Gastrointestinal Pharmacology Quiz

GI Conditions (of Concern)

• Heartburn is a burning sensation in the chest due to stomach acid refluxing up into the throat. This is also known as Gastro-oesophageal reflux disease (GORD) if it occurs frequently.
• Dyspepsia/Indigestion is an uncomfortable feeling in the stomach that can manifest as pain, indigestion, and nausea.
• Gastritis is an inflammation of the stomach lining, causing pain and discomfort.
• Nausea and Vomiting are common digestive issues that often accompany other problems.
• Peptic Ulcer Disease involves ulcers in the stomach lining.
• Constipation and Defecation Problems refer to difficulties with bowel movements, varying from infrequent stools to difficult passage.
• Diarrhea involves frequent, loose stools.
• Gastroparesis is a condition where the stomach cannot empty normally. Food moves through the stomach more slowly than usual, often caused by nerve or muscle problems.

Recap of GI Anatomy and Function

• The Alimentary Canal extends from the mouth to the anus, and includes accessory organs like liver and pancreas.
• There are six stages in the process of dealing with food: ingestion, mechanical breakdown, propulsion, digestion, absorption, and defecation.
• All sections of the alimentary canal have 4 layers (mucosa, submucosa, muscularis externa, and serosa).
• The digestive system is controlled by nerves. Short nerves in the digestive system (submucosal and myenteric plexus) and long nerves from the brain (parasympathetic).

Recap of Saliva and Swallowing

• Saliva, secreted by intrinsic and extrinsic glands, has amylase, mucin, water, and protective elements (defensin, IgA, lysozyme).
• Swallowing has a buccal phase, pharyngo-oesophageal phase (blocking off the nasopharynx and trachea), and peristalsis and sphnicter opening.
• Different types of cells in the stomach include mucus cells, parietal cells, chief cells, and enteroendocrine cells.

Regulation of Gastric Secretion

• The regulation of gastric secretion involves the cephalic phase, gastric phase, and intestinal phase.
• 1. The cephalic phase is initiated in the brain in response to the thought, smell, or sight of food.
• 2. The gastric phase is initiated by the presence of food in the stomach.
• 3. The intestinal phase is initiated when chyme enters the small intestine. These phases work together to control stomach acid production.

Gastric Glands and Juices

• Gastric glands secrete gastric juices, the most noteworthy being mucus neck cells, parietal cells, and chief cells.
• Mucus neck cells are located in the duct portion and secrete mucus.
• Parietal cells are in the middle of glands; they secrete hydrochloric acid (HCl) and intrinsic factor.
• Chief cells are the bottom of the glands and secrete pepsinogen.

Digestive Processes of the Stomach

• The stomach acts as a holding vessel for ingested food and aids in mechanical and chemical digestion.
• Protein digestion takes place with HCl denaturing proteins, activating pepsinogen to pepsin, pepsin breaking peptide bonds of proteins, and rennin breaking down casein (a protein in milk).
• Mucous barriers protect the stomach lining from its secretions, whereas intrinsic factor aids in vitamin B12 absorption.
• The stomach lining is replaced every 3 to 6 days.

Dyspepsia

• Dyspepsia is a group of upper gastrointestinal symptoms, not a diagnosis itself. Symptoms include upper abdominal pain, heartburn, gastric reflux, nausea, or vomiting.
• The causes of dyspepsia range from gastric and duodenal ulcers to gastro-oesophageal reflux disease (GORD), oesophagitis, etc to esophageal or gastric cancers.

Pharmacological Treatments

• Mucosal strengtheners such as Misoprostol.
• Reduction of acid secretion through proton pump inhibitors, e.g., omeprazole; histamine H2 receptor antagonists, e.g., ranitidine; and muscarinic antagonists, e.g., pirenzepine.
• Eradication of H pylori via dual therapy (PPI and antibiotics).

Gastroparesis

• Gastroparesis is delayed gastric emptying in the absence of mechanical obstruction.
• Associated conditions are diabetes mellitus, hypothyroidism, neurological conditions, viral infections, and autoimmune attacks.
• This can happen due to latrogenic causes including vagal nerve damage during surgery, opioid use, alpha-2-adrenergic agonist use (e.g., clonidine), tricyclic antidepressants, and anticholinergics.

Promotility Agents

• Agents used to promote the passage of ingested material in the GI tract may include:
• Gastroparesis and constipation.
• Neurogastroenterology and motility.
• Enteric neuro-modulation.
• Consideration for valid simple gut motility stimulation, as well as potentially poorly defined target disorders. Non-selective drugs often come with side effects.

How Do Promotility Agents Work?

• Promotility agents can increase wave-like contractions in the esophagus, stomach, and intestines. Methods involved include stimulating excitatory chemical messengers like acetylcholine and suppressing inhibitory neurotransmitters like dopamine and serotonin.

