Hesi Gastrointestinal System
Local GI Reflexes
- Local reflexes are confined to the gut wall and intestinal wall as part of enteric nervous system activity.
- Gastroenteric reflex: stimuli in the stomach prepare for food in the GI tract.
- Gastrocolic reflex: stimulation of the stomach increases activity in the colon.
- Duodenal-colic reflex: stretch in the duodenum stimulates colon activity and mass movement.
- Other reflexes exist but are not detailed here.
Central GI Reflexes
- Swallowing: triggered by a food bolus in the back of the throat.
- Vomiting: controlled by two centers in the medulla.
- Primitive center: can induce projectile vomiting (e.g., in children or brain injury).
- Mature center: Chemoreceptor Trigger Zone (CTZ).
Chapter 57: Drugs Affecting Gastrointestinal Secretions
Histamine-2 Antagonists (H2 antagonists)
- Drugs: ranitidine (Zantac), famotidine (Pepcid), cimetidine (Tagamet), nizatidine (Axid) – the class name ends with “-tidine”.
- Mechanism: suppress release of gastrin from parietal cells by blocking the H2 receptor; decreased gastrin → decreased hydrochloric acid production.
- Note: H2 receptors are also found in the heart; theoretical risk for arrhythmias.
- Uses:
- Short-term treatment of active duodenal or gastric ulcers
- Treatment of hypersecretion of hydrochloric acid
- Prophylaxis of stress-induced ulcers
- Treatment of GERD
- Relief of heartburn, acid indigestion, and sour stomach
- Pharmacokinetics: all are metabolized by the liver except nizatidine (Axid).
- Special combos: Famotidine in combination with an NSAID (RelEtis/RelVis term in text) to reduce NSAID-induced GI ulcers (commonly referred to in practice as a combination product; text notes people often mislabel this as an “antacid”).
- Important recall/notes:
- Confusion in textbook terminology: RelEtis may be misnamed; focus on classification, not generic mislabeling.
- Textbook page note: p. 999 contains a confusing section.
Recalls and NDMA risk
- Current recalls: ranitidine recalled; nizatidine voluntary recall.
- Reason: Increased levels of NDMA (N-Nitrosodimethylamine), a probable human carcinogen, associated with storage over time.
- Impact: Not all products tested show increased NDMA; risk outweighed benefit leading to recall.
- Market impact: Increased use of famotidine (Pepcid) causing supply shortages.
Adverse effects
- Gastrointestinal upset
- Central nervous system effects: dizziness, headache, confusion (due to CNS H2 receptors)
- Cardiovascular: arrhythmias and hypotension (due to H2 receptors in heart)
- Endocrine/sexual effects: gynecomastia, impotence
Antacids
- Common agents: calcium carbonate (Tums, Oystercal), sodium bicarbonate (baking soda), magnesium salts (Milk of Mag), aluminum salts (Amphojel), combinations (e.g., Maalox – calcium and aluminum).
- Mechanism: neutralize stomach acid.
- Individual agent caveats:
- Sodium bicarbonate: risk of electrolyte imbalances.
- Calcium carbonate (Tums): constipation and acid rebound.
- Magnesium salts (Milk of Mag): diarrhea; also used as laxative.
- Aluminum salts (Amphojel): less likely to cause acid rebound; weaker at neutralizing acid.
- Adverse effects: relate to acid-base and electrolyte imbalances; acid rebound can occur when the stomach compensates by producing more acid after neutralization.
- Drug interactions: antacids can alter absorption of other medications and create an alkaline environment that impairs absorption of certain drugs; recommendation to separate other drugs by at least 2 hours.
Proton Pump Inhibitors (PPIs)
- Drugs: omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix) – class name ends with “-prazole”.
- Mechanism: inhibit the hydrogen-potassium ATPase enzyme system (H⁺/K⁺-ATPase) in the parietal cells, thereby blocking acid release into the stomach lumen.
- Use pattern: generally short-term treatment, but can be long-term if needed.
- Uses:
- Duodenal ulcers
- GERD
- Erosive esophagitis
- Benign gastric ulcers
- Helicobacter pylori treatment (in combination with amoxicillin and clarithromycin)
- Pediatric note: lansoprazole is approved for children under 18; others used off-label in pediatrics.
