3PUD Extremely common disorder 4 million people, 350,000 new cases/year >100,000 hospitalizations/year and 3000 deaths/yearUlcerDisruption in bowel wall extending deep to the muscular mucosaResulting from imbalance of mucosal injury, protection and repair
4Stomach and Duodenum: Normal Anatomy and Histology The major regions:Fundus, Cardia, BodyTransitional ZoneAntrum, Pylorus, SphincterDuodenum
5In the body & fundus region: Deep within the glands – are parietal cells (oxyntic cells) which secrete HCl, and – chief cells – which secrete pepsinogenMucous cellsCells in the Antrum:Mucous cells, gastrin-releasing cells (no parietal or chief cells)
6Normal Gastric Physiology Human stomach secretes ~ 2L of HCl every dayParietal (oxyntic) cells in the stomach mucosaWhen stimulated secrete acid into the gastric lumenIn resting state: secrete intrinsic factor (carrier protein for Vit B12)Three substances that stimulate parietal cells: Acetylcholine, Gastrin, Histamine
7Agonist binds to a specific parietal cell receptor Second messenger systems activate the gastric proton pump (H+/K+ -ATPase)one-to-one exchange of intracellular H+ for luminal K+ ions (terminal step in acid secretion)Basal Acid Secretion:The usual circadian rhythm –higher acid secretion in afternoon (2 to 11pm)lower rates in the morning (5 to 11 am)
8Meal Stimulated Acid secretion: 3 Phases Cephalic – Sensory input initiates acid secretion (vagus nerves stimulate nerves in gut wall →ACh is released, → stimulates acid secretion)Gastric – Activated by stimuli within the stomach (acid secretion is controlled by distension → change in acidity, & chemical constituents of food activate vagal nerves to stimulate gastrin release)Intestinal – Amino acids stimulate parietal cells to release acid→ intraluminal acid, fat, and hyperosmolar solutions inhibit acid
9Pepsin and Pepsinogen: Gastric mucosal cells secrete proenzymes: pepsinogen I &IIDuring the cephalic, gastric, & intestinal phases, the factors which stimulate or inhibit acid exert the same effects on pepsinogen secretion.Pepsin is activated by acid pH ( ), inactivated at pH 4.0, destroyed at pH 7.0High acidity is required for the activation & activity of pepsin.PGI secretion is directly proportional to the rate of acid suppression.
10Contraction of gastric smooth muscle: by: ACh (parasympathetic) & by gastrin by: NE (sympathetic) & by secretin
11Pepsinogens – secreted throughout the stomach & duodenum HCl – released in the fundus & bodyGastrin – released in the antrum
18Adaptive mechanisms:Uses flagella to hide in mucous layer away from acidProduces urease – hydrolyzes urea into CO2 & ammonia (creates an alkaline microenvironment)Produces mucinase – thins viscous mucous & allows bacteria to burrow into mucous layerProvides a passageway for hydrogen ions to enter epithelium.Not all people infected with H pylori develop ulcers.The only relatively absolute requirements are:1) Secretions of acid & pepsin, 2) H. pylori infxn3) NSAID use
19DefinitionsPeptic Ulcer Disease: A group of disorders characterized by erosion of the mucosa anywhere in the GI tract that is exposed to the erosive action of acid and pepsinErosions (more superficial) may be reepithelialized rapidly by a process called restitution.Ulcers extend into the deeper layers of the mucosa and require a more complex healing process.
