Gastrointestinal DrugsByKaren Ruffin RN, MSN Ed.

Acid-Controlling Agents

Acid-Related PathophysiologyThe stomach secretes:Hydrochloric acid (HCl)BicarbonatePepsinogenIntrinsic factorMucusProstaglandins

Glands of the StomachCardiacPyloricGastric* *The cells of the gastric gland are the largest in number and of primary importance when discussing acid control

Cells of the Gastric GlandParietal cellsProduce and secrete HClPrimary site of action for many acid-controller drugs

Hydrochloric AcidSecreted by the parietal cells when stimulated by foodMaintains stomach at pH of 1 to 4Secretion also stimulated by:Large fatty mealsExcessive amounts of alcoholEmotional stress

Cells of the Gastric Gland (cont'd)Chief cellsSecrete pepsinogen, a proenzymePepsinogen becomes pepsin when activated by exposure to acidPepsin breaks down proteins (proteolytic)

Cells of the Gastric Gland (cont'd)Mucoid cellsMucus-secreting cells (surface epithelial cells)Provide a protective mucous coat Protect against self-digestion by HCl

Acid-Related DiseasesCaused by imbalance of the three cells of the gastric gland and their secretionsMost common: hyperacidityClients report symptoms of overproduction of HCl by the parietal cells as indigestion, sour stomach, heartburn, acid stomach

Acid-Related Diseases (cont'd)PUD: peptic ulcer diseaseGERD: gastroesophageal reflux diseaseHelicobacter pylori (H. pylori)Bacterium found in GI tract of 90% of patients with duodenal ulcers, and 70% of those with gastric ulcersCombination therapy is used most often to eradicate H. pylori

Treatment for H. pyloriEight regimens approved by the FDAH. pylori is not associated with acute perforating ulcersIt is suggested that factors other than the presence of H. pylori lead to ulceration

Types of Acid-Controlling AgentsAntacidsH2 antagonistsProton pump inhibitors

Antacids: Mechanism of ActionPromote gastric mucosal defense mechanismsSecretion of:Mucus: protective barrier against HClBicarbonate: helps buffer acidic properties of HClProstaglandins: prevent activation of proton pump which results in HCl production

Antacids: Mechanism of Action (cont'd)Antacids DO NOT prevent the over-production of acidAntacids DO neutralize the acid once its in the stomach

Antacids: Drug EffectsReduction of pain associated with acid-related disordersRaising gastric pH from 1.3 to 1.6 neutralizes 50% of the gastric acidRaising gastric pH 1 point (1.3 to 2.3) neutralizes 90% of the gastric acidReducing acidity reduces pain

Antacids (cont'd)Used alone or in combination

Antacids: Aluminum SaltsForms: carbonate, hydroxideHave constipating effectsOften used with magnesium to counteract constipationExamplesAluminum carbonate: BasaljelHydroxide salt: AlternaGELCombination products (aluminum and magnesium): Gaviscon, Maalox, Mylanta, Di-Gel

Antacids: Magnesium SaltsForms: carbonate, hydroxide, oxide, trisilicateCommonly cause diarrhea; usually used with other agents to counteract this effectDangerous when used with renal failure the failing kidney cannot excrete extra magnesium, resulting in hypermagnesemia

Antacids: Magnesium Salts (cont'd)Examples Hydroxide salt: magnesium hydroxide (MOM)Carbonate salt: Gaviscon (also a combination product)Combination products such as Maalox, Mylanta (aluminum and magnesium)

Antacids: Calcium SaltsForms: many, but carbonate is most commonMay cause constipationTheir use may result in kidney stonesLong duration of acid action may cause increased gastric acid secretion (hyperacidity rebound)Often advertised as an extra source of dietary calciumExample: Tums (calcium carbonate)

Antacids: Sodium BicarbonateHighly solubleBuffers the acidic properties of HClQuick onset, but short durationMay cause metabolic alkalosisSodium content may cause problems in patients with HF, hypertension, or renal insufficiency (fluid retention)

Antacids and AntiflatulentsAntiflatulents: used to relieve the painful symptoms associated with gasSeveral agents are used to bind or alter intestinal gas and are often added to antacid combination products

