Gastrointestinal Tract Drugs PDF

Drugs affecting Gastrointestinal Tract  Most common: hyperacidity terms for overproduction of Types of Acid-Controlling Agents HCI by the parietal cells  Antacids...

Drugs affecting Gastrointestinal Tract  Most common: hyperacidity terms for overproduction of Types of Acid-Controlling Agents HCI by the parietal cells  Antacids  indigestion, sour stomach,heartburn, acid stomach  H₂ antagonists  PUD: peptic ulcer disease  Proton pump inhibitors  GERD: gastroesophageal reflux disease. Acid-Related Pathophysiology  Helicobacter pylori (H. pylori) The stomach secretes:  Bacterium found in GI tract of 90% of patients with  Hydrochloric acid (HCI) - The hydrochloric acid in the gastric duodenal ulcers, and 70% of those with gastric ulcers juice breaks down the food and the digestive enzymes, split up  Antibiotics are used to eradicate H. pylori the proteins. The acidic gastric juice also kills bacteria. (tetracycline)  Pepsinogen -A substance made by cells in the stomach. Acid in Antacids: Mechanism of Action the stomach changes pepsinogen to pepsin, which breaks  Promote gastric mucosal defense mechanisms down proteins in food during digestion.  Secretion of:  Mucus - a gel-mucous barrier secreted by epithelial cells and - Mucus: protective barrier against HCI glandular cells in the stomach wall. It acts as part of a barrier - Bicarbonate: helps buffer acidic properties of HCI that protects the stomach wall from the acid and digestive - Prostaglandins: prevent activation of proton pump enzymes within the stomach lumen. Antacids DO NOT prevent the overproduction of acid  Bicarbonate – bicarbonate buffer system is an acid-base Antacids DO neutralize the acid once it's in the stomach homeostatic mechanism involving the balance of carbonic acid Antacids: Drug Effects (H2CO3), bicarbonate ion (HCO − 3), and carbon dioxide (CO2)  Reduction of pain associated with acid related disorders in order to maintain pH in the blood and duodenum, among  Raising gastric pH from 1.3 to 1.6 neutralizes 50% of the other tissues, to support proper metabolic function. gastric acid  Prostaglandins - prostaglandins are found in high  Raising gastric pH 1 point (1.3 to 2.3) neutralizes 90% of the concentration in the gastric mucosa and gastric juice. gastric acid Exogenous prostaglandins inhibit acid secretion, stimulate  Reducing acidity reduces pain mucus and bicarbonate secretion, alter mucosal blood flow, Antacids and provide dramatic protection against a wide variety of OTC formulations available as agents which cause acute mucosal damage. o Capsules and tablets Glands of the Stomach o Powders  Cardiac - cardiac gastric glands are located at the very beginning o Chewable tablets of the stomach; cardiac and pyloric glands secrete mucus, which o Suspensions coats the stomach and protects it from self-digestion by helping o Effervescent granules and tablets to dilute acids and enzymes. Used alone or in combination  Gastric glands - in the central stomach areas; and the  Aluminum salts  Pyloric glands - in the terminal stomach portion.  Magnesium salts The cells of the gastric gland are the largest in number and of  Calcium salts primary importance when discussing acid control  Sodium bicarbonate Cells of the Gastric Gland Antacids: Aluminum Salts  Parietal cells - secrete hcl, this inhibits vit b12 absorption in the  Forms: carbonate, hydroxide small intestine, cells found in gastric glands that secrete  Have constipating effects hydrochloric acid (for hydrolysis of ingested food) and gastric  Often used with magnesium to counteract constipation intrinsic factor (for absorption of vitamin B-12). Examples  Chief cells - pepsinogen, and gastric lipase A cell of the gastric - Aluminum carbonate: Basaljel glands that secretes pepsinogen (breaks down protein) and - Hydroxide salt: AlternaGEL gastric lipase, secrete pepsinogen, a protease activated by the - Combination products (aluminum and magnesium): Gaviscon, acidic environment of the stomach Maalox, Mylanta, Di-Gel  Mucoid cells - protects endothelium -secretes viscous Antacids: Magnesium Salts mucous, this type of secretory cell lines stomach lumen and  Forms: carbonate, hydroxide, oxide, trisilicate extends into the gastric pits  Commonly cause diarrhea; usually used with other agents to Hydrochloric Acid counteract this effect.  