Lecture 1 - Gastric acid secretion and its regulation. Drugs inhibiting gastric acid secretion

Question 1

2 GI tract hormonal innervation

Answer 1

1. Endocrine secretions (bloodstream)
2. Paracrine secretions (local)

Question 2

1. Endocrine secretions (bloodstream)

Answer 2

– Gastrin
– Cholecystokinin
* Synthesis in endocrine cells of mucosa

Question 3

2. Paracrine secretions (local)

Answer 3

– Histamine
– Acetylcholine
* Specialised cells

Question 4

Give 5 elements of parietal cell

Answer 4

-Canalicular membrane
- canaliculus
- tubulovesicles
- basolateral membrane
- mitochondria

Question 5

Describe Proton Pump action in the Canalicular
Membrane

Answer 5

H+/K+ ATPase
 Cl- co-transporter
 Release isotonic HCL
(pH <1)
 Requires extrinsic
stimulation (hormones)

Question 6

3 things that control acid secretion

Answer 6

• Gastrin
• Acetylcholine
• Histamine

Question 7

what is the neurotransmitter released from vagal neurons which increases cytosolic Ca2+?

Answer 7

Acetylcholine

Question 8

what is the peptide hormone which stimulates acid secretion, pepsinogen secretion, blood flow and ^ gastric motility and cytosolic Ca2+?

Answer 8

Gastrin

Question 9

what is the hormone which increases cAMP and is a Sub-type specific action (H2 receptors) ?

Answer 9

Histamine

Question 10

Diseases associated with acid
dysregulation?

Answer 10

• Dyspepsia (indigestion, upperabdom pain, bloat, sick)
• Peptic ulceration (prolonges excess acid sec. gastric and duodenal ulceration)
• Reflux oesophagitis (Damage to oesophagus by excess acid secretion)
• Zollinger-Ellison syndrome (Gastrin producing tumour)

Question 11

How do we decrease secretions of gastric acid?

Answer 11

1. Reducing proton pump function (pp inhib.)
2. blocking histamine receptor function (H2 receptor antagonism)
3. neutralising acid secretion w antacids

Question 12

examples of PPI

Answer 12

Omeprazole
Lansoprazole

Irreversibly inhibit H+/K+ ATPase

Question 13

describe the pharmacokinetics of PPI

Answer 13

• inactive at neutral pH
• weak bases- allows accumulation in acidic environment
• degrades rapidly at low pH (enteric coating)
• Single dosing  2-3 day acid secretion inhibition

Question 14

where is PPI binding site ?

Answer 14

5, 6

Question 15

What is the half life of Rabeprazole, omeprazole, lansoprazole and pantoprazole at pH=1.2

Answer 15

Rabeprazole 1.3
Omeprazole 2.8
Lansoprazole 2
Pantoprazole 4.6

Question 16

What is the half life of Rabeprazole, omeprazole, lansoprazole and pantoprazole at pH=5.1

Answer 16

Rabeprazole 7.2
Omeprazole 84
Lansoprazole 90
Pantoprazole 282

Question 17

What are the adverse effects PPIs (uncommon)

Answer 17

• headache
• diarrhoea
• rash

-Can mask the symptoms of gastric cancer!
– Care must be taken in high risk groups i.e.
Liver failure and pregnancy.

Question 18

When are PPIs used?

Answer 18

• peptic ulcer
• reflux oesophagitis
• zollinger- Ellison

Question 19

Exampls of Histamine H2 receptor antagonists

Answer 19

• cimetidine
• ranitidine

Question 20

Where are Histamine H2 receptor antagonists used?

Answer 20

• peptic ulcer
• reflux oesophagitis

Question 21

describe the pharmacokinetics of H2 receptor antagonists

Answer 21

• rapidly absorbes orally
• dosage varies with condition
• potent inhibitor of cytochrome P450’S

Question 22

H2 receptor antagonists adverse effects (rare)

Answer 22

• diarrhoea
• dizzynes
• muscle pain
• Potent inhibitor of cytochrome P450’s –
  reduces metabolism of anticoagulants and
  tricyclic antidepressants.

Question 23

what are antacids

Answer 23

Bases that raise gastric luminal pH by neutralising gastric acid

Question 24

example of antacids

Answer 24

• sodium bicarbonate ,
• Mg2+/ Al 3+ hydroxide

Question 25

when are antacids used

Answer 25

dyspepsia, oesophageal reflux

Question 26

phacokinetics of antacids

Answer 26

- slow action - effects often short lived - acid rebound

Question 27

adverse effects of Antacids

Answer 27

- diarroea, constipation , belching - acid rebound - alkalosis -care with sodium content

Question 28

Describe helicobacter pylori infections

Answer 28

- gram -ve bacillus - peptide ulcur formation - gastric cancer risk - urea breath test - routine testing

Question 29

peptic ulcer formation

Answer 29

95% duodenal, 70% gastric ulcers

Question 30

how do you treat HPI

Answer 30

- treatment with comination triple therapy - PPI , antibacterials and cytoprotective agent

Question 31

what do cytoprotective agents do?

Answer 31

Enhance mucosal protection mechanisms or form barriers over ulcer formations.

Question 32

examples of cytoproective agents

Answer 32

- bismuth chelate - sucralfate - misopostol

Question 33

what is bismuth chelate

Answer 33

- toxic to bacillus - coats ulcer base , ^ prostaglandin and bicarbonate synthesis

Question 34

what is sulcralfate

Answer 34

- stimulates mucus production and prevents degration - ^ prostaglandin and biacarbonate synthesis

Question 35

what is misoprostol

Answer 35

- prostaglandin analogue - direct action on parietal cells (acid secretion)

Question 36

what do NSAIDs do

Answer 36

- inhibit prostaglandin formation - cause gastric bleeds , errosion > ulcer formation - specific COX 2 inhibitiors cause less GI damage

Question 37

what are prostaglandins

Answer 37

- synthesised by gastric mucosa - increased mucus and bicarb secretion - decreased acid sec

Question 38

what acts upon arachidonic acid to produce leukotriens

Answer 38

lipoxygenase (LOX)

Question 39

what acts upon arachidonic acid to produce postacyclin and thromboxanes

Answer 39

COX (cyclo-oxygenase)

Question 40

what releases arachidonic acid from pospholipids in cell membrane?

Answer 40

phospholipase A2

Question 41

what acts upon phospholipase A2 to incue lipocortin (protein inhibitor of Phopholipase A2)

Answer 41

Glucocorticosteroids