Pharmacology: PUD + GERD

Question 1

What can be targeted in PUD and GERD

Answer 1

H2RA and PPI: to decrease acid production

Question 2

What increases acid production and how

Answer 2

Gastrin via GR: released when eat food

H: H2R
AcH: MR (rest + digest)

** both result in PP: increase pumping of H against conc gradient via Ca2+ and caMP dependent paths

Question 3

What decreases acid production

Answer 3

PGE2: PGR
Misoprostol: PGR

Question 4

PUD: NSAIDS mech

Answer 4

non selective NSAIDs: block COX1 (protective; PG) and COX 2 (inflammation)

— block COX 1: decrease in PGE2 — increased in acid secretion +++ decrease in mucus + bicarbonate made by gastric cells

** 2 mechanisms

Question 5

T or F: PPIs have affinity to H2 receptors

Answer 5

F - structural related to H2RA but no affinity for H2R
— selective and specific for PP

Question 6

Pathways to target PPIs

Answer 6

prodrugs: get absorbed + metabolized to active metabolite
— then make way back to parietal cells via BS —- now at site of action

Question 7

Types of interaction bw PPI and PP

Answer 7

covalent disulfide bond

Question 8

T or F: PPIs are good at stop nocturnal secretions

Answer 8

F - H2RA are better

Question 9

Why are PPIs dosed QD is short t1/2

Answer 9

covalent bind to target (stomach)
— don’t spend much time in blood
— bound to PP.

Question 10

Toxicity of PPI

Answer 10

diarrhea and headaches

• increased risk of fracture (decrease Ca A) and infection (change gut flora)

Question 11

H2RA MoA

Answer 11

competitive H2R antagonist
- block R on parietal cells: decreased acid production

** really good at nocturnal secretions

Question 12

What H2RA has a lot of hormone SEs

Answer 12

cimetidine (increase prolactin, inhibit E metabolism )
—- a lot of DIs

Question 13

What are antacids used for

Answer 13

GERD: SL or intermittent

Question 14

MoA: antacids

Answer 14

ingest bases that directly interacts with H to form salt + H2O
—- can make CO2 too

2nd MoA: stimulate PG production

Question 15

How are antacids dosed

Answer 15

based on HCL production per meal
—- one meal: 45 mEq of Hcl

Question 16

Sodium bicarbonate antacids

Answer 16

product CO2
- may cause metabolic alkalosis if absorbed systemically

Question 17

Calcium carbonate

Answer 17

forms Co2 slower than Na bicarbonate —- less Ses

Question 18

Mg/Al combos

Answer 18

Mg: osmotic diarrhea
Al: constipation

no Co2

Question 19

MoA: misoprostol

Answer 19

acts as a methylated PGE1 analog + binds to PGE2 receptors. —- decrease acid production
—- increase bicarbonate and mucus

———- increase PG protective path

*** CI : pregnant

Question 20

Bismuth

Answer 20

don’t know full MoA

SEs: black tongue and poop

Question 21

MoA: Sucralfate

Answer 21

• sucrose binds with Al hydroxide to make viscous barrier with water
  — coats ulcers via ionic interaction (binds to area with - charge)

Question 22

Blocking of D2 causes …..

Answer 22

motility /movement through GI
- increase gastric emptying

** when dop binds : decreases this but if we block——increase

Question 23

5HT3 blocking causes ….

Answer 23

motility in GI

Question 24

5HT4 binding causes….

Answer 24

motility
—- if block: decreases motility

Question 25

D2R Antagonists

Answer 25

block D2 receptors to increase movement through GI (hopefully decrease acid production)

— included domperidone

Question 26

SEs of D2R antagonists

Answer 26

CNS : restless, insomnia, anxiety

High doses —- tardive dyskinesia (PD like)

Domperidone —- doesn’t cross BBB, less of these

Question 27

Cisapride + pruclaopride

Answer 27

5HT4 agonists — motility inducing

C- not in market bc cardiac SEs

Question 28

Alosetron MoA

Answer 28

normally used as N/V in chemo

• 5HT3 antagonist

Question 29

Erythromycin MoA

Answer 29

prokinetic ABX that mimics motilin to increase GI motility