Gastointestinal Pharmacology

Question 1

What is the pathogenesis of gastroduodenal ulcers?

Answer 1

Excess gastric acid secretion, breakdown of mucosal cytoprotection, Helicobacter pylori infection

Question 2

What are the goals of ulcer treatment?

Answer 2

reduce ulcerogenic factors, enhance defensive factors, or eradicate any infectious causes

Question 3

What are pro-ulcerogenic factors?

Answer 3

Acids (HCl, VFA, bile acids), pepsin, infections

Question 4

What are antiulcerogenic factors?

Answer 4

mucosal cytoprotection, epithelial renewal, external protection

Question 5

How does one increase the gastric pH to greater than 4 to promote healing?

Answer 5

H2-Histamine receptor blockade, stimulation of gastric PGE receptors, gastric H+-K+-ATPase inhibition (proton pump inhibitors)

Question 6

Famotidine

Answer 6

H2-Histamine antagonist, decreases acid secretion which decreases pepsin. As treatment continues effectiveness decreases due to an increased secretion of gastrin. Low oral biovalibility and renal clearance

Question 7

What are examples of H2-histamine antagonists?

Answer 7

famotidine, ranitidine, cimetidine

Question 8

What are the side effects and indications of H2-histamine antagonist?

Answer 8

Renal disease patients need lower dose, treatment of ulcers due to gastritis, stress, NSAID terapies, gastrinomas

Question 9

Misoprostil

Answer 9

PGE analogue, po administration, needs frequent administration due to rapid hepatic metabolism. Decreases acid secretion stimulated by histamine or gastrin. Less effective than H2-HR antagonists or PPI, increases gastric cytoprotection

Question 10

How do PGE and PGI promote cytoprotection?

Answer 10

Mucus production (coats surface of the gastric mucosa), bicarb production (neutralizes HCl), intrinsic mucosal barrier (resist back-diffusion of acid), and gastric blood flow (flushes away acid, prevents buildup, maintains tissue pH in normal range)

Question 11

Indications/side effects/contraindications of misoprostil?

Answer 11

NSAIDs-induced ulcers, increased mast cell influx. Side effects include diarrhea due to prokinetic action. Contraindications include IBD, pregnancy

Question 12

What is an example of a proton pump inhibitor?

Answer 12

Omeprazole

Question 13

What is the action of proton pump inhibitors?

Answer 13

Irreversibly inactivate H+/K+ ATPase, so effects extend longer than the drug’s presence in the body. Reduce acid secretions

Question 14

Omeprazole

Answer 14

Proton pump inhibitor. Oral paste that is a weak base that decreases the release of HCl

Question 15

Sucralfate

Answer 15

Binds to ulcerated tissue to form a seal after oral administration, heals existing ulcers not prevent new ones. Short duration of action. Binds and inactivates bile acids, increases local prostanoid formation.

Question 16

Antacids

Answer 16

Either systemic or non-systemic, non-systemic only affects stomach. Maalox and Mylanta examples. Relieve clinical signs, no healing.

Question 17

Na or Ca carbonate antacids onset

Answer 17

rapid

Question 18

Mg salts (sulfate, hydroxide) onset

Answer 18

intermediate with laxative effect

Question 19

all hydroxide antacids onset

Answer 19

slow

Question 20

What is the best type of drug to use to treat an ulcer: PPIs, H2-histamine antagonists, or cytoprotectants?

Answer 20

PPIs

Question 21

What are examples of locally-acting emetic agents?

