GIT pharmacology
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Questions and Answers

What is a common result of using Cimetidine due to its endocrine effects?

  • Gynaecomastia (correct)
  • Increased gastric acid secretion
  • Improved gastric mucosal protection
  • Decreased drug metabolism

    • Which of the following treatments is primarily aimed at protecting the gastric mucosa?

  • Sucralfate (correct)
  • Omeprazole
  • Amoxicillin
  • Metronidazole

    • Which drug combination represents a triple therapy for the treatment of H. pylori?

  • PPI, Amoxicillin, Clarithromycin (correct)
  • PPI, Tetracycline, Sucralfate
  • H2 antagonist, Sucralfate, Misoprostol
  • Bismuth, Metronidazole, Tetracycline

    • What is the primary action of H2 receptor antagonists?

    <p>Reduce gastric acid secretion</p> Signup and view all the answers

    Which of the following is true regarding the kinetics of H2 receptor antagonists?

    <p>They are excreted unchanged in urine.</p> Signup and view all the answers

    What is the mechanism of action of H2 receptor antagonists?

    <p>Competitive antagonism with histamine</p> Signup and view all the answers

    What is a critical consideration when administering Cimetidine, especially in elderly patients?

    <p>CNS effects may increase significantly.</p> Signup and view all the answers

    Which gastric acid secretion stimulators are mentioned?

    <p>Gastrin, Acetylcholine, Histamine</p> Signup and view all the answers

    In the treatment of peptic ulcers caused by H. pylori, what is a limitation of using PPIs alone?

    <p>They do not eliminate H. pylori infection.</p> Signup and view all the answers

    What percentage of gastric acid secretion can be reduced by H2 receptor antagonists?

    <p>70%</p> Signup and view all the answers

    Which of the following is a characteristic of Bismuth subsalicylate?

    <p>May lead to black tongue and stools</p> Signup and view all the answers

    What is a potential adverse effect of Sulfasalazine?

    <p>Neurological toxicity</p> Signup and view all the answers

    What mechanism do saline and osmotic laxatives primarily utilize?

    <p>Increasing intestinal activity by osmotic means</p> Signup and view all the answers

    Which laxative has a mechanism involving the secretion of ricinoleic acid in the small intestine?

    <p>Castor oil</p> Signup and view all the answers

    What is the primary therapeutic use of Biological agents like TNF-alpha inhibitors?

    <p>Management of moderate-severe ulcerative colitis and Crohn's disease</p> Signup and view all the answers

    Lactulose is used for treating hepatic encephalopathy because it:

    <p>Is metabolized into fatty acids by colonic bacteria</p> Signup and view all the answers

    Which of the following laxatives is contraindicated during pregnancy due to the risk of uterine contractions?

    <p>Castor oil</p> Signup and view all the answers

    Which of the following medications is contraindicated during pregnancy due to its potential to cause uterine contractions?

    <p>Misoprostol</p> Signup and view all the answers

    Which class of drugs is NOT effective in treating Crohn's disease?

    <p>5-Aminosalicylates</p> Signup and view all the answers

    Which laxative can reduce the absorption of other oral drugs and is recommended to be taken with a two-hour interval?

    <p>Psyllium</p> Signup and view all the answers

    What type of drug is used primarily to inhibit acid secretion and stimulate mucus and bicarbonate secretion in the gastric mucosa?

    <p>Prostaglandins</p> Signup and view all the answers

    Which substrate is put in place to improve liquid secretion in the intestinal lumen for chronic constipation?

    <p>Lubiprostone</p> Signup and view all the answers

    Which statement about Proton Pump Inhibitors (PPIs) is accurate regarding their absorption?

    <p>Dexlansoprazole is not affected by food timing.</p> Signup and view all the answers

    Which of the following side effects is NOT commonly associated with the use of PPIs?

    <p>Constipation</p> Signup and view all the answers

    What mechanism does Ondansetron utilize to reduce nausea and vomiting associated with chemotherapy?

    <p>5-HT3 receptor blockade</p> Signup and view all the answers

    Which medication is known to prolong the QT interval as a side effect?

    <p>Dolasetron</p> Signup and view all the answers

    Which of the following is NOT a primary therapeutic use of Misoprostol?

    <p>Symptomatic relief in heartburn</p> Signup and view all the answers

    Which of the following statements about antacids is correct?

    <p>They can cause alkalosis and hypernatremia.</p> Signup and view all the answers

    What effect does high gastric pH have on the absorption of calcium?

    <p>Decreases calcium absorption</p> Signup and view all the answers

    Which agent is primarily an antidiarrheal that inhibits ACh release?

    <p>Diphenoxylate + atropine</p> Signup and view all the answers

    What is a primary approach to treating peptic ulcers caused by H. pylori?

    <p>Eradicate H. pylori infection</p> Signup and view all the answers

    Which of the following is considered first-line therapy for H. pylori infection?

    <p>Quadruple therapy including Bismuth subsalicylate, Metronidazole, tetracycline and PPI</p> Signup and view all the answers

    Which effect do H2 receptor antagonists specifically target?

    <p>Competitive antagonism with histamine</p> Signup and view all the answers

    In which condition are H2 receptor antagonists used as a monotherapy?

    <p>Peptic ulcer recurrence due to H. pylori</p> Signup and view all the answers

    What is a potential side effect of Cimetidine?

    <p>Gynaecomastia</p> Signup and view all the answers

    Which of the following drugs is an H2 receptor antagonist?

    <p>Ranitidine</p> Signup and view all the answers

    What is the primary mechanism by which H2 receptor antagonists reduce gastric acid secretion?

