 DRUGS USED TO TREAT GASTROESOPHAGEAL REFLUX DISEASE AND ULCER DISEASE sh.alinia3

 peptic ulcer: erosion of the lining of stomach or duodenum;results from imbalance between acid produced and the mucous protection of the GI lining or possibly from infection by Helicobacter pylori bacteria.  prostaglandin: any one of numerous tissue hormones that have local effects on various systems and organs of the body, including vasoconstriction, vasodilation, increased or decreased GI activity, and increased or decreased pancreatic enzyme release.  proton pump inhibitor: drug that blocks the H+, K+- ATPase enzyme system on the secretory surface of the gastric parietal cells, thus interfering with the fi nal step of acid production and lowering acid levels in the stomach.  gastroesophageal reflux disease (GERD) sh.alinia4

 histamine-2 (H2) antagonists, which block the release of hydrochloric acid in response to gastrin;  antacids, which interact with acids at the chemical level to neutralize them;  proton pump inhibitors, which suppress the secretion of hydrochloric acid into the lumen of the stomach;  GI protectants, which coat any injured area in the stomach to prevent further injury from acid; and  prostaglandins,which inhibit the secretion of gastrin and increase the secretion of the mucous lining of the stomach, providing a buffer. sh.alinia5

 Histamine-2 (H2) antagonists block the release of hydrochloric acid in response to gastrin. These drugs include;  cimetidine (Tagamet),  ranitidine (Zantac),  famotidine (Pepcid),  nizatidine (Axid). sh.alinia6

 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 sh.alinia7

 These drugs are used in the following conditions:  Short-term treatment of active duodenal ulcer or benign gastric ulcer (reduction in the overall acid level can promote healing and decrease discomfort).  Treatment of pathological hypersecretory conditions such as Zollinger–Ellison syndrome (blocking the overproduction of hydrochloric acid that is associated with these conditions). sh.alinia8

 Prophylaxis of stress-induced ulcers and acute upper GI bleeding in critical patients (blocking the production of acid protects the stomach lining, which is at risk because of decreased mucus production associated with extreme stress).  Treatment of erosive gastroesophageal reflux (decreasing  the acid being regurgitated into the esophagus will promote healing and decrease pain).  Relief of symptoms of heartburn, acid indigestion. sh.alinia9

 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.It reaches peak levels in 1 to 1.5 hours and is metabolized mainly in the liver;  It is excreted in urine. It has a half-life of 2 hours and is known to cross the placenta and enter breast milk. sh.alinia10

 Ranitidine, which is longer acting and more potent than cimetidine, is not associated with the antiandrogenic adverse effects as cimetidine is.  It reaches peak levels in 5 to 15 minutes when given parenterally and 1 to 3 hours when given orally.  It has a duration of 8 to 12 hours and a half-life of 2 to 3 hours.  Ranitidine is metabolized by the liver and excreted in urine.  It crosses the placenta and enters breast milk. sh.alinia11

 Famotidine is similar to ranitidine, but it is much more potent than either cimetidine or ranitidine.  It reaches peak effects in 1 to 3 hours and has a duration of 6 to 15 hours.  Famotidine is metabolized in the liver and excreted in urine with a half-life of 2.5 to 3.5 hours.  Famotidine crosses the placenta and enters breast milk.  Famotidine is approved for use in children ages 1 to 16 years old. sh.alinia12

 Nizatidine, the newest drug in this class, is similar to ranitidine in its effectiveness and adverse effects.  It reaches peak effects in 0.5 to 3 hours and has a half-life of 1 to 2 hours. Like the other three drugs, it crosses the placenta and enters the breast milk. sh.alinia13

 Pregnancy or lactation.  with hepatic or renal dysfunction. sh.alinia14

 GI effects.  central nervous system (CNS) effects.  cardiac arrhythmias and hypotension (related to H2 cardiac receptor blocking; more commonly seen with intravenous (IV)  and gynecomastia (more common with long- term use of cimetidine) and impotence. or intramuscular (IM). sh.alinia15

 Administer oral drug with or before meals and at bedtime to ensure therapeutic levels when the drug is most needed.  Monitor the patient continually if giving IV doses to allow early detection of potentially serious adverse effects, including cardiac arrhythmias.  determine drug effectiveness.  Arrange for decreased dose in cases of hepatic or renal dysfunction to prevent serious toxicity. sh.alinia16

 Antacids (Table 57.1) are a group of inorganic chemicals that neutralize stomach acid.  sodium bicarbonate  calcium carbonate  magnesium salts (Milk of Magnesia and others),  aluminum salts (Amphojel). sh.alinia17

