DH206: PHARMACOLOGYCHAPTER 15 GI DRUGSLisa Mayo, RDH, BSDH

GI Drugs

HCl formation in stomach occurs in parietal cellsof the stomach (pH=1.0-2.0)

HCO3- leaves parietal cell

Cl- enter parietal cell & combo with H+ = HCl

Gastrointestinal Drugs

GI Diseases

1. Gastroesophageal reflux disease (GERD)

2. Peptic ulcer disease (PUD)

3. Chronic inflammatory bowel: Ulcerative colitis, Crohn’s

4. Constipation

5. Diarrhea

6. Nausea & Emesis(vomiting)

**The GI tract is highly susceptible to emotional changes because it is innervated by the

VAGUS nerve associated with the ANS**

1. Gastroesophageal Reflux Disease

• GERD, or “heartburn,” is the most prevalent GI disease in U.S.• Stomach contents flow back up into the esophagus through the

cardiac sphincter which is not functionally correctly• Irritation, inflammation, erosion occur because esophagus not

designed to handle the levels of acids in the stomach• Pain may be severe & felt in middle of chest

1. Gastroesophageal Reflux Disease

• Risk factors• Alcohol use• Smoking• Spicy foods• Stomach ulcers• Meds: Aspirin, NSAIDs, CCB, Fosamax, Tetracycline

• Symptoms exacerbated by:• Supine position• Large meals

• Long-term complication = Barrett’s esophagus

1. Gastroesophageal Reflux Disease

Treatment• Lifestyle changes

• Avoid eating for 4 hours prior to bed• Eat smaller meals• Pillow while sleeping

• Drugs therapy

1. Antacids

2. H2-antagonists

3. Proton-pump inhibitors (PPIs)

4. GI stimulants

2. Peptic Ulcer Disease (PUD)

• Peptic ulcer: circumscribed loss of tissue or break that occurs in the GI mucosa extending through the smooth muscle that lines the GI tract

• Occurs when imbalance of:1. Gastric acid 2. Pepsin3. Mucosal defense factors prostaglandins

• Dental Management: p.187, Box 15-1• Etiology

1. Helicobacter pylori (gram (-) & alters inflammatory response)

• Combo Tx of 2 ABX + H2-blocker/PPI 2. Long-term aspirin/NSAID or corticosteroid use

2. Treatment PUD

1. Same as GERD plus:

2. Prostaglandins

3. Protective barriers

4. ABX: H.pylori

NBQ

Which of the following risk factors are primarily involved in causing peptic ulcer disease?

a. Smoking & alcohol

b. Caffeine & smoking

c. H.pylori and NSAIDs

d. S.mutans and alcohol

NBQ

Which of the following risk factors are primarily involved in causing peptic ulcer disease?

a. Smoking & alcohol

b. Caffeine & smoking

c. H.pylori and NSAIDs

d. S.mutans and alcohol

3. Chronic Inflammatory Bowel Disease (IBD)

2 categories of inflammation1) Ulcerative colitis: sores in mucosal of colon/rectum2) Crohn’s Disease: inflammation spreads deep into

affected tissues

• Smoking cessation may exacerbate

3. Chronic Inflammatory Bowel Disease (IBD)

DRUGS FOR TX

FIBER SUPPLEMENTS 1st

ANTIINFLAMMATORY Sulfasalzine(Azulfidine) Mesalamine(Apriso) Balsalazide(Colazal) Olsalazine(Dipentum)

CORTICOSTEROIDS Prednisone

IMMUNOSUPPRESSANT 6-mercaptopurine(Purinethol) Azathioprine(Imuran) Cyclosporine

ANTIDIARRHEAL Imodium

ANTISPASMODICS Anticholinergics

TNF-ALPHA NUETRALIZER Infliximab(Remicade)

4. ConstipationRisk factors

1) Narcotics2) Anticholinergics3) CCB4) Aluminum-containing antacids5) Iron products

Agents Drugs

Bulk-forming laxatives Methycellulose, polycarbophil, psyllium

Watery evacuation (osmotic/saline laxative)

Magnesium

Lubricant Mineral oil

Soften stool/Emollients Disacodyl sodium sulfosuccinate

p.190

5. DiarrheaEtiology• Most common bacterial causes: Salmonella, E.coli• ABX: broad-spectrum most common• NSAIDs, Diuretics, Antihistamines (H2-inhibitors), Digoxin

DRUGS NOTATIONS

Ioperamide(Imodium)

Diphenoxylate + Atropine (Lomotil)

Opiate + Anticholinergic

Bismuth subsalicylate(Pepto-Bismol, Keopectate)

