NCLEX: Gastrointestinal and Antiemetic Drugs

This chapter describes drugs used to treat four common medical conditions involving the gastrointestinal (GI) tract: 1) peptic ulcers and gastroesophageal reflux disease (GERD), 2) chemotherapy-induced emesis, 3) diarrhea, and 4) constipation. Many drugs described in other chapters also find application in the treatment of GI disorders. For example, the meperidine derivative diphenoxylate, which decreases peristaltic activity of the gut, is useful in the treatment of severe diarrhea. Other drugs are used almost exclusively to treat GI tract disorders. For example, H2- receptor antagonists and proton pump inhibitors (PPIs) are used to heal peptic ulcers.

Gastrointestinal and Antiemetic Drugs: DRUGS USED TO TREAT PEPTIC ULCER DISEASE AND GASTROESOPHAGEAL REFLUX DISEASE

Focus topic: Gastrointestinal and Antiemetic Drugs

The two main causes of peptic ulcer disease are infection with gram-negative Helicobacter pylori and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Increased hydrochloric acid (HCl) secretion and inadequate mucosal defense against gastric acid also play a role. Treatment approaches include 1) eradicating the H. pylori infection, 2) reducing secretion of gastric acid with the use of PPIs or H2-receptor antagonists, and/or 3) providing agents that protect the gastric mucosa from damage, such as misoprostol and sucralfate.

Gastrointestinal and Antiemetic Drugs

A. Antimicrobial agents

Focus topic: Gastrointestinal and Antiemetic Drugs

Patients with peptic ulcer disease (duodenal or gastric ulcers) who are infected with H. pylori require antimicrobial treatment. Infection with H. pylori is diagnosed via endoscopic biopsy of the gastric mucosa or various noninvasive methods, including serology and urea breath tests. Eradication of H. pylori results in rapid healing of active ulcers and low recurrence rates (less than 15% compared with 60% to 100% per year for initial ulcers healed with acid-reducing therapy alone). Successful eradication of H. pylori (80% to 90%) is possible with various combinations of antimicrobial drugs. Currently, triple therapy consisting of a PPI combined with amoxicillin (metronidazole may be used in penicillin-allergic patients) plus clarithromycin is the therapy of choice. Quadruple therapy of bismuth subsalicylate, metronidazole, and tetracycline plus a PPI is another option. Quadruple therapy should be considered in areas with high resistance to clarithromycin. This usually results in a 90% or greater eradication rate. Treatment with a single antimicrobial drug is much less effective, results in antimicrobial resistance, and is not recommended. Substitution of antibiotics is also not recommended (that is, do not substitute ampicillin for amoxicillin or doxycycline for tetracycline). [Note: GERD (heartburn) is not associated with H. pylori infection and does not respond to antibiotics.]

Gastrointestinal and Antiemetic Drugs

Gastrointestinal and Antiemetic Drugs

B. H2-receptor antagonists and regulation of gastric acid secretion

Focus topic: Gastrointestinal and Antiemetic Drugs

Gastric acid secretion is stimulated by acetylcholine, histamine, and gastrin. The receptor-mediated binding of acetylcholine, histamine, or gastrin results in the activation of protein kinases, which in turn stimulates the H+/K+-adenosine triphosphatase (ATPase) proton pump to secrete hydrogen ions in exchange for K+ into the lumen of the stomach. By competitively blocking the binding of histamine to H2 receptors, these agents reduce the secretion of gastric acid. The four drugs used in the United States—cimetidine [si-MET-ih-deen], ranitidine [ra-NI-ti-deen], famotidine [fa-MOE-tideen], and nizatidine [nye-ZA-ti-deen]—potently inhibit (greater than 90%) basal, food-stimulated, and nocturnal secretion of gastric acid. Cimetidine was the first histamine H2-receptor antagonist. However, its utility is limited by its adverse effect profile and drug– drug interactions.

