Pharmacology II: Drugs for Peptic Ulcer Disease and GI Bleeding PDF

**OUTLINE** I. **Peptic Ulcer and Related Diseases** II. **Pharmacologic Therapy for Esophageal Varices** III. **Therapeutics for Peptic Ulcer Disease** IV. **NSAID-induced Peptic Ulcer Disease** V. **Stress-related Mucosal Injury** VI. **Functional Dyspepsia** VII. **Gastroesophageal Reflu...

**OUTLINE** I. **Peptic Ulcer and Related Diseases** II. **Pharmacologic Therapy for Esophageal Varices** III. **Therapeutics for Peptic Ulcer Disease** IV. **NSAID-induced Peptic Ulcer Disease** V. **Stress-related Mucosal Injury** VI. **Functional Dyspepsia** VII. **Gastroesophageal Reflux Disease** VIII. **Gastrointestinal Bleeding** IX. **Review Questions** X. **References** XI. **Appendix** +-----------------------+-----------------------+-----------------------+ | **LEGEND** | | | +=======================+=======================+=======================+ | ⭐ | 🖊 | 📖 | | | | | | Must | Lecture | Book | | | | | | Know | *\[lec\]* | *\[bk\]* | +-----------------------+-----------------------+-----------------------+ PEPTIC ULCER AND RELATED DISEASES {#peptic-ulcer-and-related-diseases.TransOutline} ================================= GASTRIC PITS: HISTOLOGY AND PHYSIOLOGY {#gastric-pits-histology-and-physiology.TransSubtopic1} -------------------------------------- A table with text on it Description automatically generated **Figure 1. Cells in the gastric pit** **Mucous neck cell** Responsible for protection (mucus) Secretes bicarbonate because the mucus has to be alkaline to prevent damage by gastric acid **Parietal cell** Secretes gastric acid (HCl) Activates pepsin for protein digestion Chronic inhibition with PPI like omeprazole may lead to B12 absorption problems **Enterochromaffin-like cell** Secretes histamine: one of the stimulus for release of HCl **Chief cells** Secretes enzyme for digestion Placed lower in the gastric pit because pepsin is released inactivated, and the acidity of the parietal cells will activate the pepsinogen outside the gastric mucosa If pepsin is released & activated damage the gastric pit **D cells:** secretes somatostatin which inhibits the parietal cell (HCl) **G cells:** Secretes gastrin which increases gastric acid output NEURAL AND HORMONAL REGULATION OF ACID PRODUCTION {#neural-and-hormonal-regulation-of-acid-production.TransSubtopic1} ------------------------------------------------- **Final common pathway** is the **H, K, ATPase pump** where it exchanges 1 molecule of K+ and releases 1 molecule of H+ Main inhibitory hormone: Somatostatin (D cell) It can act directly to the parietal cell Through the ECL cell to decrease histamine output Through the G cell to decrease gastrin output Factors that increases gastric acid output: Acetylcholine (vagus nerve) Histamine (ECL) Gastrin (G cell) -- endocrine-like, needs to pass through the blood vessels  **Figure 2. Gastric parietal cell** GASTRODUODENAL MUCOSAL DEFENSE AND REPAIR {#gastroduodenal-mucosal-defense-and-repair.TransSubtopic1} ----------------------------------------- The gastric epithelium is always under constant assault by series of endogenous noxious factors like HCl, pepsin, and bile salts Medication, alcohol, and bacteria also encounter the gastric mucosa H. pylori produces urease that disrupts the mucosal barrier 3 level barrier: Pre-epithelial; Epithelial; Sub-epithelial First line is the mucous bicarbonate phospholipid layer that serves as a physiochemical barrier especially to H+ ion Impedes diffusion of ions and molecules such as pepsin HCO3 forms a pH gradient Outside the gastric pit has a pH of 2 Mucus layer has a pH of 7 Second line is the surface epithelial cells Responsible for mucus and bicarbonate secretion Contains epithelial transporters that regulates intracellular pH by releasing HCO3 Continuous cell renewal in the surface epithelial cells Alkaline tide There is a slight increase in alkalinity of the blood due to the HCO3 influx after secretion of H+ ions Microcirculation through the capillaries is maintained by a continuous generation of prostaglandin, nitric oxide, and hydrogen sulfide which protects the epithelial cells Prostaglandin inhibitors like NSAIDs will lead to decrease in epithelial cell protection Sensory nerves forms a dense plexus in the mucosal base Pain sensitive **Figure 3. Components involved in providing gastroduodenal mucosal defense and repair** PROSTAGLANDINS {#prostaglandins.TransSubtopic1} -------------- Play central role in gastric epithelial defense and repair Regulation of release of mucosal bicarbonate and mucus, inhibit parietal cell secretion, maintain mucosal blood flow and epithelial cell restitution COX-1 is responsible for housekeeping (stomach) *🖊 COX-1 inhibitor or non-specific COX inhibitor destroys COX- 🖊 1 housekeeping leading to stomach injury* *🖊* *Decreases GI mucosa integrity and predisposes stomach to more ulcers* Highly selective COX-2 NSAID decreases tissue inflammation while minimizing GI tract toxicity *🖊 However, COX-2 NSAIDs increases cardiovascular risk*  **Figure 4. Synthesis of prostaglandin E2** THERAPEUTICS: PUD {#therapeutics-pud.TransOutline} ================= +-----------------------+-----------------------+-----------------------+ | **Table 1. Drugs for | | | | Peptic Ulcer | | | | Disease** | | | +=======================+=======================+=======================+ | **Drug Class** | **Agents** | **Notes** | +-----------------------+-----------------------+-----------------------+ | Antacids | Magnesium hydroxide, | Magnesium: | | | aluminum hydroxide, | **laxative** effect | | | calcium carbonate | | | | | Aluminum hydroxide: | | | | **constipating** | | | | effect | +-----------------------+-----------------------+-----------------------+ | H2 antagonists | **Cimetidine**, | Useful in PUD, GERD, | | | ranitidine, | Zollinger-Ellison | | | famotidine, | syndrome but not as | | | nizatidine | effective as PPIs | | | | | | | | Cimetidine **inhibits | | | | hepatic drug | | | | metabolizing | | | | enzymes** and has | | | | **antiandrogen | | | | effects** | +-----------------------+-----------------------+-----------------------+ | Proton Pump | **Omeprazole**, | ⭐**Irreversibly | | Inhibitors | lansoprazole, | inactivate H+/K+ | | | esomeprazole, | ATPase**, thus | | | pantoprazole, | blocking H+ secretion | | | rabeprazole | | | | | Works well in