- Adverse effects: related to reduced acidity; potential changes to gastric flora that may increase cancer risk with long-term altered microbiota..
- Dosing/administration:
- Generally short-term use of 2–4 weeks; some patients require longer therapy.
- Teach patients to take before a meal; do not crush, chew, or open capsules.
- Follow-up if symptoms persist after 4–8 weeks.
- Special relevance: often prescribed to patients who routinely take NSAIDs.
Gastrointestinal Protectant
- Sucralfate (Carafate)
- Mechanism: coats injured gastric mucosa, protecting it from acids and bile; creates a protective barrier to allow healing.
- Contraindications/ cautions:
- Renal failure or dialysis patients due to aluminum buildup.
- Caution when combined with aluminum salts due to potential aluminum toxicity.
- Administration: empty stomach; take 1 hour before or 2 hours after meals.
Prostaglandins
- Misoprostol (Cytotec) – prostaglandin E analogue
- Mechanism: protects stomach lining by inhibiting gastric acid secretion and increasing bicarbonate and mucus production.
- Primary use: prevent NSAID-induced gastric ulcers.
- Important safety measures: can cause uterine contractions; ensure a negative serum pregnancy test within 2 weeks of starting therapy; begin therapy on the 2nd or 3rd day of the menstrual cycle; use barrier contraception during treatment.
Digestive Enzymes
- Forms: saliva substitutes (for dry mouth or swallowing difficulties) and pancreatic enzyme replacements (ptyal substitutes cover bolus formation and lubrication).
- Saliva substitutes examples: MouthKote, Salivart; role: thickening agent to aid swallowing.
- Pancrelipase (Creon, Pancrease): replace enzymes needed to digest fats, proteins, and carbohydrates.
- Indications: pancreatic insufficiency (e.g., cystic fibrosis, chronic ductal obstruction), radiation/chemo-induced damage, etc.
Chapter 58: Drugs Affecting Gastrointestinal Motility
Laxatives
- Indications: short-term relief of constipation; help patients avoid straining (e.g., after surgery or in patients with cardiac conditions);
- Prep for bowel diagnostics
- Remove poisons from GI tract
- Types:
- Chemical stimulants
- Bulk stimulants
- Lubricants
Chemical stimulants
- Examples: Bisacodyl (Dulcolax), castor oil, senna
- Mechanism: stimulate the nerve plexus, increasing movement and local reflex activity; act from the small intestine through the entire GI tract when given PO.
- Considerations: frequent use can lead to laxative dependence; can cause constipation or impaction if overused.
- Specific notes: Bisacodyl is milder than castor oil; avoid taking with other meds within at least 30 minutes to prevent premature removal before absorption.
Bulk stimulants
- Examples: polyethylene glycol (MiraLax), magnesium hydroxide (Milk of Mag), polycarbophil (FiberCon), psyllium (Metamucil), polyethylene glycol-electrolyte solution (GoLYTELY), lactulose (Constilac).
- Mechanism: act by increasing stool bulk and water content, stretching the colonic wall to trigger local reflexes.
- Uses: constipation relief; bowel prep for diagnostics; similar adverse effects and precautions as chemical stimulants; dosing-dependent.
- Examples: docusate (Colace), glycerin, mineral oil
- Mechanism: soften stool, facilitate defecation without stimulating movement.
- Indications: post-surgical patients, patients with hemorrhoids.
- Cautions: prolonged use can interfere with absorption of fat-soluble vitamins A, D, E, and K.
General teaching for all laxatives
- Temporary use; maintain adequate fluid intake (increased fluids especially with bulk laxatives).
- Encourage patients to keep enemas and suppositories in place as long as possible when using.
- Do not administer laxatives in the presence of acute abdominal pain, nausea, or vomiting.
- Provide comfort and safety measures, particularly in elderly patients or those with certain medical conditions.
Gastrointestinal Stimulants
- Metoclopramide (Reglan)
- Mechanism: stimulates parasympathetic activity in the GI tract; increases GI secretions and motility.
- Indication: used when more rapid movement of GI contents is desirable.
- Adverse effects: N/V, diarrhea, intestinal spasm, cramping; parasympathetic stimulation can cause decreased BP, decreased HR, etc.
- Teaching: usually given 15–30 minutes before a meal and at bedtime; monitor BP, especially if given IV.
