GIT Disorders PUD (2) PDF

Pharmacotherapy of GIT Disorders Samson Fisseha (Bpharm,MSc in clinical therapy ) 12/16/2023 GI BY :SAMI 1  GI System Disorders Classification Upper GI Disorders (Acid-related Disorders) Gastroesophageal Reflux Disease Dyspepsia Peptic Ulcer Disease Upper G...

Pharmacotherapy of GIT Disorders Samson Fisseha (Bpharm,MSc in clinical therapy ) 12/16/2023 GI BY :SAMI 1  GI System Disorders Classification Upper GI Disorders (Acid-related Disorders) Gastroesophageal Reflux Disease Dyspepsia Peptic Ulcer Disease Upper GI Bleeding Peptic Ulcer Bleeding Stress-related Mucosal Bleeding Lower Gastrointestinal Disorders Inflammatory Bowel Disease (Ulcerative Colitis, Crohn’s Disease) Irritable Bowel Syndrome Hepatobiliary Disorders [Liver & Biliary Tract Disease] Cirrhosis & its CXN Cholelithiasis and Cholecystitis Acute and Chronic Viral Hepatitis Disorder of Pancreas (Acute and Chronic Pancreatitis) Anorectal conditions 12/16/2023 GI BY :SAMI 2  GI tract System GIT Includes the esophagus, stomach, small intestine, large intestine, colon, rectum, biliary tract, gallbladder, liver, and pancreas patient history and physical examination 12/16/2023 GI BY :SAMI 3  Symptoms of Gastrointestinal Dysfunction Common symptoms Includes: Heartburn, dyspepsia, abdominal pain, nausea, vomiting, diarrhea, constipation, and GI bleeding Signs and symptoms of malabsorption, hepatitis, & GI infection Warning symptoms include : weight loss, intractable vomiting, anemia, dysphagia, and bleeding 12/16/2023 GI BY :SAMI 4 Evaluation of the Patient with GI Disease begins with a careful history and examination Subsequent investigation to test gut structure or function as indicated Some patients exhibit normal diagnostic testing validated symptom profiles to confidently diagnose a functional bowel disorder 12/16/2023 GI BY :SAMI 5  The patient history A comprehensive patient history is the cornerstone A clear, detailed, chronologic account of patient's problems Should include: The problem onset = help for differential diagnosis The setting in which it developed = possible origin of disorder Factors that alleviate and aggravate the problem and Its presentation/manifestations warning signs & alarm symptoms = be identified quickly A thorough medication history = agents cause GI injury 12/16/2023 GI BY :SAMI 6 12/16/2023 GI BY :SAMI 7 12/16/2023 GI BY :SAMI 8 12/16/2023 GI BY :SAMI 9  Physical Examination A comprehensive evaluation of the patient should be performed  A careful examination of the abdomen Includes inspection, auscultation, percussion, and palpation in this order Inspection: may reveal scars, hernias, bulges, or peristalsis Auscultation analysis of bowel sounds and identification of bruits (significant sound) should be performed prior to percussion and/or palpation Percussion of the abdomen (tapping of abd with fingers) detection of tympany (abd distension), visceral organ size, and ascites Palpation (using finger gentle pressure) allow the clinician to identify tenderness, rigidity, masses, and hernias Digital rectal examination used to detect rectal masses and tenderness, and to assess muscle tone Stool on examiner's glove obtained subjected to testing for detection of occult blood 12/16/2023 GI BY :SAMI 10  Laboratory and Microbiologic Tests Used to assess organ function, screen for certain GI disorders, and evaluate the effectiveness of therapy Supportive to an accurate history and PE e.g. A complete blood cell count, A serum chemistry panel Specific laboratory blood tests Microbiologic and related studies Stool examination 12/16/2023 GI BY :SAMI 11  Diagnosis The patient’s Hx, PE, and routine lab tests: but frequently more specific studies are required to confirm a clinical suspicion Most