Lecture 1: Meds for GERD and Peptic Ulcer Disease

Prostaglandin E2

- produced by gastric mucosa,

- inhibits acid secretion and stimulates mucus and bicarbonate secretion = cytoprotective

- NSAIDs decrease the production

Cholinergic

Dicylcomine blocks ______________________ receptors

H2-Histamine

Cimetidine blocks the ____________________ receptor

Prostaglandin

Misoprostol stimulates the ___________________ receptor

-Proton pump inhibitors

-Histatmine H2-receptor antagonists

-Antacids

-Anti-refluxants

main categories of acid suppressants

• Weight loss

• Elevation of the head end of the bed and avoidance of food 2-3 hrs before bedtime

-Avoid foods that can cause irritation of mucosa

• Avoid alcohol consumption and no smoking.

lifestyle modifications for GERD

• LNf (Laparoscopic Nissen fundoplication)

• Bariatric surgery (in obese patients)

anti-reflux surgeries

OTC antacids, H2-receptor antagonists or [PPIs for 2 weeks QD]

how do pts typically self treat for mild GERD

increasing

Pharmacologic treatment for GERD typically involve ___________________ the pH of gastric contents

Alarm symptoms

Recurring symptoms after 2 weeks of lifestyle modification/self treatment

Prescription strength H2RAs or (PPIs for 8 weeks QD) + maintenance therapy if symptoms recur

when are prescriptions for GERD indicated?

Proton pump inhibitors (PPI's)

provide the greatest symptom relief and the highest healing rates for GERD, especially for patients with erosive disease or moderate-to-severe symptoms or with complications.

8-12 weeks of twice-daily PPI therapy

treatment for Patients with erosive esophagitis on endoscopy

Proton pump inhibitors (PPI's)

the drug of choice for maintenance of patients with moderate-to-severe GERD

Antacids

acid neutralizers

-Histamine H2-Receptor Antagonists

-Proton pump inhibitors (PPI's)

acid reducers

aka antisecretory agents

-Calcium carbonate

-Magnesium

-Magnesium-Aluminum-Simethicone

-Sodium Bicarbonate

-Antacid + Alginic Acid

Antacids

Antacids

• Mechanism: neutralize gastric acid → ↑ gastric pH

• Fast acting (w/in minutes) & short duration (30-60 min)

• Most suitable for mild, infrequent symptoms

• Unpleasant taste

• Electrolyte disturbances

adverse effects for antacids

constipation or loss stools

AEs for antacid: calcium carbonate

Constipation

AEs for antacid: aluminum

Loss stools, Diarrhea

AEs for antacid: magnesium

-Gastric distension

-belching

-metabolis alkalosis

AEs for antacid: sodium bicarbonate and calcium carbonate

Antacids

GERD medication that is a safer choice for pregnancy

• Tetracyclines

• Fluoroquinolones

• Itraconazole

• Iron

Antacids should not be taken within 2 hours of ______________________________________

• Famotidine

• Ranitidine

• Nizatidine

• Cimetidine

Histamine-2 receptor antagonists (H2RAs)

Histamine-2 receptor antagonists (H2RAs)

Indications:

• GERD

• PUD

• Dyspepsia/indigestion (non-ulcer)

• Stress ulcer prophylaxis

• Critically ill patients (ICU)

Histamine-2 receptor antagonists (H2RAs)

-reversibly inhibit H2 receptors on gastric parietal cells

-decrease gastric acid secretion

-increase gastric acid pH

-highly selective and last 4-10 hours

• IV admin in critically ill

Cimetidine

may cause gynecomastia or impotence in men & galactorrhea in women with long-term use

Can cause Vitamin B12 deficiency

Histamine-2 receptor antagonists (H2RAs)

• Diarrhea or constipation

• Headache

• Fatigue

• Myalgias

-increased risk for pneumonia

-mental status changes

Histamine-2 receptor antagonists (H2RAs)

• ↓ absorption of drugs requiring low stomach pH for dissolution

• May have additive effects with CNS depressants

• May inhibit gastric first-pass metabolism of ethanol

• Antacids reduces the absorption

Proton pump inhibitors (PPI's)

-irreversibly binds and inactivates active H+/K+ ATPase pumps in parietal cells

-blocks acid secretion

Proton pump inhibitors (PPI's)

-take on an empty stomach 1 hour before meal

-duration is 24 hours

-all are prodrugs

-It takes 3-4 days of daily dosing for full acid-inhibition.

• >90% duodenal ulcers healed w/in 4 wks

• >90% gastric ulcers healed w/in 8 wks

• *Omeprazole

• *Esomeprazole

• *Lansoprazole

• Dexlansoprazole

• Rabeprazole

• Pantoprazole

Proton pump inhibitors (PPI's)

Proton pump inhibitors (PPI's)

Indications:

• GERD

• PUD

• A drug of choice for maintenance therapy in GERD

• Non-ulcer dyspepsia (benefit 10-20% of pts. above placebo)

• Erosive esophagitis

• Esophageal stricture

• Gastric hypersecretions (e.g., gastrinoma)

• Stress ulcer prophylaxis (critically ill patients)

Proton pump inhibitors (PPI's)

AEs:

-C. diff infection

-pneumonia

-fractures of hip, wrist, and spine

-gastric acid rebound or reflux symptoms

-iron deficiency anemia

• Calcium citrate

• B12 via intranasal or IM route

• Iron via IV route

if needed, what supplementation can you give with Proton pump inhibitors (PPI's)