Gastrointestinal and Antiemetic Drugs

1. Actions: The histamine H2-receptor antagonists act selectively on H2 receptors in the stomach, but they have no effect on H1 receptors. They are competitive antagonists of histamine and are fully reversible.

2. Therapeutic uses: The use of these agents has decreased with the advent of PPIs.

  • Peptic ulcers: All four agents are equally effective in promoting the healing of duodenal and gastric ulcers. However, recurrence is common if H. pylori is present and the patient is treated with these agents alone. Patients with NSAID-induced ulcers should be treated with PPIs, because these agents heal and prevent future ulcers more effectively than H2 antagonists do.
  • Acute stress ulcers: These drugs are given as an intravenous infusion to prevent and manage acute stress ulcers associated with high-risk patients in intensive care units. However, because tolerance may occur with these agents in this setting, PPIs have gained favor for this indication.
  • Gastroesophageal reflux disease (GERD): Low doses of H2 antagonists, currently available for over-the-counter sale, are effective for the treatment of heartburn (GERD) in only about 50% of patients. H2-receptor antagonists act by stopping acid secretion. Therefore, they may not relieve symptoms for at least 45 minutes. Antacids more quickly and efficiently neutralize stomach acid, but their action is only temporary. For these reasons, PPIs are now used preferentially in the treatment of GERD, especially for patients with severe heartburn.

3. Pharmacokinetics: After oral administration, the H2 antagonists distribute widely throughout the body (including into breast milk and across the placenta) and are excreted mainly in urine. Cimetidine, ranitidine, and famotidine are also available in intravenous formulations. The half-life of all of these agents may be increased in patients with renal dysfunction, and dosage adjustments are needed.

4. Adverse effects: In general, the H2 antagonists are well tolerated. Cimetidine can have endocrine effects because it acts as a nonsteroidal antiandrogen. These effects include gynecomastia and galactorrhea (continuous release/discharge of milk). The other agents do not produce the antiandrogenic and prolactin-stimulating effects of cimetidine. Other central nervous system effects (such as confusion and altered mentation) occur primarily in elderly patients and after intravenous administration. Cimetidine inhibits several cytochrome P450 isoenzymes and can interfere with the metabolism of many other drugs, such as warfarin, phenytoin, and clopidogrel. All H2 antagonists may reduce the efficacy of drugs that require an acidic environment for absorption, such as ketoconazole.

Gastrointestinal and Antiemetic Drugs

C. PPIs: Inhibitors of the H+/K+-ATPase proton pump

Focus topic: Gastrointestinal and Antiemetic Drugs

The PPIs bind to the H+/K+-ATPase enzyme system (proton pump) and suppress the secretion of hydrogen ions into the gastric lumen. The membrane-bound proton pump is the final step in the secretion of gastric acid. The available PPIs include dexlansoprazole [DEX-lan-SO-pra-zole], esomeprazole [es-oh-MEH-pra-zole], lansoprazole [lan-SO-pra-zole], omeprazole [oh-MEH-pra-zole], pantoprazole [pan-TOE-pra-zole], and rabeprazole [rah-BEH-pra-zole]. Omeprazole, esomeprazole, and lansoprazole are available over-the counter for short-term treatment of GERD.

1. Actions: These agents are prodrugs with an acid-resistant enteric coating to protect them from premature degradation by gastric acid. The coating is removed in the alkaline duodenum, and the prodrug, a weak base, is absorbed and transported to the parietal cell. There, it is converted to the active drug and forms a stable covalent bond with the H+/K+-ATPase enzyme. It takes about 18 hours for the enzyme to be resynthesized, and acid secretion is inhibited during this time. At standard doses, PPIs inhibit both basal and stimulated gastric acid secretion by more than 90%. An oral product containing omeprazole combined with sodium bicarbonate for faster absorption is also available over the counter and by prescription.