appropriate diagnostic test depends on: anatomic region involved suspected abnormality reliability of the test (e.g., sensitivity vs specificity) patient's overall condition, and clinical manifestations of the patient 12/16/2023 GI BY :SAMI 12  Radiology Radiologic procedures rely on differential absorption of radiation of adjacent tissues to highlight anatomy and pathology Two divisions Non-computer assisted radiologic procedures Plain Radiography of the GI System Non-contrast radiographs Using contrast agents like Barium sulfate Upper GI Series » radiographic visualization of esophagus, stomach, & small intestine Lower GI Series » to examine colon & rectum, if a colonic obstruction is suspected Computer assisted radiologicGI BYprocedures 12/16/2023 :SAMI 13  Imaging Studies computer-assisted techniques: allow a cross-sectional radiographic image of the body Transabdominal ultrasonography, CT, and MRI Endoscopy = diagnostic & therapeutic inspect intraluminal mucosal lesions and to obtain biopsies and washings for cytology studies upper GIT=esophagogastroduodenoscopy [EGD]) = esophagus, stomach & proximal small bowel For upper GI bleeding, obstructions, upper abd pain, and persistent vomiting Lower GIT = rectum and colon Colonoscopy or flexible-sigmoidoscopy 12/16/2023 GI BY :SAMI 14 12/16/2023 GI BY :SAMI 15  Conclusion Evaluation of the GI tract for diagnosis of GIT disorders involve the patient's history (careful) physical examination(comprehensive) routine laboratory tests diagnostic studies and procedures The most appropriate diagnostic test depends on: the anatomic region involved the suspected abnormality reliability of the test (e.g., sensitivity vs specificity) the patient's overall condition, and clinical manifestations of the patient 12/16/2023 GI BY :SAMI 16  Peptic Ulcer Disease (PUD) 12/16/2023 GI BY :SAMI 17  Pre- Awareness– Rx of PUD Patients with PUD should reduce psychological stress, cigarette smoking, and NSAID use and avoid foods and beverages that exacerbate ulcer symptoms Drugs PPI, H2RA, Sucralfate and Misoprostol H.Pylori: PPI + Clarithromycin+ Amox NSAID induced: DC, adding PPI or COX-s selective 12/16/2023 GI BY :SAMI 18  PUD definition Acid-related diseases (gastritis, erosions, and peptic ulcer) of the upper GIT PUD refers to a group of ulcerative disorders of the upper GI tract that require acid and pepsin for their formation. PUD differs in that ulcers typically extend deeper into the muscularis mucosa. 3 common forms: H. pylori-positive, NSAID-induced, and stress ulcers -related mucosal damage (SRMD) 12/16/2023 GI BY :SAMI 19 Comparison of common forms of peptic ulcers 12/16/2023 GI BY :SAMI 20 12/16/2023 GI BY :SAMI 21 12/16/2023 GI BY :SAMI 22 12/16/2023 GI BY :SAMI 23 12/16/2023 GI BY :SAMI 24  Peptic Ulcer Disease…..Classification Gastric ulcer Duodenal ulcer Common NSAIDs > H. H. pylori (95%) > NSAIDs cause pylori; Symptoms Epigastric pain Characteristic  Worsen by  Relieved by meal (since s of epigastric meal acid stay in stomach) pain  Lose weight b/s  Pain occurs at night of it (stomach is empty) or 1-3 hrs after a meal Mortality 12/16/2023  High mortality GI BY :SAMI  Low mortality 25  PUD-Diagnosis Symptoms presentation Testing for H. pylori ……..if +ve……. need to be treated…H.Pylori……….is carcinogen Recommend testing if……….. Hx of PUD, active ulcer, Treatment………..test-and-treat strategy Confirmation test after therapy…….not recommended 12/16/2023 GI BY :SAMI 26 12/16/2023 GI BY :SAMI 27  Type of H. pylori testing Invasive……………use endoscopic Histology …………90-95% sensitivity Rapid urase tests (CLOtest) ………. detects the presence of NH3 False negative – GI bleeding, Use of PPIs, H2RAs or bismuth Culture –time consuming but 100% specific 12/16/2023 GI BY :SAMI 