Acid Peptic Disorders The Spotlight is On!

Charmaine Rochester, PharmD, CDE, CDM, BCPS Asst Professor, University of Maryland School of Pharmacy

Objectives
At the end of this presentation, the student should be able to: Review the anatomy and physiology of the stomach Discuss the pathophysiology, risk factors, signs and symptoms, complications and diagnosis of ulcers Given a drug associated with ulcer formation, discuss the proposed mechanism of ulceration Discuss the pathophysiology, risk factors, signs and symptoms, and complications of gastroesophageal disease (GERD)

Acid Peptic Disorders

Dyspepsia Peptic Ulcers Duodenal Ulcers Stress Ulcers Gastroesophageal Reflux Disease (GERD) Gastric Cancers

Dyspepsia
A constellation of upper abdominal symptoms Accounts for up 40 - 70% of GI complaints Significant societal costs Causes

PUD,

GERD, gastric cancer Food, medications, but commonly idiopathic

Normal Stomach Anatomy

Gastric Antrum

Physiology: The Secretory Epithelial Cells

1. Mucus cells Mucus 2. Parietal cells HCL 3. Chief Cells Pepsinogen 4. G cells Gastrin
Surface Epithelium

Opening of gastric pit

Parietal cell

Chief Cell Parietal cell

Gastric Acid and its Function

Gastric Acid Contents

HCl,

salts, pepsin, mucus, water, intrinsic factor, bicarbonate

Gastric Acid Function

to

kill micro-organisms to activate pepsinogen breaks down connective tissue in food

Mucosal Defenses/Protection

Mucus layer on gastric surface

Mucosal

barrier to damage

Bicarbonate: Abundant in mucus layer

Prevent

acidic damage and auto digestion blood flow and cell regeneration by tight cell junctions

Prostaglandins are cytoprotective

Increase

Mucosal integrity
Maintained

Epidemiology of Peptic Ulcer Disease (PUD)

Development of PUD 4 -10% of Americans Gastric Ulcer peaks 55-65th year Duodenal Ulcer increases with age until 60 years

Pathophysiology of Peptic Ulcer Disease (PUD)

Luminal Aggressors H. pylori NSAIDs Acid Pepsin

Mucosal Defenses
Bicarbonate Mucus Prostaglandin

Growth factor
Mucosal regeneration

Goldin GF, et al. Gastr Endosco Clin Nor Am. 1996;6;505-526. Saggioro A, et al. Ital J Gastroenterol. 1994;269(suppl 1):3-9. Modlin IN, et al. Acid Related Diseases. 1998;317-362.

Risk Factors/Aggressors of PUD

Major Factors
Helicobacter NSAIDs Cigarette

Pylori

smoking Acid and pepsin

Other Factors
Genetics
?Foods ?Stress

Helicobacter Pylori

Bacteria

Gram ve spiral bacterium 40% of patients >60 yrs are +ve for H.pylori Transmitted: possibly person to person Most common cause of antral gastritis
Cytotoxin Breakdown of mucosal defenses Adherence to epithelial cells Increase gastrin releasing peptide (GRP) Decrease bicarbonate secretion

Mechanism of gastric injury

Drug Induced PUD

Drug Reserpine. TCA, Anticholinergics Alcohol Action sympathetic, parasympathetic tone acid output acid output (secretagogue) Causes gastritis, bleeding is possible, not thought to cause ulcer acid production (even decaffeinated); No in ulcer formation, lowers (LES) so may cause GERD symptoms Iron, K+, Tetracyclines Corrosive to mucosa

Caffeine

NSAIDS

Inhibits prostaglandin synthesis (COX inhibition) Disrupts functional mucosal integrity mucosal blood flow cell regeneration Direct GI irritation Antiplatelet effect (causing bleeding) Ion trapping acid (basal and maximal stimulation) secretion

Risk Factors for NSAID-Induced GI Injury

History of ulcer or GI complications Increasing age Concomitant anticoagulation therapy Concomitant corticosteroid use High dose NSAID use or concomitant aspirin/NSAID use

Conditions Associated with PUD

Fig. 40-2. Feldman: Sleisenger & Fortrans Gastrointestinal and Liver Disease, 7th ed.

Smoking

Impairs ulcer healing Promotes ulcer recurrence Increases the likelihood of ulcer complications Mechanisms

Stimulate gastric acid secretion Stimulate bile salt reflux Causes alteration in mucosal blood flow Decrease mucus secretion Reduces prostaglandin synthesis Decrease pancreatic bicarbonate secretion

Acid and Pepsin

? Mechanism of damage:

gastrin releasing peptide (GRP) defect in inhibition of acid production mucosal bicarbonate secretion

basal acid secretory drive postprandial acid secretory response sensitivity to secretagogues

Effects of Diet and Stress

Diet and Stress Action

Diet

Dyspepsia, may pain - not believed to cause ulcer or assist healing

Physiologic stress

mucosal blood flow, tissue hypoxia, mucosal lining degradation; e.g. ICU, sepsis, burn, trauma. Associated with multiple erosions & significant bleeding
Similar # stressful events in ulcer vs. non-ulcer patients tolerance to discomfort Recent epidemiological data suggest possible role