2. Therapeutic uses: The PPIs are superior to the H2 antagonists in suppressing acid production and healing ulcers. Thus, they are the preferred drugs for stress ulcer treatment and prophylaxis and for the treatment of GERD, erosive esophagitis, active duodenal ulcer, and pathologic hypersecretory conditions (for example, Zollinger- Ellison syndrome, in which a gastrin-producing tumor causes hypersecretion of HCl). If a once-daily PPI is only partially effective for GERD symptoms, increasing dosing to twice daily or administering the PPI in the morning and adding an H2 antagonist in the evening may improve symptom control. If an H2-receptor antagonist is needed, it should be taken well after the PPI. H2 antagonists reduce the activity of the proton pump, and PPIs require active pumps to be effective. PPIs also reduce the risk of bleeding from ulcers caused by aspirin and other NSAIDs and may be used for prevention or treatment of NSAID-induced ulcers. Finally, they are used with antimicrobial regimens to eradicate H. pylori.

3. Pharmacokinetics: All of these agents are effective orally. For maximum effect, PPIs should be taken 30 to 60 minutes before breakfast or the largest meal of the day. [Note: dexlansoprazole has a dual delayed release formulation and can be taken without regard to food.] Esomeprazole, lansoprazole, and pantoprazole are also available in intravenous formulations. Although the plasma half-life of these agents is only a few hours, they have a long duration of action due to covalent bonding with the H+/K+- ATPase enzyme. Metabolites of these agents are excreted in urine and feces.

4. Adverse effects: The PPIs are generally well tolerated. Omeprazole and esomeprazole may decrease the effectiveness of clopidogrel because they inhibit CYP2C19 and prevent the conversion of clopidogrel to its active metabolite. Although the effect on clinical outcomes is questionable, concomitant use of these PPIs with clopidogrel is not recommended because of a possible increased risk of cardiovascular events. PPIs may increase the risk of fractures, particularly if the duration of use is 1 year or greater. Prolonged acid suppression with PPIs (and H2 antagonists) may result in low vitamin B12 because acid is required for its absorption in a complex with intrinsic factor. Elevated gastric pH may also impair the absorption of calcium carbonate. Calcium citrate is an effective option for calcium supplementation in patients on acid suppressive therapy, since absorption of the citrate salt is not affected by gastric pH. Diarrhea and Clostridium difficile colitis may occur in community patients receiving PPIs. Patients must be counseled to discontinue PPI therapy and contact their physician if they have diarrhea for several days. Additional adverse effects may include hypomagnesemia and an increased incidence of pneumonia.

Gastrointestinal and Antiemetic Drugs

D. Prostaglandins

Focus topic: Gastrointestinal and Antiemetic Drugs

Prostaglandin E, produced by the gastric mucosa, inhibits secretion of acid and stimulates secretion of mucus and bicarbonate (cytoprotective effect). A deficiency of prostaglandins is thought to be involved in the pathogenesis of peptic ulcers. Misoprostol [mye-soe-PROSTole], an analog of prostaglandin E1, is approved for the prevention of NSAID-induced gastric ulcers. Prophylactic use of misoprostol should be considered in patients who are taking NSAIDs and are at moderate to high risk of NSAID-induced ulcers, such as elderly patients and those with previous ulcers. Misoprostol is contraindicated in pregnancy, since it can stimulate uterine contractions and cause miscarriage. Dose-related diarrhea and nausea are the most common adverse effects and limit the use of this agent. Thus, PPIs are preferred agents for the prevention of NSAID-induced ulcers.

Gastrointestinal and Antiemetic Drugs

E. Antacids

Focus topic: Gastrointestinal and Antiemetic Drugs

Antacids are weak bases that react with gastric acid to form water and a salt to diminish gastric acidity. Because pepsin (a proteolytic enzyme) is inactive at a pH greater than 4, antacids also reduce pepsin activity.

