peak levels in 3 to 5 hours. § They undergo extensive metabolism in the liver and are excreted in urine. § Omeprazole is faster acting and more quickly excreted than the other proton pump inhibitors. Contraindications and Cautions § Caution should be used in pregnant or lactating women because of the potential for adverse effects on the fetus or neonate. § The safety and efficacy of these drugs have not been established for patients younger than 18 years of age, except for lansoprazole, which is the proton pump inhibitor of choice if one is needed for a child. Adverse Effects § The adverse effects associated with these drugs are related to their effects on the H+, K+-ATPase pump on the parietal and other cells. § CNS effects of dizziness and headache are commonly seen; asthenia (loss of strength), vertigo, insomnia, apathy, and dream abnormalities may also be observed. § GI effects can include diarrhea, abdominal pain, nausea, vomiting, dry mouth, and tongue atrophy. § Upper respiratory tract symptoms, including cough, stuffy nose, hoarseness, and epistaxis, are frequently seen. § Less common adverse effects include rash, alopecia, pruritus, dry skin, back pain, and fever. § Recent studies show an increase in bone loss and decreased calcium levels, decreased magnesium levels, and increased incidence of Clostridium difficile diarrhea and pneumonia in patients using these drugs long term. DRUGS USED IN THE TREATMENT OF CONSTIPATION § Laxative, or cathartic, drugs are indicated for the short-term relief of constipation. § Most laxatives are available in over-the-counter (OTC) preparations, and they are often abused by people who then become dependent on them for stimulation of GI movement. Such individuals may develop chronic intestinal disorders as a result. § Kinds of laxatives include chemical stimulants (which chemically irritate the lining of the GI tract), bulk stimulants (which cause fecal matter to increase in bulk), and lubricants (which help the intestinal contents move more slowly). § Chemical stimulants directly stimulate the nerve plexus in the intestinal wall, causing increased movement and the stimulation of local reflexes. § Castor oil, an old stand by, is used when a thorough evacuation of the intestine is desirable. § All of these agents begin working at the beginning of the small intestine and increase motility throughout the rest of the GI tract by irritating the nerve plexus. § Bisacodyl acts in a similar manner but is somewhat milder in effect; it can also be given in a water enema to stimulate the activity in the lower GI tract. § Cascara is somewhat milder than castor oil and is often used when effects are needed overnight. § Senna is available orally in tablet and syrup form and as a rectal suppository. Pharmacokinetics § Most of these agents are only minimally absorbed and exert their therapeutic effect directly in the GI tract. § Changes in absorption, water balance, and electrolytes resulting from GI changes can have adverse effects on patients with underlying medical conditions that are affected by volume and electrolyte changes. Contraindications and Cautions § Laxatives are contraindicated in acute abdominal disorders, including appendicitis, diverticulitis, and ulcerative colitis, when increased motility could lead to rupture or further exacerbation of the inflammation. § Laxatives should be used with caution in heart block, coronary artery disease (CAD), or debilitation, which could be affected by the decrease in absorption and changes in electrolyte levels that can occur and with great caution during pregnancy and lactation because, in some cases, stimulation of the GI tract can precipitate labor and many of these agents cross the placenta and are excreted in breast milk. § Castor oil should not be used during pregnancy because its irritant effect has been associated with induction of premature labor. § Magnesium laxatives can cause diarrhea in the neonate if used during lactation. Adverse Effects § The adverse effects most commonly associated with laxatives are GI effects such as diarrhea, abdominal cramping, and nausea. § Central nervous system (CNS) effects, including dizziness, headache, and weakness, are not uncommon and may relate to loss of fluid and electrolyte imbalances that may accompany laxative use. § Sweating, palpitations, flushing, and even fainting have been reported after laxative use. § These effects may be related to a sympathetic stress reaction to intense neurostimulation of the GI tract or to the loss of fluid and electrolyte imbalance. § A very common adverse effect that is seen with frequent laxative use or laxative abuse is cathartic dependence. § This reaction occurs when patients use laxatives over a long period of time and the GI tract becomes dependent on the vigorous stimulation of the laxative. Without this stimulation, the GI tract does not move for a period of time (i.e., several days), which could lead to constipation and drying of the stool and ultimately to impaction. § Bulk stimulants increase the motility of the GI tract by increasing the fluid in the intestinal contents, which enlarges bulk, stimulates local stretch receptors, and activates local activity. § Lactulose is a saltless osmotic laxative that pulls fluid out of the venous system and into the lumen of the small intestine. § Magnesium citrate and hydroxide are a milder and slower-acting laxative. They works by a saline pull, bringing fluids into the lumen of the GI tract. § Polyethylene glycol-electrolyte solution is a hypertonic fluid containing many electrolytes that pulls fluid out of the intestinal wall to increase the bulk of the intestinal contents. § Psyllium, another gelatin-like bulk stimulant, is similar to polycarbophil in action and effect. Pharmacokinetics § These drugs are all taken orally. They are directly effective within the GI tract and are not generally absorbed systemically. § They are rapidly acting, causing effects as they pass through the GI tract. Contraindications and Cautions § Bulk laxatives are contraindicated in acute abdominal disorders, including appendicitis, diverticulitis, and ulcerative colitis. § Laxatives should be used with caution in heart block, CAD and debilitation, and with great caution during pregnancy and lactation. § Polyethylene glycolelectrolyte solution should be used with caution in any patient with a history of seizures because of the risk of electrolyte absorption causing neuronal instability and precipitating seizures. Adverse Effects § The adverse effects most commonly associated with bulk laxatives are GI effects such as diarrhea, abdominal cramping, and nausea. § CNS effects, including dizziness, headache, and weakness, are common and may relate to loss of fluid and electrolyte imbalances that may accompany laxative use. § Sweating, palpitations, flushing, and even fainting have been reported after laxative use. § Sometimes it is desirable to make defecation easier without stimulating the movement of the GI tract. This is done using lubricants. § Patients with hemorrhoids and those who have recently had rectal surgery may need lubrication of the stool. § Docusate has a detergent action on the surface of the intestinal bolus, increasing the admixture of fat and water and making a softer stool. § Glycerin is a hyperosmolar laxative that is used in suppository form to gently evacuate the rectum without systemic effects higher in the GI tract. § Mineral oil is the oldest of these laxatives. When the intestinal bolus is coated with mineral oil, less water is absorbed out of the bolus, and the bolus is less likely to become hard or impacted. Pharmacokinetics § These drugs are not absorbed systemically and are excreted in the feces. § Docusate and mineral oil are given orally. Glycerin is available as a rectal suppository or as a liquid for rectal retention. Contraindications and Cautions § Lubricants are contraindicated in acute abdominal disorders, including appendicitis, diverticulitis, and ulcerative colitis. § Lubricants should be used with caution in heart block, CAD and debilitation, and with great caution during pregnancy and lactation. Adverse Effects § The adverse effects most commonly associated with lubricant laxatives are GI effects such as diarrhea, abdominal cramping, and nausea. In addition, leakage and staining may be a problem when mineral oil is used and the stool cannot be retained by the external sphincter. § CNS effects, including dizziness, headache, and weakness, are common and may relate to loss of fluid and electrolyte imbalances that may accompany laxative use. § Sweating, palpitations, flushing, and even fainting have been reported after laxative use. § These effects are less likely to happen with the lubricant laxatives than with the chemical or mechanical stimulants.