    <p>Competitive inhibition of histamine at H2 receptors</p> Signup and view all the answers

    What is a risk associated with the use of IV H2 receptor antagonists in elderly patients?

    <p>CNS effects</p> Signup and view all the answers

    What is the role of Misoprostol in the treatment of peptic ulcers?

    <p>Protecting the gastric mucosa</p> Signup and view all the answers

    How are H2 receptor antagonists primarily excreted from the body?

    <p>In urine</p> Signup and view all the answers

    Which laxative is known for its potent colon stimulation and can be administered as a suppository?

    <p>Bisacodyl</p> Signup and view all the answers

    What is the main therapeutic use of Mesalamine compounds?

    <p>Ulcerative colitis management</p> Signup and view all the answers

    Which medication is strictly indicated for moderate-severe Crohn's disease?

    <p>Certolizumab</p> Signup and view all the answers

    Which laxative class primarily increases intestinal activity through an osmotic mechanism?

    <p>Saline and osmotic laxatives</p> Signup and view all the answers

    What is a major therapeutic use of proton pump inhibitors (PPIs)?

    <p>Management of GERD</p> Signup and view all the answers

    Which of the following is a common adverse effect of long-term PPI use?

    <p>Bone fractures</p> Signup and view all the answers

    What adverse effect is associated with the use of Sulfasalazine?

    <p>Severe rash</p> Signup and view all the answers

    Which agent is indicated for both chronic constipation and IBS with constipation?

    <p>Lubiprostone</p> Signup and view all the answers

    What is the primary mechanism of action of Misoprostol?

    <p>Stimulation of mucus and bicarbonate secretion</p> Signup and view all the answers

    Which of the following is a common adverse effect of the biological agent Infliximab?

    <p>Headache</p> Signup and view all the answers

    Which statement about antacids is correct?

    <p>They can lead to hypernatremia when excessive sodium bicarbonate is used.</p> Signup and view all the answers

    Which medication is known to interact with the absorption of calcium due to increased gastric pH?

    <p>Omeprazole</p> Signup and view all the answers

    In which condition is Lactulose used to reduce ammonia levels?

    <p>Hepatic encephalopathy</p> Signup and view all the answers

    What is the primary action of 5-HT3 receptor antagonists in chemotherapy-induced nausea and vomiting?

    <p>Preventing activation of the vagal afferent fibers</p> Signup and view all the answers

    Which of the following substances can impair male fertility as a potential adverse effect?

    <p>Sulfasalazine</p> Signup and view all the answers

    Which of the following is a contraindication for the use of Misoprostol?

    <p>Pregnancy</p> Signup and view all the answers

    Which laxative class is least likely to retain water in the intestines?

    <p>Stool softeners</p> Signup and view all the answers

    What is a potential adverse effect of 5-HT3 receptor antagonists when used at high doses?

    <p>QT prolongation</p> Signup and view all the answers

    Which drug class is specifically used to prevent NSAID-induced gastric ulcers?

    <p>Prostaglandins</p> Signup and view all the answers

    Which mechanism is primarily utilized by antidiarrheals such as Loperamide?

    <p>Inhibition of acetylcholine release</p> Signup and view all the answers

    What is the primary action of Proton Pump Inhibitors (PPIs)?

    <p>Suppress the secretion of hydrogen ions</p> Signup and view all the answers

    What therapeutic use do PPIs NOT serve?

    <p>Management of hypertension</p> Signup and view all the answers

    Which of the following statements about Misoprostol is TRUE?

    <p>It prevents NSAID-induced gastric ulcers.</p> Signup and view all the answers

    What is a common adverse effect associated with the prolonged use of PPIs?

    <p>Bone fractures</p> Signup and view all the answers

    Which of the following is true about 5-HT3 receptor blockers like Ondansetron?

    <p>They prevent emesis in 50-60% of Cisplatin treated patients.</p> Signup and view all the answers

    What is the mechanism of action of antacids?

    <p>Neutralize gastric acidity</p> Signup and view all the answers

    What adverse effect could arise from the use of Magnesium hydroxide?

    <p>Diarrhea</p> Signup and view all the answers

    Which of the following antidiarrheal agents inhibits the release of acetylcholine?

    <p>Diphenoxylate + atropine</p> Signup and view all the answers

    What is the main therapeutic action of Bismuth subsalicylate?

    <p>Acts as a pepsin inhibitor</p> Signup and view all the answers

    Which laxative is useful for opioid-induced constipation?

    <p>Senna</p> Signup and view all the answers

    What is a common adverse effect of Sulfasalazine?

    <p>Hemolytic anemia</p> Signup and view all the answers

    Which medication is prohibited during pregnancy due to the risk of uterine contractions?

    <p>Castor oil</p> Signup and view all the answers

    What is the primary goal when treating peptic ulcers caused by H. pylori?

    <p>Eliminate H. pylori infection</p> Signup and view all the answers

    Which of the following is NOT a component of first-line quadruple therapy for H. pylori?

    <p>Omeprazole</p> Signup and view all the answers

    Which class of drugs is effective primarily for Ulcerative Colitis but not for Crohn's Disease?

    <p>5-Aminosalicylates (5-ASA)</p> Signup and view all the answers

    What effect do H2 receptor antagonists primarily have on gastric acid secretion?

    <p>Reduce secretion</p> Signup and view all the answers

    What mechanism do saline and osmotic laxatives primarily utilize?

    <p>Osmotic pressure</p> Signup and view all the answers

    Which of the following laxatives forms gels in the large intestine?

    <p>Methylcellulose</p> Signup and view all the answers

    Which drug is commonly used in triple therapy for treating H. pylori infection in patients allergic to penicillin?

    <p>Metronidazole</p> Signup and view all the answers

    Which drug acts directly on nerve fibers in the mucosa of the colon as a stimulant?

