Nursing 3703 pharmacology digestive system drugs
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Nursing 3703 Pharmacology Digestive System Drugs. By Linda Self APN, MSN, CCRN. Effects of Drugs on the Digestive System. Digestive system and drug therapy have a reciprocal relationship

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Nursing 3703 pharmacology digestive system drugs

Nursing 3703PharmacologyDigestive System Drugs

By Linda Self APN, MSN, CCRN


Effects of drugs on the digestive system

Effects of Drugs on the Digestive System

  • Digestive system and drug therapy have a reciprocal relationship

  • Some medications cause GI symptoms (e.g. EES); conversely, some GI disorders alter the absorption and metabolism of drugs (liver failure)

  • Drugs affecting the GI tract include: laxatives, antidiarrheals, antiemetics, drugs used in acid-peptic disorders . Others include cholinergics (Aricept) anticholinergics (atropine), corticosteroids and anti-infectives.


Nursing 3703 pharmacology digestive system drugs

  • Review physiology of the digestive system

    Organs and some associated disorders

  • Oral cavity-stomatitis

  • Esophagus-GERD

  • Stomach—peptic ulcers, gastritis

  • Small intestine—malabsorption, Inflammatory bowel

  • Large intestine—diarrhea, constipation

  • Pancreas—pancreatitis, Diabetes, ARDS

  • Gallbladder—cholestasis,cholelithiasis, cholecystitis

  • Liver—hepatitis, cirrhosis


Cell protective mechanisms in stomach

Cell protective mechanisms in stomach

  • Secretion of mucus and bicarbonate

  • Dilution of gastric acid by food and secretions

  • Prevention of diffusion of HCL from the stomach lumen back into the gastric mucosal lining

  • Presence of prostaglandin E

  • Alkalinization of gastric secretions by pancreatic juices and bile


Cell destructive effects in stomach

Cell Destructive Effects in Stomach

  • Gastric acid, secreted by parietal cells

  • Paretal cells contain receptrors for acetylcholine, gastrin and histamine, all of which stimulate gastric acid production

  • Acetylcholine is released by vagus nerve endings in response to stimuli, such as thinking about food


Cell destructive effects cont

Cell destructive effects cont.

  • Gastrin is a hormone released by the stomach and duodenum in response to food ingestion. Affects parietal cells which in turn causes gastric acid to be released in stomach.

  • Histamine is released from cells in the gastric mucosa and diffuses into nearby parietal cells

  • Pepsin is a proteolytic enzyme that helps digest protein foods and also can digest the stomach wall


Cell destructive effects

Cell destructive effects

H. pylori is a gram negative bacterium found in the gastric mucosa of most clients with chronic gastritis

  • In 75% of those with gastric ulcers and in 90% of clients with duodenal ulcers

  • Spread by oral fecal route or by iatrogenic spread

  • Thought to affect mucosal function


Peptic ulcer disease

Peptic Ulcer Disease

Gastric Ulcers

  • Associated with stress, NSAIDs or H. pylori

  • Manifested by painless bleeding

  • Take longer to heal than duodenal ulcers

  • When associated w/stress, can occur at any age

  • With H. pylori and NSAIDs generally are in 6th or 7th decade

  • chronic


Pud cont

PUD cont.

Duodenal Ulcers

  • Can occur at any age

  • Occur equally in men and women

  • Manifested by abdominal pain

  • Associated with cigarette smoking

  • Also associated with NSAIDs and H. pylori


Peptic ulcer and acid reflux disorders

Peptic Ulcer and Acid Reflux Disorders

  • Characterized by ulcer formation in the esophagus, stomach or duodenum

  • Occurs in areas that are exposed to gastric acid and pepsin

  • Gastric and duodenal ulcers are more common than esophageal ulcers

  • Parietal cells contain receptors for acetylcholine—implication of which is stimulation by/of vagus


Upper gi disorders

Upper GI Disorders

  • Gastritis—acute or chronic inflammatory reaction of gastric mucosa.

    Usually will see peptic ulcers with gastritis

  • Non-steroidal anti-inflammatory Drug Gastropathy

  • Occurs with damage to mucosa by ASA or other NSAIDs

    Chronic ingestion causes irritation of the gastric mucosa, inhibits the synthesis of prostaglandins (which protect mucosal lining) and increasess the synthesis of leukotrienes and other substances that can cause mucosal damage


Selected upper gastrointestinal disorders

Selected Upper Gastrointestinal Disorders

  • Review p. 853 in text

  • Include Gastritis

  • Nonsteroidal anti-Inflammatory Drug Gastropathy

  • Stress Ulcers

  • Zollinger-Ellison Syndrome-rare; excessive secretion of gastric acid and a high incidence of ulcers. Caused by gastrin-secreting tumors in pancreas, stomach or duodenum. Often malignant.