PUD, | | | | Zollinger-Ellison | | | | syndrome, and GERD | +-----------------------+-----------------------+-----------------------+ | Mucosal protective | **Sucralfate | Polymerizes in the | | agents | (paste)** | stomach and forms | | | | protective coating | | | Misoprostol | over ulcer beds | | | | | | | | PGE 1 derivative used | | | | for peptic ulcers | | | | caused by NSAIDs | +-----------------------+-----------------------+-----------------------+ | Antibiotics | Macrolides, | Treat ***H.pylori*** | | | metronidazole, | | | | tetracyclines (var. | | | | combinations) | | +-----------------------+-----------------------+-----------------------+ *🖊 Antacids attacks H+ ion in the stomach* *🖊 H2 receptor antagonist reduces histamine thus decreases stimulation of parietal cell* *🖊 PPIs is the only agent that best promotes epithelial healing of the gastric mucosa* *🖊 Sucralfate enhance mucus bicarbonate interface to protect ulcer* *🖊 Misoprostol is an abortifacient and is not available in the Philippines* *🖊 Vagotomy can be offered to decrease ACh* A table with a list of drugs Description automatically generated **Figure 5. Drugs used in the treatment of PUD** ANTACIDS {#antacids.TransSubtopic1} -------- - Mechanism of Action: - Weak bases, react with gastric HCl to form salt and water - Single dose of 156mEqs antacid can neutralize gastric acid up to 2 hours (**brief duration of action**) - 🖊 *In clinical practice it is used as a temporizing measure while waiting for definitive therapy (omeprazole) to take effect* - Acid neutralization capacity vary depending on: - Rate of dissolution (tablet vs liquid form) -- liquid is more effective - Water solubility - Rate of reaction to acid and gastric emptying - DO NOT co-administer with other medications (2 hours apart with tetracycline, fluoroquinolone, itraconazole, iron) - Interacts with absorption of other drugs thru: - Alkaline binding to the drug - ↑ gastric acid pH → inactivate drug and decrease drug solubility - Sodium Bicarbonate - Baking soda, alka seltzer - NaHCO3 + HCl → NaCl + CO2 gas - Adverse Effects: - Gastric distention and belching (CO2 gas) - Metabolic alkalosis - Exacerbation of fluid retention (inc. sodium load) for HF/CKD patients - Calcium Carbonate - Tums, Os-Cal - CaCO3 + HCl → CaCl2 + CO2 gas - Adverse Effects: - Gastric distention (CO2 gas), metabolic alkalosis - Hypercalcemia on chronic administration - Aluminum Hydroxide PLUS Magnesium Hydroxide - *🖊 Preferred clinically if you want antacids because the reaction intrinsically do not produce any gas. Therefore, the patient won't present belching and gastric distention.* - **MgOH + AlOH + HCl ➔ MgCl2 + AlCl2 + H20** - No CO2 gas formed → Less belching, gastric distention - Neutralization rxn is more efficient → Less Met. Alkalosis - Aluminum (constipation) and Magnesium (diarrhea) cancels each other avoiding GI upset - Absorbed and Eliminated by Kidneys → avoid in renal impairment Clinical Indications: Often used as **symptomatic relief of dyspepsia** Nonprescription remedies for intermittent heartburn and dyspepsia *🖊 OTC, so Patient may abuse this.* - Preparations: - Combination of aluminum hydroxide and magnesium hydroxide (Maalox, Mylanta) - Preferred; avoid in CKD → risk for hypermagnesemia and chronic neurotoxicity from aluminum - Calcium carbonate - Risk for milk-alkali syndrome (hypercalcemia, hyperphosphatemia, renal calcinosis +/- renal insufficiency) with long term use - Sodium carbonate - Risk for systemic alkalosis HISTAMINE 2-RECEPTOR ANTAGONIST (H2RA) {#histamine-2-receptor-antagonist-h2ra.TransSubtopic1} -------------------------------------- Homologous structure to histamine Significantly inhibit basal and stimulated acid secretion at therapeutic doses, with similar ulcer-healing rates Patient may develop tolerance to H2 blocker (decreased response to drug when used repeatedly) vs PPIs *🖊 the efficacy of this medication may decrease*  **Figure 6. Histamine 2-receptor Antagonist** Pharmacodynamics Ranitidine, Famotidine, Nizatidine → more potent than Cimetidine Dosing: Cimetidine 800 mg, Ranitidine 300 mg, Famotidine 40 mg, Nizatidine 300 mg ODHS *🖊 remember the dosing* Pharmacokinetics Cimetidine and Famotidine undergo extensive first pass metabolism Clearance: hepatic and renal; half-life: 1.1 to 4 hours; *dose adjustment required for renal/hepatic insufficiency* Able to cross the placenta → avoid in pregnant women Side effects: **Cimetidine** Weak anti-androgenic side effects (**gynecomastia**, impotence) Inhibits metabolism of estradiol *🖊 one of the main reasons here is because of ots reaction with cytochrome p450* Elevation of creatinine, transaminases Rare side effects Hematologic: pancytopenia, neutropenia, anemia, thrombocytopenia **Interactions:** **Cimetidine\>\>Ranitidine → may bind to cytochrome P450 (more drug interaction)** **Famotidine and Nizatidine do not have this interaction** *🖊 if your patient is taking many drugs (polypharmacy), you would want to use Famotidine and Nizatidine because it has less binding to cytochrome p450 compared to Cimitidine, which can affect the metabolism of other medications*  **Figure 7. Efficacy of H2 receptor blockers** *🖊 This is a diagram from Katzung 16th showing the efficacy of H2 receptor blockers. As you can see in this illustration, we have less acid before eating breakfast. However, it increases at night. Take note that the acid peaks after a meal, which makes sense because acid facilitates digestion, but if you have an ulcer, you get more symptoms with more acid secretion. H2 blockers are particularly important in the inhibition of nocturnal acid secretion. If you remember, the defining feature of a duodenal ulcer is the pain that wakes the patient up at night. This is because the peak acid concentration happens around 3 AM, and H2 inhibitors block this. However, this is not anymore, the gold standard. Look at the PPI, because it acts on the final common pathway, and it's irreversible, the acid inhibition is sustained. PPI is more effective in meal-induced increase in gastric acid production than H2 blockers, but they're equally efficacious in nocturnal acid secretion.