    <p>Bisacodyl</p> Signup and view all the answers

    What is a common therapeutic use of H2 receptor antagonists?

    <p>Treating gastrophageal reflux disease (GERD)</p> Signup and view all the answers

    Which agent is primarily indicated for chronic constipation and irritable bowel syndrome with constipation (IBS-C)?

    <p>Lubiprostone</p> Signup and view all the answers

    Which of the following drugs can lead to endocrine effects, such as gynecomastia?

    <p>Cimetidine</p> Signup and view all the answers

    Which class of medications aims to protect the gastric mucosa?

    <p>Misoprostol</p> Signup and view all the answers

    What is the mechanism of action of Docusate?

    <p>Softening stool</p> Signup and view all the answers

    Which mechanism do H2 receptor antagonists utilize to achieve their effect?

    <p>Competitively block histamine at H2 receptors</p> Signup and view all the answers

    Which medication can potentially reduce the absorption of other oral drugs?

    <p>Psyllium</p> Signup and view all the answers

    What is a potential consequence of using IV H2 receptor antagonists in elderly patients?

    <p>Increased incidence of CNS effects</p> Signup and view all the answers

    Which gastric acid secretion stimulator is involved in the activation of protein kinase related to acid secretion?

    <p>Histamine</p> Signup and view all the answers

    Study Notes

    Peptic Ulcer Disease

    • Two main causes of peptic ulcers are infection with Helicobacter pylori (H. pylori) and nonsteroidal anti-inflammatory drug (NSAID) use.
    • Treatment approaches include eliminating H. pylori infection, reducing gastric acid secretion, and protecting the gastric mucosa.
    • Quadruple therapy for H. pylori infection consists of bismuth subsalicylate, metronidazole, tetracycline, and a proton pump inhibitor (PPI).
    • Triple therapy includes a PPI, amoxicillin (metronidazole in penicillin allergies), and clarithromycin.
    • H2 receptor antagonists, such as cimetidine, famotidine, nizatidine, and ranitidine, are effective in reducing gastric acid secretion by competitively antagonizing histamine at H2 receptors.
    • PPIs, including dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole, suppress hydrogen ion secretion into the gastric lumen by irreversibly inhibiting the H+/K+-ATPase proton pump.
    • Prostaglandins, such as misoprostol, are used to prevent NSAID-induced gastric ulcers by stimulating mucus and bicarbonate secretion and inhibiting acid secretion.
    • Antacids, including aluminum hydroxide, calcium carbonate, magnesium hydroxide, and sodium bicarbonate, are weak bases that neutralize gastric acid and increase pH to inhibit pepsin activity.
    • Mucosal protective agents, such as bismuth subsalicylate and sucralfate, create a physical barrier over the ulcer to protect it from pepsin and acid.

    Gastrophageal Reflux Disease (GERD)

    • H2 receptor antagonists and PPIs are effective in reducing acid secretion in GERD, but PPIs are preferred due to their longer duration of action and greater efficacy.

    Chemotherapy-Induced Nausea and Vomiting (CINV)

    • CINV is triggered by the area postrema (chemoreceptor trigger zone, CTZ) and the lateral reticular formation of the medulla.
    • Vomiting mediators include dopamine, serotonin (5-HT3), and other substances.
    • Antiemetic drugs work by blocking the actions of these mediators or by acting directly on the vomiting center.
    • Phenothiazines, such as prochlorperazine, block dopamine receptors in the CTZ and are effective against low or moderately emetogenic chemotherapy agents.
    • 5-HT3 receptor blockers, including dolasetron, granisetron, ondansetron, and palonosetron, block 5-HT3 receptors in the periphery (visceral vagal afferent fibers) and the CTZ, preventing nausea and vomiting induced by various chemotherapy regimens.
    • Metoclopramide, a substituted benzamide, inhibits dopamine in the CTZ and enhances gastric motility.
    • Butyrophenones, such as droperidol and haloperidol, block dopamine receptors and have sedative properties.
    • Benzodiazepines, such as lorazepam and alprazolam, have low potency and are used for anticipated vomiting.
    • Corticosteroids, such as dexamethasone and methylprednisolone, are effective against mildly to moderately emetogenic chemotherapy agents.
    • Substance P/neurokinin-1 receptor antagonists, including aprepitant, fosaprepitant, netupitant, and rolapitant, block the actions of substance P in the vomiting center, effectively preventing nausea and vomiting, especially in the delayed phase of CINV.

    Diarrhea

    • Antimotility agents, such as diphenoxylate/atropine and loperamide, control diarrhea by inhibiting acetylcholine release.
    • Adsorbents, such as aluminum hydroxide and methylcellulose, control diarrhea by adsorbing intestinal toxins or microorganisms and protecting the intestinal mucosa.
    • Agents that modify fluid and electrolyte transport, such as bismuth subsalicylate, decrease fluid secretion in the bowel.

    Constipation

    • Irritant and stimulant laxatives, such as senna, bisacodyl, and castor oil, increase peristalsis by directly stimulating nerve fibers in the colon.
    • Bulk laxatives, such as methylcellulose and psyllium, form gels in the large intestine, increasing intestinal distention and peristalsis.
    • Saline and osmotic laxatives, including polyethylene glycol (PEG) and lactulose, increase intestinal activity by osmotic mechanisms.
    • Stool softeners, such as docusate, soften the stool by mixing with it.
    • Lubricant laxatives, such as glycerin suppositories and mineral oil, facilitate stool passage.
    • Chloride channel activators, such as lubiprostone, increase fluid secretion in the intestinal lumen.

