Acid Suppression GI Drugs

Question 1

H2 antagonists and role

Answer 1

Cimetidine, famotidine, ranitidne, nizatidine
Selectively bind to H2 in the stomach( competitive with histamine and fully reversible) causing decreased basal, food-stimulated and nocturnal secretion of gastric acid

Question 2

Usage of H2 antagonists

Answer 2

Peptic ulcers (if cause is H.pylori infection), acute stress ulcers, GERD

Question 3

Pharmacokinetics of H2 antagonists

Answer 3

Administered orally going to all the body including milk and placenta and excreted by urine
Cimetidine, famotidine and ranitidine could be found in IV formulations

Question 4

Adverse effects of H2 antagonists

Answer 4

Cimetidine work as antiandrogenic agent that causes gynecomastia and galactorrhea (release of discharged milk)+ inhibit cytochrome P450 isoenzymes leading to decreased metabolism of some drugs like warfarin, diazepam…
IV formulation->confusion and alteted mental state

Question 5

PPIs and mechanism

Answer 5

-prazole (dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)
Ingested as a prodrug that is absorbed in the duodenum and converted into the active drug in parietal cells that blocks the H+/K+ ATPase therefore stopping acid secretions.

Question 6

Usage of PPIs

Answer 6

Stress ulcers, GERD, erosive esophagitis, active duodenal ulcers and ZES (gastrin producing tumor), peptic ulcers (caused by NSAIDs to decrease risk of bleeding)

Question 7

Pharmacokinetics of PPIs:

Answer 7

Taken orally, 30-60 mins before breakfast (except for dexlansoprazole taken without regard to food)
Esomeprazole, lansoprazole, pantoprazole are found as IV formulations
Omeprazole can be taken with sodium bicarbonate for faster absorption
Metabolites are found in urine or feces

Question 8

Adverse effects of PPIs

Answer 8

Nausea, diarhea, headache, bone fractures, GI disturbances, clostridium difficle collitis, decreased VitB12 absorption, hypomagnesemia
Omeprazole and esomeprazole decrease effectivenes of clopidogrel (inhibiting CYP2C19)

Question 9

Prostaglandins usage, contraindications and adverse effects

Answer 9

-Misoprostol (analog of prostaglandin E1) used for NSAID-induced gastric ulcers.
Prophylactic use of misoprostol in case of: elderly patients, with previous ulcers.
-not used in pregnancy (causes uterus contractions and miscarriage)
-diarrhea and nausea

Question 10

Antacids and adverse effects

Answer 10

Aluminum hydroxide (constipation), magnesium hydroxide (diarrhea), calcium carbonate (upset GI, increased urination) and sodium bicarbonate (metabolic alkalosis)

Question 11

Sucralfate

Answer 11

Mucosal protective agent made up of aluminum hydroxide and sulfated sucrose fucntionning in acid environment so cannot be taken with PPIs, antacids or H2 antagonists.
Not used for stress ulcers or duodenal ulcers (multiple doses are needed), doesn’t prevent NSAID induced ulcers and does not heal gastric ulcers.

Question 12

Bismuth subsalicylate

Answer 12

Antimicrobial agent and mucosal protective agent by secreting mucus coating the ulcers and inhibiting activity of pepsin

Question 13

Therapy for H.pylori infection

Answer 13

Triple therapy: PPIs, amoxicillin (or metronidazle in case of penicillin resistance) and clarithromycin
Quadruple therapy: PPIs, metronidazole, bismuth subsalicylate, and tetracyclin

Question 14

Drugs for motion sickness

Answer 14

Scopolamine (M antagonist), cyclizine (H1 antagonist), dimehydrinate and meclizine

Question 15

For chemotherapy induced nausea and vomiting:

Answer 15

-Dopamine receptor blockers: prochlorperazine, metoclopramide (used after cisplatin), droperidol, haloperidol (butyphenones)
They can prolong QT intervals and have extrapyramidal symptoms
-5HT3 receptor blockers: -setron like ondansetron, granisetron (used for cisplatin), dolansetron . Used as oral or IV formulations single dose before chemo also can be used for postoperative N&V. They have a long duration of action and superior efficacy to others.
High doses of ondansetron and dolansetron (cannot be used for prophylaxis) cause prolonged QT interval
-corticosteroids: dexamethasone and methylprednisolone.
-substance P/neurokinin-1 receptor blockers: aprepitant
If administered with 5HT3 antagonists or dexamethasone interfere with metabolism of warfarin and OCPs
-benzodiazepins: lorazepam, alprazolam for anticipatory vomiting for sedative, anxiolytic and amnesic properties
Cannot be used in case of alcohol because it would lead to depressive CNS states.

Question 16

Antidiarrheals

Answer 16

-Opioids: diphenoxylate, loperamide (decrease peristalsis, inhibit acetylcholine release)
Not used for younger children, patients with collitis
-adsorbents: aluminum hydroxide, methylcellulose (absorb intestinal toxin or coat intestinal mucosa)
-bismuth subsalicylate: reduce fluid secretion in bowel used for traveler’s diarrhea
Side effects: black tongue and stool

Question 17

Laxatives

Answer 17

-Stimulants: senna (taken orally causes water and electrolyte secretion leading to evacuation within 8-10 hrs),
Bisacodyl (acts on nerve fibers in the mucosa of colon), castor oil (ricinoleic acid- product of break down- irritates stomach so increases peristalsis)
Castor oil cannot be used in pregnant women
- bulk laxatives: hydrophilic colloids (increase peristalsis, water retention, intestinal distention)
-saline and osmotic laxatives: magnesium citrate and hydroxide are nonabsorbable salts that retain water in intestines by osmosis
Polyethene glycol PEG used as colonic lavage for operations causing less gas and cramps
Lactulose is a semisynthetic disaccharide sugar that cannot be hydrolyzed by GI enzymes and is degraded in colon by colonic bacteria (^osmotic pressure, ^fluid levels leading to distended colon, soft stools and defecation) could be used for hepatic encephalopathy
-stool softeners: docusate sodium and calcium
-lubricant laxatives: mineral oid, glycerin suppositories (taken orally in upright position to avoid lipid aspiration)
-chloride channel activators: lubiprostone, linaclotide
Used in chronic constipation to increase fluid secretion by activating chloride channels