Gastrointestinal Pharmacology The gastrointestinal tract has many important

Gastrointestinal Pharmacology

The gastrointestinal tract has many important functions: • • Digestive Excretory Endocrine Exocrine

Gastrointestinal Pharmacology • Because of the complexity of GI functions and disorders, many classes of drugs are used in the treatment of the various GI disorders

We will divide the disorders into groups: • • • Acid/Peptic Diseases Vomiting Motility Disorders Inflammatory Bowel Disease Irritable Bowel Syndrome

Acid/Peptic Disease • The stomach produces hydrochloric acid, with a p. H of about 3 • The main purpose of this acidic secretion is to sterilize food as it enters the body

In certain situations, this acid can do damage to: • Esophagus • Stomach • Duodenum

Acid/Peptic Disease • The stomach produces mucous that lines the stomach and protects the stomach from the acid • Sometimes the stomach does not produce enough of this protective mucous

Acid/Peptic Disease • Sometimes the stomach does not produce enough of this protective mucous, this can be caused by: STRESS!

• If more stomach acid is produced than what the protective mucous lining can handle, the result can be: • - gastritis • - errosions – preulcers • - ulcers (peptic ulcer disease, PUD)

Picture of Gastrointestinal Tract

Stomach errosion

Stomach errosion

Acid/Peptic Disease • Sometimes the stomach acid is refluxed into the esophagus – Gastro Esophageal Reflux Disease (GERD)

Acid/Peptic Disease • If GERD is severe enough, it can change the lining of the esophagus: • - esophagitis • - errosions • - strictures • - Barrett’s Esophagitis – precancerous

Esophageal Stricture

Acid/Peptic Disease • Sometimes GERD is caused by hiatal hernia, a herniation of the stomach through the opening in the diaphragm for the esophagus • A hernia happens when part of an internal organ or tissue bulges through a weak area of muscle or any part of a bulb that sticks through a hole where it doesn’t belong

Acid/Peptic Disease • Sometimes excess stomach acid production can lead to ulcers of the duodenum as well

Acid/Peptic Disease • A rare disorder, Zollinger-Ellison is due to tumors of the pancreas that secrete gastrin, signalling the stomach to produce too much acid, which results in severe gastric and duodenal ulcers

Acid/Peptic Disease • Sometimes peptic ulcer disease is caused by bacteria – Helicobacter Pylori – (H. Pylori)

Pharmacologic Treatment of Acid/Peptic Disease • • • Strategies for treating acid/peptic disease are: - neutralize acid - decrease acid production - protect stomach lining - antibiotics for H. Pylori

Pharmacologic Treatment of Acid/Peptic Disease • Antacids are weak bases that help to neutralize acid

Pharmacologic Treatment of Acid/Peptic Disease • • • Antacids are weak bases: - magnesium hydroxide - aluminum hydroxide - calcium carbonate - sodium bicarbonate

Magnesium Hydroxide • Not absorbed by the GI tract • Laxative Effect

Aluminum Hydroxide • Not absorbed by the GI tract • Constipating Effect

Calcium Carbonate and Sodium Bicarbonate • Are absorbed systemically and can affect the bodies acid base balance

Drugs used to decrease acid production • Proton Pump Inhibitors (PPI) • H 2 Blockers • - Histamine receptor type 2 antagonists

Proton Pump Inhibitors (PPI) • • • Omeprazole (Prilosec) Ansoprazole (Prevacid) Esomeprazole (Nexium) Pantoprazole (Protonix) Rabeprazole (Aciphex)

Pharmacologic Treatment of Acid/Peptic Disease • • • H 2 Blockers - cimetidine (Tagamet) - famotidine (Pepcid) - nizatidine (Axid) - ranitidine (Zantac)

Protect stomach lining Drugs used to protect stomach lining: - sucrusulfate (Carafate) - colloidal bismuths (Pepto Bismol) - misoprostol/ Cytotec – contraindicated in pregnancy • *prostaglandin analog • •

Antibiotics used to treat H. Pylori • • Tetracycline Metronidazole (Flagyl) Amoxicillin Clarithromycin (Biaxin)

Pharmacologic Treatment of Acid/Peptic Disease • Colloidal bismuths have antimicrobial properties as well

Gastrointestinal Pharmacology • • • We will divide the disorders into groups: - Acid/Peptic Diseases - Vomiting - Motility Disorders - Inflammatory Bowel Disease - Irritable Bowel Syndrome

Gastrointestinal Pharmacology • Drugs that prevent vomiting are called antiemetics. Many classes of drugs are used as antiemetics.