* PROTON PUMP INHIBITORS (PPI) {#proton-pump-inhibitors-ppi.TransSubtopic1} ---------------------------- - Substituted benzmidazole derivatives **→** covalent, IRREVERSIBLE binding to H/K ATPase pump → most potent acid inhibitory agent - *🖊 Irreversible blocker of H/K ATPase pump* - *🖊 Acts on the final common pathway most potent* - Rapid Onset of Action; Maximum acid inhibitory effect 2-6H; duration of inhibition 72-96H - *🖊 Antacid (duration of action): up to 2hrs; if nagbigay ng Omep/Lansoprazole/Pantoprazole, max. inhibitory effect achieved at 2hrs pagkainom ng px ng sabay (Antacid + PPI), there is sustained pain relief* - Basal (Fasting) and Secretagogue (Meal) stimulated acid prduction inhibited - By \>95% after 1 eek of therapy (HPIM) - By 90-98% of 24-h acid secretion (Katzung) - Once discontinued, acid secretion return normal in 2-5 days, gastrin in 1-2 wks - *🖊 Epithelium (epithelial cells) renew themselves matatanggal new parietal cells uninhibited H/K ATPase acid returns in 2-5 days, gastrin levels return to normal in about 1-2 wks* **Figure 8. Proton Pump Inhibitor MOA**  **Figure 9. Pharmacokinetics of PPI** *🖊 Highlighted: usual dosages for PUD/GERD* - Half-life is less important because of **IRREVERSIBLE proton pump inhibition**. - *🖊 The action of PPI is IRREVERSIBLE at the level of H/K ATPase; ibig sabihin, the effect of PP inhibition depends on the renewal of the parietal cell* - Formulations of PPI - Omeprazole, Esomeprazole, Lansoprazole, Rabeprazole, Pantoprazole - Omeprazole, Lansoprazole → acid labile; administered as enteric coated, sustained release capsules - Esomeprazole → S-enantiomer of omeprazole - Lansoprazole → orally disintegrating tablet may be taken +/- water; for pts with dysphagia - Favorable interactions - Omeprazole + NaHCO3 (*🖊 favorable interaction)*: **NaHCO3 protects omeprazole from acid disintegration** and promote rapid alkalinization with subsequent proton pump activation - Administration: - Administer **30-60 min before breakfast** ➡ so that peak serum concentration coincides with the highest activity of proton pump secretion - *🖊 Remember: After eating breakfast acid secretion increases after 2 hours, diba remember peak acid inhibition is about 2-6 hours it coincides with the highest activity of Proton pump secretion* - Pharmacokinetics: - Half-life is about 1.5 hours, but acid inhibition lasts up to 24 hours due to **irreversible** inhibition of H/K ATPase (i.e. at least 18h needed to create new molecules of H/K ATPase) - Maximum acid inhibition: 2-6 hours from administration - 3-4 days required for full acid-inhibition to effect; 3-4 days to withhold for usual acid production to return - Para lahat ng H/K ATPase covered (3-4 days) - It takes 3-4 days to return to normal acid secretion after this inhibition - Pharmacodynamics: - Block BOTH fasting and meal-stimulated secretion as its effects on the final common pathway of acid secretion (proton pump) - **Refer to Figure 7 above:** 🖊 *H2 blockers are useful for nocturnal acid secretion but for H2 blockers so nocturnal lang siya tumataas parin yung meal stimulated acid secretion. Unlike sa PPI talagang wala, it does not produce H/K ATPase* - **Rebound gastric acid hypersecretion** can occur with stopping therapy: worsening of GERD/Dyspepsia after stopping PPI - Described in *H. pylori* negative individuals after stopping PPI - 🖊 *Eto yung med student na nag kakape tapos in-acid binigyan ng omeprazole, then maintained omeprazole for 2 months tapos titigil at mag rereklamo siya bakit sumakit ulit tiyan niya. Its because of rebound gastric acid hypersecretion.* - d/t gastrin induced hyperplasia and hypertrophy of histamine secreting ECL cells - *🖊 decreased acid secretion mag fefeedback mechanism (negative) sa G and ECL cell, so mag hyperplasia and dadami secretion nila so pag tanggal ng PPI mataas gastrin, histamine at acid secretion levels kaya mataas rin symptoms* - Occur after short term use (2 months); symptoms last up to 2 months of discontinuation - 📖 Katzung: abates 2-4 weeks after gastrin and acid secretion normalize - Treatment: gradually taper PPI or (TEMPORARILY) SHIFT to an H2RA - A/E: - Patients \>65 y/o = Higher risk - Long-term use: Increase bone fracture (hip) in women - Higher incidence of CAP, C. difficile disease - *🖊 If you limit the acid, it limits the defenses against C. difficile / CAP* - Iron, Vitamin B12 and Magnesium deficiency - *🖊 Hypermagnesemia can be there* - Decrease intrinsic factor production = Vitamin B12 deficiency anemia uncommon - May exert negative effect on antiplatelet action of Clopidogrel - Competes with same cytochrome P450 - (Katzung) Use pantoprazole or rabeprazole for patients on Clopidogrel - Give PPI at breakfast and Clopidogrel at bedtime - Nametabolizee na kasi yung PPI mo and irreversible kasi yung effect ng pantoprazole - So less CYP450 interaction A graph with black and white text Description automatically generated **Figure 10. Evidence supporting the potential adverse effects of PPI** CYTOPROTECTIVE AGENTS {#cytoprotective-agents.TransOutline} ===================== +-----------------------+-----------------------+-----------------------+ | **Table 2. | | | | Cryoprotective | | | | Agents** | | | +=======================+=======================+=======================+ | **Agents and Types** | **MOA** | **A/E & Toxicity** | +-----------------------+-----------------------+-----------------------+ | Sucralfate | Insoluble in water ➡ | Constipation (most | | | viscous paste in | common) Avoid in | | \*Sucralfate 1g QID | stomach and duodenum | renal insufficiency➡ | | | that binds in sites | increase aluminum | | | of active ulcers | induced neurotoxicity | | | | hypophosphatemia and | | | \*Physiochemical | gastric bezoar (rare) | | | barrier | | | | | | | | \*Promote trophic | | | | action | | | | | | | | \*Enhance | | | | prostaglandin | | | | synthesis | | | | | | | | \*Increase mucus and | | | | bicarbonate secretion | | | | | | | | \*enhance mucosal | | | | defense, repair | | +-----------------------+-----------------------+-----------------------+ | Bismuth containing | Unclear | Black stools | | preparation | | | | | | Constipation | | \*Colloidal bismuth | | | | SO4 | | Darkening of Tongue | | | | | | \*Bismuth | | Neurotoxicity (long | | Subsalicylate | | term use) | +-----------------------+-----------------------+-----------------------+ | Prostaglandin analogs | Rapidly absorbed | Diarrhea (10-30%) | | | | | | Misoprostol 200 mcg | Enhances mucosal | Uterine | | QID | integrity and repair | Bleeding/Contractions | | | | | | | | C/I in pregnancy | | | | (Abortifacient) | | | | | | | | Banned