28  Urea breath tests Radioactive CO2 after the ingestion of 13C labeled urea False negative – recent use of antibiotic or PPI (up to 40%) 12/16/2023 GI BY :SAMI 29  PUD=Diagnosis- Noninvasive Urea breath test: Tests for active H. pylori infection; 95% sensitive and specific False negative interference Serologic – detects antibody to H. pylori … 85% sensitive Detects both active infection vs. past exposure Not a good monitoring test for eradication d/c PPIs 2 wks prior and Antibiotics 4 weeks prior Stool antigen Test (active H. pylori ) Antibody test s to detect the presence of H. pylori in the stool (88-92%) sensitive Bismuth, PPI, antibiotics….interfere with the test 12/16/2023 GI BY :SAMI 30  PUD Treatment Over all : treatment Goals Rapid relief of symptoms Healing of ulcer Preventing ulcer recurrences Reducing ulcer-related complications Reduce the morbidity (including need for endoscopic therapy or surgery) Reduce the mortality 12/16/2023 GI BY :SAMI 31  Goal: continued The treatment of chronic PUD varies depending on: The etiology of the ulcer, whether the ulcer is initial or recurrent, and whether complications have occurred Goal H. pylori–positive patients with active ulcer, previously documented ulcer, or history of ulcer- related complication to eradicate H. pylori, heal the ulcer, and cure the disease Goal for NSAID-induced ulcer to heal the ulcer as rapidly as possible Pts on increased risk of ulcer due to NSAID……prophylactic cotherapy or switch to COX-2 inhibitors 12/16/2023 GI BY :SAMI 32  General Strategy Treat complications aggressively if present Determine etiology of ulcer Discontinue NSAID use if possible Eradicate H. pylori if present or strongly suspected, even if other risk factors (e.g., NSAID use) are also present; Use antisecretories to heal the ulcer if H. pylori is not present Lifestyle modifications such as reducing stress & Smoking cessation should be encouraged PPI-based H. pylori eradication regimen is recommended when the patient with an active ulcer is taking an NSAID and is H. pylori–positive Prophylactic cotherapy with either a PPI or misoprostol decreases ulcer risk and upper GI complications for patients taking nonselective NSAIDs Selective COX-2 inhibitor NSAIDs (if available) may be used as an alternative to a nonselective NSAID 12/16/2023 GI BY :SAMI 33  Non-pharmacologic Therapy eliminate or reduce psychological stress, cigarette smoking, and the use of NSAIDs (including aspirin). avoid foods and beverages (e.g., spicy foods, caffeine, and alcohol) that cause dyspepsia or that exacerbate ulcer symptoms 12/16/2023 GI BY :SAMI 34  Drugs Therapy H2-Receptors antagonists Proton pump inhibitors Cyto-protective agents Prostaglandin agonists Antacids Antimicrobials for H. pylori eradication Such as clarithromycin, metronidazole, amoxicillin 12/16/2023 GI BY :SAMI 35 Oral Drugs Used to Heal PUD & Maintain Ulcer Healing 12/16/2023 GI BY :SAMI 36 12/16/2023 GI BY :SAMI 37  1. H pylori-induced PUD 12/16/2023 GI BY :SAMI 38  H.Pylori Eradication Therapy H. pylori eradication significantly reduce the risk of ulcer recurrence & re-bleeding & less expensive than chronic antisecretory therapy Continuing antisecretory therapy for > 2 weeks following antimicrobial treatment is unnecessary after H.pylori eradication To Select Therapy for H. pylori Eradication Duration of treatment & adverse effects should be considered Successful eradication depends on: the drug regimen, resistance to the antibiotics used, duration of therapy, medication adherence, 12/16/2023 and genetic polymorphism 39 GI BY :SAMI 12/16/2023 GI BY :SAMI 40 12/16/2023 GI BY :SAMI 41 12/16/2023 GI BY :SAMI 42  H pylori - Treatment Antisecretary agent + two antibiotics Preferable antisecretary ……..use PPI