 Antacids neutralize stomach acid by direct chemical reaction (see Figure 57.1). They are recommended for the symptomatic relief of upset stomach associated with hyperacidity sh.alinia18

 Magnesium salts are very effective in buffering acid in the stomach but have been known to cause diarrhea; they are sometimes used as laxatives.  They are available as tablets, chewable tablets, and capsules and in liquid forms.  Although these agents are not generally absorbed systemically and are excreted in the feces, absorbed magnesium can lead to nerve damage and even coma, if absorbed; it is excreted in the urine. sh.alinia19

 Aluminum salts, available as tablets, capsules, suspensions,and in a liquid form,  bound in feces for excretion.  They have been related to severe constipation.  Aluminum binds dietary phosphates and causes hypophosphatemia, which can then cause calcium imbalance. sh.alinia20

 Magaldrate, an aluminum and magnesium salt combination that is available as a suspension and in a liquid form, minimizes the GI effects of constipation and diarrhea by combining these two salts but may cause a rebound hyperacidity and alkalosis.  Magaldrate is not generally absorbed systemically and is excreted in the feces.  It has an onset of action of 30 minutes and a duration of 30 to 60 minutes. sh.alinia21

 Caution should be used in the following instances:  any condition that can be exacerbated by electrolyte or acid–base imbalance.  GI obstruction, which could cause systemic absorption of the drugs and increased adverse effects;  renal dysfunction  and pregnancy and lactation sh.alinia22

 The adverse effects associated with these drugs relate to their effects on acid–base and electrolyte balance.  Administering an antacid frequently causes acid rebound,in which the stomach produces more acid in response to the alkaline environment.  Alkalosis (nausea, vomiting, neuromuscular changes, headache,irritability, muscle twitching, and even coma).  Constipation or diarrhea.  Hypophosphatemia with the use of aluminum salts. sh.alinia23

 Antacids can greatly affect the absorption of drugs from the GI tract. Most drugs are prepared for an acidic environment,and an alkaline environment can prevent them from being broken down for absorption.  Patients taking antacids should be advised to separate them from any other medications by 1 to 2 hours.  If the pH of urine is affected by large doses of antacids, levels of drugs, such as quinidine, may increase, and levels of salicylates may decrease. sh.alinia24

 Administer the drug apart from any other oral medications approximately 1 hour before or 2 hours after to ensure adequate absorption of the other medications.  Have the patient chew tablets thoroughly and follow with water to ensure that therapeutic levels reach the stomach to decrease acidity.  Obtain specimens for periodic monitoring of serum electrolytes to evaluate drug effects.  Monitor the patient for diarrhea or constipation to institute a bowel program before severe effects occur. sh.alinia25

 Proton pump inhibitors (Table 57.1) suppress the secretion of hydrochloric acid into the lumen of the stomach.  Six proton pump inhibitors are available:  omeprazole  esomeprazole  lansoprazole  dexlansoprazole  pantoprazole  rabeprazole. sh.alinia26

 Therapeutic Actions and Indications 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 sh.alinia27

 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. sh.alinia28

 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.It has a half-life of 30 to 60 min.  Esomeprazole is a longer-acting drug; it has a half- life of 60 to 90 minutes and a duration of 17 hours.  Lansoprazole has a half-life of 2 h. and a duration of 12 h.  Pantoprazole and rabeprazole have half-lives of 90 minutes and durations of 12 to 14 hours. sh.alinia29

 Caution should be used in pregnant or lactating women.  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. sh.alinia30

 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.  Other, less common adverse effects include rash, alopecia, pruritus, dry skin, back pain, and fever sh.alinia31

 Administer drug before meals to ensure that the patient does not open, chew, or crush capsules;  Monitor the patient for diarrhea or constipation in order to institute an appropriate bowel program as needed.  Arrange for medical follow-up if symptoms are not resolved after 4 to 8 weeks of therapy. sh.alinia32

 GI protectants coat any injured area in the stomach to prevent further injury from acid.  Sucralfate is the only GI protectant currently available.  Therapeutic Actions and Indications:  Sucralfate forms an ulcer-adherent complex at duodenal ulcer sites, protecting the sites against acid, pepsin, and bile salts.  Pharmacokinetics:  is rapidly absorbed after oral administration, metabolized in the liver, and excreted in feces.  It crosses the placenta and may enter breast milk. sh.alinia33

 It should not be given to individuals with renal failure or undergoing dialysis because a buildup of aluminum may occur if it is used with aluminum-containing products.  Caution should be used in patients who are pregnant.  Constipation is the most frequently seen adverse effect. sh.alinia34