Gastroesophageal reflux disease

Gastroesophageal Reflux Disease

  • Most common disorder of the esophagus

  • Characterized by regurgitation of gastric contents into the esophagus

  • Occurs most often after a meal

  • Worse when recumbent

  • Caused by incompetent lower esophageal sphincter

  • Foods that cause relaxation include: etoh, caffeine, fats, chocolate, cigarrette smoking, gastric distention and medications (beta adrenergic blockers, calcium channel blockers, nitrates)


Gerd cont

GERD cont.

  • Occurs in men, women, and children

  • Common during pregnancy

  • More common after 40 years of age


Classifications and individual drugs

Classifications and Individual Drugs

  • Antacids—alkaline substances that neutralize acids. Raising the pH to approximately 3.5 neutralizes more than 90% of gastric acid and inhibits conversion of pepsinogen to pepsin. Commonly used antacids are aluminum, magnesium, and calcium compounds.


Antacids

Antacids

  • Antacids vary in onset of active and dosage needed for neutralization

  • Aluminum compounds require large doses for effectiveness. They can cause constipation, hypophosphatemia and osteomalacia.

  • Magnesium based antacids have more rapid onset than Al++ but can cause diarrhea and hypermagnesemia

  • Calcium compounds can cause hypercalcemia and hypersecretion of gastric acid==“rebound”


Antacids1

Antacids

  • May be in combinations such as aluminum and magnesium hydroxide

  • Decreases the diarrhea and constipation

  • Most antacids are pregnancy category C

  • Antacids may be used in children

  • Antacides with magnesium are contraindicated because hypermagnesemia may result

  • Additives such as simethicone may be added

  • pills are as effective as liquids


Use in older adults

Use in Older Adults

  • Smaller doses as they secrete less acid

  • May have some renal compromise

  • Older adults often take large doses of NSAIDs

  • H2 receptor antagonists sometimes cause more side effects

  • Sucralfate is well tolerated

  • PPIs are drugs of choice in this population


Helicobacter pylori

Helicobacterpylori

  • Requires combination of two antimicrobials and a PPI or an H2RA

  • Use amoxicillin, clarithromycin, metronidazole or tetracycline for antibiotic portion

  • More than antimicrobial is indicated to prevent resistance

  • Bismuth compound is added for its antibacterial effects as well as increasing the HCO3- and mucous contents of the stomach

  • Adding an H2RA or PPI decreases S/S and hastens healing


Histamine 2 receptor antagonists

Histamine 2 Receptor Antagonists

  • Histamine release causes contraction of smooth muscle in bronchi, GI tract, increases permeability of capillaries,stimulation of sensory nerve endings and strong stimulation of gastric acid secretion

  • Vagal stimulation causes release of histamine from cells in stomach, acts on receptors in parietal cells>>>>increases HCL production.

  • Called H2 receptors


Histamine 2 receptor antagonists1

Histamine 2 Receptor Antagonists

  • Traditional antihistamines or H1 receptor antagonists generally reduce the effects of histamine in the body but do not block histamine effects on gastric acid production.

  • Replaced as first choice drugs by the PPIs

  • Prototype is cimetidine

  • Generally are pregnancy category B

  • May have multiple drug interactions and SE

  • Available OTC and by Rx


Nursing 3703 pharmacology digestive system drugs

H2RA

  • Reduce dosage in pregnancy

  • Cimetidine affects the cytochrome p450 drug metabolizing system in the liver; may cause confusion and antiadrogenic effects (gynecomastia)

  • Ranitidine more powerful

  • Use for up to 8 weeks

  • May be used long term but with variable dosing

  • Antacids may be given concurrently to relieve pain


Proton pump inhibitors

Proton Pump inhibitors

  • Strong inhibitors of gastric acid secretion

  • Bind irreversibly to the gastric proton pump to prevent the release of gastric acid from parietal cells

  • Suppresses acid secretion in response to all primary stimuli including histamine, gastric, and acetylcholine

  • Are the drugs of first choice in erosive esophagitis, erosive gastritis and Zollinger-Ellison


Nursing 3703 pharmacology digestive system drugs

PPIs

  • More effective than H2RA

  • Faster symptom relief and faster healing

  • Used in prevention of esophagitis

  • Tx H. pylori associated ulcers

  • Side effects are nausea, diarrhea and HA

  • Long term effects??? Implications??