Antidiarrheals
- Subsalicylate (Pepto-Bismol) and loperamide (Imodium)
- Mechanisms:
- Pepto-Bismol acts on the lining of the GI tract to inhibit local reflexes.
- Imodium acts on the GI tract muscles to slow activity.
- Cautions/contraindications: history of GI obstruction or acute abdominal conditions; diarrhea due to poisoning; hepatic impairment.
- Adverse effects: constipation, N/V, abdominal pain; fatigue, weakness, dizziness
Traveler’s Diarrhea
- Rifaximin
- Use: antibiotic specifically for treatment of traveler’s diarrhea; active against E. coli (the most common cause).
- Regimen: started once symptoms occur; typically three times daily (t.i.d.) for 3 days.
- Prevention: best intervention is prevention; recommendations include:
- Drink only bottled water
- Avoid fresh fruits/vegetables washed in local water unless peeled
- Avoid ice cubes in drinks
- Avoid undercooked or rare foods
- Be cautious when brushing teeth with local water; use bottled water when possible
Irritable Bowel Syndrome (IBS) Drugs
- Symptoms: abdominal distress, diarrhea or constipation, bloating, nausea, flatulence, HA, fatigue, depression, anxiety.
- No known single cause; possibly stress-related.
- Lubiprostone: chloride-channel activator that increases chloride-rich intestinal fluid production (does not change Na or K), increasing fluid -> increased motility; used for IBS-C or chronic constipation.
- Alosetron: serotonin 5-HT antagonist; decreases perception of gastric pain and decreases GI motility; was removed from the market due to ischemic bowel risk, then re-released with Black Box Warning; requires patient-physician agreement; only approved for women; used for IBS-D.
Chapter 59: Antiemetic Agents
Emetics (inducing vomiting)
- Ipecac syrup was historically used for poisoning at home but is no longer recommended.
- Guidelines emphasize poison safety: keep poisons out of reach, childproof caps, keep substances in original containers, dispose of unused medications, do not refer to meds as candy, and post Poison Control number.
- Pts should dispose of any ipecac syrup they may still have.
Antiemetic Agents (overview)
- Goal: reduce hyperactivity of vomiting reflex via two mechanisms:
- Local (peripheral): decrease response to stimuli reaching the medulla
- Examples: antacids, local anesthetics, adsorbents, GI protectants, anti-distention drugs
- Central: block CTZ in the medulla
- Groups:
- Phenothiazines
- Nonphenothiazines
- Serotonin (5-HT) receptor blockers
- Substance P / neurokinin 1 (NK1) receptor antagonists
- Miscellaneous agents
Phenothiazines
- Example: prochlorperazine
- Mechanism: centrally acting antiemetic; alters response to CTZ stimulation in the medulla.
- Adverse effects: pink-to-brown urine discoloration, photosensitivity (use sunscreen), CNS effects (drowsiness, headache, weakness); concurrent CNS depressants (e.g., alcohol) should be avoided.
- Note: also used as an antipsychotic medication.
Nonphenothiazines
- Example: metoclopramide (Reglan)
- Mechanism: reduces responsiveness of CTZ nerve cells to circulating emetic chemicals.
- Role: antiemetic, often used postoperatively or with chemotherapy-induced N/V.
5-HT Receptor Blockers
- Examples: ondansetron (Zofran), dolasetron (Anzemet)
- Mechanism: block serotonin receptors in CTZ and locally in GI tract.
- Uses: highly effective in cancer patients (chemo and radiation) and postoperative patients; available in PO and IV forms; side effects are generally mild.
Substance P / Neurokinin-1 (NK1) Receptor Antagonists
- Examples: aprepitant (Emend), rolapitant (Varubi)
- Use: in combination with dexamethasone; rolapitant used in combination with other antiemetics.
- Nature: newer class; effective for chemotherapy-induced nausea and vomiting, including delayed N/V; acts in the CNS to block NK1 receptors; no direct effect on serotonin, dopamine, or corticosteroid receptors.
Miscellaneous antiemetics
- Dronabinol (Marinol) and nabilone
- Content: cannabinoids (THC) as part of antiemetic therapy; Schedule III controlled substances; approved for managing N/V in cancer chemotherapy patients who have not responded to other treatments in some jurisdictions; legal status varies.