GI 04 Flashcards
From where gastric acid, secretion happen?
ATPase pump in our parietal cells which is in our stomach.
To get acid into our stomach what are the three mechanism happen ?
Neuronal (Acetylcholine ,M3), Paracrine (Histamine,H2) and Endocrine (Gastrin CCK2) all three things are happening to get acid in our stomach.
Where is the location of the receptors, responsible to bring acid in our stomach?
The receptors M3, H2 and CCK2 are located in the body and fundus in stomach.
Which cells are responsible for acid production in our stomach?
Parietal cell. It secretes H+ and cl-.
Chef cells secrets ?
Pepsinogen=> Pepsin (enzymes help break down our food)
What Goblet cells does in the stomach ?
Mucus production (to protect stomach).
What are the stages of Production of Gastric acid in our stomach?
Step 1
We think about the food we start producing gastric acid because of through stomach to a neuronal activity called parasympathetic preganglionic neurons traveling in the vagus nerves.
Through neuronal direct effect, Ach released on => Muscarinic receptor.
Indirectly Ach activates through the paracrine effect & released histamine to=> Histamine receptor.
Ach activates G cells and releases Gastrin=> Gastrin receptor by the endocrine effect.
Step 2
Food stretches the stomach walls then Mechanoreceptor activates and creates a neural reflex that activates acid secretion.
(Peptides and amino acids in) food stimulates G cells to release gastrin.
An empty stomach is an acidic environment after adding Food it makes the acidic environment less acidic or ph. gets up. Somatostatin is a natural process which shuts off the acid secretion. That means enough acid in there no need for more acid to digest the food.
Step 3
When food passes through and enters the duodenum,
Somatostatin in the intestinal phase activates a negative feedback mechanism to reduce further acid secretion.
Somatostatin released from antrum D cells Less than 3 ph.
Ach =Nurotransmitter.
Somatostatin released from?
Antrum D cells. When stomach acid is less than pH 3
Who turn on the proton pumps?
H2 M3 & CCk2 receptors in the parietal cell activates G protein couple receptor which then turns on the pump. The pump exchange H for K. Once we get H then Cl join and make HCl
What are the Gastric defences against acid ?
Oesophegeal Sphincter
Mucous Layer
Prostaglandin stimulate more mucous and turn down proton pump pathway and increase bicarbonate pathway.
Bicarbonate work as buffer to increase ph
What does prostaglandin do?
By stopping Prostaglandin which stops the Pump and no acid production.
Prostaglandin also increase secretion of mucous
Why we get gastric mucosal injury ?
When stomach fails to maintain protective factors as a result its aggravating factors cause stress to our stomach and when we loss the balance we experience gastric mucosal injury.
What is GORD?
Burning of Oesophagus with stomach acid which is also known as hurt burn.
It is a chronic condition
And common in pregnancy.
GORD: Symptoms ?
Hurtburn Cough
What if we do not stop GORD?
Can erode the esophagus and cause harm like ulcer or carcinomas(Cancer).
how many Types of Ulcer can occour in stomach?
Gastric and duodenal
Why Peptic ulcer happen in people
Acid bile and pepsin taking up the balance and your protective factors cant control as a result create hole in your stomach
Create ulcer or whole into the stomach
It 90 % h duodenum and 70 % stomach
What are the Red flag for Peptic ulcer ?
Vomiting black or tarry stools
Unexpected weight loss.
Main causative factors for causing Peptic Ulcer ?
Smoking excess alcohol
Genetic factor
NSAID
Why would you we be concerned about black or tarry stools ?
Sign of bleading old denatured blood in stomach or intestine or somewhere.
It can lead to cancer so need to treat asap after 10 years 5% cause cancer
So why we need to treat peptic ulcer ?
Because it may lead to stomach cancer so stop the risk of cancer
What is Zollinger Ellison syndrome?
Pancreatic gastrinomas. As a result severe gastroduodenal ulceration. A rare disorder, which stimulates the production of a huge amount of acid.
Symptoms of Zollinger Ellison syndrome ?
Abdominal pain, diarrhoea, aching, heartburn, vomiting
What is Stress-related mucosal injury?
A major body trauma only experiences stress to the body: i.e. people with intensive care.
What is the risk for stress related mucosal injury?
Risk for Gastric haemorrhage(overflow blood vassels).
What are the Treatment options for stress related mucosal injury?
IV H2 blocker or IV PPI
What is the Mechanisms by which somatostatin reduces gastrin release ?
Somatostain works in all three areas i.e Paraital cell ECL and G cell Histamine
l
Ip
What is the Therapeutic strategies to solve Gastric acid secretion ?
- Suppress gastric production by PPI or H2
- Enhance mucosal defence mechanism. by Prostaglandin analogs:Misoprostol & Antacids
How antacid enhance mucosal defence ?
Antacids binds with H+ As a result there is no available H+ to bind with Cl as a result less acid production. Rapid neutralize and short time effect.