    Inflammatory Bowel Disease (IBD)

    • IBD is an immune-mediated inflammation of the gastrointestinal tract.
    • Two main types of IBD are Crohn's disease (CD) and ulcerative colitis (UC).
    • CD can affect any part of the gastrointestinal tract from the mouth to the anus, while UC is confined to the colon.
    • Treatment for IBD includes 5-aminosalicylates (5-ASA), corticosteroids, biological agents, and immunomodulators.
    • 5-ASA compounds, such as balsalazide, olsalazine, and sulfasalazine, are effective in UC and have anti-inflammatory and immunosuppressive properties.
    • Corticosteroids, such as budesonide, have minimal systemic effects and are used in CD and UC.
    • Biological agents, including TNF-alpha inhibitors (infliximab, adalimumab, certolizumab, and golimumab), alpha-4 integrin inhibitors (vedolizumab), and other agents, target specific components of the inflammatory pathway.
    • Immunomodulators, such as methotrexate (MTX) and thiopurines (azathioprine, 6-mercaptopurine), suppress the immune response.

    Irritable Bowel Syndrome (IBS)

    • IBS is a chronic condition characterized by abdominal pain and altered bowel habits.
    • Two main types of IBS are IBS-C (constipation) and IBS-D (diarrhea).

    Peptic Ulcer

    • Peptic ulcers are sores that develop in the lining of the stomach or duodenum.
    • Two main causes are infection with the bacterium Helicobacter pylori (H. pylori) and use of nonsteroidal anti-inflammatory drugs (NSAIDs).
    • Treatment for peptic ulcers includes H. pylori eradication, reduction of gastric acid secretion, and protection of the gastric mucosa.

    Helicobacter pylori Eradication

    • Typically, a combination therapy is used for H. pylori eradication.
    • First-line therapy is quadruple therapy: bismuth subsalicylate, metronidazole, tetracycline, and a proton pump inhibitor (PPI).
    • Triple therapy consists of a PPI, amoxicillin (metronidazole if allergic to penicillin), and clarithromycin.

    Gastric Acid Secretions

    • Gastric acid secretion is stimulated by acetylcholine, histamine, and gastrin.
    • These stimulants activate protein kinase, leading to the H+/K+ adenosine triphosphate (ATPase) proton pump secreting hydrogen ions in exchange for potassium ions into the stomach lumen.
    • Approximately 70% of gastric acid secretion is reduced by this process.

    H2 Receptor Antagonists

    • H2 receptor antagonists are selective for H2 receptors and do not affect H1 receptors.
    • They competitively antagonize histamine, and the effect is reversible.

    Therapeutic Uses

    • H2 receptor antagonists are used for peptic ulcers, acute stress ulcers, and gastroesophageal reflux disease (GERD).

    Pharmacokinetics

    • H2 receptor antagonists are administered orally and are highly soluble.
    • They are excreted in urine.
    • Intravenous (IV) forms are available for cimetidine, ranitidine, and famotidine.

    Adverse Effects

    • Cimetidine can cause endocrine effects such as gynecomastia and galactorrhea.
    • Central nervous system (CNS) effects are more common in the elderly, especially after IV administration.
    • H2 receptor antagonists may interfere with drugs that require an acidic environment.
    • Cimetidine inhibits multiple cytochrome P450 (CYP450) isoenzymes, leading to the accumulation of other drugs, such as warfarin, phenytoin, and clopidogrel.

    Proton Pump Inhibitors (PPIs)

    • PPIs suppress the secretion of hydrogen ions into the gastric lumen.
    • They act on the final step of gastric acid secretion.

    Actions

    • PPIs are prodrugs that are absorbed and activated in parietal cells.
    • Inhibit about 90% of gastric acid secretion.
    • Omeprazole is combined with bicarbonate for faster absorption.

    Therapeutic Uses

    • PPIs are the preferred treatment for GERD, erosive esophagitis, active duodenal ulcers, and pathologic hypersecretory conditions like Zollinger-Ellison syndrome.
    • They can reduce the risk of bleeding from ulcers caused by aspirin or NSAIDs.
    • PPIs are used for stress ulcer prophylaxis.
    • They should be combined with antibiotics for H. pylori eradication.

    Pharmacokinetics

    • PPIs are administered orally, usually 30-60 minutes before meals, except for dexlansoprazole.
    • IV formulations are available for esomeprazole, lansoprazole, and pantoprazole.
    • PPIs have a short half-life but long duration of action due to forming a covalent bond.

    Adverse Effects

    • Omeprazole and esomeprazole inhibit CYP2C19.
    • Long-term use (>1 year) is associated with an increased risk of bone fractures.
    • PPIs can reduce vitamin B12 absorption due to interference with intrinsic factor secretion, which requires an acidic environment.
    • PPIs can decrease calcium absorption due to the high gastric pH.
    • Other adverse effects include diarrhea, Clostridium difficile colitis, hypomagnesemia, and pneumonia.

    Prostaglandins

    • Misoprostol is the only prostaglandin drug used for peptic ulcers.
    • Prostaglandin E, produced by gastric mucosa, inhibits acid secretion and stimulates mucus and bicarbonate secretion.
    • Misoprostol is a synthetic analog of prostaglandin E1 and helps prevent NSAID-induced gastric ulcers.
    • Misoprostol is contraindicated in pregnancy because it can cause uterine contractions and miscarriage.
    • Diarrhea is a common side effect.

    Antacids

    • Antacids are weak bases that neutralize gastric acid.
    • They include aluminum hydroxide, calcium carbonate, magnesium hydroxide, and sodium bicarbonate.
    • Antacids increase the pH to above 4, inhibiting pepsin activity.