Traveler’s diarrhea (NBQ)

Yogurt or acidophilus Use when on broad-spectrum ABXYogurt 2hrs before tetracycline (NBQ)

NBQ

All of the following drugs reduce GI motility and are used to treat diarrhea EXCEPT which one?

a. Loperamide(Imodium)

b. Bismuth subsalicylate(Pepto-Bismol)

c. Furosemide(Lasix)

d. Diphenoxylate and atropine(Lomotil)

e. Attapulgite(Kaopectate)

NBQ

All of the following drugs reduce GI motility and are used to treat diarrhea EXCEPT which one?

a. Loperamide(Imodium)

b. Bismuth subsalicylate(Pepto-Bismol)

c. Furosemide(Lasix) Loop diuretic for HBP

d. Diphenoxylate and atropine(Lomotil)

e. Attapulgite(Kaopectate)

NBQ

Which of the following drugs has the potential to cause severe diarrhea?

a. Clindamycin

b. Ciaspride

c. Diazepam

d. Metronidazole

e. Vancomycin

NBQ

Which of the following drugs has the potential to cause severe diarrhea?

a. Clindamycin

b. Ciaspride

c. Diazepam

d. Metronidazole

e. Vancomycin

6. Nausea & Emesis• NO Clindy• Drugs used to tx

1) Anticholinergic2) Antiemetic3) Depress chemoreceptor trigger zone4) Cannabinoids

DRUG CLASS DRUGS

Phenothiazide Phenergan, Compazine

Anticholinergic Dramamine, Bonine

Block chemoreceptor trigger zone Zofran, Anzemet, Tigan

I Promise I Won’t Do This to You!!!

Drugs Used to Treat GI Diseases

Acid Neutralizers1. Antacids

Antisecretory Drugs: Receptor-Mediated Drug Action2. Antihistamines (H2-blocking agents)3. PPIs4. Prostaglandins5. GI stimulants

Protective Barrier Drugs6. Sucralfate(Carafacte)

Drugs Used to Treat GI Diseases

Acid Neutralizers1. Antacids

Antisecretory Drugs: Receptor-Mediated Drug Action2. Antihistamines (H2-blocking agents)3. PPIs4. Prostaglandins5. GI stimulants

Protective Barrier Drugs6. Sucralfate(Carafacte)

Acid NeutralizersAntacids

Used to relieve the pain & indigestion Many brands OTC: magnesium, aluminum, calcium Oldest antacid: sodium bicarb (Alka-Seltzer) but can create

alkalosis, cannot be used by cardiac patients Pepto-Bismol: used in tx PUD

P.189

Acid Neutralizers

Antacid Use

Calcium carbonate(Tums, Maalox) GERD

Magnesium hydroxide(Milk of Magnesium) GERD

Aluminum/magensium hydroxide/simethicone(Maalox, Mylanta) GERD

Calcium carbonate/magensium hydroxide(Rolaids) GERD

Sodium bicarbonate (Gaviscon) GERD

Bismuth subsalicylate(Pepto-Bismol) PUDH.pylori

Acid NeutralizersAntacids

Action: Basic saltsNeutralize HCl acids in stomach Raise pH of stomach

Can alter absorption of MANY other drugs Short duration (30min)

Guidelines for Patients

Antacids taken 2hrs prior to tetracycline (CH7)

Hypertensive pt’s: avoid sodium-based antacids

NBQ

Which of the following GI drugs should not be given concurrently with doxycycline?

a. Omeprazole

b. Cimetidine

c. Antacids

d. Lansoprazole

NBQ

Which of the following GI drugs should not be given concurrently with doxycycline?

a. Omeprazole

b. Cimetidine

c. Antacids

d. Lansoprazole

Drugs Used to Treat GI Diseases

Acid Neutralizers1. Antacids

Antisecretory Drugs: Receptor-Mediated Drug Action2. Antihistamines (H2-blocking agents)3. PPIs4. Prostaglandins5. GI stimulants

Protective Barrier Drugs6. Sucralfate(Carafacte)

Drugs Used to Treat GI DiseasesAntisecretory Drugs: Receptor-Mediated Drug Action

1. Antihistamines (H2-blocking agents)2. PPIs3. Prostaglandins: Misoprostol4. GI stimulants: Metoclopramide

P-450 inhibitors – MANY drug interactions

Parietal cell are the site of action of Antihistamines, PPI, Prostaglandins

Drugs Used to Treat GI Diseases

Antisecretory Drugs: Receptor-Mediated Drug Action1. H2-blocking agents

Histamine ReviewHistamine located in GI mucosa within mast cellsHistamine Receptors (called H2-receptors)