Answer 21

warm water, sodium chloride, 3% hydrogen peroxide, syrup of ipecac (emetine akaloid substance)

Question 22

Apomorphine

Answer 22

centrally acts on D2 dopamine receptors, produces vomiting in 2-10 minutes

Question 23

Xylazine

Answer 23

simulates alpha2-adrenergic receptors to produce emesis in cats

Question 24

Indications of anti-emetic drugs

Answer 24

motion sickness, uremia, liver disease, cancer chemo, parvo, trauma

Question 25

Famotidine

Answer 25

H2-histamine antagonist that lessens irritating effects of acid on the stomach

Question 26

muscarinic acetylcholine antagonist anti-emetic effects

Answer 26

decrease vagal afferent transmission to vomiting center to decrease vomiting

Question 27

kaolin-pectin and other coating agents anti-emetic efficacy

Answer 27

not very effective

Question 28

Metoclopramide

Answer 28

Simulate gastric motility, block CNS dopamine receptors and 5-HT3 receptors

Question 29

Action of diphenhydramine, meclizine

Answer 29

may reduce motion sickness by blocking histamine and muscarinic cholinergic receptors

Question 30

Ondanestron

Answer 30

blocks type three serotonin receptors on gastric vagal fibers and are effective at inhibiting emesis in dogs associated with chemo or parvo

Question 31

Maropitant

Answer 31

Blocks type 1 neurokinin (substance P) receptors present in vomiting center, broad spectrum anti-emetic

Question 32

What effect do mAChR antagonists have on the GI tract?

Answer 32

increased peristalsis

Question 33

What affect do opiods have on the GI tract?

Answer 33

increased segmentation

Question 34

What affect do opiod antagonists or mAChR antagonists have on the GI tract?

Answer 34

inhibit increased segmentation

Question 35

Bethanechol

Answer 35

mAChR agonist that is a cholinomimetric that increases GI motility

Question 36

Neostigmine

Answer 36

anticholinesterase drug that increases GI motility

Question 37

Ranitidine and Nizatidine

Answer 37

weak cholinesterase inhibitors that can increase upper GI motility

Question 38

Metoclopramide

Answer 38

Acts on upper GI tract to increase smooth muscle contractions, blocks D2 dopamine receptors and is an agonist at the 5-HT4 serotonin receptors

Question 39

Cisapride

Answer 39

Partial agonist at 5-HT4 receptors, increase acetylcholine release from enteric neurons to stimulate motility, indicated by chronic constipation, ileus in dogs

Question 40

Erythromycin

Answer 40

agonist at receptors in smooth muscle and gastroenteric nerves for motilin, stimulates motility of stomach and upper SI (not colon). Metabolized by CYP450 and eliminated in bile

Question 41

Lidocaine

Answer 41

Blocks voltage-gated Na+ channels in enteric nerves, stimulates intestinal motility although mechanism unclear

Question 42

What are contraindications of prokinetic drugs?

Answer 42

GI tract obstructions and post-surgical anastomoses

Question 43

What are the major types of laxatives and cathartics?

Answer 43

Osmotic, bulk, lubricants/surfactants, and irritants

Question 44

What are examples of osmotic laxatives?

Answer 44

Mannitol, sorbitol (draws water into intestinal tract)

Question 45

What is an example of a irritant laxative?

Answer 45

Bisacodyl- stimulates enteric sensory nerves to increase intestinal motility and decrease water absorption

Question 46

What is an example of a bulk laxative drug?

Answer 46

Canned pumpkin- increase mass of non-digestible matter

Question 47

What is an example of a lubricant/surfactant laxative drug?

Answer 47

Mineral oil, docusate sodium- coat fecal surface with hydrophobic film

Question 48

Bismuth subsalicylate

Answer 48

breaks down to salicylic acid (NSAID) and bismuth oxychloride (bacteriocide?), bismuth salts absorb enterotoxins

Question 49

Kaolin-Pectin

Answer 49

Aluminum silicate, changes fecal consistency (maybe??) but clinical efficacy questionable

Question 50

Propantheline, Isopropramide, N-butylscopolammonium bromine

Answer 50

Types of quarternary ammonium anticholinergic drugs (act through intestinal mAChR) that do not enter CNS and inhibit intestinal motility and secretion as antidiarrheal drugs

Question 51

Naloxone

Answer 51

antagonize opiod actions in GI tract (opiods inhibit GI propulsion)

Question 52

What are examples of opiate antidiarrheal drugs?

Answer 52

Loperamide (no abuse) and codine (acts at perif and CNS cites too)

Question 53

What are examples of opiod antagonists that are peripherally-specific?

Answer 53

Alvimopan and methynaltrexone