    Chemistry

    • Antacids have a food-dependence mechanism, meaning food increases the duration of action.
    • They can cause alkalosis and hypernatremia.

    Therapeutic Uses

    • Antacids provide symptomatic relief for peptic ulcers, heartburn, and GERD.
    • They are most effective after meals.
    • Calcium carbonate is used to prevent osteoporosis.

    Adverse Effects

    • Aluminum hydroxide can cause constipation.
    • Magnesium hydroxide can cause diarrhea.
    • Accumulation of cations can occur in patients with renal impairment.

    Mucosal Protective Agents

    • Mucosal protective agents create a physical barrier to protect the ulcer from pepsin and acid.
    • They include bismuth subsalicylate and sucralfate.

    Sucralfate

    • Sucralfate is a combination of aluminum hydroxide and sulfated sucrose.
    • It requires an acidic environment to work and should not be combined with PPIs, H2 antagonists, or antacids.
    • Sucralfate needs to be taken multiple times daily.

    Bismuth Subsalicylate

    • Bismuth subsalicylate is part of quadruple therapy for H. pylori-related peptic ulcers.
    • It inhibits pepsin and increases mucus secretion.
    • It also interacts with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer.

    Antidiarrheals

    • Antidiarrheal medications are used to control and manage diarrhea through various mechanisms.
    • They can inhibit intestinal motility, adsorb toxins and microorganisms, protect the intestinal mucosa, or modify fluid and electrolyte transport.
    • Common treatments include antimotility agents, adsorbents, and agents that modify fluid and electrolyte transport.

    Antimotility Agents

    • Antimotility agents are used to control diarrhea and inhibit acetylcholine release.
    • They are used in various forms of diarrhea, including traveler's diarrhea.
    • Examples include diphenoxylate with atropine and loperamide.
    • These agents may cause toxic megacolon, making their use in children and patients with severe colitis prohibited.

    Adsorbents

    • Adsorbents like aluminum hydroxide and methylcellulose are used for diarrhea control.
    • They adsorb intestinal toxins or microorganisms, coating and protecting the intestinal mucosa.
    • While they are less effective than antimotility agents, they can interfere with the absorption of other medications.

    Agents that Modify Fluid and Electrolyte Transport

    • Bismuth subsalicylate is used for traveler's diarrhea.
    • It decreases fluid secretion in the bowel but can cause black tongue and stools.

    Laxatives

    • Laxatives are used to treat constipation by facilitating stool passage, increasing intestinal activity, or softening feces.
    • They are classified into irritants/stimulants, bulk laxatives, saline/osmotic laxatives, stool softeners, lubricant laxatives, and chloride channel activators.

    Irritants and Stimulants

    • Senna is a bowel stimulant that causes water and electrolyte secretion into the bowel, leading to evacuation within 6-12 hours.
    • It can be combined with a stool softener like docusate and is useful for opioid-induced constipation.
    • Bisacodyl is available as suppositories and enteric-coated tablets, acting directly on nerve fibers in the colon mucosa for potent stimulation.
    • Castor oil, broken down into ricinoleic acid, irritates the stomach and is prohibited in pregnancy due to uterine contractions. It is not commonly used.

    Bulk Laxatives

    • Bulk laxatives, such as methylcellulose and psyllium, form gels in the large intestine, retaining water and causing distension, thus increasing peristalsis.
    • Psyllium might reduce the absorption of other oral medications, so a 2-hour interval between taking them is recommended.

    Saline and Osmotic Laxatives

    • These laxatives increase intestinal activity by osmotic mechanisms.
    • Electrolyte solutions with polyethylene glycol (PEG) are used as colonic lavage for bowel preparation for radiological or endoscopic procedures.
    • PEG powder is used as a laxative, with a lower potency than other options.
    • Lactulose, not hydrolyzed by GI enzymes, reaches the colon and degrades into lactic, formic, and acetic acids.
    • Lactulose is also used to reduce ammonia levels in hepatic encephalopathy.

    Stool Softeners

    • Stool softeners, like docusate sodium or calcium, mix with stool, making it softer.
    • Docusate takes days to act and is prohibited with mineral oil due to the risk of oil absorption.

    Lubricant Laxatives

    • Lubricant laxatives, such as glycerin suppositories and mineral oil, facilitate stool passage.
    • Oral administration of mineral oil should be done in an upright position to avoid aspiration and lipid pneumonia.

    Chloride Channel Activators

    • Lubiprostone activates chloride channels, increasing fluid secretion in intestinal lumen.
    • It is used for chronic constipation and irritable bowel syndrome with constipation (IBS-C).
    • It has no known drug-drug interactions.

    Inflammatory Bowel Disease (IBD)

    • IBD is an immune-mediated inflammation of the gastrointestinal tract (GIT) often linked to bacteria.
    • Subtypes include Crohn's disease (CD) and ulcerative colitis (UC).
    • CD can affect any portion of the GIT from the mouth to the anus, while UC primarily affects the colon.

    Treatment for IBD

    • Four major classes of drugs are used for IBD: 5-aminosalicylates (5-ASA), corticosteroids, biological agents, and immunomodulators.

    5-Aminosalicylates (5-ASA)

    • Two compounds are available: AZO compounds and mesalamine compounds.
    • AZO compounds are prodrugs, including balsalazide, olsalazine, and sulfasalazine.
    • Sulfasalazine is a prodrug consisting of 5-ASA linked to sulfapyridine.
    • Sulfapyridine is associated with adverse effects.

    Actions

    • 5-ASAs have anti-inflammatory and immunosuppressive properties.
    • The exact mechanism of action is unknown.

    Therapeutic Uses

    • 5-ASAs are the mainstay of treatment for UC but are not effective for CD.

