GI meds

Question 1

Gastric antacids

Answer 1

• Magnesium hydroxide produce Mg salt, which is very poorly absorbed and cause diarrhea.
• Aluminum hydroxide reacts with HCl to form Aluminum chloride, which is insoluble and cause constipation and hypophosphatemia
• Calcium carbonate: Hypercalcemia, nephrolithiasis, and constipation –fecal compaction
• Ca, Mg, Al molecules can chelate tetracyline.

Question 2

H2 antagonists

Answer 2

• Ranitidine, Famotidine and Nizatidine are longer acting and more potent than older cimetidine.
• Unlike cimetidine, newer drugs does not produce the antiandrogenic or prolactin stimulating effects.
• They do not inhibit the mixed function oxygenase system in the liver (CYP450 enzymes).
• Most common side effects are nausea, headache, and dizziness.

Question 3

Cimetidine

Answer 3

• Cimetidine SE’s - gynecomastia, elevated serum PRL, and confusion in elderly people
• Strong inhibitor of CYP450 system -> slow metab of warfarin, procainamide, phenytoin, BZOs, theophylline, imipramine, and quinidine

Question 4

Omeprazole

Answer 4

• In animals, is associated w/gastric carcinoid tumors
• Inhibs the metabolism of warfarin, phenytoin, diazepam, and cyclosporine
• Small increase in resp and GI infxns. Decrease in sr. Mg2+ and hip fx’s w/LT use
• Rarely pancreatitis, hepatotoxicity, and interstitial nephritis
• Prolonged use of PPI and H2 blockers -> decreased bioavailability of B12, digoxin, and ketoconazole bc acid is required for absorption

Question 5

Sucralfate

Answer 5

• Sulfated disacch used in PUD
• MOA - drug undergoes polymerization and selective binding to necrotic tissue -> barrir to acid Also stimulates endogenous PG synth
• Sucralfate is INEFFECTIVE w/action of H2 rec blockers or PPI -> needs acidic pH to be activated. Do NOT administer w/antacids

Question 6

Bismuth

Answer 6

• Selectively binds ulcer and forms coating, protects from acid and pepsin
• Some anti microbe effect on H. pylori

Question 7

Misoprostol

Answer 7

• PGE1. Decreases acid secretion, stimulates mucin and bicarbonate production
• For gastric ulcers induced by NSAIDs
• SE’s: diarrhea, abortions (d/t induction of uterine contractions during pregnancy), exacerbations of BID

Question 8

Metoclopramide

Answer 8

• Prokinetic via 5-HT4 agonist activity -> increased gastric emptying and intestinal motility
• Higher doses - anti 5-HT3 and anti-D2 - anti-emetic
• Uses: diabetic, post op gastroparessis, anti-emetic
• Especially useful at high doses against highly emetogenic cisplatin
• SE’s: anti-dopaminergic -> sedation, diarrhea, Parkinson’s

Question 9

Cisapride

Answer 9

• Gastroparesis, GERD, and constipation

* SE’s: arrhythmias

Question 10

Cholinomimetics

Answer 10

• Neostigmine - used for colonic pseudo-obstruction

* Bethanechol - used in GI and bladder atony. Opposite is atropine

Question 11

Erythromycin

Answer 11

• Macrolide. Acts on motilin recs of GIT
• Used for gastric emptying before upper GI endoscopic procedures
• Tolerance develops in gastroparesis

Question 12

Substances that act on area postrema

Answer 12

• D2, 5-HT3, opioid/ACh, substance P

Question 13

Aprepitant, Fosaprepitant

Answer 13

• NK-1 rec blocker in CNS
• Decreases early and delayed emesis in CA chemotherapy
• Fosaprepitant is used IV
• SE’s: dizziness, fatigue, diarrhea, CYP interaction

Question 14

Prochlorperazine

Answer 14

• Blocks D2 recs and muscarinic recs

* SE’s: extrapyramidal sx’s, hypotension, etc

Question 15

BZOs

Answer 15

• Antiemetic potency of lorazepam, alprazolam, and diazepam is low
• Beneficial d/t sedative, anxiolytic, and amnesic properties
• Useful in anticipatory vomiting