in PH | +-----------------------+-----------------------+-----------------------+ SUCRALFATE {#sucralfate.TransSub-subtopic2} ---------- - Salt of sucrose complexed to sulfated aluminum hydroxide - Forms vicious, tenacious paste that bind to ulcers/erosions up to 6 hours; Less than 3 % is absorbed, mostly are excreted in the feces - MOA: negatively charged sucrose (green) bind to positively charge proteins at the ulcer base  protects mucosa and stimulates PG and HCO3 secretion - **Refer to Figure 12 (see also in appendix)** - Administration: - Sucralfate 1g 4x daily on an EMPTY stomach, 1H before meals - Administered as a slurry through NGT - May still be of use in stress-related bleeding if other acid-inhibiting therapies (antacids, H2RA, PPI) may increase nosocomial pneumonia - Side effects - Not so absorbed, virtually no systemic side effect - May impair absorption of other medications PROSTAGLANDIN ANALOGS {#prostaglandin-analogs.TransSub-subtopic2} --------------------- - Stimulation of the prostaglandin receptors (prostaglandin E and F) - Prostaglandin E1 analog - Misoprostol 200 mcg QID - Preferred in BOTH acid inhibition and mucosal protection - Pharmacokinetics - Half-life: \ - Pharmacokinetics - Dissociates in the stomach as bismuth and salicylate - In PUD we are more concerned with Bismuth - But be aware of salicylate because it can cause toxicity - Bismuth is retained in GIT and excreted (99%) via stool - A/E - Harmless: blackening of the stool; darkening of the tongue - Bismuth Toxicity (when prolonged use) - Encephalopathy (ataxia, headache, confusion, seizure) - Main risk factor: prolonged use - Salicylate toxicity for bismuth subsalicylate - Avoid in renal insufficiency A diagram of a human body Description automatically generated **Figure 12. Diagram for different medication therapies for acid inhibition** PHARMACOLOGIC THERAPY: ESOPHAGEAL VARICES {#pharmacologic-therapy-esophageal-varices.TransOutline} ========================================= - Common differential diagnosis for Bleeding Peptic Ulcer disease. - Especially for Alcoholics SOMATOSTATIN {#somatostatin.TransSubtopic1} ------------ - 14-amino acid peptide - Dose 250mcg/hour IV infusion, 3-5 days - Very Short half-life (3 Minutes) - Pag very short half-life need to be given via IV - Physiological effect - Inhibitory effects directly to the parietal cell - Inhibits secretion of hormones/neurotransmitter including **gastrin, histamine**, cck, glucagon, GH, insulin, secretin, pancreatic polyupeptide, VIP, 5-HT; as well as secretion of some anterior pituitary hormones - Slows GI Motility and Inhibit GB contraction - **Reduces portal and splanchnic blood flow** by reducing glucagon and other gut peptides - Inhibit secretion of some anterior pituitary hormone - Variceal hemorrhage -- decreases blood flow - TLDR: LAHAT TITIGIL  **Figure 13. Effects of Somatostatin** OCTREOTIDE {#octreotide.TransSubtopic1} ---------- - Synthetic octapeptide with actions similar to somatostatin - Half-life - 1.5 hours -- IV - Duration of action: 6-12 hours -- Subcutaneous - Uses - Neuroendocrine tumors (carcinoid, VIPoma) - Reduces secretory diarrhea, flushing, and wheezing; may slow tumor progression - Diarrheas (Dose-dependent) - Stimulates on low dose (50mcg) - Inhibits (100-250mcg) - Pituitary Tumors (Acromegaly) - Variceal Hemorrhage - Adverse Effects - Impaired pancreatic secretion - Steatorrhea; can lead to Fat soluble Vitamin Deficiency - Hypo/Hyperglycemia - GU Motility alteration (Dose Dependent - Nausea, Abdominal Pain, Flatulence - 50mcg (in low doses) -- diarrhea - 100-250 -- prevents diarrhea - Impaired Gallbladder contractility - Accumulation of Gallbladder sludge - Gallstones - Acute Cholecystitis - Endocrine - Hypothyroidism - Bradycardia VASOPRESSIN {#vasopressin.TransSubtopic1} ----------- - Vasopressin used if Octreotide is not available - Polypeptide secreted by the hypothalamus - Stored in posterior pituitary. - For Variceal Hemorrhage: Potent Arterial Vasoconstrictor - Splanchnic vasoconstriction - Reduced blood flow - Lowers Portal Venous Pressure - Dose 0.04IU/min -- IV **Table 3. Vasopressin Receptors** ------------------------------------ ------------------------ -------------------------------------------------- **Receptor** **Location** **Stimulation** V1R Vascular Smooth Muscle Intracellular Ca inc. - vasoconstriction V2R Renal Collecting Duct ADH analog -- retains water and inc. urine conc. V3R Pituitary Inc serum cortisol V1 Receptor lang ang gusto mo inhibit *🖊* *Pero si Vasopressin kumakapit sa tatlo* Less preferred than Somatostatin and Octreotide Adverse effects Hypertension Myocardial Ischemia/Infarction Mesenteric ischemia (d/t vasospasms) Antidiuretic effect Retention of Water Dilutional HYPOnatremia Pulmonary edema Coadminister with Nitroglycerin To control hypertension and ischemia Further reduces portal venous pressure by reduction of portohepatic vascular resistance Reduces coronary and peripheral vasospasms Terlipressin Vasopressin analog with fewer side effects NONSELECTIVE BETA BLOCKERS (PROPANOLOL, NADOLOL) {#nonselective-beta-blockers-propanolol-nadolol.TransSubtopic1} ------------------------------------------------ - Reduces portal venous pressure via decrease in portal venous inflow - More effective than selective B1 blocker in reducing portal pressures - Indications - Px with cirrhosis and esophageal varices WITHOUT variceal hemorrhage - *🖊 If may history gumagana parin pero walang mortality benefit* THERAPEUTICS FOR PEPTIC ULCER DISEASE {#therapeutics-for-peptic-ulcer-disease.TransOutline} ===================================== PEPTIC ULCER {#peptic-ulcer.TransSubtopic1} ------------ - Disruption in the mucosal integrity of the stomach/duodenum - Leads to local defect or excavation due to local inflammation - Ulcers - Breaks in the submucosal surface \5mm in size - Depth to the **submucosa** *(🖊 If mucosa only, it's only an erosion)* - \>90% of patients with dyspepsia **DO NOT** have ulcer - **Majority** of patients with peptic ulcers are **ASYMPTOMATIC** GASTRIC VS DUODENAL {#gastric-vs-duodenal.TransSub-subtopic2} ------------------- +-----------------------+-----------------------+-----------------------+ | **Table 4. Gastric | | | | vs. Duodenal Ulcer** | | | +=======================+=======================+=======================+ | | **Gastric Ulcer** | **Duodenal