Pharm: H2 Receptor Blockers, PPIs

Question 1

What cells are responsible for acid secretion in the stomach?

Answer 1

parietal cells (think “Pour-IT-ALL” lemonade)

Question 2

Where are parietal cells of the stomach located?

Answer 2

fundus and body

Question 3

What type of receptor/pump secretes protons

Answer 3

H+/ K+ exchanger ATPase (think of the mom putting bananas in to the puree pump fueled by three “P” batteries)

Question 4

What kind of receptor do parietal cells have?

Answer 4

H2 receptors- Gs receptor- on the basolateral side of parietal cells (think of the bees around a honey pot with TWO S-shaped handles- Gs activates kinases that turn on H+/K+ ATPase)

Question 5

The histamine that stimulates H2-R on parietal cells is released by ____________.

Answer 5

Neighboring enterochromaffin-like (ECL) cells (think Enter CarefulLy: bees misting and the lea-blowing guy)

Question 6

What activates enterochromaffin-like (ECL) cells?

Answer 6

Gastrin from G cells in the antrum (think the gas tank fueling the leaf blower that’s disturbing the bees)

Question 7

True or false: The vagus nerve stimulates G cells to release gastrin using ACh.

Answer 7

False: vagus nerve releases gastrin releasing peptide (think of the Gate Release Pull on the gas truck with a <3 Las Vegas sticker on it)

Question 8

Gastrin binds to __________ on the parietal cells and ECL cells.

Answer 8

CCK-B receptors

Question 9

Gastrin stimulates ___________ and _____________ cells.

Answer 9

ECL cells and parietal cells directly

Question 10

What two things stimulate gastrin release from the G cells?

Answer 10

1. vagus nerve stimulating by GRP

2. peptides in the lumen of the antrum

Question 11

What two things do the vagus nerve stimulates?

Answer 11

1. parietal cells through M3 receptors - directly stimulate acid secretion
2. G cells through GRP - gastrin stimulates acid directly and through ECL histamine release

Question 12

What blocks H2 receptors?

Answer 12

“-tidine” = ranitidine, cimetidine, famotidine, nizatidine (think of the boy in a Tie-dye shirt wielding TWO beeswatters)

Question 13

H2 receptors do NOT block what mechanism of acid secretion?

Answer 13

Vagus nerve and Gastrin that stimulates parietal cells DIRECTLY

Question 14

H2 antagonists are especially good at inhibiting acid secretion at what time?

Answer 14

Nocturnal- NOT meal stimulated acid secretion (when vagus nerve and gastrin are stimulated)

Question 15

Though 2nd line, H2 antagonists are used to treat ________ and __________.

Answer 15

1. GERD (gargling lady)

2. gastric/duodenal ulcers (ulcerated sidewalk under gargling lady)

Question 16

Most H2 drugs are well-tolerated except one of them. Which one is it?

Answer 16

cimetidine (think of the kid with a tie-dye putting his hand on CEMENT)

Question 17

What are side effects of cimetidine?

Answer 17

1. inhibit CYP-450 in the liver (think of the kid weaing tie-dye and jumping on the hood of the car with a dented CYP-450 license plate on the chrome bumper)
2. antiandrogenic effects: gynecomastia (think of tie-dye kid with two pot lids on his chest), impotence (think of the kid with a floppy honey wand), hyperprolactinemia (think of the milk shooting out of tie-dye kid’s nose)

Question 18

What and how do PPIs inhibit acid secretion?

Answer 18

Irreversibly inhibit (through covalent disulfide bond) H+/K+ ATPase (think of the girl scout in front of the puree pump, blocking it)

Question 19

What is the PPI suffix?

Answer 19

“-prazole” (think of the banner for the young entrepreneur badge PRIZE)

Question 20

Why are PPIs more effective than H2 antagonists?

Answer 20

Because it inhibits H+/K+ exchanger which is the common final endpoint for histamine-, gastrin-, and ACh-mediated induction of acid secretion (all three)

Question 21

PPIs are good a blocking what kind of acid secretion?

Answer 21

1. meal time AND

2. nighttime

Question 22

What do PPIs treat?

Answer 22

1. GERD (1st line)
2. Ulcers (1st line)
3. NSAID-induced ulcers
4. H. pylori infection (think of the helicopter hat on the girl scout)

Question 23

Gastrinomas cause overactivation of which cell type?

Answer 23

ECL

• Tumor of G-cells leads to hypersecretion of gastrin which mainly targets ECL (think of the lawn mower with a jumbo gas tank and a swam of bees)

Question 24

What is the syndrome do gastrinomas cause?

Answer 24

Zollinger-Ellison syndrome

Question 25

How do you treat gastinomas?

Answer 25

PPIs (because H2 can’t block direct stimulation of gastrin onto parietal cells)

Question 26

What are the symptoms of Zollinger-Ellison syndrome?

Answer 26

• chronic diarrhea
• heartburn
• ab pain
• GI bleeds

Question 27

What does triple therapy for H. Pylori include?

Answer 27

azithromycin, PPI, amoxcillin/metronidazole

Question 28

PPIs are generally safe with few side effects; however it can cause malabsorption of what three things?

Answer 28

Ca2+, Mg2+ and Fe2+ since it requires acid (think of the medals on the girl’s cart)

Leads to osteoporosis (think of the fracture axel of the wagon for hip fractures and porous wagon wood)

Question 29

Somatostatin inhibits ___________ and ___________.

Answer 29

histamine release by ECL cells and gastrin release by G cells (think of the STop signs on the bee tree and gas truck)

Question 30

If PPIs are not enough to inhibit gastrin from gastrinomas, what do you use?

Answer 30

somatstatin analogs because

somatostatin receptors can also be expressed on gastrinomas

Question 31

What is an example of a somatostatin analog?

Answer 31

octreotide is a long-acting somatostatin analog (think octagon stop sign) which inhibits both histamine and gastrin release)

Question 32

What is galactorrhea?

Answer 32

inappropriate production of milk

Question 33

PPis increase risk of what infections?

Answer 33

1. C. diff infection (think of the chocolate fondue fountain attached to the girl scout wagon)
2. Pneumonia (think of the chocolate-y lung spots on the girl)

because lack of acid promotes bacterial survival