Prostaglandin

Prostaglandin

  • Naturally occurring prostaglandin E is produced by mucosal cells of the stomach and duodenum. It inhibits gastric acid secretion and increases mucous and bicarbonate, mucosal blood flow and mucosal repair. With inhibition of Prostaglandin E, erosion and ulceration of the gastric mucosa may occur.

  • Implications


Cytotec misoprostol

Cytotec (misoprostol)

  • Synthetic form of prostaglandin E

  • Indicated for clients at high risk for GI ulceration and bleeding and in those who take NSAIDs

  • Contraindicated in women of childbearing age and during pregnancy (see text p. 862)

  • May induce abortion

  • Side effects include diarrhea and abdominal cramping


Sucralfate

Sucralfate

  • Preparation of sulfated sucrose and aluminum hydroxide that binds to normal and ulcerated mucosa

  • Mechanism of action is unclear

  • Thought to possible bind to the ulcer and form a protective barrier between the mucosa and gastric acid, pepsin and bile salts; and stimulating prostaglandin synthesis

  • Effective in healing duodenal ulcers and in prevention of recurrence


Sucralfate1

Sucralfate

  • Side effects include constipation and dry mouth

  • Must be given Bid

  • Cannot be given with an antacid, H2RA or PPI

  • May bind other drugs and prevent their absorption

  • Give 2 hours before or after other drugs


Effects of acid suppressant drugs on nutrients

Effects of Acid Suppressant Drugs on Nutrients

  • Dietary folate, iron and Vitamin B12 are better absorbed from an acidic environment

  • Less acidic environment can cause deficiencies of these nutrients

  • Sucralfate interferes with the absorption of the fat soluble vitamins

  • Magnesium containing antacids interfere with absorption of Vitamin A


Nursing actions

Nursing Actions

  • Review administration on p. 865-867


Antiemetics

Antiemetics

  • Used to prevent or treat nausea and vomiting

  • Vomiting is the expulsion of stomach contents through the mouth

  • Vomiting can occur w/o nausea


Origin of vomiting

Origin of vomiting

  • Vomiting center is located in medulla oblongata

  • Stimuli are relayed to the vomiting center from the periphery (gastric mucosa, peritoneum, intestines, joints(?)) and centrally (from the cerebral cortex; vestibular apparatus and from neurons in the fourth ventricle==chemoreceptor trigger zone) sites


Nursing 3703 pharmacology digestive system drugs

  • The vomiting center, chemoreceptor trigger zone and GI tract contain benzodiazepine, cholinergic, dopamine, histamine, opiate and serotonin receptors that are stimulated by emetogenic drugs and toxins

  • For example: chemotherapy may stimulate the CTZ which then signals the vomiting center

  • Motion sickness—changes in body motion>>stimulate receptors in inner ear>>transmitted to the CTZ and the vomiting center


Triggering the vomiting center

Triggering the vomiting center

  • Efferent impulses cause glottic closure

  • Contraction of abdominal muscles and diaphragm

  • Relaxation of the GE sphincter

  • Reverse peristalsis

  • Projection or expulsion


Causes of nausea and vomiting

Causes of nausea and vomiting

  • Pain

  • Emotional disturbances

  • Radiation therapy

  • Motion sickness

  • Drug therapy: especially with alcohol, ASA, digoxin, anticancer drugs, antimicrobials, estrogen preparations and Opioids


Causes of nausea and vomiting1

Causes of Nausea and Vomiting

  • GI disorders such as inflammation of the GI tract, liver, gallbladder, pancreas, impaired GI motility and muscle tone (gastroparesis) and ingestion of food that is irritating to the mucosa

  • Cardiovascular, infectious, neurologic or metabolic disorders


Antiemetic drugs

Antiemetic Drugs

  • Most have anticholinergic, antidopaminergic, antihistaminic or antiserotonergic effects

  • Generally are more effective in prophylaxis than treatment

  • Most act on the vomiting center, the chemoreceptor trigger zone, the cerebral cortex, vestibular apparatus or any of the above