Antacids and Antiflatulents (cont'd)OTC antiflatulentsActivated charcoalSimethiconeAlters elasticity of mucus-coated bubbles, causing them to breakUsed often, but there are limited data to support effectiveness

Antacids: Side EffectsMinimal, and depend on the compound usedAluminum and calciumConstipationMagnesiumDiarrheaCalcium carbonateProduces gas and belching; often combined with simethicone

Antacids: Drug InteractionsAdsorption of other drugs to antacidsReduces the ability of the other drug to be absorbed into the bodyChelationChemical binding, or inactivation, of another drugProduces insoluble complexesResult: reduced drug absorption

Antacids: Nursing ImplicationsAssess for allergies and preexisting conditions that may restrict the use of antacids, such as:Fluid imbalances Renal disease HFPregnancy GI obstructionPatients with HF or hypertension should use low-sodium antacids such as Riopan, Maalox, or Mylanta II

Antacids: Nursing ImplicationsUse with caution with other medications due to the many drug interactionsMost medications should be given 1 to 2 hours after giving an antacidAntacids may cause premature dissolving of enteric-coated medications, resulting in stomach upset

Antacids: Nursing ImplicationsBe sure that chewable tablets are chewed thoroughly, and liquid forms are shaken well before givingAdminister with at least 8 ounces of water to enhance absorption (except for the rapid dissolve forms)Caffeine, alcohol, harsh spices, and black pepper may aggravate the underlying GI condition

Antacids: Nursing ImplicationsMonitor for side effectsNausea, vomiting, abdominal pain, diarrheaWith calcium-containing products: constipation, acid reboundMonitor for therapeutic responseNotify heath care provider if symptoms are not relieved

Histamine Type 2 (H2) Antagonists

H2 AntagonistsReduce acid secretionAll available OTC in lower dosage formsMost popular drugs for treatment of acid-related disorderscimetidine (Tagamet)famotidine (Pepcid)ranitidine (Zantac)

H2 Antagonists: Mechanism of ActionBlock histamine (H2) at the receptors of acid-producing parietal cellsProduction of hydrogen ions is reduced, resulting in decreased production of HCl

H2 Antagonists: IndicationsGERDPUDErosive esophagitisAdjunct therapy in control of upper GI bleedingPathologic gastric hypersecretory conditions (Zollinger-Ellison syndrome)

H2 Antagonists: Side EffectsOverall, less than 3% incidence of side effectsCimetidine may induce impotence and gynecomastiaMay see:Headaches, lethargy, confusion, diarrhea, urticaria, sweating, flushing, other effects

H2 Antagonists: Drug InteractionsCimetidine (Tagamet)Binds with P-450 microsomal oxidase system in the liver, resulting in inhibited oxidation of many drugs and increased drug levelsAll H2 antagonists may inhibit the absorption of drugs that require an acidic GI environment for absorption

H2 Antagonists: Drug Interactions (cont'd)

SMOKING has been shown to decrease the effectiveness of H2 blockers (increases gastric acid production)

H2 Antagonists: Nursing ImplicationsAssess for allergies and impaired renal or liver functionUse with caution in patients who are confused, disoriented, or elderly (higher incidence of CNS side effects)Take 1 hour before or after antacidsFor intravenous doses, follow administration guidelines

Proton Pump Inhibitors

Proton PumpThe parietal cells release positive hydrogen ions (protons) during HCl productionThis process is called the proton pumpH2 blockers and antihistamines do not stop the action of this pump

Proton Pump Inhibitors: Mechanism of ActionIrreversibly bind to H+/K+ ATPase enzymeResult: achlorhydriaALL gastric acid secretion is blocked

Proton Pump Inhibitors: Drug EffectTotal inhibition of gastric acid secretionlansoprazole (Prevacid)omeprazole (Prilosec)*rabeprazole (AcipHex)pantoprazole (Protonix)esomeprazole (Nexium)

*The first in this new class of drugs

Proton Pump Inhibitors: IndicationsGERD maintenance therapyErosive esophagitisShort-term treatment of active duodenal and benign gastric ulcersZollinger-Ellison syndromeTreatment of H. pyloriinduced ulcers