Ulcer** | +-----------------------+-----------------------+-----------------------+ | **Pain** | - Onset ½ to 1 hour | - Onset 2 to 3 hour | | | post meals | post meals (worst | | | | at night) | | | - Greater with | | | | meals  **weight | - Decreased with | | | loss** | meals  **weight | | | | gain** | +-----------------------+-----------------------+-----------------------+ | **H. pylori | Around 70% | Around 90% | | infection** | | | +-----------------------+-----------------------+-----------------------+ | **Mechanism** | Decreased mucosal | Decreased mucosal | | | protection | protection, increased | | | | gastric acid | | | | secretion | +-----------------------+-----------------------+-----------------------+ | **Other cause** | NSAIDS | ZES | +-----------------------+-----------------------+-----------------------+ | **Risk of carcinoma** | Increased: **biopsy | Generally benign: | | | with margins r/o | biopsy will show | | | carcinoma** | **Hypertrophy of | | | | brunner glands** | +-----------------------+-----------------------+-----------------------+ | **Peak Age** | 50-60 years | 35-45 years | +-----------------------+-----------------------+-----------------------+ | **Common | MC location for | Anterior ulcers | | Complication** | perforation = lesser | perforate; Posterior | | | curvature of the | ulcers hemorrhage | | | stomach **(Left | **(gastroduodenal | | | gastric artery)** | artery)** | +-----------------------+-----------------------+-----------------------+ | **Epidemiology** | Peak incidence at 6th | Decreasing incidence | | | decade (later) | with declining H | | | | pylori frequency | +-----------------------+-----------------------+-----------------------+ | **Etiology** | H pylori and NSAID | H pylori and NSAID | | | induced injury | induced injury | | | \*Gastric acid output | **\*Higher basal/ | | | (basal/stimulated) is | nocturnal gastric | | | normal or decreased | acid** | | | in GU. | | | | | \*HCO3 secretion | | | **\*Impaired mucosal | decreased in duodenal | | | defense factor** | bulb | +-----------------------+-----------------------+-----------------------+ | **Location** | Distal to the | First portion of the | | | junction between the | duodenum | | | antrum and acid | | | | secreting mucosa | Within 3cm from | | | | pylorus | | | **4 types** | | +-----------------------+-----------------------+-----------------------+ | **Malignancy** | COMMON. Should be | RARE | | | biopsied | | | | | | | | - 3cm in size | | | | | | | | - Associated with a | | | | mass. | | +-----------------------+-----------------------+-----------------------+ | **Abdominal Pain** | COMMON in BOTH; Poor | | | | predictive value | | | | (pain ≠ ulcer) | | | | EPIGASTRIC, burning | | | | or gnawing | | +-----------------------+-----------------------+-----------------------+ | **Temporal | | 90 min to 3h post | | Relations** | | meal, **awakens | | | | patient from sleep** | +-----------------------+-----------------------+-----------------------+ | **Associated | Nausea, **Weight | | | symptoms** | Loss** | | +-----------------------+-----------------------+-----------------------+ | **Food** | Pain **precipitated** | **Relieved** by food | | | by food. | and antacid | +-----------------------+-----------------------+-----------------------+ | **PE Findings** | Epigastric Tenderness | | | | is most frequent | | | | finding in GU or DU | | +-----------------------+-----------------------+-----------------------+ COMPLICATIONS OF PUD {#complications-of-pud.TransSub-subtopic2} -------------------- +-----------------------+-----------------------+-----------------------+ | **Table 5. | | | | Complications of | | | | PUD** | | | +=======================+=======================+=======================+ | **Complication** | **History and PE | **Notes from HPIM** | | | Findings** | | +-----------------------+-----------------------+-----------------------+ | ⭐ **GI Bleed** | History: Tarry Stools | - Most common | | | or Coffee ground | complication | | | emesis | | | | | - Greater in | | | PE: Tachycardia and | elderly (NSAID | | | Orthostasis | use) | | | | | | | | - High 30-day | | | | mortality | | | | (2.5-10%) most | | | | from nonbleeding | | | | causes (ie MODS, | | | | pulmonary | | | | complication, | | | | malignancy) | | | | | | | | - \>50% bleed | | | | without warning | | | | signs/sx | +-----------------------+-----------------------+-----------------------+ | **Perforation** | History: sudden | - Second most | | | onset, severe | common | | | generalized abdominal | | | | pain (peritonitis) | - Also greater in | | | | elderly (NSAID | | | PE: severely tender, | use) | | | board like abdomen | | | | | - GU\>\>DU (due to | | | | decreasing H | | | | pylori) | +-----------------------+-----------------------+-----------------------+ | **Penetration** | History: change in | - DU penetrate | | | pain pattern (i.e. | posteriorly | | \*Form of perforation | non-remitting with | (pancreas) | | | food; radiate to the | | | \*Ulcer bed tunnels | back (pancreatitis) | - GU → L hepatic | | to an organ | | lobe; colon | | | | (gastrocolic | | | | fistula) | +-----------------------+-----------------------+-----------------------+ | **Gastric Outlet | History: New onset | - Least common | | Obstruction** | early satiety, | complication | | | increase postprandial | | | | abd pain, N/V of | - d/t ulcer | | | undigested food, | inflammation/edem | | | weight loss | a | | | | OR obstruction | | | PE: succussion splash | from scar tissue | | | | at peripyloric | | | | area | | | | | | | | - Tx: endoscopic | | | | dilation vs | | | | surgical | | | | intervention for | | | | scarred tissues. | +-----------------------+-----------------------+-----------------------+ ETIOLOGY OF PEPTIC ULCER DISEASE {#etiology-of-peptic-ulcer-disease.TransSub-subtopic2} -------------------------------- - Helicobacter pylori Infection - Nonsteroidal Anti-inflammatory Drugs (NSAIDs) #### *HELICOBACTER PYLORI* INFECTION {#helicobacter-pylori-infection.TransSub-subtopic3} - Account for majority of PUD (DU\>\>GU) - Associations: - Peptic Ulcer Disease - Gastric Mucosa Associated Lymphoid Tissue (MALT) Lymphoma - Gastric Adenocarcinoma - End result is an interplay of bacterial/ host factors **Figure 14. Bacterial and Host Factors** - ***Helicobacter pylori*** - Gram negative microaerophilic rod - Deep layer