GI Pharmacology Flashcards
UPPER GI TRACT GASTRIC GLANDS CHEIF CELLS PARIETAL CELLS ENTEROENDOCRINE CELLS
•Gastric glands in mucosal stomach lining secrete:
•Chief cells-pepsinogen inactive form of the enzyme pepsin that chemically breaks down proteins
•Parietal cells-
1.secrete 1-3 L/day of hydrochloric acid that breaks down food, activates pepsinogen, and kills microbes.
2.Secrete intrinsic factor needed for the absorption of vitamin B12
•Enteroendocrine cells- secrete hormones that modify digestive processes; an example is gastrin that stimulates acid production
LOWER GI TRACT
-SMALL INTESTINE
•Small intestine is:
• The longest portion of the alimentary canal
•*Primary organ for absorption
•Stomach mucosa secretes intestinal juice (mucus, digestive enzymes, and hormonal mixture) that has alkaline pH and neutralizes stomach acidity
•Secretes cholecystokinin- hormone promotes pancreatic enzyme secretion and secretin that stimulate bicarbonate production that makes the small intestine more alkaline
•Comprised of-
1.Duodenum
2.Jejunum- majority of nutrient and drug absorption
3.Ileum- primary site for absorption of vitamin B12, long-chain fatty acids, and fat-soluble vitamins
LOWER GI TRACT
-LARGE INTESTINE
- Large intestine:
- Major site of water and electrolyte reabsorption from waste material
- Excrete remaining waste material from the body
- Secretes mucus that lubricates fecal material
- ***Contains host flora (bacteria and fungi) responsible for synthesizing B-complex vitamins and Vitamin K
- Disruption of normal flora causes diarrhea
Physiology of the GI Accessory Organs
•Liver is the most important accessory organ
•All drugs eventually pass through the liver
•Cytochrome P450 enzyme system in liver cells metabolize drugs
•Liver function- filter and process nutrients and drugs
•Other liver functions:
1.Regulation- stabilize the serum levels of glucose, triglycerides and cholesterol
2.Protection- removes toxic substances and waste products such as ammonia
3.Synthesis- synthesizes bile, plasma proteins, and certain clotting factors
4.Storage- stores iron and fat-soluble vitamins
LOWER GI TRACT
-HEPATIC PORTAL TRACT
- Hepatic portal system:
- Network venous vessels that collects blood draining from the stomach, small intestine, small and most of large intestine
- Blood in this system rich in nutrients absorbed
- *Blood in this system goes to liver to remove, store, excrete or perform metabolic aspects before it is sent to the IFC and heart before it reaches system circulation; this first pass effect influences the decision to give some medications via buccal, SL or rectal routes to bypass first-pass effect
- Digestion is regulated by numerous hormonal and nervous factors
- Digestive enzymes chemically breakdown food
Peptic Ulcer Disease (PUD)
- Peptic ulcer is a lesion/erosion located in stomach (gastric) or small intestine (duodenal mucosa) that usually involves acute inflammation.
- Results from an imbalance of protective mucus and bicarbonate ions AND the aggravating pepsin and gastric acids.
- Complications of PUD include bleeding, perforation, penetration and GI obstruction due to scarring
- Increased incidence with risk factors:
- Infection with bacterium Heliobacter pyori (H. pylori)
- Use of drugs: corticosteroids, NSAIDs, and platelet inhibitors (ASA, clopedigrel)
- Blood group O (antigen may be a target of H. pylori)
- Smoking tobacco (increases gastric secretion and decreased bicarbonate production
- Excessive caffeine
- Increased psychological stress
Gastroesophageal Reflux Disease (GERD)
- Gastroesophageal reflux disease (GERD) is a chronic disease that happens when acidic stomach contents enter the esophagus
- Etiology is transient weakness/relaxation of the lower esophageal sphincter, that allows the acidic gastric contents it to the esophagus
- Untreated GERD can result in complications such as esophagitis, esophageal ulcers or strictures.
- 10% with GERD will eventually develop Barrett’s esophagus
- In Barrett’s esophagus, the normal tissue lining changes to tissue that resembles the lining of the intestine. It is more likely to progress to cancer
GERD SYMPTOMS
- Heartburn
- Dysphagia
- Dyspepsia
- Chest pain
- Nausea
- Belching
- Other symptoms that may develop: chronic cough, wheezing, bronchitis, sore throat or hoarseness
Pharmacotherapy of GERD and PUD
- Major drug classes
- H2-receptor antagonists
- Proton pump inhibitors
- Antacids
- Miscellaneous drugs
Proton Pump Inhibitors (PPIs)
- Indicated for the treatment of:
- Gastric and duodenal ulcers for 4-8 weeks; drug of choice for
- GERD- drug of choice for
- Zollinger-Elliason Syndrom (ZES)- less common cause of PUD, tumor signals increased HCL leading to ulcer development
- OTC indicated for the relief of heartburn
- MOA: act by blocking H+, K+ ATPase enzyme that secretes stomach HCL. PPIs bind irreversibly to this enzyme, so the acid production is stopped
- Reduce acid secretion to a greater extend and for a longer duration of action than Hs receptor antagonists
H2 Receptor Antagonists
- ***Suppress gastric acid secretion
- H2 receptors located in parietal stomach cells and promote gastric acid secretion if activated
- Indicated for treating and preventing reoccurrence of mild to moderate hyperacidity in GI tract, heartburn, PUD, and GERD
- May take a several days to weeks for patients to obtain relief
- Duodenal ulcers take 6-8 weeks to heat
- Gastric ulcers may take 12 weeks to heal
- H2 Receptor antagonist with most drug interactions is cimetidine (Tagamet) potent inhibition of the P450 system; more than the other H2 receptor antagonists
- Cimetidine has the most drug interactions including with that of: warfarin, phenytoin, diazepam, theophylline
What is constipation?
- Constipation is a decrease in the frequency of bowel movements
- Diagnosis requires at least two symptoms:
- Two or fewer bowel movements per week
- Lumpy or hard stools at least 25% of time
- Straining to pass stools at least 25% of time
- Feeling of incomplete evacuation at least 25% of time
Lifestyle Changes for Constipation
- Normal pattern does NOT have to be once a day
- Encourage:
- Activity
- High fiber diet (20-40 grams of fiber daily)
- Adequate fluid intake (~3000 mL)
What is diarrhea?
- Diarrhea is an abnormal increase in the frequency and fluidity of bowel movements
- Etiology: drugs, infection, inflammation (ulcerative colitis, Crohn’s disease, IBS), foods (lactose intolerance), alcohol, malabsorption diseases
- Common drugs: codeine (for severe diarrhea), OTC- diphenoxylate (lomotil).
- Prolonged diarrhea:
- May cause imbalances in fluid, acid-base, electrolytes
- Indication for pharmacotherapy
- Symptom of underlying disorder