Proton Pump Inhibitors: Side EffectsSafe for short-term therapyIncidence low and uncommon

Proton Pump Inhibitors: Nursing ImplicationsAssess for allergies and history of liver diseasepantoprazole (Protonix) is the only proton pump inhibitor available for parenteral administration, and can be used for patients who are unable to take oral medicationsMay increase serum levels of diazepam, phenytoin, and cause increased chance for bleeding with warfarin

Proton Pump Inhibitors: Nursing ImplicationsInstruct the patient taking omeprazole (Prilosec):It should be taken before mealsThe capsule should be swallowed whole, not crushed, opened, or chewedIt may be given with antacidsEmphasize that the treatment will be short term

Other Drugssucralfate (Carafate)misoprostol (Cytotec)

sucralfate (Carafate)Cytoprotective agentUsed for stress ulcers, erosions, PUDAttracted to and binds to the base of ulcers and erosions, forming a protective barrier over these areasProtects these areas from pepsin, which normally breaks down proteins (making ulcers worse)

sucralfate (Carafate) (cont'd)Little absorption from the gutMay cause constipation, nausea, and dry mouthMay impair absorption of other drugs, especially tetracyclineBinds with phosphate; may be used in chronic renal failure to reduce phosphate levelsDo not administer with other medications

misoprostol (Cytotec)Synthetic prostaglandin analogProstaglandins have cytoprotective activityProtect gastric mucosa from injury by enhancing local production of mucus or bicarbonatePromote local cell regenerationHelp to maintain mucosal blood flow

misoprostol (Cytotec) (cont'd)Used for prevention of NSAID-induced gastric ulcersDoses that are therapeutic enough to treat duodenal ulcers often produce abdominal cramps, diarrhea

Antidiarrheals and Laxatives

DiarrheaAbnormal frequent passage of loose stool orAbnormal passage of stools with increased frequency, fluidity, and weight, or with increased stool water excretion

Diarrhea (cont'd)Acute diarrheaSudden onset in a previously healthy personLasts from 3 days to 2 weeksSelf-limitingResolves without sequelae

Diarrhea (cont'd)Chronic diarrheaLasts for more than 3 weeksAssociated with recurring passage of diarrheal stools, fever, loss of appetite, nausea, vomiting, weight loss, and chronic weakness

Causes of DiarrheaAcute DiarrheaBacterialViralDrug inducedNutritional ProtozoalChronic DiarrheaTumorsDiabetesAddisons diseaseHyperthyroidismIrritable bowel syndrome

Antidiarrheals: Mechanism of ActionAdsorbentsCoat the walls of the GI tractBind to the causative bacteria or toxin, which is then eliminated through the stoolExamples: bismuth subsalicylate (Pepto-Bismol), kaolin-pectin, activated charcoal, attapulgite (Kaopectate)

Antidiarrheals: Mechanism of Action (cont'd)AnticholinergicsDecrease intestinal muscle tone and peristalsis of GI tractResult: slowing the movement of fecal matter through the GI tractExamples: belladonna alkaloids (Donnatal), atropine

Antidiarrheals: Mechanism of Action (cont'd)Intestinal flora modifiersBacterial cultures of Lactobacillus organisms work by:Supplying missing bacteria to the GI tractSuppressing the growth of diarrhea-causing bacteriaExample: L. acidophilus (Lactinex)

Antidiarrheals: Mechanism of Action (cont'd)OpiatesDecrease bowel motility and relieve rectal spasmsDecrease transit time through the bowel, allowing more time for water and electrolytes to be absorbedExamples: paregoric, opium tincture, codeine, loperamide (Imodium), diphenoxylate (Lomotil)

Antidiarrheal Agents: Side EffectsAdsorbentsIncreased bleeding timeConstipation, dark stoolsConfusion, twitchingHearing loss, tinnitus, metallic taste, blue gums

Antidiarrheal Agents: Side Effects (cont'd)AnticholinergicsUrinary retention, hesitancy, impotenceHeadache, dizziness, confusion, anxiety, drowsinessDry skin, rash, flushingBlurred vision, photophobia, increased intraocular pressureHypotension, hypertension, bradycardia, tachycardia