What effect does Mg have?
A laxative effect. Because it pools out lots of water from your intestine to the bowel result diarrhea.
What Al causes ?
However, We know that Al causes constipation. So if we can bind them together than it balanced so we formulate
What will happen if we use Mg and Al together for treatment of constipation?
If we combine Mg and Al together then it becomes balanced which formed called Antacid.
What will happen If we formulate CaCo3 ?
Then we will may be burp. Like fizzy drink cause it has carbonate.
How we can enhance mucosal defence by using misoprostol or prostaglandin?
If we take misoprostol (which is the synthetic form of prostaglandins) which binds with EP3 and inhibit AC and decrease cAMP and gastric acid secretion. PGE2 also stimulated mucin and bicarbonate secretion.
How we can suppress Acid by using H2 recenptor antagonist?
By blocking Histamine so blocking histamine receptor as a result not much H+ from the pump as a result not much joining with Cl and pump not much activated . Can suppress about 70 percent.
What H2 receptors predominantly inhibits ?
Basal acid (jeta as usual toiri hoy) secretion. Not that acid when we eat and secret.
Ranitidine Inhibits which CYP enzyme?
Ranitidine Inhibit CYP450 (subsidised).
Which one is more potent ? Ranitidine or Cimetidine
Ranitidine is potent than cimetidine.
What are the name of ranitidine in NZ market
Peptisoothe, Zantac.
Does famotidine inhibit CYP 450?
No, does not inhibit CYP 450.
What is the Proton Pump Inhibitor Mechanism?
Irreversibly Inhibit the proton Pump. So no H+ to bind with Cl.
Prodrug so needs an acidic environment to activate.
or stop the pump so there is no H+ and no acid. It is a prodrug so require an acidic environment to activate them.
PPI is a prodrug and requires an acidic environment to activate so they go into our stomach and activate and stop the pump.
Proton pump inhibitor binds to part of the pump and irreversibly inactivate it.
Once we inactivate the pump there is less acid for 24 to 48 hours because it takes at least 24 to 48 hours to install the new pump into the lumen and start acid secretion again so we need to continue to get the effect.
Proton pump inhibitor bind to part of the pump and how ?
Irreversibly inactivate it.
PPIs have very short half life for ?
Only 0.5- 2 hours
PPIs are more effective than H2 receptor for ?
GORD or peptic ulcers
Some patients have higher rate of pump turnover require
BD dosing to get their desired effect.
To get maximum effect we need to take continue doses PPIs cause ?
cause PRN won’t work.
Second most common prescribed medicine in NZ
Omeprazole
Side effects of PPIs
Headache abdominal pain and nausea
Why PPI need a few days for the patient to get the maximum effect?
PPI irreversibly binds the proton pump.
But on the other hand, cell inserts a new pump continuous process so gradually PPI blocks all pumps for more than 24 hours, slowly it gives maximum effect
Why we need to wait of getting maximum concentration of using PPIs ?
Because not all pumps are inactivate simultaneously. So maximum suppression of acid secretion is required several dosage. This is the reason why PRN dose should not be used for patients for PPI.
What is the major metabolizer pathway for PPIs
CYP2C19
Side effects of PPIs
Other side effect is headache abdominal pain and nausea.
Side effects of PPI
As PPIs are extensively metabolised so patient needed monitoring or be cautious with hepatic injury.
People with poor metabolite of CYP2C19 specially Asians so variations or less efficacy.
So we can give them Lansoprazole as they do not depend on CYP2C19 pathway
Lansoprazole does not reliant on ?
CYP2C19
Why Increase risk of pneumonia for prolong use of PPIs ?
PPI reduces stomach acid so there would be less acid into the stomach as a result bacteria can come up to oesophagus and pass to our lungs and can cause pneumonia.
Why Increase risk of hip fracture for prolong use of PPIs ?
Hip fracture: long term use of PPI, if we do not have acid in our stomach we wouldn’t absorb much calcium as a result we experience hip fracture.
What Omeprazole inducer is?
inducer of CYP1A2
Imipramine(tofranil) is metabolised by which pathway ?
CYP1A2 pathway
So if we use Omeprazole which is inducer(produce) of CYP1A2 so imipramine will metabolise quickly.
PPIs inhibit CYP2C19 so diazepam ?
As there is less CYP2C19 after using PPIs So Diazepam and amitriptyline will metabolize very slowly as a result accumulation into body and cause sleepy by diazepam
Why people need to give omeprazole while they are taking NSAIDs though they do not have any problem with their stomach?
NSAIDswork by inhibiting (COX-1 or COX-2) Inhibition of COX-1 in the gastrointestinal tract leads to a reduction of prostaglandin secretion and its cytoprotective effects in gastric mucosa. This therefore increases the susceptibility to mucosal injury So dr prescribed PPI to reduces the risk of ulceration by NSAIDS.