1. Chemistry: Antacid products vary widely in their chemical composition, acid-neutralizing capacity, sodium content, palatability, and price. The efficacy of an antacid depends on its capacity to neutralize gastric HCl and on whether the stomach is full or empty (food delays stomach emptying allowing more time for the antacid to react). Commonly used antacids are combinations of salts of aluminum and magnesium, such as aluminum hydroxide and magnesium hydroxide [Mg(OH)2]. Calcium carbonate [CaCO3] reacts with HCl to form CO2 and CaCl2 and is also a commonly used preparation. Systemic absorption of sodium bicarbonate [NaHCO3]can produce transient metabolic alkalosis. Therefore, this antacid is not recommended for long-term use.

2. Therapeutic uses: Antacids are used for symptomatic relief of peptic ulcer disease and GERD, and they may also promote healing of duodenal ulcers. They should be administered after meals for maximum effectiveness. [Note: Calcium carbonate preparations are also used as calcium supplements for the treatment of osteoporosis.]

3. Adverse effects: Aluminum hydroxide tends to cause constipation, whereas magnesium hydroxide tends to produce diarrhea. Preparations that combine these agents aid in normalizing bowel function. Absorption of the cations from antacids (Mg2+, Al3+, Ca2+) is usually not a problem in patients with normal renal function; however, accumulation and adverse effects may occur in patients with renal impairment.

F. Mucosal protective agents

Also known as cytoprotective compounds, these agents have several actions that enhance mucosal protection mechanisms, thereby preventing mucosal injury, reducing inflammation, and healing existing ulcers.

1. Sucralfate: This complex of aluminum hydroxide and sulfated sucrose binds to positively charged groups in proteins of both normal and necrotic mucosa. By forming complex gels with epithelial cells, sucralfate [soo-KRAL-fate] creates a physical barrier that protects the ulcer from pepsin and acid, allowing the ulcer to heal. Although sucralfate is effective for the treatment of duodenal ulcers and prevention of stress ulcers, its use is limited due to the need for multiple daily dosing and drug–drug interactions. Because it requires an acidic pH for activation, sucralfate should not be administered with PPIs, H2 antagonists, or antacids. Sucralfate is well tolerated, but it can interfere with the absorption of other drugs by binding to them. This agent does not prevent NSAID-induced ulcers, and it does not heal gastric ulcers.

2. Bismuth subsalicylate: This agent is used as a component of quadruple therapy to heal peptic ulcers. In addition to its antimicrobial actions, it inhibits the activity of pepsin, increases secretion of mucus, and interacts with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer.

Gastrointestinal and Antiemetic Drugs: DRUGS USED TO CONTROL CHEMOTHERAPYINDUCED NAUSEA AND VOMITING

Focus topic: Gastrointestinal and Antiemetic Drugs

Although nausea and vomiting occur in a variety of conditions (for example, motion sickness, pregnancy, and hepatitis) and are always unpleasant for the patient, the nausea and vomiting produced by chemotherapeutic agents demands especially effective management. Nearly 70% to 80% of patients who undergo chemotherapy experience nausea and/or vomiting. Several factors influence the incidence and severity of chemotherapy-induced nausea and vomiting (CINV), including the specific chemotherapeutic drug; the dose, route, and schedule of administration; and patient variables. For example, young patients and women are more susceptible than older patients and men, and 10% to 40% of patients experience nausea and/or vomiting in anticipation of chemotherapy (anticipatory vomiting). CINV not only affects quality of life but can also lead to rejection of potentially curative chemotherapy. In
addition, uncontrolled vomiting can produce dehydration, profound metabolic imbalances, and nutrient depletion.

Gastrointestinal and Antiemetic Drugs

A. Mechanisms that trigger vomiting

Focus topic: Gastrointestinal and Antiemetic Drugs

Two brainstem sites have key roles in the vomiting reflex pathway. The chemoreceptor trigger zone (CTZ) is located in the area postrema (a circumventricular structure at the caudal end of the fourth ventricle). It is outside the blood–brain barrier. Thus, it can respond directly to chemical stimuli in the blood or cerebrospinal fluid. The second important site, the vomiting center, which is located in the lateral reticular formation of the medulla, coordinates the motor mechanisms of vomiting. The vomiting center also responds to afferent input from the vestibular system, the periphery (pharynx and GI tract), and higher brainstem and cortical structures. The vestibular system functions mainly in motion sickness.