Antibiotics :clarithromycin + amoxicillin or metronidazole Duration…………7 vs. 14 days (most 10 days) Confirmation test …………… urea breath test or stool antigen test Levofloxacin-based triple therapy for ………resistant patients 12/16/2023 GI BY :SAMI 43 12/16/2023 GI BY :SAMI 44 Factors Predicting H. Pylori Eradication Outcomes Include: Antibiotic resistance Poor medication adherence Short duration of therapy High bacterial load Low intragastric pH, and Genetic polymorphism 12/16/2023 GI BY :SAMI 45  Recurrence of H.Pylori infection Recurrence of H. pylori infection is defined by: A positive result on urea breath or stool antigen testing six or more months after documented successful tt Risk factors for recurrence include: Non-ulcer dyspepsia Persistence of chronic gastritis after eradication therapy Intellectual disability High rates of primary infection Higher urea breath test values 12/16/2023 GI BY :SAMI 46  Recurrence : cont’d… Recurrence rates worldwide vary but lower in developed countries Rx of recurrence: alternative eradication regimen, depending on symptoms & risk factors for complications of infection It is too early to know whether shorter courses of eradication therapy will be associated with a higher resistance rate 12/16/2023 GI BY :SAMI 47  2. NSAID-Induced PUD 12/16/2023 GI BY :SAMI 48 12/16/2023 GI BY :SAMI 49  Which of the following drug is categorized under non acetylalted salicylate A. Asprin B. ibuprofen C. salicylates D. Meloxicam 12/16/2023 GI BY :SAMI 50  Risk factors for NSAID induced PUD Additive risks 12/16/2023 GI BY :SAMI 51  Management of NSAIDs Ulcers This can be considered under two headings: 1. The healing of an ulcer that has developed during NSAID ; & 2. Strategies for preventing NSAID ulcers in patients who currently are ulcer free 12/16/2023 GI BY :SAMI 52 12/16/2023 GI BY :SAMI 53 12/16/2023 GI BY :SAMI 54 12/16/2023 GI BY :SAMI 55  NSAID-Induced ……….. Prevention Prevention is a key Use the least GI-Toxic agent that is ……nonselective at the lowest effective dose 3 Strategies: If possible DC the NSAID, then use H2RA, PPI, or sucralfate for about 8 weeks IF not, reducing dose, switching to acetaminophen or a nonacetylated salicylate and add antisecretary agents like PPI (for 12 weeks) or misoprostol or H2RA? Use selective agent (Cox-2)??? 12/16/2023 GI BY :SAMI 56  Drug effect monitoring 12/16/2023 GI BY :SAMI 57  PUD NSAID-Induced Ulcer - Drug-Therapy Proton Pump Inhibitors Misoprostol ……….. the only indication is NSAID-induced ulcer Dose………..100-200 mcg qid H2RAs (Cimetidine) 12/16/2023 GI BY :SAMI 58  NSAID-Induced ……….. Prevention Cyclooxygenase inhibitors (COX) COX-1….generates thromboxane A2 produces protective prostaglandins COX-2…...generates PGE1 (prostacycline)… produces prostaglandins involved with inflammation, fever, & pain Misoprostol + NSAID poorly tolerated – diarrhea (40%), abdominal cramping pain, frequent dosing H2 antagonists ……..not effective 12/16/2023 GI BY :SAMI 59  NSAID-Induced - Prevention PPI + NSAID---Preferred > 65 years………if on chronic NSAIDs No prior GI event receiving……….. aspirin, steroids, or wafarin regardless of age……chronically Patients with CVS risk factors ischemic heart disease, CVA, HTN, dyslipidemia, DM, and smokers 12/16/2023 GI BY :SAMI 60  NSAID-Induced - Prevention COX-2 alone Indicated for no prior GI event but receiving aspirin, steroids, or wafarin regardless of age Watch for ……………..Sulfa allergy & Celecoxib But has NO CVS protection…………….. COX-2 lacks antiplatelet action Low-dose aspirin plus celecoxib ………………. Reduces the gastroprotective effects of COX-2 12/16/2023 GI BY :SAMI 61 12/16/2023 GI BY :SAMI 62  Peptic Ulcer Disease Concomitant use of Antiplatelet Includes clopidogrel or aspirin Before starting antiplatelet