between mucus layer and gastric epithelium - Does not appear to invade cells - **Virulence Factors:** - Urease: neutralize gastric acid  gastric mucosal injury by ammonia - Exotoxins: vacuolating toxin (vacA)  gastric mucosal injury - Secretory enzymes (mucinase, protease, lipase)  gastric mucosal injury  **Figure 15. Virulence Factors of H. pylori** - **Epidemiology** - Prevalence varies worldwide -- depend largely on overall standard of living - Industrialized countries → less rate of infection - Risk Factors that include colonization rate: poor socioeconomic status and less education - Other risk factors: birth/residence in a developing country, domestic crowding, unsanitary living conditions, unclean food or water, exposure to gastric content of infected individual - Transmission: person to person - Oral to oral OR fecal to oral - Virtually always associated with **chronic active gastritis** - Only 10-15% develop frank ulceration #### NATURAL HISTORY OF *H. PYLORI* INFECTION {#natural-history-of-h.-pylori-infection.TransSub-subtopic3} **Figure 16. Natural History of *H. pylori* infection** - 🖊 Initially as H. pylori enters magkakaroon ng acute infection - 🖊 Most are asymptomatic - 🖊 Occasionally may epigastric pain pero mawawala - Chronic H. pylori infection may manifests into - Antral predominant gastritis Duodenal ulcer - Non atrophic pangastritis MALT Lymphoma - Corpus-predominant atrophic gastritis - Usually asymptomatic - Develop into Gastric Ulcer - More linked to gastric cancer - Can lead to intestinal metaplasia - Dyspepsia - Eventually gastric cancer #### *H. PYLORI* ERADICATION {#h.-pylori-eradication.TransSub-subtopic3} - Major role in prevention of PUD recurrence - Documented eradication of *H.pylori* - Dramatically decreases ulcer recurrence to \H2RA) then rest - 🖊 *Example: prescribe OCA for 2 weeks AND continue Omeprazole for another 2 weeks so your regimen for omeprazole will be 4 weeks in total.* - Document *H. pylori* eradication 4 wks after completion of antibiotics - Options: Laboratory-based monoclonal stool antigen OR urea breath test - Patients must be OFF antisecretory agents (PPI, H2RA) during testing - Serologic testing is NOT useful; will NOT become undetectable with TX. - Biopsy the ulcer if gastric - Initial multiple biopsies of the body and the fundus - Repeat endoscopy to document healing in 8-12 weeks, rebiopsy if ulcer still present. (70% of ulcers that had partial healing → eventually was malignant) REFRACTORY ULCER {#refractory-ulcer.TransSubtopic1} ---------------- - Gastric ulcer that fails to heal in 12 weeks - Duodenal ulcer that fails to heal in 8 weeks - Exclude poor compliance or persistent H. pylori, NSAID use - Cigarette smoking must be eliminated - Rule out gastric acid hypersecretory state (ie. Zollinger Ellison Syndrome/gastrinoma) 🖊 *test for fasting gastrin levels* - More than 90% will respond to higher dose of PPI (Omep 40 OD or Lansop 60 OD) - Consider surgical therapy NSAID-INDUCED PEPTIC ULCER DISEASE {#nsaid-induced-peptic-ulcer-disease.TransOutline} ================================== ETIOLOGY OF BPUD {#etiology-of-bpud.TransSubtopic1} ---------------- Represents a group of most used medication worldwide Side effects and complications Nausea and dyspepsia (50%-60%) Endoscopy documented peptic ulcer (15%-30%) May be complicated by bleeding/perforation 4-5% develop symptomatic ulcer in 1 year Small (75mg) dose can lead to serious GI ulceration Seen in hospitals -- px with myocardial infarction Can lead to hematemesis and melena - H. pylori increase risk of PUD associated GI bleed in chronic users of low dose aspirin - 70% gastric ulcer - 90% duodenal - 🖊 ***Obliged to treat for H.pylori*** - Other Risk factors: - Advanced Age - History of ulcers - Steroid use - High/Multiple dosage of NSAID - Anticoagulants/Clopidogrel - Serious/Multisystem disease - Possible Risk factors - H. pylori infection: 🖊 *independently ↑ risk on top of NSAID use* - Cigarette smoking - Alcohol consumption MECHANISM OF DAMAGE {#mechanism-of-damage.TransSubtopic1} ------------------- - "Ion Tapping" (Direct Toxicity) - NSAID is trapped in the cell in ionized form - 🖊 *Since this is negatively charged, it will attract more H+ ion more pepsin  more damage  affect healing* - H+ and Pepsin diffuses back  Increased cellular damage  **Figure 19. NSAID induced mucosal injury** - 🖊 ***Figure Interpretation*** - Stasis which will result in Ischemia - Epithelial effects (due to prostaglandin depletion) - Increased HCl secretion - Decreased Mucin secretion - Decreased HCO~3~ secretion - Decreased Surface active phospholipid secretion - Decreased Epithelial cell proliferation - [All of these injuries will eventually affect the healing process] NSAID RELATED PUD {#nsaid-related-pud.TransSubtopic1} ----------------- - Medical intervention include **treatment of active ulcer and prevention of future injury** - [Ideally the injurious agent (NSAID) should be stopped] - Cessation of NSAID is not always possible due to severe underlying disease - 🖊 *E.g. Stroke patients, MI patients* - **If this is not possible, then treatment with one of the inhibitory agents (PPI, H2RA) is indicated** - Only PPI can heal GU or DU independent of whether NSAIDS are discontinued +-----------------------------------+-----------------------------------+ | **Table 6. Recommendation for | | | Treatment of NSAID-related | | | Mucosal Injury** | | +===================================+===================================+ | **Clinical Setting** | **Recommendation** | +-----------------------------------+-----------------------------------+ | **Active ulcer** | H2 receptor antagonist or PPI | | | | | | PPI | +-----------------------------------+-----------------------------------+ | **Prophylactic therapy** | Misoprostol | | | | | | PPI | | | | | | Selective COX-2 inhibitor | +-----------------------------------+-----------------------------------+ | **H. pylori infection** | Eradication if active ulcer | | | present or there is a past | | | history if peptic ulcer disease | +-----------------------------------+-----------------------------------+ - 🖊 ***Table Interpretation*** - If NSAID can be discontinued  Switch to H2 receptor antagonist or PPI - If NSAID is continued  Give PPI - Prophylactic therapy - Misoprostol (not available) - PPI (used in the Philippines) - Selective COX-2 inhibitors (🖊especially for