Antiemetics • • • 5 -HT 3 antagonists – serotonin antagonists D 2 antagonists – antipsychotics H 1 antagonists – antihistamines Antimuscurinics Cannabinoids – active ingredient in marijuana

Antiemetics • • 5 -HT 3 antagonists - ondansetron (Zofran) D 2 antagonists - metoclopramide (Reglan) - prochlorperazine (Compazine) - promethazine (Phenergan) - droperidol (Inapsine)

Antiemetics • • • H 1 antagonists - diphenhydramine (Benadryl) - meclizine (Bonine) Antimuscurinics - scopolamine - dimenhydrinate

• Many H 1 antagonists have anticholinergic, antimuscurinic properties, you will often see these cross listed

Antiemetics • Cannabinoids are the active ingredient in marijuana: • - Dronabinal • - Nabilone

Motility Disorders • Common motility disorders are: • - Gastroparesis – stomach weakness/stomach paralysis • - Neuropathy • - Diabetes mellitus • - Parkinsons, other neurologic disorders • Ileus • - postsurgical

Drugs used to treat motility disorders are also called prokinetics: • Cholinomimetics • - bethanecol – muscurinic agonist • - neostigmine – acetylcholinesterase inhibitor

Gastrointestinal Pharmacology • Drugs used to treat motility disorders are also called prokinetics. • - metoclopramide (Reglan)

Inflammatory Bowel Disease (IBD) • Inflammatory bowel disease disorders that cause the intestines to become inflamed (red and swollen). The inflammation lasts a long time and usually recurs

IBD • Symptoms include abdominal cramps and pain, diarrhea, weight loss and bleeding from the intestines

IBD • There are two main forms of inflammatory bowel disease: • - Crohn’s disease • - ulcerative colitis

Pharmacology Treatment of IBD • Drugs used to treat inflammatory bowel disease are: • - immunosuppresive antimetabolites • - azathiorine • - 6 mercaptopurine • - methotrexate

Drugs used to treat IBD are: • Antitumor necrosis factor alpha • - infliximab (Remicade)

Drugs used to treat IBD are: • Aminosalicylates (prostaglandin inhibitor) • - mesalamine (Pentasa, Rowasa, Asacol) • - sulfasalazine (Azulfidine)

Do not confuse • • IBD – Inflammatory Bowel Disease - Crohn’s - Ulcerative Colitis IBS – Irritable Bowel Syndrome

IBS • Some people have constipation which means hard, difficult-to-pass, infrequent bowel movements. Often these people report straining and cramping when trying to have a bowel movement but cannot eliminate any stool

IBS • Some people with IBS experience diarrhea, which is frequent, loose, watery, stool. People with diarrhea frequently feel an urgent and uncontrollable need to have a bowel movement.

IBS • Most people with IBS alternate between constipation and diarrhea.

IBS • Sometimes people find that their symptoms subside for a few months and then return, while others report a consistent worsening of symptoms over time.

IBS • STRESS is a contributing factor in IBS • IBS does not result in blood in stool

Pharmacologic Treatment of IBS • • Drugs used to treat IBS include: - 5 -HT 3 receptor antagonists - alosetron (Lotronix) - IBS with predominant diarrhea

Drugs used to treat IBS include • 5 -HT 4 receptor antagonists • - tegaserod (Zelnorm) • - IBS with predominant constipation

Drugs used to treat IBS include: • Anticholinergics • - hyoscyamine (Levsin)