• Helicobacter pylori

• Chronic NSAIDs (including aspirin)

• Acid hypersecretion

common causes of PUD

Bismuth Quadruple Therapy:

-Bismuth + metronidazole + tetracycline + PPI

Concomitant Quadruple Therapy:

-Clarithromycin + amoxicillin + metronidazole + PPI

Triple Therapy:

-Clarithromycin + Metronidazole + PPI

or

-Clarithromycin + amoxicillin + PPI

Preferred treatment regimen for H. pylori induced ulcer

• Discontinue NSAID, (may give sucralfate)

• Initiate H2RA or PPI

treatment for NSAID-associated ulcers

PPI to promote ulcer healing

treatment for NSAID-associated ulcers if NSAID cannot be discontinued

-Metronidazole

-Tetracycline

-Clarithromycin

-Amoxicillin

Abx used to erradicate H. pylori in PUD

Metronidazole

-Metabolized by bacteria into reduced reactive compounds

-damages bacterial DNA, proteins, and membranes to cause cell death

-anaerobic bacteria, protozoans, and H. pylori

Metronidazole

CIs:

-alcohol use within 3 days

-Use within 2 weeks of disulfiram

AEs:

-GI upset

-headache

Tetracycline

-Binds 30s ribosomal subunit

-inhibits attachment of aminoacyl-tRNA

-decreases protein synthesis

-for G+ and G- bacteria, some anaerobes, Rickettsia, Chlamydia, Mycoplasma

-H. pylori

Tetracycline

CIs:

-last half of pregnancy

-children

Clarithromycin

-binds 50s ribosomal subunit

-decreases peptide bond formation

-decreases protein synthesis

-G+ bacteria (not enterococci), intracellulars, atypicals, and H. pylori

Clarithromycin

AEs:

-motility (GI issues)

-Arrhythmias

-Cholestatic hepatitis

-rash

-eosinophilia

Amoxicillin

-Bind PBPs

-decreases peptidoglycan crosslinking

-decreases bacterial cell wall synthesis

-G+ bacteria, enhanced G- bacteria coverage, H. pylori

-often used with beta-lactamase inhibitor

Amoxicillin

AEs:

-rash

-GI upset (diarrhea)

-serious allergic rxn (Contraindication)

• May ↓ effectiveness of hormonal contraception.

-Sucralfate

-Misoprostol

-Bismuth Compounds

gastric mucosa protectants

Sucralfate

-forms viscous protective paste that binds selective ulcers and erosions

-may stimulate mucosal prostaglandin and bicarbonate secretion

-primarily excreted in feces

-administer on an empty stomach

Sucralfate

• Indication: Ulcer (duodenal, gastric, stress prophylaxis)

• Clinical use limited by H2RAs and PPIs

-AE: constipation

Misoprostol

-prodrug

-prostaglandin (PGE1) analog

-acid inhibitory and mucosal protective properties

• Admin' TID or QID

Misoprostol

Indications:

• Duodenal ulcer

• Prophylaxis of NSAID-induced ulcer (PPIs preferred)

• Adverse effects: GI upset (pain, nausea, diarrhea)

• Contraindications: pregnancy, childbearing potential

Bismuth compounds

• Coats ulcers & erosions, protects against acid & pepsin

• Direct antimicrobial (H. pylori) effects; binds enterotoxins

• May stimulate prostaglandin, mucus, and bicarbonate secretion

Bismuth compounds

Indications

• Dyspepsia, indigestion

• Acute diarrhea, upset stomach

• H pylori GI infection

Bismuth Subsalicylate

Contraindications

• Salicylate allergy

• Child/teenager recovering from viral infection (e.g., chicken pox, flu) — risk of Reye's Syndrome

• Nursing

• Pregnancy >20 weeks

Adverse effects

• Dark tongue or stool (harmless) (bismuth)

• Salicylate toxicity (high dose/prolonged use)

-Bethanechol

-Metoclopramide

promotility agents

Bethanechol

• Stimulates M3 receptors on muscle cells and at myenteric plexus synapses

• Increases LES pressure in GERD

Bethanechol

Indication

• Urinary retention

• No longer used for GERD due to adverse effects + better agents available

AEs: GI upset, decreased BP with reflex tachycardia, urinary urgency

Metoclopramide

-Blocks dopamine (D2) receptors

-prevents inhibition of cholinergic smooth muscle stimulation

-increases esophageal peristaltic amplitude

-increases LES pressure and gastry emptying

-potential antinausea and antiemetic action in chemoreceptor trigger zone of medulla

Metoclopramide

Indications

• GERD (not effective in erosive esophagitis)

• Diabetic gastroparesis

• Nausea/vomiting (chemotherapy-induced, postoperative)

Metoclopramide

Adverse effects

• Drowsiness, insomnia, anxiety, agitation

• Dystonia, akathisia, parkinsonism

• Elevated prolactin levels → galactorrhea, gynecomastia, impotence, menstrual disorders

• Tardive dyskinesia (avoid long term use, if possible!)

Contraindications

• Epilepsy (↑ risk of seizures)

• GI hemorrhage, mechanical obstruction, or perforation

• Pheochromocytoma (↑ risk of hypertensive crisis)