elderly patients with arthritis) consider naproxen or celecoxib low dose - Always check for H. pylori infection and eradicate it APPROACH TO PRIMARY PREVENTION OF NSAIDS {#approach-to-primary-prevention-of-nsaids.TransSubtopic1} ---------------------------------------- - Avoiding the agent - Use of highly selective COX2 inhibitor (celecoxib, rofecoxib) (SE: increased CV risk) - 🖊 *Naproxen is the safest for CV risk* - Using the lowest dose possible - Use of NSAIDS that are theoretically less injurious - Naproxen \>\> ibuprofen  less GI and CV toxicity - Benefit effect may be eliminated at higher doses - Use of topical NSAID preparations - Use of Concomitant Medical Therapy - A proton pump inhibitor + Misoprostol 200 mcg QID (if tolerated) - ⭐ Note: PPIs: superior than high-dose H2RA (Famotidine 40) - ⭐PPIs: only proven agent that is capable of healing ulcers - **Individuals with CV + GI risk who require aspirin must be considered for non-NSAID therapy** - [If this is not possible, gastric protection must be considered] - Long-term NSAID therapy  Do H. pylori test and treat if positive +-----------------------+-----------------------+-----------------------+ | ⭐**Table 7. Guide to | | | | NSAID Therapy** | | | +=======================+=======================+=======================+ | | **No/Low NSAID GI | **NSAID GI Risk** | | | risk** | | +-----------------------+-----------------------+-----------------------+ | **No CV risk** (no | Traditional NSAID | Coxib or | | Aspirin) | | | | | | Traditional NSAID + | | | | PPI or misoprostol | | | | | | | | Consider non-NSAID | | | | therapy | +-----------------------+-----------------------+-----------------------+ | **CV risk** (consider | Traditional NSAID + | A gastroprotective | | Aspirin) | PPI or misoprostol if | agent must be added | | | GI risk warrants | if a traditional | | | gastroprotection | NSAID is prescribed | | | | | | | Consider non-NSAID | Consider non-NSAID | | | therapy | therapy | +-----------------------+-----------------------+-----------------------+ - 🖊 ***Table Interpretation*** - GI Risk: are there any factors for GI bleeding or previous GI Bleeding (e.g. hematemesis, melena, complaints of persistent epigastric pains) - CV risk: Major CV events (e.g. stroke, MI) - If no CV risk and GI risk  Traditional NSAID - If no CV risk but with GI risk  Celecoxib or Trad. NSAID + PPI - If with CV risk but no GI risk  Traditional NSAID + PPI or misoprostol - If both CV and GV risk  Gastroprotective agent (PPI) + NSAID STRESS-RELATED MUCOSAL INJURY {#stress-related-mucosal-injury.TransOutline} ============================= - Erosive gastric mucosal changes or frank ulceration among patients in **shock, sepsis, massive burns, severe trauma, or head injury** - Head Trauma (Cushing's Ulcer) - Severe Burns (Curling Ulcer) - Most common in acid-producing portions of the stomach (fundus, body) - **GI Bleed in the most common presentation** - Risk factors for bleeding: Respiratory Failure requiring Mechanical Ventilation, Underlying Coagulopathy - 48-72 hours after injury STRESS ULCER PROPHYLAXIS {#stress-ulcer-prophylaxis.TransSubtopic1} ------------------------ - 🖊 ***YOU HAVE TO GIVE IT!*** - 🖊 *Failure to give prophylaxis will result in catastrophic results* - High mortality in stress-induced clinically important GI bleeding (\40-year-old  Check for alarm symptoms If negative, proceed with the non-invasive H. pylori Testing (mandatory) - If negative for H. pylori  Start on empiric trial H2 blocker (🖊 *or PPI*) - If positive for H. pylori  Start anti-Hp therapy  4 week after therapy, confirm eradication  If symptoms occur/remain  Refer to gastroenterologist ⭐ **If positive with alarm symptoms  Refer to gastroenterologist (need endoscopy)**  ⭐**Figure 21. Alarm symptoms** A table of test results Description automatically generated **Figure 22. Test for Detection of H. pylori** 🖊 ***Figure Interpretation*** Priority is the non-invasive tests Urea breath test and Stool Antigen test are of the same sensitivity and specificity however urea breath test is simpler and rapid A lot of patients refuse to submit stool samples for stool antigen testing Rapid urease test outperforms the rest of the invasive test Get a sample of the ulcer via endoscopy and if positive, will change color from purple to yellow Can result in false negative with recent use of PPIs, antibiotics, or bismuth compounds (🖊same as the urea breath test) GASTROESOPHAGEAL REFLUX DISEASE (GERD) {#gastroesophageal-reflux-disease-gerd.TransOutline} ====================================== - Esophagitis → refluxed gastric acid and pepsin causes necrosis of esophageal mucosa causing erosions and ulcers. - Due to the Esophagogastric junction incompetence - Mechanisms: - Transient LES relaxation (vasovagal reflex caused by gastric distention) → accounts for 90% of reflux (🖊most *common mechanism)* - LES hypotension - Anatomic distortion (eg hiatal hernia) **SYMPTOMS** - Heartburn and Regurgitation are typical symptoms of GERD. - 🖊 minsan *parang may "water brash" sa likod ng throat, parang mapait na acid reflux the bitter taste sa mouth* - Very common in medical students na mahilg magkape - Dysphagia and Chest pain are less common. - The perceived frequency and severity of heartburn correlate poorly with the severity of esophagitis. **DIFFERENTIAL DIAGNOSIS** - With chest pain, cardiac disease must carefully be considered. - Extraesophageal syndromes: chronic cough, laryngitis, asthma, dental erosions. - Chronic reflux complications: stricture formation; adenocarcinoma **DIAGNOSTICS** - Usually clinical. - EGD is reserved for those with warning signs - Important to distinguish differential diagnosis: - **Erosive Esophagitis at Esophagogastric junction → endoscopic hallmark of GERD** - Peptic esophagitis: solitary and distal ulceration VS - Infectious esophagitis: Diffuse, Punctate ulcerations VS - Pill esophagitis: singular ulcers; deep at points of luminal narrowing near the carina; spares distal esophagus VS - Barrett's metaplasia (🖊most severe histologic consequence of GERD) → tongues of salmon colored mucosa extending proximally from GEJ → precursor of adenocarcinoma - Refer to **Figure 19** for the Alarm Symptoms **TREATMENT** **NONPHARMACOLOGIC** - Dietary modification - AVOID: - Foods that reduce LES pressure (fatty food, alcohol, spearmint/peppermint, coffee/tea) - Acidic foods that are inherently irritating (citrus, tomato based food) - Adopt behaviors that minimize reflux and/or heartburn - Elevate HOB (head of bed); Avoid eating before retiring (to bed) - Weight Reduction → most broadly applicable recommendation. - Strong epidemiologic impact bet. BMI and GERD is beyond dispute **PHARMACOLOGIC** **Inhibition of gastric acid secretion → does not ameliorate reflux but allow esophagitis to heal.