therapy………… Test and eradicate H. Pylori Prevention……. PPIs as the preferred agents for……. Patients with GI risk factors who require aspirin, heparin, clopidogrel, and warfarin Aspirin plus PPI is superior to Clopidogrel 12/16/2023 GI BY :SAMI 63  COX-2 Cardiovascular Safety COX-2 may reduce ………… the CV protective effect of ASA Rofecoxib in 2004 & Valdecoxib in 2005 Withdrawn from the U.S. market secondary to ………… increase in MI, stroke and thrombotic events Inhibition of COX-2-mediated prostacyclin ………vs.. continuous production of PG thromboxane A2 by COX- 1 leading to the development of thrombic state 12/16/2023 GI BY :SAMI 64  Analgesic use – To Prevent PUD approach in patients with CV risk factors Start with acetaminophen, aspirin, tramadol, short acting narcotics Non-COX-2 NSAIDS Use lower-risk NSAIDS such as ibuprofen, etodolac, diclofenac Plus PPI in patients with increased risk of thromboembolic events………or coadministration with low dose ASA COX-2 inhibitors………..reserve for last Maximum dose: Celecoxib 400 mg/day; Naproxen 440 mg/day Recommendation Smoking cessation, Control of BP, lipid, and glucose 12/16/2023 GI BY :SAMI 65  Stress induced PUD Critically ill patients at the highest risk of developing stress-related mucosal bleeding (SRMB) who require prophylactic drug therapy include those with respiratory failure on mechanical ventilation or those with coagulopathy. 12/16/2023 GI BY :SAMI 66  Stress induced PUD management There are limited data to support the selection of a PPI over an intravenous H2RA for SRMB prophylaxis. The decision based upon appropriate individual characteristics (e.g., nothing by mouth, presence of nasogastric tube, renal failure). Patients who are at risk for SRMB include: those with respiratory failure [mechanical ventilation], coagulopathy (INR >1.5) and 2 or more of the following risks: platelet count 250 mg/day hydrocortisone or equivalent) multiple trauma, severe burns (>35% of body surface area), head injury, traumatic spinal cord injury, major surgery, prolonged ICU admission (>7 days), or history of GI bleeding. 12/16/2023 GI BY :SAMI 67  SRMB treatment Antisecretory therapy is generally preferred for SRMB prophylaxis for several reasons Parenteral H2RAs may be administered as either continuous infusions or intermittent bolus doses intravenous ranitidine was superior to oral sucralfate in preventing SRMB ranitidine did not increase the risk for nosocomial pneumonia use of H2RAs remain a recommended option for the prevention of SRMB though PPIs would appear to be the main stay options for Px of SRMB Very little evidence showing clinical superiority of PPI than H2RA or placebo 12/16/2023 GI BY :SAMI 68  Summary: SRMB Px Decision: most appropriate pharmacotherapy plan for the prevention of SRMB for a specific patient dependens on clinical presentation of the patient and medication costs Patients who: can take oral medication or have a working NG tube in place an oral or compounded PPI suspension as a cost-effective measure not able to utilize one of these routes: intravenous H2RA discontinue prophylactic therapy if Resolution of risk factors, discharge from the ICU, extubation and oral intake 12/16/2023 GI BY :SAMI 69  Prophylaxis Options for of SRMB 12/16/2023 GI BY :SAMI 70  Pharmacologic Agents Histamine-2 Receptor antagonists Reversibly inhibit histamine-2 receptors on the parietal cell Less efficacious………..vs. PPI ADR: mild, adjust dose in renal disease cimetidine (gynecomastia) tolerance Drug Interactions: Cimetidine is an enzyme inhibitor (warfarin, theophylline) Reduced absorption (itraconazole, ketoconazole, iron) 12/16/2023 GI BY :SAMI 71  Pharmacologic Agents Histamine-2 Receptor antagonists Ranitidine 75, 150, and 300-mg tablets, 15 mg/ml