20Definitions Duodenal Gastric ( in Stomach) Associated with acid output usually seen in the proximal duodenum [the 1st few cm past pyloric sphincter]Increased pepsinogen I (parietal cell mass)Gastric ( in Stomach)Usually not associated with acid outputoccur mainly in the antrum of the stomach
25Types of PUD 1-Non ulcer dyspepsia Dyspepsia: an imprecise symptom complex that includes: epigastric pain or discomfort, Nausea, belching, bloating.There is over lap between the symptoms reposted by patients diagnosed with peptic ulcer and dyspepsia
262-NSAID-Induced Ulcers Symptomatic ulcers occur in only 1% of patients after 3-6 months of NSAIDsThis type of ulcer does not correlate with pain because analgesic action may mask ulcer painMechanisms of Injury:Produce gastric damage by two mechanismsDirect irritant effectSystemic effect →inhibition of cyclooxygenase COX-1 → ↓ PG synthesis
27PG protect the GI mucosa by maintaining blood flow & stimulating bicarbonate & mucus Low PG impair the ability of the gastric mucosa to withstand aggressive factorsCOX –2 inhibitions is responsible for anti-inflammatory and analgesic effectsUlcers occur more frequently in the stomach than in the duodenum.Many are painlessacute, low-dose NSAID-induced lesions usually heal spontaneously
28Risk factorsAge > 60 yrs,High-NSAID dose OR Use of multiple NSAIDs,Hx of ulcer/complication,Co-morbid illness,Concurrent steroid use,GI sx in past 6 mos requiring discontinuation of the NSAID or the addition of another drug.Patients taking anticoagulantsHigh surgical risk or Debilitated patients
293-Adrenocorticosteroids Association of steroids and PUD is controversial.Steroids may induce ulcers:↑ gastric acid secretion, ↓ PG productionMay delay or inhibit healing of ulcers caused by NSAIDs.Patients taking steroids considered at high riskRecent studies: elderly taking both steroids and NSAIDs are at much higher risk of PUD than those receiving either agent alone (related to dose & duration of therapy)
304-Disorders of Acid Hypersecretion Increased basal & postprandial acid secretionMechanisms:Enhanced sensitivity of the parietal cell to vagal stimulation,Impaired acid inhibitory mechanismsZollinger-Ellison Syndrome: caused by a gastrin-secreting tumor of the duodenum or pancreas → marked gastric acid hypersecretion & recurrent peptic ulceration.2/3 of tumors are malignant.Found in ~ 0.1% of patients with duodenal ulcers.
33Chief complaint:Pain (25% are painless) doesn’t always correlate w/presence of acid or ulcer cratersDuodenal Ulcer Gastric UlcerMost common symptom Most common symptomSharp, burning, or gnawing Less typical & predictableOccurs 1-3 hrs after meals May occur during a mealRelieved by alkali & food Food offers little/no relief; may precipitate itUsually located in RUQ May extend over a wide area of epigastrumNocturnal; awakens patient (1-2am)
34Clinical Manifestations Symptom analysis of the chief complaint : PQRSTAPrecipitating factors – what brings on the problem?Quality – describe what the problem is like.Radiating/Relief factors – does the problem start in one place in your body, then move elsewhere? What have you done to make it better (did it work)?Severity – try to rate how bad the problem is right now on a scale from 1-10, with “10” being the absolute worst.Temporal factors – does the problem seem to occur at a particular time of the day or with a specific activity?Associated symptoms – do you have any other sensations, feelings around the same time as this problem?
36Clinical presentation of ZE Syndrome Similar to sever PUDMore persistentLess responsive to standard therapyAbdominal pain; most common SxDiarrhea: because gastrin inhibits sodium and water reabsorption from intestine
37Complications Three Major Complications Hemorrhage Perforation Gastric outlet obstructionInitially treated conservativelyMay require surgery at any time during course of therapy
38Hemorrhage Most common complication of peptic ulcer disease Develops from erosion ofGranulation tissue found at base of ulcer during healingUlcer through a major blood vessel
39Perforation Most lethal complication of peptic ulcer Commonly seen in large penetrating duodenal ulcers that have not healed and are healed and arelocated on posterior mucosal wallOccurs when ulcer penetrates serosal surfaceSize of perforation directly proportional to length of time patient has had ulcer
40Gastric Outlet Obstruction Active ulcer formation is associated with edema, inflammationDuodenum can predispose to gastric outlet obstruction↑ contractile force needed to empty stomach results in hypertrophic stomach wallObstruction is not totally due to fibrous scar tissueShort duration or absence of pain indicative of a malignant obstructionVomiting and Constipation are a common complaint
41Diagnosis Visualization of the ulcer defines the disease 1-Barium Upper GI Study (X-rays)Can show obstruction, perforation, or penetrationCannot show bleeding30-60% of ulcers can be detected