Antidiarrheal Agents: Side Effects (cont'd)OpiatesDrowsiness, sedation, dizziness, lethargyNausea, vomiting, anorexia, constipationRespiratory depressionBradycardia, palpitations, hypotensionUrinary retentionFlushing, rash, urticaria

Antidiarrheal Agents: InteractionsAdsorbents decrease the absorption of many agents, including digoxin, clindamycin, quinidine, and hypoglycemic agentsAdsorbents cause increased bleeding time when given with anticoagulantsAntacids can decrease effects of anticholinergic antidiarrheal agents

Antidiarrheal Agents: Nursing ImplicationsObtain thorough history of bowel patterns, general state of health, and recent history of illness or dietary changes, and assess for allergiesDO NOT give bismuth subsalicylate to children younger than age 16 or teenagers with chickenpox because of the risk of Reyes syndrome

Antidiarrheal Agents: Nursing ImplicationsUse adsorbents carefully in geriatric patients or those with decreased bleeding time, clotting disorders, recent bowel surgery, confusionAnticholinergics should not be administered to patients with a history of glaucoma, BPH, urinary retention, recent bladder surgery, cardiac problems, myasthenia gravis

Antidiarrheal Agents: Nursing ImplicationsTeach patients to take medications exactly as prescribed and to be aware of their fluid intake and dietary changesAssess fluid volume status, I&O, and mucous membranes before, during, and after initiation of treatment

Antidiarrheal Agents: Nursing ImplicationsTeach patients to notify their physician immediately if symptoms persistMonitor for therapeutic effect

Laxatives

ConstipationAbnormally infrequent and difficult passage of feces through the lower GI tractSymptom, not a diseaseDisorder of movement through the colon and/or rectumCan be caused by a variety of diseases or drugs

Laxatives: Mechanism of ActionBulk formingHigh fiberAbsorbs water to increase bulkDistends bowel to initiate reflex bowel activityExamples: psyllium (Metamucil)methylcellulose (Citrucel)Polycarbophil (FiberCon)

Laxatives: Mechanism of Action (cont'd)EmollientStool softeners and lubricantsPromote more water and fat in the stoolsLubricate the fecal material and intestinal wallsExamples:Stool softeners: docusate salts (Colace, Surfak)Lubricants: mineral oil

Laxatives: Mechanism of Action (cont'd)HyperosmoticIncrease fecal water contentResult: bowel distention, increased peristalsis, and evacuationExamples:polyethylene glycol (GoLYTELY)sorbitol (increases fluid movement into intestine)glycerinlactulose (Chronulac)

Laxatives: Mechanism of Action (cont'd)SalineIncrease osmotic pressure within the intestinal tract, causing more water to enter the intestinesResult: bowel distention, increased peristalsis, and evacuation

Laxatives: Mechanism of Action (cont'd)Saline laxative examples:magnesium sulfate (Epsom salts)magnesium hydroxide (MOM)magnesium citrate sodium phosphate (Fleet Phospho-Soda, Fleet enema)

Laxatives: Mechanism of Action (cont'd)StimulantIncreases peristalsis via intestinal nerve stimulationExamples:castor oil (Granulex)senna (Senokot)cascara

Laxatives: IndicationsLaxative GroupBulk forming

EmollientUseAcute and chronic constipationIrritable bowel syndromeDiverticulosisAcute and chronic constipationSoftening of fecal impaction; facilitation of BMs in anorectal conditions

Laxatives: Indications (cont'd)Laxative GroupHyperosmotic

SalineUseChronic constipationDiagnostic and surgical prepsConstipationDiagnostic and surgical prepsRemoval of helminths and parasites

Laxatives: Indications (cont'd)Laxative GroupStimulantUseAcute constipationDiagnostic and surgical bowel preps

Laxatives: Side EffectsBulk formingImpactionFluid overloadEmollientSkin rashesDecreased absorption of vitaminsHyperosmoticAbdominal bloatingRectal irritation

Laxatives: Side Effects (cont'd) SalineMagnesium toxicity (with renal insufficiency)CrampingDiarrheaIncreased thirst StimulantNutrient malabsorptionSkin rashesGastric irritationRectal irritation

Laxatives: Side Effects (cont'd)All laxatives can cause electrolyte imbalances!