Question 16

Sulfasalazine

Answer 16

• Tx CD and UC. Inhibs pro-inflam IL1 and TNF-a
• Sulfa derivative
• Sulfapyridine (antibacterial) and 5-ASA (anti-inflam) released by colonic bacteria
• SE’s: nausea, vomiting, diarrhea, hypersensitivity, reversible oligospermia, BM suppression d/t sulfapyrazine

Question 17

6-MP, MTX

Answer 17

• Tx CD and UC. 6-MP may promote apoptosis of immune cells. MTX blocks DHF reductase
• Cause generalized immune suppression
• SEs: GI mucositis, myelopsuppression. Hepatotoxicity w/6-MP. Toxicities w/low dose MTX is rare

Question 18

Infliximab

Answer 18

• Especially good for CD w/fistulas and acute flares. Also in RA
• SEs: reactivate latent TB and other infxns. Given IV -> fever, chills, urticarial rxn, hypotension, Ab formation

• Adalimumab is similar

Question 19

Natalizumab

Answer 19

• Tx CD and UC. Blocks leukocyte integrins. Can produce multifocal leukoencephalopathy

Question 20

Corticosteroids in IBD

Answer 20

• Hydrocortisone, prednisone, prednisolone used in acute cases
• Inhibit TNF-a, IL-1, IL-8
• Budesonide - ctrl-release formulaiton in distal ileum and colon

Question 21

Alosetron

Answer 21

• Tx IBS- D. 5-HT3 antagonist w/long duration of action
• Reduces smooth mm activity in the gut for IBS-D
• Recommended for severe diarrhea
• SEs: rare, serious constipation, ischemic colitis, infarction

Question 22

Anticholinergics used for IBS-D

Answer 22

• Hyoscyamine, dicyclomeine, glycopyrrolate, methscopolamine

Question 23

Lubiprostone

Answer 23

• Tx IBS-C. Chloride channel activator

Question 24

Loperamide, Diphenoxylate

Answer 24

• Opiate derivatives. Antidiarrheals that slow motility w/negligible CNS effects
• Acts via GI mu-opioid recs. Inhibs ACh release and decreases peristalsis
• Diphenoxylate is formulated w/atropine to reduce abuse potential. High doses of diphenoxylate -> CNS effects

Question 25

Bile salt-binding resins

Answer 25

* Cholestyramine, colestipol, colesevelam * Prevent diarrhea of IBS and IBD by blocking osmotic and irritating actions of bile salt * Form insoluble complexes w/bile in intestine * SEs: bad taste, GI discomfort, decreased fat-soluble vitamin absorption

Question 26

Stimulant laxatives

Answer 26

* Castor oil, Senna, Bisacodyl, Cascara * May cause cramping * Chronic use -> habit of perceived need for laxatives

Question 27

Bulk forming agents

Answer 27

* Agar, methylcellulose, psyllium, bran. Laxatives | * Increase water retention -> stools become bulky -> distention -> peristaltic stim of gut

Question 28

Osmotic laxatives

Answer 28

* Mg citrate and MgOH (saline cathartics). Lactulose, sorbitol (non-digestible sugars) * Osmotically draw water into GIT -> stimulate motility * Used in simple constipation, bowel prep for endoscope * Lactulose -> lactic, formic, and acetic acid that also increase osmotic effect. Also used in hepatic encephalopathy to draw out ammonia (NH3), useful for preventing hyper ammonia * PEG - used for colonic lavage for endoscopic and radiological procedures

Question 29

Stool softeners

Answer 29

* Mineral oil and docusate sodium. Emulsify stool. soften it, lubricate * Senna combined w/docusate for opioid constipation

Question 30

Opioid receptor antagonists

Answer 30

• Alvimopan, methylnaltrexone. Tx opioid-induced constipation -> block GI mu recs, do not enter CNS

Question 31

Ursodiol

Answer 31

* Secondary bile acid, used to tx gallstones * Reduces chol absorption by breaking up micelles containing chop * Used in pt who refuses or not eligible for surgery * SE: diarrhea

Question 32

Octreotide

Answer 32

* Long-acting SST * Uses: carcinoid tumors (appendix, ileum, rectum), VIPoma, acute variceal bleeding, and acromegaly * SEs: abdominal cramps, nausea, steatorrhea, gallstones, decreased endocrine and exocrine pancreatic activity • Variceal hemorrhage - MOA uncertain. Alter portal blood flow and variceal pressure. Can also use propranolol and nadolol to reduce portal pressure