    Pharmacokinetics

    • Mesalamine kinetics vary depending on the route of administration.
    • Absorption increases in severe disease and decreases with decreasing pH.
    • Local effects in UC with oral sulfasalazine absorption ranging from 60% to 80% due to sulfapyridine.

    Adverse Effects

    • Sulfasalazine adverse effects occur in up to 45% of patients, mainly due to sulfapyridine.
    • It can impair male fertility.
    • Sulfasalazine inhibits intestinal folate absorption.
    • Common dose-related side effects include headache, nausea, and fatigue.
    • Severe adverse effects include hemolytic anemia, myelosuppression, hepatitis, pneumonitis, neurotoxicity, rash, and Stevens-Johnson syndrome.
    • Treatment should be stopped at the first sign of skin rash or hypersensitivity.

    Corticosteroids

    • Budesonide has minimal systemic effects due to low bioavailability and high first-pass metabolism.
    • Budesonide delayed release is delivered to the ileum and proximal large bowel for ileocecal CD.
    • Budesonide extended release is delivered throughout the colon for UC patients with pancolitis.

    Biological Agents

    • Biological agents, including TNF-alpha inhibitors, alpha-4 integrin inhibitors, and other agents under investigation, are used to treat IBD.
    TNF-alpha Inhibitors
    • TNF-alpha inhibitors, such as infliximab, adalimumab, certolizumab, and golimumab, are first-line for CD patients and second-line for UC.
    • TNF-alpha inhibitors may become less effective over time.
    Alpha-4 Integrin Inhibitors
    • Alpha-4 integrin inhibitors, such as vedolizumab, bind to the alpha-4/beta-7 integrin, an adhesion molecule promoting leukocyte migration to inflammation sites.
    • Vedolizumab is indicated for refractory UC and CD.
    Adverse Effects of Biological Agents
    • Biological agents can cause adverse effects like headache, arthralgia, nausea, fatigue, and musculoskeletal pain.

    Immunomodulators

    • Immunomodulators are medications that suppress the immune system, primarily used to manage IBD and other autoimmune diseases.
    Methotrexate (MTX)
    • Methotrexate (MTX) inhibits folic acid production.
    • IM or subcutaneous administration of MTX is effective for CD but the mechanism of action is unknown.
    • It is not recommended for maintenance in UC.
    Methotrexate Adverse Effects
    • MTX can cause nausea, vomiting, abdominal discomfort, elevated serum aminotransferase, and rash.
    • Folic acid administration can reduce GI adverse effects.
    Thiopurines (Azathioprine, 6-Mercaptopurine)
    • Thiopurines, such as azathioprine and 6-mercaptopurine, are administered orally.
    • They have corticosteroid-sparing effects in UC and CD.
    • They are considered a first-line monotherapy option for IBD.
    • Their use is limited due to high toxicity, including bone marrow suppression and hepatotoxicity.

    Irritable Bowel Syndrome (IBS)

    • IBS is a chronic condition characterized by abdominal pain, bloating, and changes in bowel habits.
    • IBS is categorized into IBS-C (constipation) and IBS-D (diarrhea).

    Peptic Ulcer

    • Peptic ulcers are sores that develop in the lining of the stomach or duodenum.

    • Main causes:

      • Helicobacter pylori (H. pylori): A gram-negative bacteria that infects the stomach lining.
      • NSAID: Nonsteroidal anti-inflammatory medications like ibuprofen and naproxen.

    Treatment Approaches

    • Eliminating H. pylori infection: Eradicating the infection using a combination of antimicrobial agents.
    • Reduce gastric acid secretion: Employing proton pump inhibitors (PPIs) or H-2 receptor antagonists.
    • Protecting gastric mucosa: Using medications like misoprostol and sucralfate to protect the stomach lining.

    Antimicrobial Agents

    • First-line treatment includes quadruple therapy: bismuth subasalicylate, metronidazole, tetracycline, and a PPI.
    • Triple therapy consists of a PPI, amoxicillin (metronidazole if penicillin allergy), and clarithromycin.

    H-2 Receptor Antagonists

    • Drugs: Cimetidine, famotidine, nizatidine, ranitidine.

    • Mechanism of action:

      • Selectively block H-2 receptors, preventing histamine from stimulating acid secretion.
      • Competitve antagonism with histamine.
      • Reversible effect.

    • Therapeutic uses:

      • Peptic ulcer: Used as monotherapy, especially in patients with recurrent ulcers caused by H. pylori. PPIs are preferred for NSAID-induced ulcers.
      • Acute stress ulcers: Given intravenously, but tolerance can develop quickly.
      • Gastroesophageal reflux disease (GERD): Effective in reducing acid secretion, but PPIs are usually preferred.

    • Kinetics:

      • Administered orally.
      • Highly soluble, crosses the breast milk and placental barriers.
      • Excreted in urine.
      • Intravenous (I.V.) formulations available for cimetidine, ranitidine, and famotidine.

    • Adverse effects:

      • Cimetidine: Endocrine effects like gynecomastia and galactorrhea (continuous milk release).
      • Central nervous system (CNS) effects, especially in elderly patients after I.V. administration.
      • Interference with drugs requiring an acidic environment.
      • Inhibition of multiple cytochrome P450 (CYP450) isoenzymes, leading to drug accumulation, potentially affecting warfarin, phenytoin, and clopidogrel.

    H+/K+ ATPase Pump Inhibitors (PPIs)

    • Drugs: Dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole.

      • Mechanism of action:

        • Suppress the secretion of hydrogen ions into the gastric lumen.
        • Inhibit the final step in gastric acid secretion by blocking the H+/K+ ATPase pump.

