GI Pharmacology Flashcards

Question

What is the function of prostaglandin analogs?

Answer 1

- Reduce gastric acid secretion - Increase mucosa blood flow - Augment the secretion of mucus and bicarbonate, and prostaglandins (they increase the formation of the barrier) - Misoprostol - Synthetic PGE1 (prostoglandin E1) - Common side effects: Diarrhoea and abdominal cramps.

Answer 2

Form a complex gel with the mucus, creating a protective coat - Sucralfate: it is a complex of aluminium hydroxide and sulphated sucrose. - In acidic solutions it polymerises to form sticky gel that adheres to the ulcer base and protects it (for up to 6h). - Form barrier against acid-pepsin - Bismuth salicylates and colloidal bismuth subcitrate. - React with proteins in the base of ulcer and protect it from peptic digestion. - Stimulates secretion of PGE2, mucus and bicarbonate. - Anti-microbial effects against H. pylori. - Binds to enterotoxins, used in travelers diarrhoea

Answer 3

Aim to: Promote rapid ulcer healing, eradicate H. pylori infection, and prevent relapse - TRIPLE THERAPY (7 days) – Lansoprazole + Amoxicillin/metronidazole + clarithromycin (1st & 2nd line, alternative 2nd line tetracycline) - Quadruple therapy (10 days) – 3rd line treatment Lansoprazole + bismuth subsalicylate + 2 antibiotics

Answer 4

All of the following lead to mucosal injury and bleeding Inhibit COX-1 -> prostoglandins not stimulated to secrete mucus and bicarbonates: - Reduced mucosal blood flow -> Impaired defence - Reduced mucus & bicarbonate secretion -> impaired defence - Impaired platelet aggregation Epithelial damage - due to aspirin and salicyclic acid removing epithelium -> acid back-diffusion: - Impaired platelet aggregation - Impaired healing Inhibit COX-2: - Reduced angiogenesis -> impaired healing - Increased leukocute adherence -> leukocyte activation

Answer 5

Even though stomach lining is thick, the pits in the stomach can be eroded. As there is a lot of acid produced as well as pepsinogen, if the barrier is not there and a peptic ulcer is formed – leads to bleeding, sepsis, infection, and clots - as it goes into the blood to clot; can lead to strokes, heart attack, and ischaemia.

Answer 6

Important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. Linked to GI toxicities While endoscopic ulcers can be documented in up to 40% of chronic NSAID users, it is estimated that as many as 85% of these never become clinically apparent. Serious NSAID induced GI complications such as haemorrhage, perforation or death are much less common, occurring collectively with an incidence of about 1.5% per year.

Answer 7

-Consider: - reducing the dose of the NSAID OR - Change NSAID to one of the following: Acetaminophen (AKA paracetamol), a nonacetylated salicylate (salsalate, trisalicylate) - A partially selective COX-2 inhibitor (etodalac, nabumetone, meloxicam, diclofenac, celecoxib) -Could also use a PPI to treat the ulcer: - When an NSAID needs to be continued, PPIs are the drugs of choice to treat and heal the ulcer OR switch to misprostol (PGE1 analogue maintains mucosal defence (increases mucus secretion mucus blood flow) but at clinical doses is an acid suppressant)) for maintenance therapy. Also bismuth preps: e.g., tripotassium dicitratobismuthate. Switching to an alternative acid suppression therapy, e.g. H2-receptor antagonists may be beneficial if the response to proton pump inhibitor therapy is inadequate.

Answer 8

“Mucosal strengtheners” | Sticky gel coats base of ulcer, gives physical protection, HCO3- secretion restores pH gradient

Answer 9

Small intestine has a lot villi – highly absorptive organ. A lot of peristalsis takes places. Following law of gut, whatever isn’t absorbed (mainly fats due to alkalinic environment) is passed into the large intestine – where water and minerals are absorbed.

Answer 10

Any damage to the muscles or nerves in the intestines reduces peristalsis, which reduces the movement of bulk in the intestines.

Answer 11

Generally defined hard stools with infrequent and/or unsatisfactory defecation fewer than 3 times per week. Patients may define constipation as passing hard stools or straining, incomplete or painful defecation. Constipation is a symptom, NOT a disease. Symptoms: painful bowel movements, bloated, uncomfortable, and sluggish Complications: haemorrhoids, and fissures