Psychological stress

Gastric Ulcer

Duodenal Peptic Ulcers

Stages of Ulcer Formation

Erosion Ulcer Chronic Ulcer

Sclerosis

Signs and Symptoms of GU or DU

Epigastric pain

Not well localized Annoying, burning, gnawing, aching On an empty stomach During the night Between meals Relieved by food and antacids Episodic followed with symptomatic periods then no occurrence

Duodenal ulcers

Complications of PUD
Hematemesis Perforation Diarrhea Obstruction

Nausea Vomiting

Weight Loss Weakness

Complications: PUD
Stress Ulcer Duodenal Ulcer Gastric Ulcer
Hemorrhage: Frequent, associated mortality Perforation: Common Common in posterior wall of duodenal bulb, associated with melena When in anterior wall of duodenum Less common (associated with hematemesis, coffee grind emesis), melena More common in anterior wall of stomach Rare 7%

Obstruction: ? Common Malignancy: Rare Rare

Objective Measures
Melena Hct, Hgb

Microcytic,

hypochromic indices Pale conjunctiva

BUN/Cr Ratio Heme +ve stool

Diagnosis

Gastric Ulcer/Duodenal Ulcer

Upper

endoscopy (gold standard)

H. pylori
Noninvasive:

Urea breath test, serology Invasive: biopsy (histology, culture, rapid urease)

NSAID- induced
History
Still

need to rule out H pylori infection

Gastroesophageal Reflux Disease (GERD)

Reflux of gastric or intestinal contents Results in heartburn, burping bitter taste

Signs and Symptoms

Heartburn - hallmark symptom Typical: Belching, regurgitation Alarm symptoms: Atypical

Weight loss Bleeding Choking Hoarseness, cough, wheeze Dysphagia (difficulty swallowing) Odynophagia (painful swallowing) Atypical chest pain Infants: spitting up, vomiting (uncommon: failure to gain weight, Fe def anemia, recurrent pneumonia, near SIDS)

Spectrum of Gastroesophageal Reflux Disease (GERD)

Acid

reflux Esophagitis Esophageal ulceration Barretts esophagus

Possible Extraesophageal Manifestations of GERD

ENT Pharyngitis Otitis media Sinusitis Vocal cord granulomas Laryngitis Hoarseness Voice changes Chronic cough Dental enamel loss

Pulmonary Chronic cough Asthma Idiopathic pulmonary fibrosis Chronic bronchitis Pneumonia Other Chest pain Sleep apnea Dental erosions

GERD Pathophysiology
Aggressive Factors
Loss of LES pressure -Inappropriate relaxation -Increase in intraabdominal pressure
Defects in defense mechanisms -Anatomical -Mucosal resistance -Esophageal clearance -Gastric emptying

Composition acid/pepsin -Volume of refluxate

Lower Esophageal Sphincter

LES Closed

LES Open

Risk Factors

Factors that decrease LES pressure

Diet Alcohol Smoking

Drugs

Factors that increase intra-abdominal pressure

Obesity

Pregnancy
Bending

over

Foods and Drugs Affecting LES

RAISE LES Pressure LOWER LES Pressure
Caffeine, Carminatives, Chocolates, Citrus, Garlic, Fat, Tomatoes Alcohol, antagonists, Anticholinergics Barbiturates Beta-agonists Calcium channel blockers Diazepam Dopamine Meperidine Methylxanthines Narcotics Nicotine Nitrates Progesterone Prostaglandins Tricyclic antidepressants Estrogen

Foods Drugs

Proteins, carbohydrates Alpha-agonists Beta-blockers Cholinergics Cisapride Metoclopramide

Adapted from Gonzales et al. DICP 1990;24:1065

Non Pharmacologic Interventions

Helps 20% of patients Weight loss Small size food portions Loose fitting clothes Cigarette smoking cessation Avoid chocolate, alcohol, peppermint, fatty meals, spicy meals, citric juices, cola, beer Avoid meals 2 hours before lying down Elevate the head of the bed with a 6-8 block

Elevation of Head of Bed

Complications of GERD
Infants: Failure to Thrive Esophagitis (histopathological changes)

Gradations
Grade

I- erythema, edema Grade II- isolated erosions Grade III- confluent erosions, superficial ulceration Grade IV- erosions, deep ulcers, stricture

Peptic stricture Worsening obstructive lung disease Barretts esophagus Malignancy

GERD and Cancer Risk

Esophageal adenocarcinoma 8 times higher in patients with heartburn, regurgitation, or both at least once a week Esophageal carcinoma 11 times higher in patients with nighttime symptoms of GERD

Lagergren J, et al. New Engl J Med. 1999;240:825-831

GERD in Obstructive Lung Disease

Lung Effects Reflux Effects Acid aspiration Chronic airflow trapping, irritates airways diaphragmatic flattening may reduce VagallyLES competency mediated Lung Dx: -ve bronchospasm intrathoracic pressure/+ abdominal via transient pressure acid reflux Bronchodilators
LES pressure