Laxatives: Nursing ImplicationsObtain a thorough history of presenting symptoms, elimination patterns, and allergiesAssess fluid and electrolytes before initiating therapyPatients should not take a laxative or cathartic if they are experiencing nausea, vomiting, and/or abdominal pain

Laxatives: Nursing ImplicationsA healthy, high-fiber diet and increased fluid intake should be encouraged as an alternative to laxative useLong-term use of laxatives often results in decreased bowel tone and may lead to dependencyAll laxative tablets should be swallowed whole, not crushed or chewed, especially if enteric coated

Laxatives: Nursing ImplicationsPatients should take all laxative tablets with 6 to 8 ounces of waterPatients should take bulk-forming laxatives as directed by the manufacturer with at least 240 mL (8 ounces) of water

Laxatives: Nursing ImplicationsBisacodyl and cascara sagrada should be given with water due to interactions with milk, antacids, and H2 blockersPatients should contact their provider if they experience severe abdominal pain, muscle weakness, cramps, and/ or dizziness, which may indicate fluid or electrolyte loss

Laxatives: Nursing ImplicationsMonitor for therapeutic effect

Antiemetic and Antinausea Agents

DefinitionsNauseaUnpleasant feeling that often precedes vomitingEmesis (vomiting)Forcible emptying of gastric, and occasionally, intestinal contentsAntiemetic agentsUsed to relieve nausea and vomiting

VC and CTZVomiting center (VC)Chemoreceptor trigger zone (CTZ)Both located in the brainOnce stimulated, cause the vomiting reflex

Mechanism of ActionMany different mechanisms of actionMost work by blocking one of the vomiting pathways, thus blocking the stimulus that induces vomiting

IndicationsSpecific indications vary per class of antiemeticsGeneral use: prevention and reduction of nausea and vomiting

Mechanism of Action and IndicationsAnticholinergic agents (ACh blockers)Bind to and block acetylcholine (ACh) receptors in the inner ear labyrinthBlock transmission of nauseating stimuli to CTZ Also block transmission of nauseating stimuli from the reticular formation to the VCScopolamine Also used for motion sickness

Mechanism of ActionAntihistamine agents (H1 receptor blockers)Inhibit ACh by binding to H1 receptorsPrevent cholinergic stimulation in vestibular and reticular areas, thus preventing N&VDiphenhydramine (Benadryl), meclizine (Antivert), promethazine (Phenergan)Also used for nonproductive cough, allergy symptoms, sedation

Mechanism of Action (cont'd)Neuroleptic agentsBlock dopamine receptors on the CTZchlorpromazine (Thorazine), prochlorperazine (Compazine)Also used for psychotic disorders, intractable hiccups

Mechanism of Action (cont'd)Prokinetic agentsBlock dopamine in the CTZCause CTZ to be desensitized to impulses it receives from the GI tractAlso stimulate peristalsis in GI tract, enhancing emptying of stomach contentsMetoclopramide (Reglan)Also used for GERD, delayed gastric emptying

Mechanism of Action (cont'd)Serotonin blockersBlock serotonin receptors in the GI tract, CTZ, and VCDolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran)Used for N&V for patients receiving chemotherapy and postoperative nausea and vomiting

Mechanism of Action (cont'd)Tetrahydrocannabinoids (THC)Major psychoactive substance in marijuanaInhibitory effects on reticular formation, thalamus, cerebral cortexAlter mood and bodys perception of its surroundings

Mechanism of Action (cont'd)Tetrahydrocannabinoids (cont'd)dronabinol (Marinol)Used for N&V associated with chemotherapy, and anorexia associated with weight loss in AIDS patients

Side EffectsVary according to agent usedStem from their nonselective blockade of various receptors

Nursing ImplicationsAssess complete nausea and vomiting history, including precipitating factorsAssess current medicationsAssess for contraindications and potential drug interactions