B. Emetic actions of chemotherapeutic agents

Focus topic: Gastrointestinal and Antiemetic Drugs

Chemotherapeutic agents can directly activate the medullary CTZ or vomiting center. Several neuroreceptors, including dopamine receptor type 2 and serotonin type 3 (5-HT3), play critical roles. Often, the color or smell of chemotherapeutic drugs (and even stimuli associated with chemotherapy) can activate higher brain centers and trigger emesis. Chemotherapeutic drugs can also act peripherally by causing cell damage in the GI tract and by releasing serotonin from the enterochromaffin cells of the small intestine. Serotonin activates 5-HT3 receptors on vagal and splanchnic afferent fibers, which then carry sensory signals to the medulla, leading to the emetic response.

C. Antiemetic drugs

Focus topic: Gastrointestinal and Antiemetic Drugs

Considering the complexity of the mechanisms involved in emesis, it is not surprising that antiemetics represent a variety of classes and offer a range of efficacies . Anticholinergic drugs, especially the muscarinic receptor antagonist scopolamine and H1-receptor antagonists, such as dimenhydrinate, meclizine, and cyclizine, are very useful in motion sickness but are ineffective against substances that act directly on the CTZ. The major categories of drugs used to control CINV include the following:

Gastrointestinal and Antiemetic Drugs

Gastrointestinal and Antiemetic Drugs

1. Phenothiazines: The first group of drugs shown to be effective antiemetic agents, phenothiazines, such as prochlorperazine [proe-klor-PER-ah-zeen], act by blocking dopamine receptors. Prochlorperazine is effective against low or moderately emetogenic chemotherapeutic agents (for example, fluorouracil and doxorubicin). Although increasing the dose improves antiemetic activity, side effects are dose limiting.

2. 5-HT3 receptor blockers: The 5-HT3 receptor antagonists include ondansetron [on-DAN-seh-tron], granisetron [gra-NI-sehtron], palonosetron [pa-low-NO-seh-tron], and dolasetron [dol-Aseh- tron]. These agents selectively block 5-HT3 receptors in the periphery (visceral vagal afferent fibers) and in the brain (CTZ). This class of agents is important in treating emesis linked with chemotherapy, largely because of their longer duration of action and superior efficacy. These drugs can be administered as a single dose prior to chemotherapy (intravenously or orally) and are efficacious against all grades of emetogenic therapy. Ondansetron and granisetron prevent emesis in 50% to 60% of cisplatin-treated patients. These agents are also useful in the management of postoperative nausea and vomiting. 5-HT3 antagonists are extensively metabolized by the liver; however, only ondansetron requires dosage adjustments in hepatic insufficiency. Elimination is through the urine. Electrocardiographic changes, such as a prolonged QTc interval, can occur with dolasetron and high doses of ondansetron. For this reason, dolasetron is no longer approved for CINV prophylaxis.

3. Substituted benzamides: One of several substituted benzamides with antiemetic activity, metoclopramide [met-oh-kloe-PRAH-mide] is effective at high doses against the emetogenic cisplatin, preventing emesis in 30% to 40% of patients and reducing emesis in the majority of patients. Metoclopramide accomplishes this through inhibition of dopamine in the CTZ. Antidopaminergic side effects, including extrapyramidal symptoms, limit long-term high-dose use. Metoclopramide was previously used as a prokinetic drug for the treatment of GERD. However, due to the adverse effect profile and the availability of more effective drugs, such as PPIs, it should be reserved for patients with documented gastroparesis.