** Common management strategy is **INDEFINITE PPI/H2RA as needed for symptom control.** 🖊 *Anong problem natin kapag nagbaba tayo ng recommendation ng indefinite PPI/H2RA treatment? Ang problem dito is that H2RA will induce tolerance, habang tumatagal yung effect niya nagdwindle. Eventually sasakit ang tiyan niyan, so you should shift to PPI* 🖊 *Yung problem naman with indefinite PPI are the complications such as iron malabsorption, vitamin B12 deficiency, hip fractures in the elderly* 🖊 *And if sudden discontinue of PPI, magkakaron ng reflux or rebound symptoms because of increased gastrin and histamine*🖊And *if sudden discontinue of PPI, magkakaron ng reflux or rebound symptoms because of increased gastrin and histamine* Drugs: **Proton Pump Inhibitor** → more efficacious than H2RA H2 Receptor Antagonist **SURGICAL: LAPAROSCOPIC NISSEN FUNDOPLICATION** - Proximal stomach is wrapped around the distal esophagus to create anti-reflux barrier - Similar efficacy with PPI therapy - Side effects: surgical morbidity and mortality, postoperative dysphagia, failure or breakdown requiring reoperation, inability to belch, increased bloating, flatulence.  **Figure 23. Laparoscopic Nissen Fundoplication** GASTROINTESTINAL BLEEDING {#gastrointestinal-bleeding.TransOutline} ========================= **SOURCES OF GI BLEEDING** - Upper GI Bleeding - Peptic Ulcer Disease (most common cause) - Erosive Disease - Mallory Weiss Tears - Dieulafoy lesion ➔ aberrant vessel in the mucosa bleeds from a pinpoint mucosal defect **Figure 24. Duodenal ulcers. (A) Ulcer with a small flat, pigmented spot in its base. (B) Ulcer with a visible vessel (arrow) in a patient with recent hemorrhage** **PHARMACOLOGIC MANAGEMENT OF UGIB FROM BLEEDING PUD** ⭐ **High dose, CONSTANT infusion IV proton pump inhibitor is necessary!** ⭐ **Omeprazole 80mg IV bolus NOW then 8mg/h IV infusion** ⭐ **Recent study show that high dose intermittent PPI (Omeprazole 40mg IV q12H) is non-inferior to the drip**. Objective is to **sustain intragastric pH \>6** to enhance clot stability Decreases further bleeding for **HIGH-RISK ulcers** ([actively bleeding, nonbleeding visible vessel, adherent clot]) when given after endoscopic therapy. ⭐ **Standard dose of oral PPI is enough for those with LOW-RISK lesions (flat pigmented spot or clean base ulcer) without the need for endoscopic therapy** ⭐ **Omeprazole 40mg tablet 30 mins before breakfast.** Use of PPI at presentation decreases high risk ulcer stigmata (high risk bleeding) and need for endoscopic therapy but does not improve further bleeding, surgery or death. Upper endoscopy should be performed **within 24 hours** in most patients hospitalized with UGIB (🖊 *nag hematemesis or melena*) **Erythromycin** may be given 250mg 30-90 min [prior] to endoscopy to improve visualization Risk stratification: [Low-risk] patients➔ **less** hospital stay; may safely discharge. [High-risk] patients ➔ **early hemostatic therapy** at endoscopy (varices, actively bleeding ulcers) ⭐ **Figure 25. Suggested algorithm for patients with acute upper GI bleeding based on endoscopic findings *(might be asked in the exams, case questions)*** **Figure 26. Suggested algorithm for patients with acute lower GI bleeding** PREVENTION OF REBLEEDING {#prevention-of-rebleeding.TransSubtopic1} ------------------------ - Risk is 10-50% if no preventive strategy employed - Eradication of *H. pylori* - Decreases rebleeding to \33% BSA, major intracranial disease and severe medical illness including ventilator dependence and coagulopathy - **[There is small benefit for use of PPIs for clinically important bleeding without a difference in mortality or infections]** (C. difficile, pneumonia) ➔ only consider for those with high-risk features. - **[PPI \>\> H2RA in reduction of overt and clinically important UGIB without difference in mortality or nosocomial pneumonia]**  **Figure 27. Erosions (L) and Esophageal Varices (R)** ESOPHAGEAL VARICES {#esophageal-varices.TransSubtopic1} ------------------ - Patients with UGIB from esophageal varices have poorer outcomes than with other sources. - Refer to **Figure 27**: 🖊️ This may result in massive bleeding - You ligate here and give vasoactive medications ➔ octreotide ➔ to decrease the caliber of this vessel TREATMENT {#treatment.TransSub-subtopic2} --------- - Endoscopic ligation and **IV Vasoactive Medication (Octreotide, Somatostatin, Terlipressin) x 2-5 days** - Action of Octreotide- constricts the splanchnic circulation resulting in less bleeding - Action of Vasopressin (co-administered with nitroglycerin) - Further reduces portal venous pressure by reduction of portohepatic vascular resistance - Reduce coronary and peripheral vasospasm ➔ prevent coronary/ mesenteric ischemia - If bleeding esophageal varices ➔ add endoscopic injection of tissue adhesive (cyanoacrylate)  **Figure 28. Veins** PROPHYLAXIS {#prophylaxis.TransSub-subtopic2} ----------- - Upper endoscopy (active cirrhosis ➔ q2yr; inactive ➔ q3yr) THEN Endoscopic Ligation, AND - **[Beta blockers to decrease splanchnic pressures (Propranolol/ Nadolol)- nonselective ]** - **[SBP \> 90mmHg; HR 55-60]** - Trans jugular Intrahepatic Portosystemic Shunt (TIPS) - for those with persistent or recurrent bleeding despite endoscopic and medical therapy; and in those with advanced liver disease (Childs Pugh Score 10-13; Class B and C) **Figure 29. Direct Intrahepatic Portosystemic Shunt** - 🖊️ *Problem with DIPS- dahil hindi siya dumaan sa liver, potentially may mga toxins na can cause hepatic encephalopathy* OTHER RECOMMENDATIONS {#other-recommendations.TransSub-subtopic2} --------------------- - Additional management for Cirrhotic patients with UGIB: - Antibiotics (Ceftriaxone) decrease bacterial infection (SBP), rebleeding and mortality - **[IV Vasoactive medication (octreotide) may control bleeding in the 1st 12 h of presentation]** - Endoscopy is recommended at the time of hepatic decompensation. - Blood Transfusion: Indicated at Hgb \