syrup Cimetidine 200, 300, 400, 800-mg tablets; 300 mg/5 ml syrup Nizatidine 150 mg tablet; 15 mg/ml solution Famotidine 20, 40-mg tablets, 40 mg/mL suspension Pepcid Complete…….contains CaCO3+MgOH+Famotidine 10 mg/800 mg famotidine/Ca Carbonate + 165 mg MgOH chewable tablet 12/16/2023 GI BY :SAMI 72  Pharmacologic Agents-PPIs Inhibit irreversibly at the ………… final step in gastric acid secretion Greater degree and duration of acid suppression Most costly agent Meals vs. divided doses ? Pharmadynamics………….and pharmacokinetics T ½ ……….3 hrs……….effect lasts……36 hrs Evening meals vs. hs 12/16/2023 GI BY :SAMI 73  ADR………well tolerated, neoplasma (long term) ? rebound acid upon discontinuation Withdrawal from PPIs can lead to severe rebound acid secretion, a complication that can force users to become dependent on them - this should be mentioned in a black-box warning, consumer group Public Citizen has told the FDA 12/16/2023 GI BY :SAMI 74  Long-Term Complications Increased risk of ………….. community-acquired pneumonia…higher pH Patients at risk……….. Immunocompromised the elderly, children, asthmatics or those with COPD Overgrowth of Clostridum Difficle (PPI) Increased incidence of hip fracture Patient at risk: high dose of PPI or longer duration Attributable to reduction of Ca absorption 12/16/2023 GI BY :SAMI 75  PPI Drug interactions-rare PPIs can undermine the effectiveness of clopidogrel, raising the risk of heart attack Omeprazole & esomeprazole… has a greater interaction than other PPIs, such as pantoprazole a potential interaction w/.. methotrexate and mycophenolate mofetil. Increase in the levothyroxine dose may be needed with PPIs Decrease oral bioavailability of Atazanavir, keto-, Digoxin, Vitamin B12 (deficiency--long-term use) Acute interstitial nephritis ……….. 12/16/2023 GI BY :SAMI 76  Pharmacologic Agents Proton Pump Inhibitors Esomeprazole (Nexium) Omeprazole (Prilosec, Zegerid) Lansoprazole (Prevacid) Rabeprazole (Aciphex) Pantoprazole (Protonix) Dexlansoprazole 12/16/2023 GI BY :SAMI 77  Proton Pump Inhibitors Omeprazole……..The first proton pump inhibitor, introduced in 1989. ……………….as Prilosec or Zegerid..omeprazole plus Na bicarbonate. It comes in 10, 20 and 40 mg capsules. Dose……..once daily or BID for approved for children as young as age one. Possible side effects include headache, dizziness, rash, diarrhea, nausea or vomiting, and alteration in taste. Lansoprazole…… Prevacid……comes in 15 &30 mg can be given IV and also in an orally-disintegrating tablet. adverse reactions are fatigue, dizziness, headache, abdominal pain, diarrhea, nausea and increased appetite. 12/16/2023 GI BY :SAMI 78  Proton Pump Inhibitors Rabeprazole……….. Aciphex or in generic versions. It comes in 20 mg tablets and is usually taken once daily. approved for those over age twelve for up to 16 weeks. The most frequent side effect is headache. Pantoprazole……Protonix or in a generic drug. available in 20 or 40 mg extended-release tabs or can be given IV. not approved for use in children. Side effects are uncommon but it could cause a rash, headache or diarrhea. 12/16/2023 GI BY :SAMI 79  Proton Pump Inhibitors Esomeprazole………Nexium Comes in 20 & 40 mg caps. It can also be given IV. The oral form is most often taken one time a day, The most likely side effects are headache, dizziness, rash, diarrhea, nausea or vomiting, and change in taste. Dexlansoprazole………………Kapidex received FDA approval in early 2009. It is supplied in 30 mg & 60 mg caps administered once daily. It is not recommended for children, but adults may take it for up to six months for some conditions. It may be associated with stomach upset, abdominal pain or upper respiratory infections, 12/16/2023 but is generally well tolerated. GI BY :SAMI 80