Antiemetic drugs1

Antiemetic Drugs

Phenothiazines—CNS depressants used in psychoses

  • Block dopamine from receptor sites in the brain

  • Act on CTZ and the vomiting center

  • Not all phenothiazines are anti-emetics

  • Cause drowsiness

  • Prochlorperazine (Compazine) and promethazine (Phenergan) are examples

  • Some are pregnancy category B, others C, should check 1st


Side effects continued

Side effects continued

  • Extrapyramidal symptoms which include:

    Dyskinesias (rhythmic movements), dystonias (rhythmic jerks) and akathesia (inability to sit still) related to dopamine receptor blockade


Antihistamines

Antihistamines

  • Prevent histamine from exerting its widespread effects on the body

  • Classic antihistamines or H1 receptor blocking agents are thought to block the action of acetylcholine in the brain (anticholinergic)

  • Indicated in Motion sickness

  • Examples are Dramamine, hydroxyzine (Vistaril), meclizine (Antivert)


Corticosteroids

Corticosteroids

  • May affect prostaglandin activity in the cerebral cortex

  • Dexamethasone and methyprednisolone are commonly used in the management of chemotherapy induced emesis, usually in combination with other anti-emetics


Benzodiazepine antianxiety drugs

Benzodiazepine antianxiety drugs

  • Not classic anti-emetics but often used in multidrug regimens to prevent nausea and vomiting associated with cancer chemotherapy

  • Inhibit cerebral cortex input to the vomiting center

  • May give to those with anticipatory nausea before chemotherapy

  • Example is Ativan (lorazepam)


5 hydroxytryptamine 5 ht3 or serotonin receptor antagonists

5 Hydroxytryptamine (5-HT3 or Serotonin)Receptor Antagonists

  • Ondansetron, granisetron and dolasetron are used to prevent or treat moderate to severe nausea and vomiting r/t cancer chemotherapy, radiation therapy and postoperatively

  • Some anticancer drugs seem to affect a subset of 5-HT3 recptors in the CTZ and the GI tract

  • These drugs antagonize receptors both peripherally (GI) and in the CTZ to prevent activation


5 ht3 receptor antagonists cont

5-HT3 receptor antagonists cont.

  • Can be given IV or orally

  • Side effects are mild to moderate and include: diarrhea, headache, dizziness, constipation, muscle aches and transient liver enzymes elevation

  • Ondansetron (Zofran) is the prototype

  • Metabolized by the liver


Miscellaneous antiemetics

Miscellaneous Antiemetics

  • Dronabinol (Marinol) is a cannabinoid used in the management of nausea and vomiting associated with anticancer drugs and unrelieved by other drugs.

  • Schedule III under federal narcotic laws

  • Withdrawal S/S may occur

  • Sleep disturbances


Reglan

Reglan

  • Prokinetic that increases GI motility and the rate of gastric emptying by increasing the release of acetylcholine from nerve edings in the GI tract

  • Can cause decreased n/v associated with gastroparesis

  • Has central antiemetic effects, antagonizes the action of dopamine

  • Can be given IV, PO or IM


Reglan continued

Reglan continued

  • Side effects include sedation, restlessness, and extrapyramidal reactions

  • May increase the effects of alcohol and cyclosporine and decrease the effects of cimetidine and digoxin (decrease time for passage)


Emetrol

Emetrol

  • Phosphorated carbohydrate solution

  • Hyperosmolar solution with phosphoric acid

  • OTC

  • Felt to work by reducing smooth muscle contraction in the GI tract


Scopolamine

Scopolamine

  • Anticholinergic drug

  • Transdermal patch

  • Excellent for motion sickness


Contraindications

Contraindications

  • When can delay or prevent diagnosis

  • When s/s of toxicity may be masked

  • Reglan is relatively contraindicated in Parkinson’s disease because it further dples dopamine


Management considerations

Management Considerations

  • 5-HT3 antagonists 1st choice in chemotherapy induced or postoperative N/V

  • Drugs with anticholinergic and antihistaminic properties are preferred for motion sickness

  • If ambulatory, opt for drug that causes less sedation

  • Phenergan is used for its antihistaminic, antiemetic and sedative effects


Management considerations cont

Management Considerations cont.