422-Endoscopy Most often used Superior test for diagnosis More costly & less patient acceptanceCan visualize the ulcerCan visualize any bleedingCan treat bleedingDetermines degree of ulcer healing after treatmentTissue specimens can be obtained to identify and to rule out gastric cancer
43Indications for Endoscopy: New onset dyspepsia in pts > 45 yrs old (to rule out gastric cancer)Patients with “alarm” symptoms:Evidence of GI bleeding, anemia, unexplained weight loss, recurrentvomiting, decreased appetite, easy fullness, dysphagia, abdominal mass,lymphadenopathyPatients whose symptoms have failed to respond to initial therapyPatients with recurrent or difficult to control disease
44Laboratory tests Guaiac test on stool sample CBC should be done if the patient’s stool is guaiac positiveAcute blood loss:Red cell indices: RBC, Hct, Hgb,Normocytic (MCV), Normochromic (MCH)Chronic blood loss:Iron deficiency: RBC, Hct, Hgb, MCV, MCH
45Tests for GUT BloodVery important tool for screening in the clinic settingHemoccult (stool)Gastroccult (stomach)Both are based on the catalytic activity of hemoglobin during the conversion of guiac into a blue pigment in the presence of peroxide
46Diagnosis of ZE syndrome Measurement of gastric acid secretion>15 mmol/hr in patients with no prior gastric surgery> 5 mmol/hr in patients with prior gastric surgeryfasting gastrin level > 1000 pg/mlsecretin provocative test:secretion will cause a marked increase in serum gastrin
47H. pylori Testing Indications for H. pylori testing: New onset dyspepsia in patients < 45 years old (with no alarm symptoms)Active peptic ulcer diseasePMH of documented peptic ulcer, which has not been tested for H. pyloriGastric lymphoma
4913C Breath Test+ +Can be used multiple times; noninvasive; Non radioactiveMay not be widely available; requires expensive equipment (cost ~ $300)14C Breath TestGood for follow-up; noninvasive; rapid (60 min), Less expensive than 13C test (cost ~ $50)Small radiation exposure; not able to repeat test multiple timesSerology+Noninvasive; least expensive; rapid; simplest Look for IgG antibodies to H. pyloriNot useful for short-term f/u of antimicrobial therapy, preferred when endoscopy not done Not useful for pts s/p H. pylori Tx
50Stool AntigensA stool antigen enzyme immunoassay has a sensitivity of about 94% and specificity of about 90%.It should not be used to test for eradication of H. pylori until 6- 8 weeks after therapy.
52Gold Standard: Gastric biopsy The Rapid UreaseTest is the most popular and recommended because of its excellent sensitivity & low cost.The labeled C breath tests utilize H pylori’s ability to hydrolyze urea into ammonia.Urea labeled with carbon isotope is administered orallyIf organism is present, urea is hydrolyzed & pt will exhale labeled Co2 which can be quantified.14C is radioactive – not recommended for children, pregnant women, or for multiple uses in the same person. 13C is non-radioactive
53The Serological TestAn excellent initial screen to determine infection because the result is known in 20 min.H. pylori infection elicits an immune response with an increase in IgG and IgA antibodies. There are commercially available tests that measure IgG antibody.All of the tests – with the exception of serological testing – may be falsely negative in pts who have taken antibiotics, bismuth compounds, or omeprazole in the recent past.
54Therapy Therapeutic Objectives Indices of Therapeutic Effect: Relieve pain; control symptomsPrevent pain recurrencePrevent further irritation while healing occursRemove or treat cause if possiblePromote healingPrevent complicationsMaintain the healed ulcer conditionIndices of Therapeutic Effect:A. Pain relief/Absence of painB. Frequency of antacid useC. Endoscopy (to confirm healing – if symptom response is inadequate
58H2-blockers MOA Efficacy Selectively and competitively Inhibit the action of histamine on H2 receptors of the parietal cells → reducing basal and stimulated secretion of gastric acidEfficacyEqually Effective for:Treatment of acute ulcers in the absence of H. pyloriTreatment of NSAID-induced ulcersMaintenance therapy in patients unable to tolerate a course of antimicrobial therapy to eradicate H. pylori
591-H2-blockers Efficacy 70-95% heal rate in 4-8 weeks Standard doses inhibit % of 24-hour acid secretionEqual in efficacy to antacid, and sucralfate therapyEffective as single therapy in pts with no H pylori infection
60Side effectsSafe, Frequency of SE is lowCommon SE:Diarrhea, constipation, Mental confusion, headache, dizziness, drowsiness, and rashesConfusion/agitation occurs more frequently in elderly, renal & hepatic dysfxnSimilar profile (reported more frequently with cimetidine)Mental status changes, diarrhea, headache (2-3%)Rare: bone marrow suppression (thrombocytopenia, agranulocytosis)