Nursing ImplicationsMany of these agents cause severe drowsiness; warn patients about driving or performing any hazardous tasksTaking antiemetics with alcohol may cause severe CNS depressionTeach patients to change position slowly to avoid hypotensive effects

Nursing ImplicationsFor chemotherapy, antiemetics are often given to 3 hours before a chemotherapy agentMonitor for therapeutic effectsMonitor for adverse effects

***HCl an acid that aids digestion and also serves as a barrier to infection

Bicarbonate a base that is a natural mechanism to prevent hyperacidity

Pepsinogen an enzymatic precursor to pepsin, an enzyme that digests dietary proteins

Intrinsic factor a glycoprotein that facilitates gastric absorption of vitamin B12

Mucus protects the stomach lining from both HCl and digestive enzymes

Prostaglandins serve a variety of antiinflammatory and protective functions*The stomach is divided into three functional areas, each with specific glands.

The cardiac zone(cells), the uppermost area of the stomach by the cardiac sphincter, contains the cardiac glands.

The pyloric zone is the lowermost part of the stomach and contains the pyloric glands.

The greater part of the body of the stomach, the fundus, contains the gastric glands.

The gastric glands play the most significant role in acid-related disorders.**Caffeine and chocolate*****There are three basic categories of acid-controlling agents.

Antacids first developed by the ancient Greeks who used crushed coral (calcium carbonate) to treat dyspepsia.

H2 Antagonists - It wasnt until the 1970s that a new class of acid-controllling agent (H2 blockers) was developed.

**They have a quick onset of relief but last for a short duration.**********Excess use of any calcium ant acid can cause kidney stones

Rebound of hyperacidity with overuse of these medications

Long-term self medication of these medications can mask more serious problems such as bleeding ulcers or malignancies, pt with ongoing symptoms should see a physician b/c other meds ma need to be used to control the hyperacidity or r/o more serious conditions.*Increased stomach pH- increase adsorption of the basic drug and decreased absorption of the acidic drugs.

Decreased stomach pH-increases excretion of the acidic drug and decreases excretion of the basic drug.

Most drugs are either weak acids or weak bases. Therefore, pH conditions in both the GI and urinary tracts will affect the extent to which drug molecules are ionized (changed)

*******Up to 90% inhibition of vagal and gastrin stimulated acid secretion occurs when histamine is blocked.

However complete inhibition has not been shown, the drug effect of the H2 blocker is it reduces hydrogen ion secretion from the p;arietal celss, chich results in an increase in pH of the stomach giving he patient relief from symtpoms.********The action of the hydrogen-potassium-ATPase pump is the final step in the acid-secretion process of the parietal cell. If the chemical energy is present to run the pump it will transport the hydrogen ions out of the parietal cell, which increases the acid content of eh surrounding gastric lumen and lowers the pH. B/C hydrogen ions are protons (positively charged hydrogen atoms) this ion pump is also called the proton pump. The PPI bind irreversibly to the proton pump. The binding of this enzyme prevents the movement of the hydrogen ion out of the parietal cells into the stomach and therefore blocks all acid production. PPI effectively stop over 90% of acid production in the stomach. For acid secretion to return to normal after the pt. stops the PPI the parietal cell must synthesize new hydrogen potassium ATPase.

*The are also used to prevent PUD in hospitalized patients. *b/c if the lining of your stomach broke down what would be exposed, the muscle which is protien.***Pepto-Bismol- is a salicytate and there fore if over used will cause the side effects such as tinnitus and hearing loss also dark stools and black gums if overused. Be careful with it use in children.*They have a narrow window of safe use in like the other antidiarrheals that can be less harmful if overused. That is why they are only available by prescription. Because these drugs are anticholinergics they have all the same side effects and can effect other systems such as increase HR, dysrhythmias, CNS excitation, restlessness, disorientation, dilated pupils see the box on page 308, box 20-2, these are3 all effects of the atropine.*What are the side effects of opiates and think of the danger of them if they are over usded.*Teach patient to take medications 1 hour before or 2 hours after other medications. Just to be safe dont take with any other medicaitons.**