      • Actions:

        • Prodrugs absorbed and activated in parietal cells.
        • Inhibit up to 90% of gastric acid secretion.
        • Omeprazole is formulated with bicarbonate to enhance absorption.

      • Therapeutic uses:

        • Preferred for GERD, erosive esophagitis, active duodenal ulcers, and pathological hypersecretory conditions like Zollinger-Ellison syndrome.
        • Reduce bleeding risk in ulcers caused by aspirin or NSAIDs.
        • Stress ulcer prophylaxis, especially before surgery.

      • Kinetics:

        • Administered orally, ideally 30-60 minutes before meals, except for dexlansoprazole.
        • I.V. formulations available for esomeprazole, lansoprazole, and pantoprazole.
        • Relatively short half-life, but long duration of action due to covalent binding to the pump.

      • Adverse effects:

        • Inhibition of CYP2C19 by omeprazole and esomeprazole.
        • Increased risk of bone fractures with long-term use (over 1 year).
        • Decreased vitamin B12 absorption due to interference with intrinsic factor secretion.
        • Decreased calcium absorption due to high gastric pH, potentially requiring calcium citrate supplementation.
        • Diarrhea, Clostridium difficile colitis, hypomagnesemia, and pneumonia.

    Prostaglandins: Misoprostol

    • Mechanism of action:

      • Prostaglandin E1 analog.
      • Increases gastric mucus and bicarbonate secretion, reducing acid secretion.

    • Therapeutic uses:

      • Prevents NSAID-induced gastric ulcers
      • Can be used prophylactically.

    • Contraindications:

      • Pregnancy: May induce uterine contractions and lead to miscarriage.

    • Adverse effects:

      • Diarrhea is a common side effect.

    Antacids

    • Drugs: Aluminum hydroxide, calcium carbonate, magnesium hydroxide, sodium bicarbonate.

      • Mechanism of action:

        • Weak bases that neutralize gastric acid by increasing pH above 4.
        • Inhibit pepsin activity.

      • Chemistry:

        • Food-dependent mechanism, with food prolonging duration of action.
        • May cause alkalosis and hypernatremia.

      • Therapeutic uses:

        • Symptomatic relief of peptic ulcers, heartburn, and GERD.
        • Optimal efficacy after meals.
        • Calcium carbonate is used to prevent osteoporosis.

      • Adverse effects:

        • Aluminum hydroxide: Constipation.
        • Magnesium hydroxide: Diarrhea.
        • Accumulation of cations can occur in patients with renal impairment.

    Mucosal Protective Agents

    • Drugs: Bismuth subsalicylate, sucralfate

      • Sucralfate:

        • Combination of aluminum hydroxide and sulfated sucrose.
        • Creates a physical barrier, protecting the ulcer from pepsin and acid.
        • Requires an acidic environment, not typically combined with PPIs, H-2 antagonists, or antacids.
        • Multiple daily doses recommended.

      • Bismuth subasalicylate:

        • Used in quadruple therapy to treat H. pylori-related peptic ulcers.
        • Inhibits pepsin activity.
        • Increases mucus secretion.
        • Forms a protective coating over the ulcer by interacting with glycoproteins in necrotic mucosal tissue.

    Chemotherapy-Induced Nausea and Vomiting (CINV)

    • Mechanisms triggering vomiting:

      • Area postrema (chemoreceptor trigger zone, CTZ).
      • Lateral reticular formation of the medulla, responsible for motor control.

    • Vomiting mediators:

      • Dopamine (D2) receptors.
      • Serotonin (5-HT3) receptors.
      • Chemotherapy can directly damage the gastrointestinal tract, leading to a vomiting response.

    Antiemetic Drugs

    • Phenothiazines (Prochlorperazine): Block dopamine receptors in the CTZ. Effective for low to moderately emetogenic chemotherapy agents.

    • 5-HT3 Receptor Blockers: Dolasetron, granisetron, ondansetron, palonosetron.

      • Mechanism of action:

        • Block 5-HT3 receptors in the periphery (visceral vagal afferent fibers) and the CTZ.

      • Therapeutic use:

        • Prophylactic use prior to chemotherapy, effective in all grades of emetogenic chemotherapy.

      • Adverse effects:

        • QT prolongation at high doses (ondansetron and dolasetron).
        • I.V. dolasetron is not recommended for prophylaxis.

    • Substituted Benzamides (Metoclopramide):

      • Inhibits dopamine in the CTZ.
      • High doses are needed for effective treatment of cisplatin-induced emesis (30-40% success rate).
      • Main adverse effect: Extrapyramidal symptoms.
      • Enhances gastric motility.

    • Butyrophenones (Droperidol, haloperidol):

      • Block dopamine receptors.
      • Droperidol used for sedation.
      • Can prolong the QT interval.

    • Benzothiazepines (Lorazepam, alprazolam):

      • Low-potency antiemetics.
      • Used for anticipated vomiting.
      • Contraindicated with alcohol due to CNS sedation.

    • Corticosteroids (Dexamethasone, methylprednisolone):

      • Effective against mildly to moderately emetogenic chemotherapy.
      • Main mechanism is unknown.
      • Block prostaglandins.

    • Substance P/Neurokinin-1 Receptor Antagonists: Aprepitant, fosaprepitant, netupitant, rolapitant.

      • Mechanism of action:

        • Block neurokinin-1 receptors in the vomiting center, preventing the action of substance P.

      • Therapeutic use:

        • Highly or moderately emetogenic chemotherapy.
        • Often used in combination with dexamethasone and 5-HT3 antagonists.
        • Effective for delayed phase of CINV (after 24 hours of chemotherapy).

      • Adverse effects:

        • Fatigue, diarrhea, abdominal pain, hiccups.