 Administer the drug on an empty stomach, 1 hour before or 2 hours after meals and at bedtime,to ensure the therapeutic effectiveness of the drug.  Administer antacids or antibiotics, if ordered,between doses of sucralfate, not within 30 minutes of a sucralfate dose, because sucralfate can interfere with absorption of oral agents. sh.alinia35

 Prostaglandins are used to protect the stomach lining.  The prostaglandin available for this use is the synthetic prostaglandin E1 analogue misoprostol (Cytotec).  Prostaglandin E1 inhibits gastric acid secretion and increases bicarbonate and mucous production in the stomach,thus protecting the stomach lining.  Misoprostol is given orally. It is rapidly absorbed from the GI tract, metabolized in the liver, and excreted in urine.  Misoprostol crosses the placenta and enters breast milk.  Misoprostol is primarily used to prevent NSAID-induced gastric ulcers in patients who are at high risk for complications from a gastric ulcer. sh.alinia37

 CHEMICAL STIMULANTS:  Chemical stimulants directly stimulate the nerve plexus in the intestinal wall, causing increased movement and the stimulation of local reflexes.  Most of these agents are only minimally absorbed and exert their therapeutic effect directly in the GI tract.  Laxatives classified as chemical stimulants include:  bisacodyl (Dulcolax),  cascara (generic),  castor oil (Neoloid),  and senna sh.alinia38

 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.  A very common adverse effect that is seen with frequent laxative use or laxative abuse is cathartic dependence.  Without this stimulation, the GI tract does not move for a period of time, which could lead to constipation. sh.alinia39

 Bulk stimulants (also called mechanical stimulants) are rapid-acting, aggressive laxatives that cause the fecal matter to increase in bulk.  They 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.  Available bulk stimulants include the following agents: sh.alinia40

 magnesium sulfate  magnesium citrate  magnesium hydroxide (Milk of Magnesia),  lactulose  polycarbophil  psyllium  and polyethylene glycol-electrolyte solution (GoLYTELY, MiraLAX).

 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:  in acute abdominal disorders, including appendicitis, diverticulitis, and ulcerative colitis, sh.alinia42

 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.  Lubricating laxatives include docusate (Colace), glycerin (Sani-Supp), and mineral oil (Agoral Plain). sh.alinia43

 Antidiarrheals block stimulation of the GI tract for symptomatic relief from diarrhea.  Available agents include bismuth subsalicylate (Pepto-Bismol), loperamide (Imodium), and opium derivatives (paregoric). sh.alinia44

 Antidiarrheal agents slow the motility of the GI tract through direct action on the lining of the GI tract to inhibit local reflexes (bismuth subsalicylate),  through direct action on the muscles of the GI tract to slow activity (loperamide),  or through action on CNS centers that cause GI spasm and slowing (opium derivatives; sh.alinia45

 These drugs are indicated for the relief of symptoms of acute and chronic diarrhea, reduction of volume of discharge from ileostomies, and prevention and treatment of traveler’s diarrhea.).  Bismuth subsalicylate has been found to be very helpful in treating traveler’s diarrhea.

 Caution should be used in pregnancy and lactation.  Care should also be taken in individuals with any history of GI obstruction;  acute abdominal conditions, which could be exacerbated by the effects of the drugs, or sh.alinia47

 diarrhea due to poisonings, which could be worsened by slowing of the GI tract, allowing increased time for absorption of the poison;  or with hepatic impairment,

 If no response is seen within 48 hours, the diarrhea could be related to an underlying medical condition.  Arrange to discontinue the drug and arrange for medical evaluation. sh.alinia49

 Drugs used in managing nausea and vomiting are called antiemetics.  All of them work by one of two ways:  locally, to decrease the local response to stimuli that are being sent to the medulla to induce vomiting.  centrally, to block the chemoreceptor trigger zone (CTZ) or suppress the vomiting center directly. sh.alinia50

 1-PHENOTHIAZINES:  The two phenothiazines most commonly used as antiemetics are prochlorperazine and promethazine (Phenergan).  2-NONPHENOTHIAZINE:  The only nonphenothiazine currently available for use as an antiemetic is metoclopramide (plasil), which acts to reduce the responsiveness of the nerve cells in the CTZ to circulating chemicals that induce vomiting. sh.alinia51

 3-ANTICHOLINERGICS/ANTIHISTAMINES:  cyclizine (Marezine), and meclizine  These drugs are anticholinergics that act as antihistamines and block the transmission of impulses to the CTZ.  They are recommended for the nausea and vomiting associated with motion sickness or vestibular (inner ear) problems. sh.alinia52

 if used to prevent motion sickness,should be given 30 minutes before activity that involves motion. sh.alinia53