4. Butyrophenones: Droperidol [droe-PER-i-doll] and haloperidol [hal-oh-PER-i-doll] act by blocking dopamine receptors. The butyrophenones are moderately effective antiemetics. Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines. However, it may prolong the QTc interval and should be reserved for patients with inadequate response to other agents. High-dose haloperidol was found to be nearly as effective as high-dose metoclopramide in preventing cisplatin-induced emesis.

5. Benzodiazepines: The antiemetic potency of lorazepam [lor-Aze-pam] and alprazolam [al-PRAH-zoe-lam] is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties. These same properties make benzodiazepines useful in treating anticipatory vomiting. Concomitant use of alcohol should be avoided due to additive CNS depressant effects.

6. Corticosteroids: Dexamethasone [dex-a-MEH-tha-sone] and methylprednisolone [meth-ill-pred-NIH-so-lone], used alone, are effective against mildly to moderately emetogenic chemotherapy. Most frequently, however, they are used in combination with other agents. Their antiemetic mechanism is not known, but it may involve blockade of prostaglandins.

7. Substance P/neurokinin-1 receptor blocker: Aprepitant [ah-PRE-pih-tant] targets the neurokinin receptor in the brain and blocks the actions of the natural substance. Aprepitant is indicated only for highly or moderately emetogenic chemotherapy regimens. It is usually administered orally with dexamethasone and a 5-HT3 antagonist. It undergoes extensive metabolism, primarily by CYP3A4, and it may affect the metabolism of other drugs that are metabolized by this enzyme, such as warfarin and oral contraceptives.

8. Combination regimens: Antiemetic drugs are often combined to increase antiemetic activity or decrease toxicity. Corticosteroids, most commonly dexamethasone, increase antiemetic activity when given with high-dose metoclopramide, a 5-HT3 antagonist, phenothiazine, butyrophenone, or a benzodiazepine. Antihistamines, such as diphenhydramine, are often administered in combination with high-dose metoclopramide to reduce extrapyramidal reactions or with corticosteroids to counter metoclopramide- induced diarrhea.

Gastrointestinal and Antiemetic Drugs

Gastrointestinal and Antiemetic Drugs: ANTIDIARRHEALS

Focus topic: Gastrointestinal and Antiemetic Drugs

Increased motility of the GI tract and decreased absorption of fluid are major factors in diarrhea. Antidiarrheal drugs include antimotility agents, adsorbents, and drugs that modify fluid and electrolyte transport.

Gastrointestinal and Antiemetic Drugs

A. Antimotility agents

Focus topic: Gastrointestinal and Antiemetic Drugs

Two drugs that are widely used to control diarrhea are diphenoxylate [dye-fen-OX-see-late] and loperamide [loe-PER-ah-mide]. Both are analogs of meperidine and have opioid-like actions on the gut. They activate presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis. At the usual doses, they lack analgesic effects. Because these drugs can contribute to toxic megacolon, they should not be used in young children or in patients with severe colitis.

B. Adsorbents

Focus topic: Gastrointestinal and Antiemetic Drugs

Adsorbent agents, such as aluminum hydroxide and methylcellulose [meth-ill-CELL-you-lowse], are used to control diarrhea. Presumably, these agents act by adsorbing intestinal toxins or microorganisms and/or by coating or protecting the intestinal mucosa. They are much less effective than antimotility agents, and they can interfere with the absorption of other drugs.

C. Agents that modify fluid and electrolyte transport

Focus topic: Gastrointestinal and Antiemetic Drugs

Bismuth subsalicylate, used for traveler’s diarrhea, decreases fluid secretion in the bowel. Its action may be due to its salicylate component as well as its coating action. Adverse effects may include black tongue and black stools.

Gastrointestinal and Antiemetic Drugs: LAXATIVES

Focus topic: Gastrointestinal and Antiemetic Drugs

Laxatives are commonly used for constipation to accelerate the movement of food through the GI tract. These drugs can be classified on the basis of their mechanism of action. Laxatives increase the potential for loss of pharmacologic effect of poorly absorbed, delayed-acting, and extended-release oral preparations by accelerating their transit through the intestines. They may also cause electrolyte imbalances when used chronically. Many of these drugs have a risk of dependency for the user.