  • Phenothiazines can have serious side effects

  • Reglan may be preferred for non-obstructive gastric retention


Herbals

Herbals

  • Efficacy still debatable


Chemotherapy induced nausea and vomiting

Chemotherapy-induced Nausea and Vomiting

  • Chemo may be given during sleeping hours

  • Decrease food intake few hours before Tx

  • Antiemetics should be given before the emetogenic Tx and may be given for 2-3 days

  • 5-HT2 receptor antagonists are drugs of choice for this indication

  • Reglan is valid option but may need to give diphenhydramine to prevent the EPS

  • Sometimes combo of steroid and 5-HT3 RA useful


Laxatives and cathartics

Laxatives and Cathartics

  • When stomach and duodenum are distended with food, gastrocolic and duodenocolic reflexes are initiated

  • The cerebral cortex controls the defecation reflex so that defecation can occur at acceptable times and places

  • In people who inhibit the defecation reflex or fail to respond to the urge to defecate, constipation develops


Nursing 3703 pharmacology digestive system drugs

  • Laxatives are chemical substances that act to facilitate passage of bowel contents

  • Cathartics—a purgative action of the bowels, action is stronger and generally produces elimination of liquid stools


Indications for use

Indications for Use

  • Reduce cholesterol

  • Obtain stool sample

  • Accelerate excretion of parasites after anthelminthics started

  • Accelerate elimination of potentially toxic substances (Kayexalate)

  • Pre-op

  • Prevent straining at stool w/CAD, hemorrhoids

  • Relieve constipation in pregnancy, in the elderly; in children with megacolon, and in those w/decreased motility


Nursing 3703 pharmacology digestive system drugs

  • Laxatives and cathatics should not be used in the presence of undiagnosed abdominal pain

  • Could cause an inflamed organ to rupture

  • Oral agents are contraindicated in intestinal obstruction and fecal impaction


Laxatives

Laxatives

  • Bulk-forming laxatives—Citrucel, Metamucil

  • Surfactant Laxatives—mainly prevent straining. They allow water to penetrate stool and act as detergent to facilitate admixing of fat and water in the stool. Colace (docusate) or Surfak.

  • Saline—magnesium citrate. Nulytely.Increase osmotic pressure in intestinal lumen.Not safe for frequent use. Affect fluids and lytes.


Cathartics

Cathartics

  • Stimulant type are the strongest and most abused

  • Cascara,bisacodyl, castor oil and senna products

  • Mineral oil is a lubricant laxative. It slows colonic absorption of water.


Other

Other

  • Lactulose—a disaccharide that is not absorbed from the GI tract. Pulls water into intestinal lumen. Used to treat constipation and hepatic encephalopathy. Lactulose reduces production of ammonia in the intestine. Can affect lyte and water balance.

  • Sorbitol—monosaccharide that puls water into the intestinal lumen and has laxative effects. It is given with Kayexalate (potassium removing resin to treat hyperkalemia).


Laxative abuse

Laxative Abuse

  • Public health problem in elderly

  • Use in patients with cancer

  • What is normal?

  • What are some measures to prevent constipation?


Safety in use

Safety in Use

  • Saline cathartics must be used cautiously in the renally impaired

  • Lactulose may be indicated in those with hepatic encephalopathy

  • Seen frequently in form of enemas in hyperkalemia in hospital


Antidiarrheals

Antidiarrheals

  • Diarrhea is a symptom of numerous conditions that increase bowel motility; cause secretion or retention of fluids in the intestinal lumen and cause inflammation or irritation of the GI tract. End result: bowel contents are rapidly propelled and absorption of fluids and electrolytes is limite.d


Causes of diarrhea

Causes of Diarrhea

  • Abuse of laxatives

  • Intestinal infections—E. Coli 0157:H7 (can result in a hemolytic uremic syndrome), Traveller’s diarrhea (E. coli), Campylobacter jejuni, Salmonella, Shigella, rotatvirus

  • Inflammatory bowel diseases

  • Drug therapy—pseudomembranous colitis—Clostridium difficile (anaerobic, spore forming rods)


Antidiarrheals1

Antidiarrheals

Opiate related drugs

  • Paregoric

  • Defenoxin with atropine—Motofen

  • Diphenoxylate with atropine--Lomotil


Antibacterials

Antibacterials

  • Azithromycin for Traveller’s diarrhea

  • Cipro—E.coli, Camylobacter, Shigella

  • EES—amebiasis

  • Flagyl—Clostridium difficile

  • Bactrim-Traveller’s diarrhea

  • Vancomycin—Clostridium difficile, even in form of enemas


Miscellaneous

Miscellaneous

  • Questran—Crohns’. Binds and inactivates bile salts in the intestine.

  • Octreotide—diarrhea associated with HIV, carcinoid tumors, cancer therapies or intractable diarrhea caused by other drugs.

  • Pancreatin—pancreatic enzymes used for replacement in patients w/deficiency of pancreatic enzymes


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