Secreted by the parietal cells when stimulated by food  Dangerous when used with renal failure-the failing kidney  Maintains stomach at pH of 1 to 4 cannot excrete extra magnesium, resulting in accumulation.  Secretion also stimulated by:  Examples - Large fatty meals - Hydroxide salt: magnesium hydroxide (milk of magnesia) - Excessive amounts of alcohol - Carbonate salt: Gaviscon (also a combination product) - Emotional stress - Combination products such as Maalox, Mylanta Acid-Related Diseases (aluminum and magnesium) Caused by imbalance of the three cells of the gastric gland and their Antacids: Calcium Salts secretions  Forms: many, but carbonate is most common.  May cause constipation   Their use may result in kidney stones.  Most medications should be given 1 to 2 hours after giving  Long duration of acid action may cause increased gastric an antacid acid secretion (hyperacidity rebound)  Antacids may cause premature dissolving of enteric-coated  Often advertised as an extra source of dietary calcium medications, resulting in stomach upset - Example: Tums (calcium carbonate) Histamine Type 2 (H2) Antagonists Antacids: Sodium Bicarbonate Reduce acid secretion  Highly soluble  All available OTC in lower dosage forms  Buffers the acidic properties of HCI  Most popular drugs for treatment of acid-related disorders  Quick onset, but short duration  cimetidine (Tagamet) – nizatidine  May cause metabolic (systemic) alkalosis when used  famotidine (Pepcid) excessively  ranitidine (Zantac)  Sodium content may cause problems in patients with HF, H2 Antagonists: Mechanism of Action hypertension, or renal insufficiency  Block histamine (H2) at the receptors of acid-producing Antacids and Antiflatulents parietal cells  Antiflatulents: used to relieve the painful symptoms  Production of hydrogen ions is reduced, resulting in associated with gas. decreased production of HCl  Several agents are used to bind or alter intestinal gas and are H2 Antagonists: Drug Effect often added to antacid combination products  Suppressed acid secretion in the stomach  OTC antiflatulents H2 Antagonists: Indications  Activated charcoal  GERD  Simethicone - Alters elasticity of mucus-coated bubbles  PUD causing them to break  Erosive esophagitis  Used often, but there are limited data to support effectiveness  Adjunct therapy in control of upper GI bleeding Antacids: Side Effects  Pathologic gastric hypersecretory conditions Minimal, and depend on the compound used H2 Antagonists: Side Effects  Aluminum and calcium  Overall, less than 3% incidence of side effects Constipation  Cimetidine may induce impotence and gynecomastia  Magnesium  May see: Diarrhea  Headaches, lethargy, confusion, diarrhea, urticaria,  Calcium carbonate sweating, flushing, other effects Produces gas and belching; often combined with simethicone H2 Antagonists: Drug Interactions Antacids: Drug Interactions  cimetidine  Adsorption of other drugs to antacids - Binds with P-450 microsomal oxidase system in the liver,  Reduces the ability of the other drug to be absorbed into resulting in inhibited oxidation of many drugs and increased the body drug levels  Chelation - process of chelating.... Medicine/ Medical a - All H2 antagonists may inhibit the absorption of drugs that method of removing certain heavy metals from the require an acidic GI environment for absorption bloodstream. (Example: Ketoconazole) - Chemical binding, or inactivation, of another drug SMOKING has been shown to decrease the effectiveness of - Produces insoluble complexes H2 blockers - Result: reduced drug absorption H2 Antagonists: Nursing Implications  Increased stomach pH  Assess for allergies and impaired renal or liver function  Increased absorption of basic drugs  Use with