62Drug Interaction Profile Table 27-4Cimetidine inhibits oxidative metabolism CYP450Magnitude of interaction varies from patient to patientGenerally it will reduce clearance of another drug by 20-30%Clinically significant in drugs with narrow therapeutic windowAddition of cimetidine may require ↓ dosage of the object drug to avoid increased serum concentrationlidocaine, valium, propranolol, metoprolol, warfarin, phenytoin, theophylline
63Other H2-blockers have lower affinity for p450 system; fewer drug interactions: Cimetidine > ranitidine, nizatidine > famotidineCimetidine and ranitidine inhibit renal tubular secretion of procanamide and its metaboliteAll 4 drugs can affects absorption and reduce bioavailability of some drugs by requiring gastric PHCimetidine ↑ PH →slows dissolution of ketoconazole → ↓ absorptionCimetidine, ranitidine, nizatidine ↑ absorption of ethanol
64Route of Administration and Dosing See Table 27-1 and Table 1Control of night time acid secretion is more effective in healing ulcersMay be given as a single bedtime dose for treatment of DUFor ZES: Not totally effective, require large doses and more frequent dosingThe dose to heal an ulcer – DU=GUThe dose to maintain a healed ulcer –DU=GUMaintenance dose is cut in half, single daily dose
652-Sucralfate MOA Efficacy Protects ulcerated mucosa from aggressive factorsIt binds to damaged tissue forming a physical barrier to injuryEfficacy1 gm 4 times daily as effective as 2 gms twice dailyRequires acid medium to work (don’t combine with H2-blocker)As effective as H2-blockers in promoting DU healing
66Side effects Not absorbed systemically Constipation, xerostomia, skin eruptions, nausea, indigestion, dizzinessContains aluminum (Al); accumulates in pts with renal dysfxn;Neuro toxicity; seizuresDrug Interaction profileAl dissociates from sucralfate: absorption of TCN, phenytoin, warfarinChelation with other drugs given simultaneously
67Route of Administration and Dosing Frequency Dosing: 1 gram, four times daily, before meals & at bedtime (compliance)For duodenal ulcer, 2 grams bid (before breakfast & at bedtime) may be as effectiveLarge tablet size – may be difficult to swallow
683-Antacids MOA Efficacy Relive pain and promote healing by providing a cytoprotective effect through stimulation of PGNeutralizing gastric acidStimulating restitution of the gastric mucosaEfficacyLow to moderate doses may be as effective in healing duodenal ulcers as H2 blockers if taken multiple times a dayneutralize acid; inhibit pepsinogen to pepsin, bile salts
69Antacids High dose as effective as H2-blockers May provide less symptom relief than H2-blockersHigh dose: 30 cc po 1hr before & 3 hrs after each meal & at bedtime (7 doses)May accelerate healing of GU (lack of data to confirm it, but likely)Currently used for symptomatic relief in addition to H2-blockers or sucralfatePrimarily used on as PRN for painLiquid formulation are more rapid acting
70Side Effects Aluminum antacids Reacts with intestinal bicarbonate low alkalosis riskConstipation, hypophosphatemia, renal accumulationMagnesium antacids :Reacts with intestinal bicarbonate - low alkalosis risk, Diarrhea (dose-related), avoid in CRFCombination (Al/Mg) Less ADRs; lower doses usedSodium bicarb:Patients with poor renal fxn –metabolic alkalosis, Sodium overload – 12 Meq/g (edema, CHF, CRF, HTN)
71Calcium antacidsConstipation, rebound hyperacidity (may not be clinically signif.)More potent & prolonged neutralization, Systemicalkalinization, milk alkali syndrome, pH , Ca++ kidney stonesMalgaldrate:chemical entity composed of aluminum & magnesium hydroxides (not a physical mixture & lower neutralizing capacity)
72Drug Interaction Profile Chelation – divalent/trivalent cations bind drugs & absorption e.g ciprofloxacin, TCNGastric pH – interfere w/drugs requiring low pH for absorption e.g digoixn, phenytion, isoniazidUrinary pH – may affect drugs requiring acidic/basic urine for eliminationMay reduce absorption of tetracyclines, iron, digoxin, & many other drugsCan reduce absorption of H2-blockers, may effect of sucralfateAvoid taking other meds 1-2 hrs before & after taking an antacid
73Route of Administration and Dosing frequency Tablets: chewed/dissolved, palatable. Suspensions work faster; more surface area
744-Proton Pump Inhibitors: PPI MOA:Specific inhibitors of gastric acid secretion by irreversible biding to K+-H+ - ATPase ( enzyme which transports acid across parietal cells)Inhibit basal and stimulated acid secretionIndicated for short-term treatment of DUIndicated for long-term treatment of ZES
75PPI Efficacy Absolute healing rates are similar Superior to H2-blockers with regard to onset of healing & pain reliefEffective in patients refractory to H2-blockers.may be more efficacious than H2-blockers for the prevention of recurrent GU and DU in patients who must continue on NSAID therapy.