Mediate secretion of gastric acid & pepsinLocated in parietal cells of the GI system (parietal cells produce acids)

H2 stimulation = parietal cells release more acids (↓pH)

If block receptors: reduce acid & pepsin production

Parietal cells (secrete

histamine)Site of action of antihistamines

↓Reduce acid &

pepsin production

Drugs Used to Treat GI DiseasesAntisecretory Drugs: Receptor-Mediated Drug Action

1. Antihistamines• Inhibit P-450 – interact with MANY drugs (NBQ)• Similar onset of action to antacids (quick) but longer duration of

action• Uses: PUD & GERD

Antihistaminescimetidine(Tagamet) PROTYPE Drug interactions due to CYP1A2 liver

metabolismDo NOT use more than 6wks (agranulocytosis, diarrhea)

Ranitidine(Zantac)

Famotidine (Pepcid, Mylanta AR)

Nizatidine(Axid)

All end in ~tidine

Drugs Used to Treat GI Diseases

Antisecretory Drugs: Receptor-Mediated Drug Action2. PPIs

• Drug of choice for patients with daily symptoms or those not responding to antihistamines

• Reduce peak acid output• Achieve almost total suppression of acid secretion because they

bind irreversibly to parietal cells• Many drug interactions (P-450 inhibition) (NBQ)

Guidelines for Patients

Valium & Dilantin interactions

No aspirin

Xerostomia

Drugs Used to Treat GI Diseases

Antisecretory Drugs: Receptor-Mediated Drug ActionPPIs

PPIs

Omeprazole(Prilosec) PROTYPE

Omeprazole/sodium bicarbonate(Zegerid)

Lansoprazole(Prevacid)

Esomeprazole(Nexium)

Rabeprazole(AcipHex)

Pantoprazole(Protonix)

Rabeprazole(AcipHex)

Drugs Used to Treat GI Diseases

Antisecretory Drugs: Receptor-Mediated Drug Action3. Prostaglandins: Misoprostol(Cytotec)

• Synthetic prostaglandin (PGE2α)

• Management of NSAID/Aspirin-induced ulcers• Inhibits gastric acid secretions• Increases gastric mucosal defenses• Pregnancy category X

p.189

Drugs Used to Treat GI DiseasesAntisecretory Drugs: Receptor-Mediated Drug Action

4. GI stimulants: Metoclopramide(Reglan)• Stimulates contraction of the lower esophageal sphincter by

enhancing action of ACH (acetylcholine)

↓• Decrease reflex gastric juices back into esophagus• GERD ONLY, not PUD

NBQWhich 3 GI drugs below reduce the formation of stomach acid by inhibiting the proton pump of the stomach parietal cells?

a. Ranitidine(Zantac)b. Esomeprazole(Nexium)c. Famotidine(Pepcid)d. Omeprazole(Prilosec)e. Lansoprazole(Prevacid)

NBQWhich 3 GI drugs below reduce the formation of stomach acid by inhibiting the proton pump of the stomach parietal cells?

a. Ranitidine(Zantac)b. Esomeprazole(Nexium)c. Famotidine(Pepcid)d. Omeprazole(Prilosec)e. Lansoprazole(Prevacid)

Drugs Used to Treat GI Diseases

Acid Neutralizers1. Antacids

Antisecretory Drugs: Receptor-Mediated Drug Action2. Antihistamines (H2-blocking agents)3. PPIs4. Prostaglandins5. GI stimulants

Protective Barrier Drugs6. Sucralfate(Carafacte)

Barrier Enhancer

Sucralfate(Carafate)• Complex of aluminum hydroxide + sulfated sucrose• “Bandage” over ulcer• PUD short-term tx• Forms a protective barrier over damaged mucosa, binds to

PRO in ulcers• Inhibits the action of pepsin• Absorbs bile salts that can cause irritation of the gastric

lining• Most common side effect: constipation

Summary Tx for PUD/GERD

PUD TX2 ABX + Antihistamine + Antacid

GERD TXAntacid + Antihistamine/PPI

NBQ

Which of the following drugs is best for starting initial treatment of mild, intermittent heartburn?

a. Sodium bicarbonate/alginic combination

b. Cimetidine

c. Omeprazole

d. Lansoprazole

NBQ

Which of the following drugs is best for starting initial treatment of mild, intermittent heartburn?

a. Sodium bicarbonate/alginic combination

b. Cimetidine

c. Omeprazole

d. Lansoprazole