caution in patients who are confused, disoriented,  Decreased absorption of acidic drugs or elderly  Increased urinary pH  Take 1 hour before or after antacids  Increased excretion of acidic drugs  For intravenous doses, follow administration guidelines  Decreased excretion of basic drugs Proton Pump Antacids: Nursing Implications  The parietal cells release positive hydrogen ions (protons)  Assess for allergies and preexisting conditions that may during HCl production restrict the use of antacids, such as:  This process is called the “proton pump” - Fluid imbalances  H2 blockers and antihistamines do not stop the action of this - Renal disease pump - HF Proton Pump Inhibitors: Mechanism of Action - Pregnancy  Irreversibly bind to H+/K+ ATPase enzyme - GI obstruction  This bond prevents the movement of hydrogen ions from  Patients with HF or hypertension should use low-sodium the parietal cell into the stomach antacids such as Riopan, Maalox, or Mylanta II  Result: achlorhydria—ALL gastric acid secretion is blocked  Use with caution with other medications due to the many  In order to return to normal acid secretion, the parietal cell drug interactions must synthesize new H+/K+ ATPase Proton Pump Inhibitors: Drug Effect - Doses that are therapeutic enough to treat duodenal ulcers Total inhibition of gastric acid secretion often produce abdominal cramps, diarrhea  lansoprazole (Prevacid) Antidiarrheals and Laxatives  omeprazole (Prilosec)* Diarrhea  rabeprazole (Aciphex)  Abnormal frequent passage of loose stools or  pantoprazole (Protonix)  Abnormal passage of stools with increased frequency,  esomeprazole (Nexium) fluidity, and weight, or with increased stool water excretion  *The first in this new class of drugs  Sudden onset in a previously healthy person Proton Pump Inhibitors: Indications  Lasts from 3 days to 2 weeks  GERD maintenance therapy  Self-limiting  Erosive esophagitis  Chronic diarrhea Lasts for more than 3 weeks  Short-term treatment of active duodenal and benign gastric  Associated with recurring passage of diarrheal stools, fever, ulcers loss of appetite, nausea, vomiting, weight loss, and chronic  Zollinger-Ellison syndrome weakness  Treatment of H. pylori–induced ulcers; usually combined Causes of Diarrhea with antibiotic such as clarithromycin (Biaxin) Acute Diarrhea Chronic diarrhea Proton Pump Inhibitors: Side Effects Bacterial Tumors  Safe for short-term therapy Viral Diabetes  Incidence low and uncommon Drug Induced Addison’s disease Proton Pump Inhibitors: Nursing Implications Nutritional Hyperthyroidism  Assess for allergies and history of liver disease Protozoal Irritable bowel syndrome  pantoprazole is the only proton pump inhibitor available for Antidiarrheals: Mechanism of Action parenteral administration, and can be used for patients who Adsorbents are unable to take oral medications Coat the walls of the GI tract  May increase serum levels of diazepam, phenytoin, and Bind to the causative bacteria or toxin, which is then cause increased chance for bleeding with warfarin eliminated through the stool Instruct the patient taking omeprazole: For relief of diarrhea and cramps  It should be taken before meals Examples: OTC bismuth subsalicylate (Pepto-Bismol),  The capsule should be swallowed whole, not crushed, kaolin-pectin, activated charcoal, attapulgite (Kaopectate) opened, or chewed Anticholinergics  It may be given with antacids Decrease intestinal muscle tone and peristalsis of GI tract  Emphasize that the treatment will be short term Result: slowing the movement of fecal matter through the Other Drugs GI tract  sucralfate (Carafate) Examples: belladonna alkaloids (Donnatal), atropine  misoprostol (Cytotec) (Lomotil), hyoscyamine sucralfate (Carafate) Intestinal flora modifiers  Cytoprotective agent - stimulate mucus production and Bacterial cultures of Lactobacillus organisms work by: enhance blood flow throughout the lining of the Supplying missing bacteria to the GI tract gastrointestinal tract. These agents also work by forming a Suppressing the growth