76PPIEfficacyStandard doses inhibit more than 90% of 24-hour acid secretion.For DU: Omeprazole 20 mg qd 90 –100% healing in 4 weeksLansoprazole 30 mg qd 90 – 100% healing in 4 wksFor GU: As effective as H2-blockers for healing ulcerHigher doses may provide faster relieof pain, recurrence
77For ZES: Side Effects Long-term efficacy has been observed Decreases diarrhea, heals ulcersDaily dose of 120 mg (mean daily dose 60-70mg) controls symptoms in > 90% of ptsSide EffectsMay cause headache, diarrhea, abdominal pain, nausea, dizziness.Concern over long-term use & development of carcinoid tumorsTreatment: acid will pH; which gastrin secretion – possible ECL cellhyperplasia (recommended to check serum gastrin levels annually in pts on long-term therapy)
78PPI : Drug Interaction Profile All agents are extensively metabolized by cytochrome p450Omeprazole:Inhibitor of oxidative metabolism by p450 systemMay diazepam, phenytoin, warfarin, etc.Omeprazole and Clarithromycin → concentration of both drugsLansoprazoleMetabolized through p450 system: may clearance of theophylline (10%)SucralfateReduces absorption of PPIsDrugs whose absorption may be impaired from reduced acidity: Ketoconazole, iron, ampicillin, etc.
79Route of Administration and Dosing See table 1 & 2Rabeprazole is available as a 20mg enteric-coated tablet; dosed once daily.Pantoprazole is dosed 40mg po qdFor ZES:Longer duration of action so require less frequent dosingLarge doses are necessaryStart at 60mg lansoprazole or 80mg omeprazole po qd
805-Prostaglandin E1 Analog MOAInhibits basal & nocturnal gastric acid secretion;Enhances mucous & bicarb secretion;Reduces pepsin concentration but does not affect histamine stimulated secretion.
81Prostaglandin E1 Analog EfficacyFor prevention of NSAID-induced gastric ulcers in patients at high risk.Superior to sucralfate in preventing NSAID-induced gastric ulcersSuperior to H2-blockers in reducing mucosal injury, but may relieve pain less rapidly (H2-blockers more effective for inhibiting gastric acid output, especially at night)May be effective in healing H2 blocker-resistant ulcers
82Side Effects:Diarrhea, abdominal pain, nausea, headache, flatulence, constipationCan GFR and improve renal functionContraindicated in women of childbearing age unless effective contraceptive measures are used (may cause uterine contractions; abortifacient).Take with or after meals and at bedtime to reduce ADRs
83Drug Interaction Profile No effect on cytochrome p450 systemUse of Mg-containing antacids can worsen misoprostol-induced diarrhea (use an Al-antacid)Dosing:200 g qidIf patient unable to tolerate: can be given 100 g qid OR 200 g bid or tid (also a small in effectiveness at lower doses)
846-Bismuth Subsalicylate MOADirect mucosal protective effect; anti-infective actions, weak antacid propertiesIt complexes deposit on the surface of H. pylori, diminishing its ability to adhere to the gastric epithelium. The end result is lysis of the organism within min.The addition of an antimicrobial agent produces a synergistic effect.May also stimulate production of prostaglandins & modulate the immune response.Side EffectsAbdominal pain, constipation, headache, confusion, anxiety, tinnitus, tremor.