Dopamine Antagonists

• Metoclopramide and domperidone are first-line therapies for hypomotility disorders.
• These drugs block dopamine's effects in the central nervous system and the chemoreceptor trigger zone to improve peristalsis and may lessen nausea.
• Metoclopramide can cause side effects in about 25% of patients.
• Domperidone is generally preferred due to fewer central nervous system effects.

Serotonergic Agonists

• Cisapride and Prucalopride are serotonergic antagonists and may help to accelerate intestinal transit, reduce esophageal acid exposure, and improve gastric emptying.

Motilides

• Erythromycin is a macrolide antibiotic that can be used to treat gastric stasis and may enhance peristalsis.

Description of Constipation

• Infrequent or difficult stool passage or seeming incomplete defecation is a sign of constipation.
• It occurs at any age but is common in women, especially during pregnancy, and in the elderly.
• New-onset constipation, especially in patients over 50 years old, with accompanying symptoms such as anemia, abdominal pain, weight loss, or blood in the stool, may indicate malignancy.
• Certain medications can also cause secondary constipation.

Colon

• The colon's role is to convert chyme into feces and excrete it.
• The large intestine lacks villi and has many Lieberkühn crypts, which contain mucus-secreting goblet cells.
• The colonic mucosa absorbs substances, such as water, sodium, and chloride, through active transport.
• Longitudinal bands called the tenia coli help to structure the colon.

Secretion in the Colon

• Mucus in the colon neutralizes stomach acid, protects against irritation, lubricates feces, and binds them together.
• Defecation reflexes stimulate pelvic nerves, causing increased peristaltic motility, which leads to a marked increase in mucus secretion.
• Bacterial infections can cause the colon to secrete water and electrolytes, leading to rapid bowel movements.

Absorption in the Large Intestines

• About 0.5 to 1.5 liters of water are absorbed daily in the large intestines.
• Key elements include absorption of water, sodium, chloride, and several different vitamins, depending on the specific vitamin.
• Certain drugs, such as steroids and aspirin, are absorbed, whereas Vitamin B12 is not absorbed.

Control of Motility in the Colon

• Haustrations (mixing movement) occur in the proximal colon with contractions in the circular and longitudinal muscles that form pockets or haustra.
• Simultaneous contraction and relaxation of these pockets move material forward.
• Mass propagated contractions occur in the distal portion of the colon, occurring roughly 15 minutes after breakfast, and moving stool forward.

Defecation

• Defecation is regulated by the stretch of the rectal wall, which sends signals to the spinal cord (SC).
• Efferent pelvic impulses cause reflex contractions of the rectum while relaxing the internal anal sphincter.
• Tonic contractions of the external anal sphincter can be overridden to allow voluntary control of defecation.
• The process is assisted by pelvic floor muscles that contract to expel feces.

Constipation

• Constipation is characterized by infrequent bowel movements with small, hard stools or fecal impaction.
• Possible causes include poor diet (lack of fiber), decreased gastrointestinal motility, GI tract disorders (like IBS), medications (e.g., opioids), and physical blockages (like colonic carcinoma).

Note on Saline Laxatives

• Magnesium citrate and sodium phosphate are used rectally to cleanse the bowels in preparation for procedures.
• Laxatives containing magnesium should be avoided in children, individuals with renal impairment, and those with cardiac conditions or pre-existing electrolyte imbalances due to increased risk of hypermagnesemia (associated potentially with heart block/neuromuscular block/CNS depression) and hyperphosphatemia.

Diarrhea

• Inflammatory diarrhea involves inflammation of the gastrointestinal tract epithelium, possibly caused by invasive pathogens or inflammatory bowel disease.
• Non-inflammatory diarrhea types may be secretory (increased water and electrolyte secretion due to factors like lactose) or osmotic (undigested nutrients pulling water into the gut).

Treatment of Diarrhea

• Treating dehydration is crucial, use oral rehydration solutions.
• Diet adjustments, avoiding dairy, and antibiotics are common treatment methods.
• Antimotility drugs like loperamide may be used when appropriate. Certain considerations such as geographic predisposition to disease and patient's immune status, as well as stool testing and/or blood work should be considered.

Vomiting

• The vomiting reflex involves the following steps: initial stimulation, vomiting center activation, retching, and expulsion.
• Different parts of the nervous system control the reflex through cranial nerves and the chemoreceptor trigger zone/central vomiting center activation.
• The process involves relaxation of esophageal sphincters, contraction of abdominal muscles, and forceful expelled contents.

Anti-emetics

• Anti-emetics are used to treat nausea and vomiting, they work by blocking specific receptors.
• Drugs in this category include: histamine 1 receptor antagonists, 5-HT3 receptor antagonists, dopamine 2 receptor antagonists, and muscarinic receptor antagonists. These drugs directly block or counteract the neurotransmitters/chemicals that elicit nausea/vomiting symptoms.

Test your knowledge on gastrointestinal pharmacology with this quiz. Questions cover topics such as colonic function, secretion mechanisms, and drug actions related to digestive health. Perfect for students and professionals in the medical field.