of diarrhea-causing bacteria coating that protects the ulcerated tissue. Example: L. acidophilus (Lactinex)  Used for stress ulcers, erosions, PUD Opiates  Attracted to and binds to the base of ulcers and erosions,  Decrease bowel motility and relieve rectal spasms forming a protective barrier over these areas  Decrease transit time through the bowel, allowing more  Protects these areas from pepsin, which normally breaks time for water and electrolytes to be absorbed down proteins (making ulcers worse)  Examples: paregoric, opium tincture, codeine, loperamide  May cause constipation, nausea, and dry mouth (Imodium), diphenoxylate  May impair absorption of other drugs, especially Antidiarrheal Agents: Side Effects tetracycline Adsorbents  Binds with phosphate; may be used in chronic renal failure  Increased bleeding time to reduce phosphate levels  Constipation, dark stools  Do not administer with other medications  Confusion, twitching misoprostol (Cytotec)  Hearing loss, tinnitus, metallic taste, blue gums Synthetic prostaglandin analog Anticholinergics Prostaglandins have cytoprotective activity  Urinary retention, hesitancy, impotence - Protect gastric mucosa from injury by enhancing local  Headache, dizziness, confusion, anxiety, drowsiness production of mucus or bicarbonate  Dry skin, rash, flushing - Promote local cell regeneration  Blurred vision, photophobia, increased intraocular pressure - Help to maintain mucosal blood flow  Hypotension, hypertension, bradycardia, tachycardia - Used for prevention of NSAID-induced gastric ulcers Opiates  Drowsiness, sedation, dizziness, lethargy   Nausea, vomiting, anorexia, constipation Saline  Respiratory depression  Increase osmotic pressure within the intestinal tract,  Bradycardia, palpitations, hypotension causing more water to enter the intestines  Urinary retention  Result: bowel distention, increased peristalsis, and  Flushing, rash, urticaria evacuation Antidiarrheal Agents: Interactions Saline laxative examples: Adsorbents  magnesium sulfate (Epsom salts)  Adsorbents decrease the absorption of many agents,  magnesium hydroxide (MOM) including digoxin (Lanoxin), clindamycin, quinidine, and  magnesium citrate hypoglycemic agents  sodium phosphate (Fleet Phospho-Soda, Fleet enema)  Adsorbents cause increased bleeding time when given with Stimulant anticoagulants  Increases peristalsis via intestinal nerve stimulation  Antacids can decrease effects of anticholinergic Examples: antidiarrheal agents  castor oil Antidiarrheal Agents: Nursing Implications  senna  Use adsorbents carefully in geriatric patients or those with  cascara decreased bleeding time, clotting disorders, recent bowel  bisacodyl surgery, confusion Laxatives: Indications  Anticholinergic should not be administered to patients with Laxative Group Use a history of glaucoma, urinary retention, recent bladder Bulk forming Acute and chronic constipation, surgery, cardiac problems, myasthenia gravis Irritable bowel syndrome, Laxatives Diverticulosis Constipation Emollient Softening of fecal impaction; facilitation of BMs  Abnormally infrequent and difficult passage of feces in anorectal conditions through the lower GI tract Hyperosmotic Chronic constipation  Symptom, not a disease Diagnostic and surgical preps  Disorder of movement through the colon and/or rectum Saline Diagnostic and surgical preps  Can be caused by a variety of diseases or drugs Constipation Laxatives: Mechanism of Action Removal of helminths and parasites  Bulk forming Stimulant Acute constipation  Emollient Diagnostic and surgical bowel preps  Hyperosmotic Laxatives: Side Effects  Saline Bulk forming  Stimulant  Impaction Bulk forming  Fluid overload  High fiber Emollient  Absorbs water to increase bulk  Skin rashes  Distends bowel to initiate reflex bowel activity  Decreased absorption of fat-soluble vitamins A, D, E, & K Examples: Hyperosmotic  psyllium (Metamucil)  Abdominal bloating  methylcellulose (Citrucel)  Rectal irritation  polycarbophil Saline Emollient  Magnesium toxicity (with renal insufficiency)  