Gastrointestinal and Antiemetic Drugs

[sociallocker]

A. Irritants and stimulants

Focus topic: Gastrointestinal and Antiemetic Drugs

  • Senna: This agent is a widely used stimulant laxative. Its active ingredient is a group of sennosides, a natural complex of anthraquinone glycosides. Taken orally, senna causes evacuation of the bowels within 8 to 10 hours. It also causes water and electrolyte secretion into the bowel. In combination products with a docusate-containing stool softener, it is useful in treating opioid-induced constipation.
  • Bisacodyl: Available as suppositories and enteric-coated tablets, bisacodyl is a potent stimulant of the colon. It acts directly on nerve fibers in the mucosa of the colon.
  • Castor oil: This agent is broken down in the small intestine to ricinoleic acid, which is very irritating to the stomach and promptly increases peristalsis. Pregnant patients should avoid castor oil because it may stimulate uterine contractions.

B. Bulk laxatives

Focus topic: Gastrointestinal and Antiemetic Drugs

The bulk laxatives include hydrophilic colloids (from indigestible parts of fruits and vegetables). They form gels in the large intestine, causing water retention and intestinal distension, thereby increasing peristaltic activity. Similar actions are produced by methylcellulose, psyllium seeds, and bran. They should be used cautiously in patients who are immobile because of their potential for causing intestinal obstruction.

C. Saline and osmotic laxatives

Focus topic: Gastrointestinal and Antiemetic Drugs

Saline cathartics, such as magnesium citrate and magnesium hydroxide, are nonabsorbable salts (anions and cations) that hold water in the intestine by osmosis. This distends the bowel, increasing intestinal activity and producing defecation in a few hours. Electrolyte solutions containing polyethylene glycol (PEG) are used as colonic lavage solutions to prepare the gut for radiologic or endoscopic procedures. PEG powder for solution is available as a prescription and also as an over-the-counter laxative and has been shown to cause less cramping and gas than other laxatives. Lactulose is a semisynthetic disaccharide sugar that acts as an osmotic laxative. It cannot be hydrolyzed by GI enzymes. Oral doses reach the colon and are degraded by colonic bacteria into lactic, formic, and acetic acids. This increases osmotic pressure, causing fluid accumulation, colon distension, soft stools, and defecation. Lactulose is also used for the treatment of hepatic encephalopathy, due to its ability to reduce ammonia levels.

D. Stool softeners (emollient laxatives or surfactants)

Focus topic: Gastrointestinal and Antiemetic Drugs

Surface-active agents that become emulsified with the stool produce softer feces and ease passage. These include docusate sodium and docusate calcium. They may take days to become effective and are often used for prophylaxis rather than acute treatment. Stool softeners should not be taken concomitantly with mineral oil because of the potential for absorption of the mineral oil.

E. Lubricant laxatives

Focus topic: Gastrointestinal and Antiemetic Drugs

Mineral oil and glycerin suppositories are lubricants and act by facilitating the passage of hard stools. Mineral oil should be taken orally in an upright position to avoid its aspiration and potential for lipid or lipoid pneumonia.

F. Chloride channel activators

Focus topic: Gastrointestinal and Antiemetic Drugs

Lubiprostone [loo-bee-PROS-tone], currently the only agent in this class, works by activating chloride channels to increase fluid secretion in the intestinal lumen. This eases the passage of stools and causes little change in electrolyte balance. Lubiprostone is used in the treatment of chronic constipation, particularly because tolerance or dependency has not been associated with this drug. Also, drug–drug interactions appear minimal because metabolism occurs quickly in the stomach and jejunum.

[/sociallocker]

FURTHER READING/STUDY:

Resources:

 

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.