Upper GI Pharmacology

Question 1

Antacid pharmacokinetics

Answer 1

tablets/powder, suspension
Poorly absorbed (unless poor renal function), thus minimal undesired systemic side effects
Di/tri-valent cations; may chelate other drugs, separate dosing

Question 2

Antacid MOA

Answer 2

Locally buffer H+ to increase pH

Question 3

Antacid indications

Answer 3

heartburn, dyspepsia

Question 4

Antacid SE

Answer 4

Mg-containing: osmotic diarrhea (explosive)
Ca-containing: constipation, hypercalcemia, calculi, bloating, nausea (due to CO2 liberated)
Al-containing: constipation, hyperphosphatemia

Question 5

H2 antagonist prototypes

Answer 5

ranitidine, cimetidine

Question 6

H2 antagonist PK

Answer 6

po; some iv and im
rapidly absorbed
renal elimination (filtration and secretion) - adjust dosing in renally impaired patients

Cimetidine: notorious CYP450 blocker

Question 7

H2 antagonist MOA

Answer 7

H2 receptors on parietal cells mediate basal, nocturnal, and meal-stimulated release of acid (histamine binding stimulates H/K ATPase via cAMP)
Reversible blockage

Question 8

H2 antagonist indications

Answer 8

GERD
PUD
Dyspepsia
Prevention of bleeding from stress-related gastritis

Question 9

H2 antagonist SE

Answer 9

generally well-tolerated
diarrhea/constipation, headache, fatigue, MSK pain
Cimetidine only: gynecomastia and galactorrhea

Question 10

PPI prototypes

Answer 10

omeprazole, pantoprazole

Question 11

PPI PK

Answer 11

must be absorbed into systemic circulation
act locally on GI tract cells (parietal cells)
Prodrugs: activated in acidic canaliculi of parietal cells
hepatic clearance - adjust dosing in liver impaired patients

Question 12

PPI MOA

Answer 12

antagonist of proton-secreting pump in stomach (K/H pump) on parietal cells
irreversible

Question 13

PPI indications

Answer 13

gastric and duodenal ulcers, NSAID-induced ulcers
GERD
Pathological hypersecretory conditions (Zollinger-Ellison, where levels of hormone are increased due primarily to gastrinoma tumour of non-beta islet cells in the pancreas)

Question 14

PPI SEs

Answer 14

generally well-tolerated short term
nausea, ab pain, constipation/diarrhea, flatulence (alteration in intestinal flora due to pH change)
less common: hypergastrinemia, due to rebound secretion of gastric acid if PPI is stopped after short-term use

Question 15

Misoprostol PK

Answer 15

short half-life

Question 16

Misoprostol MOA

Answer 16

PG analogue
endogenous PGE2 binds EP3 on parietal cells –> reduces activity of proton pump and stimulates mucin and bicarb secretion to bolster mucosal barrier
endogenous PGE2 is made by COX1
PGE-1 analogues (misoprostol) given as adjuncts in patients on NSAIDs

Question 17

Misoprostol indications

Answer 17

NSAID-induced gastric ulcer

Question 18

Misoprostol SEs

Answer 18

diarrhea, abd cramping (stimulates smooth muscle contraction in GI and uterus)

Question 19

Sucralfate PK

Answer 19

local GI action, minimal absorption (fecally excreted)
activated by acid
contains Al, which is excreted renally - adjust for renal impaired patients

Question 20

Sucralfate MOA

Answer 20

complex of sucrose and AlOH –> viscous paste in acid aqueous media (direct
stimulates PG synthesis of mucus and bicarb secretion (indirect)

Question 21

Sucralfate indications

Answer 21

Tx and prevention of gastric and duodenal ulcer

Question 22

Sucralfate SE

Answer 22

constipation (Al)

minimal systemic effects due to poor absorption

Question 23

Bismuth MOA

Answer 23

form protective barrier on ulcer
enhance PG, mucus, bicarb secretion
inhibit H. pylori growth and adherence

Question 24

Bismuth indications

Answer 24

Adjunctive therapy in H. pylori eradication

acute diarrhea

Question 25

Bismuth SE

Answer 25

black tarry stool (benign discolouration, commonly mistaken for blood) benign discolouration of tongue constipation tinnitus

Question 26

Prokinetic prototypes

Answer 26

metoclopramide, domperidone

Question 27

Prokinetic PKs

Answer 27

metoclopramide: rapidly absorbed, hepatic metabolism, renal excretion, oral/parental dosage Domperidone: rapidly absorbed, low oral bioavailability because of extensive first pass mechanism (increased availability with food)

Question 28

Prokinetic MOAs

Answer 28

endogenous dopamine inhibits GI motility, since D2 receptors inhibit ACh release D2 antagonists --> increase LES tone, stimulates GI contraction (upper) also anti-nauseants via central inhibition of vomiting centre

Question 29

Prokinetic indications

Answer 29

gastroparesis, nausea/vomiting (anti-emetic) GERD facilitate small bowel intubation

Question 30

Antacid prototypes

Answer 30

Ca carbonate | Mg, Al hydroxide