Stool softeners and lubricants  Cramping  Promote more water and fat in the stools  Diarrhea  Lubricate the fecal material and intestinal walls  Increased thirst Examples: Stimulant  Stool softeners: docusate salts (Colace, Surfak)  Nutrient malabsorption  Lubricants: mineral oil  Skin rashes Hyperosmotic  Gastric irritation  Increase fecal water content  Rectal irritation  Result: bowel distention, increased peristalsis, and  Can cause dependence if overused evacuation  All laxatives can cause electrolyte imbalances! Examples: Antiemetic and Antinausea Agents  polyethylene glycol (GoLYTELY) – Used before diagnostic or Nausea surgical bowel procedures Unpleasant feeling that often precedes vomiting  sorbitol Emesis (vomiting)  glycerin Forcible emptying of gastric, and occasionally, intestinal  lactulose (Chronulac) contents Antiemetic agents  Most work by blocking one of the vomiting pathways, thus Used to relieve nausea and vomiting blocking the stimulus that induces vomiting VC and CTZ Vomiting center (VC) Chemoreceptor trigger zone (CTZ) Indications  Both located in the brain Specific indications vary per class of antiemetics  Once stimulated, cause the vomiting reflex General use: prevention and reduction of nausea and vomiting Mechanism of Action and Indications Anticholinergic agents (ACh blockers) - Bind to and block acetylcholine (ACH) receptors in the inner ear labyrinth - acetylcholine is the most common neurotransmitter to induce gastrointestinal smooth muscle contractions. - Block transmission of nauseating stimuli to CTZ - Also block transmission of nauseating stimuli from the reticular formation to the VC– scopolamine - Also used as a transdermal patch for motion sickness Antihistamine agents (H1 receptor blockers) - Inhibit ACh by binding to H1 receptors - Prevent cholinergic stimulation in vestibular and reticular areas, thus preventing Nausea &Vomiting - Example: dimenhydrinate, diphenhydramine, meclizine, promethazine - Also used for non-productive cough, allergy symptoms, sedation. Neuroleptic agents  Block dopamine receptors on the CTZ Example: Chlorpromazine, perphenazine, triflupromazine, prochlorperazine (Compazine)  Also used for psychotic disorders, intractable hiccups Prokinetic agents - Prokinetic agents, or prokinetics, are medications that help control acid reflux. Prokinetics help strengthen the lower esophageal sphincter (LES) and cause the contents of the stomach to empty faster. Block dopamine in the CTZ- Cause CTZ to be desensitized to impulses it receives from the GI tract. Also stimulate peristalsis in GI tract, enhancing emptying of stomach contents - Metoclopramide (Reglan), cisapride - Also used for GERD, delayed gastric emptying Serotonin blockers - Block serotonin receptors in the GI tract, CTZ, and VC. Example : dolasetron, granisetron, ondansetron (Zofran) - Used for N&V for patients receiving chemotherapy and CTZ postoperative nausea and vomiting  The CTZ contains receptors for dopamine, serotonin, opioids, Tetrahydrocannabinoids acetylcholine and the neurotransmitter substance P. - Major psychoactive substance in marijuana  When stimulated, each of these receptors gives rise to - Inhibitory effects on reticular formation , thalamus, cerebral pathways leading to vomiting and nausea. cortex Neurotransmitters Involved in Nausea and Vomiting - Alter mood and body's perception of its surroundings Neurotransmitter Site in the Vomiting Pathway Example : dronabinol (Marinol) Acetylcholine VC in brain; vestibular and labyrinth - Used for N&V associated with chemotherapy, and anorexia pathways in inner ear associated with weight loss in AIDS patients Dopamine GI tract and CTZ in brain, VC in brain Side Effects (D2)Histamine (H1) vestibular and labyrinth pathways in inner  Vary according to agent used ear.  Zofran = headache  Stem from their nonselective blockade of various receptors (H₁)Prostaglandins GI tract (PGs) Serotonin(5- GI tract; CTZ and VC in brain HT3) Chemoreceptor trigger zone (CTZ) Mechanism of Action  Many different mechanisms of action