85Drug Interaction Profile Anticoagulants (plt fxn),May potentiate hypoglycemic effects of diabetic agentsMay displace other drugs from protein binding sitesMay form complexes with other drugs (TCN, quinolones)May effects of uricosuric agents,use with omeprazole may systemic absorption of bismuth (unknown significance)Dosing2 tablets QID (1 tablet = 262mg bismuth subsalicylate; equiv to 100mg salicylate)
867-Prokinetic Agents: Metoclopramide MOAIncreases GI motility and peristalsisIncreases LES toneAntagonizes dopamine receptors.Side EffectsExtrapyramidal symptomsDrug Interaction ProfileIncreased sedative effect of benzodiazepines or alcohol.DosingMetaclopramide mg dose, up to 4 times a day (take 30 min before meals).Single dose of 20 mg may be needed in a provoking situation
87Treatment of NSAID induced ulcer 1-Stop NSAIDs when possible.2- Treat with low dose H-2 antagonist for 8 weeksProphylactic therapyIn patients unable to discontinue NSAIDs and have risk factors for development of ulcer1-PPIs: they are preferred if NSAIDs are to be continued2-Misoprostol3-H2 antagonist are more effective in healing duodenal ulcer than gastric ulcer
89Treatment plan & Monitoring 1. Assess risk factors for NSAID-induced ulcers and ulcer-related complications, and when indicated 2.recommend appropriate strategies for reducing ulcer risk (see Table 35-10). 3. Recommend eradication treatment for H. pylori-positive patients taking NSAIDs.
90Treatment plan & Monitoring 4. Monitor patients for signs and symptoms of NSAID-related upper GI complications.5. Assess and monitor patients for potential drug interactions and adverse effects (especially misoprostol).
91Treatment plan & Monitoring 6. Provide patient education to patients who are at risk of NSAID-induced ulcers or GI-related complications, includingwhy cotherapy is used with nonselective NSAIDs;when and how to take medications;adverse effects;alarm symptoms;when to contact their healthcare provider;the importance of adherence to drug treatment.
92Eradication of Helicobacter pylori In the past, PUD was considered a chronic disorder because the ulcer tended to recur.Eradication of H. pylori dramatically reduces ulcer recurrence & cures many patients of their disease.Advantages of eradication:Inflammatory changes return to normalRestoration of microvilli by 4 monthsDecrease in disease recurrenceProblems:Eradication may be difficult;resistance to antibioticsAdverse reactions to antibiotics
93Who should be treated for H. pylori? All pts with established duodenal ulcers with H. pylori.All pts with gastric ulcers with H. pylori.First or recurrent H. pylori infectionWho should not be treated for H. pyloriAsymptomatic (H. pylori positive or negative)Non-ulcer dyspepsia* (H. pylori positive or negative)Gastric ulcer (H. pylori negative)Duodenal ulcer (H. pylori negative)Gastroesophageal reflux diseaseGallbladder or pancreatic diseaseIrritable bowel or inflammatory bowel disease
94Disadvantages of Maintenance Treatment: recurrence despite long-term treatmentdoesn’t change H. pylori colonizationlong-term drug exposureincreased costpotential for disease complications from recurrence
95H. pylori Eradication Regimens Monotherapy with antibiotics or acid suppressants have not been optimalCombination of acid suppressants with antibioticsShould contain one anti-secretory agent & at least 2 antibiotics)DosingClarithro 500 mg bid, Amoxil 1000mg bid, Metronidazole 500mg bid, Tetracycline 500mg bidBMT-1: Bismuth 525mg qid + Metronidazole 500mg tid + Tetracycline 500mg qidBMT-2: Bismuth 525mg qid + Metronidazole 250mg qid + Tetracycline 500mg qid
97Treatment plan & Monitoring 1. Assess patient allergies to determine if allergic to penicillin (or other antibiotics) so that drug regimens that contain penicillin (or other antibiotics) can be avoided.2. Assess patient use of alcohol or alcohol-containing products with metronidazole and oral birth control medications with antibiotics and counsel appropriately.3. Assess likelihood of nonadherence to the drug regimen as a cause of treatment failure.
98Treatment plan & Monitoring 4. Recommend a different antibiotic combination if H. pylori eradication fails and a second treatment is planned.5. Inform the patient of change in stool color when bismuth salicylate.6. Assess and monitor patients for potential adverse effects, especially those associated with metronidazole, c1arithromycin, and amoxicillin.
99Treatment plan & Monitoring 7. Assess and monitor patients for potential drug interactions, especially those receiving metronidazole, clarithromycin, or cimetidine. 8.Monitor patients for salicylate toxicity, especially patients receiving cotherapy with other salicylates, anticoagulants, and patients with renal failure. 9.Monitor patients for persistent or recurrent symptoms within 14 days after completion of a course of therapy.
100Treatment plan & Monitoring 10. Provide patient education to patients includingwhy antibiotic and antiulcer combinations are used;when and how to take medications;adverse effects;the importance of adherence to the entire course of drug treatment;to contact their healthcare provider if alarm symptoms develop (e.g., blood in the stools, black tarry stools, vomiting, severe abdominal pain), or if symptoms persist or return.