    Antidiarrheals

    • Antimotility Agents (Diphenoxylate/atropine, Loperamide):

      • Mechanism of action: Control diarrhea by inhibiting acetylcholine release.

      • Therapeutic use:

        • Acute diarrhea, including traveler's diarrhea.

      • Adverse effect:

        • Potential for toxic megacolon (prohibited in children and patients with severe colitis).

    • Adsorbents (Aluminum hydroxide, methylcellulose):

      • Mechanism of action:
        • Absorb intestinal toxins or microorganisms.
        • Coat or protect intestinal mucosa.
        • Less effective than antimotility agents.
        • May interfere with the absorption of other drugs.

    • ** Agents Modifying Fluid and Electrolyte Transport (Bismuth subsalicylate):**

      • Therapeutic use:

        • Traveler's diarrhea.

      • Mechanism of action:

        • Decreases fluid secretion in the bowel.

      • Adverse effects:

        • Black tongue and stools.

    Laxatives

    • Irritants/Stimulants (Senna, bisacodyl, castor oil):

      • Mechanism of action: Cause water and electrolyte secretion into the bowel, stimulating bowel movements.
      • Therapeutic use:
        • Opioid-induced constipation.

    • Bulk Laxatives (Methylcellulose, psyllium):

      • Mechanism of action:
        • Form gels in the large intestine, increasing the volume of stool.
        • Promote peristalsis.

    • Saline/Osmotic Laxatives (Polyethylene glycol, lactulose):

      • Mechanism of action:
        • Increase intestinal activity by drawing water into the bowel lumen.
        • Used in colonic lavage for bowel preparation.
        • Lactulose is metabolized by colonic bacteria, reducing ammonia levels in hepatic encephalopathy.

    • Stool Softeners (Docusate):

      • Mechanism of action:
        • Increase stool water content, making it softer.

    • Lubricant Laxatives (Glycerin suppositories, mineral oil):

      • Mechanism of action:
        • Facilitate stool passage.
        • Mineral oil should be taken in an upright position to avoid aspiration.

    • Chloride Channel Activators (Lubiprostone):

      • Mechanism of action:

        • Increase fluid secretion in the intestinal lumen.

      • Therapeutic use:

        • Chronic constipation.
        • Irritable bowel syndrome with constipation (IBS-C).

    Inflammatory Bowel Diseases (IBD)

    • Immune-mediated gastrointestinal tract inflammation: Caused by various factors, possibly including bacteria.
    • Subtypes: Crohn's disease (CD), ulcerative colitis (UC).
      • CD: Can affect any portion of the GIT from mouth to anus.
      • UC: Inflammation predominantly affects the mucosal layer.

    IBD Medications

    • 5-Aminosalicylates (5-ASA):

      • Types: AZO compounds (balsalazide, olsalazine, sulfasalazine) and mesalamine compounds.
      • Sulfasalazine: Prodrug consisting of 5-ASA linked to sulfapyridine. Sulfapyridine is associated with adverse effects.
      • Mechanism of action:
        • Anti-inflammatory and immunosuppressive properties.
        • Main mechanism unknown.
      • Therapeutic use:
        • Mainstay treatment for UC.
        • Not effective in CD.
      • Adverse effects:
        • Primarily associated with sulfapyridine.
        • Can impair male fertility.
        • Can inhibit intestinal folate absorption.
        • Headache, nausea, fatigue (common and dose-related).
        • Severe adverse effects include hemolytic anemia, myelosuppression, hepatitis, pneumonitis, neurotoxicity, rash, Steven-Johnson syndrome.
        • Stop treatment immediately if skin rash or hypersensitivity occurs.

    • Corticosteroids:

      • Budesonide:
        • Minimal systemic effects due to low oral bioavailability and high first-pass metabolism.
        • Delayed release (ileum and proximal large bowel): Used for ileocecal CD.
        • Extended release (throughout colon): Used for UC with pancolitis.

    • Biological Agents:

      • TNF-alpha Inhibitors:

        • Infliximab, adalimumab: For moderate to severe CD and UC.
        • Certolizumab: For moderate to severe CD only.
        • Golimumab: For moderate to severe UC only.
        • First-line for CD, second-line for UC (after 5-ASAs).

      • Alpha-4 Integrin Inhibitors:

        • Vedolizumab:
          • Inhibits alpha-4 integrin, which are adhesion molecules promoting leukocyte migration.
          • Used for refractory CD and UC.
          • Adverse effects: Headache, arthralgia, nausea, fatigue, musculoskeletal pain.

    • Immunomodulators:

      • Methotrexate (MTX):

        • Inhibits folinic acid production.
        • Only intramuscular (IM) or subcutaneous administration is effective in CD (mechanism unknown).
        • Not recommended for UC maintenance.
        • Adverse effects: Nausea, vomiting, abdominal discomfort, elevated serum aminotransferases, rash.
        • Folic acid supplementation can reduce GI adverse effects.

      • Thiopurines (Azathioprine, 6-mercaptopurine):

        • Administered orally.
        • Corticosteroid-sparing effects in UC and CD.
        • First-line as monotherapy.
        • Limited due to high toxicity, including bone marrow suppression and hepatotoxicity.

    Irritable Bowel Syndrome (IBS)

    • Chronic abdominal pain with alterations in bowel habits.
    • Classified into:
      • IBS-C (constipation-predominant).
      • IBS-D (diarrhea-predominant).

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    Description

    This quiz covers the causes, treatment options, and medication therapies for peptic ulcer disease. Learn about Helicobacter pylori, NSAIDs, and the various treatment modalities, including quadruple and triple therapies. Test your understanding of how H2 receptor antagonists and proton pump inhibitors function in ulcer management.

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