Answer 12

``` Female gender - Pregnancy Over 65 years of age Low caloric intake (eating less food) Greater number of medications used Sedentary lifestyle (lack of exercise) Ignoring the urge to defecate Smoking – Tobacco addiction Eating too little fibre Not drinking enough liquids Change in routine – travel Frequent use of laxatives Certain diseases or conditions ``` ``` Medications: Pain (narcotics) Antacids containing aluminum Antidepressants Iron supplements Diuretics ```

Answer 13

High fibre diet Minimum fluid consumption of 1500mL daily Regular, private toilet routine Heed the urge to defecate – allow time Become more physically active Use of a laxative if using constipating medication or in presence of diseases associated with constipation

Answer 14

Bulk-Forming Agents - Absorb water into the intestine increasing faecal bulk and stimulating peristalsis. The drug of choice for prevention, not for immediate relief: Dietary fibers Bran Ispaghula husk (seeds of Plantago ovata) – increases water – forms a bulk Methylcellulose Sterculia Not absorbed from the intestines, safe for long-term use. Safe for elderly patients. Helpful in patients with irritable bowel syndrome, diverticulosis, and colostomies. Onset of action: 8-24 hours up to 72h

Answer 15

Damages epithelium, causes melanosis coli and apoptosis – inflammatory response, fluid secretion, diarrhoea Not recommended for chronic use Melanosis coli (epithelial cells migrating toward the submucose in the process of apoptosis obtain a black colour from anthaquinone and are then phagocytosed. The macrophages take on the black pigment and then migrate away by way of lymphatic vessels) may be harmless or linked to a possible increased risk of colon cancer.

Answer 16

``` Prevent hardening of the faeces by adding moisture to the stool. Become emulsified with stool, decreasing surface tension of the faecal mass to allow water to penetrate into the stool: Docusate (DOSS) – Di Octyl Sodium Sulfosuccinate Glycerol Liquid Paraffin Arachis oil (ground-nut oil, peanut oil) ``` Patients who should avoid straining while defecating: Patients recovering from abdominal, pelvic, or rectal surgery, childbirth, or a heart attack. Patients with severe high blood pressure or abdominal hernias patients with painful hemorrhoids and/or anal fissures.

Answer 17

Hyperosmolar salts or saline products: Insoluble, remain in lumen pulling water into colon, increasing water in the faeces and increasing bulk – increase peristalsis: Magnesium citrate, hydroxide, oxide, sulphate Sodium biphospahte, phosphate Lactulose: Draws water into intestine and promotes water and electrolytes retention Glycerin: Acts like Lactulose, increasing water in the faeces Therapeutic Uses: Preparation of bowel for colonoscopy, sigmoidoscopy, and barium enema. Lactulose: liver disease (Hepatic encephalopathy)

Answer 18

Stimulants - Increase water and electrolyte secretion by the mucosa. Stimulate sensory nerve endings in GI mucosa → Increasing peristalsis. The faeces are moved through the bowel too rapidly to allow colonic absorption of faecal water so a watery stool is eliminated. Usually given at bedtime and they usually provide overnight relief (work within 8-12 hours): ``` Phenolphthalein Diphenyl Methanes Bisacodyl (Dulcolax) Sodium Picosulfate (Dulcolax liquid) Anthraquinones (glycosides) Senna (Cassia ssp), aloes (emodin) Danthron (limited indications, carcinogenic) Cascara sargada 5-HT4 agonist – Prucalopride Fixed oil – Castor Oil emulsion Colax: Stimulant laxative/probiotic: Aloe Vera concentrate, Lactobacillus Acidophilus, and a herbal blend ``` Therapeutic Use - Cleansing the colon for colonoscopies, barium enemas, and intestinal surgeries. Precaution - Chronic, long-term use of stimulant laxatives can lead to loss of colon function. Consequently, constipation becomes increasingly worse and unresponsive to laxatives. Too much use can also cause diarrhea short-term.

Answer 19

Laxatives: ``` Macrogol (polyethylene glycol) Stimulant laxatives - Anthraquinones Bulk-forming laxatives Sterculia Stool softeners - Docusate OTHERS - Bowel cleansing preparations, Peripheral opioid-receptor antagonists ```

Answer 20

Bowel cleansing preparations: Used before colonic surgery, colonoscopy or radiological examination to ensure the bowel is free of solid contents Peripheral opioid-receptor antagonists: Block / Decrease the gastro-intestinal (constipating) effects of opioids without altering their central analgesic effects. Recommended for the treatment of opioid-induced constipation when response to other laxatives is inadequate. Naloxegol, Methylnaltrexone bromide

Answer 21

Abnormal passing of loose or liquid stools, with increased frequency, increased volume, or both. Pathophysiology: Increased active anion secretion, decreased absorption of water and electrolytes. Overall weight and volume of stool is increased to >200mg or ml/day, and water content of stool is increased to 60-90%. Causes can be Infectious: Mostly faeco-oral route Bacterial, Viral, Parasitic, and Non-infectious: Normal mucosa: Osmotic diarrhoea Mal-absorption Abnormal mucosa: Inflammatory Bowel disease Celiac disease, microscopic colitis, eosinophilic and allergic Gastroenteritis, radiation enteritis.

Answer 22

Oral rehydration therapy (ORT): -Mainstay of treatment for acute diarrhoea to prevent or correct diarrhoea dehydration and to maintain the appropriate fluid intake once rehydration is achieved - Disodium hydrogen citrate with glucose, potassium chloride and sodium chloride - Potassium chloride with sodium chloride - Potassium chloride with rice powder, sodium chloride and sodium citrate - Intravenous rehydration fluid: - In patients with severe dehydration and in those unable to drink - Antimotility drugs: Loperamide - Mu-Opioid-receptor agonist, decreases the activity of the myenteric plexus, which decreases the tone of the longitudinal and circular smooth muscles of the intestinal wall. - Antibiotics if necessary