Lecture 9: OTC Digestives Flashcards
How does Histamine affect airways and bloodvessels?
It causes vasodilation of blood vessels and constriction of the airways
What receptor G receptor is histamine linked to?
Gq
What does Histamine being Gq linked do in airways?
It increases intracellular calcium and causes constriction of muscles
How does histamine being Gq linked affect blood vessels?
The increase in intracellular calcium causes an increase of synthases that produce NO diffuses into smooth muscle around blood vessels and causes dilation
What is another name for heartburn?
GERD
What is Acid-Peptic Disease?
A group a of disorder involving either excessive acid secretion or erosion of mucosal lining of the GI tract
What are the Acid-Peptic diseases?
- GERD
- Peptic ulcers
- Stress-related gastritis
How do drugs used to treat acid-peptic disease work?
They reduce intragastric acidity by manipulating acid secretion, promote mucosal defense, or eradicate bacterium
What are the two parts of the stomach?
The antrum and fundus
What do parietal cells in the fundus do?
Secrete acid into the stomach
Which cells does a pH less <3 in the stomach act on?
D and G cells
What cells in the stomach do amino acids act on?
G cells
What is responsible for the acidity in the stomach?
The H+/K+ ATPase proton pump
What does the The H+/K+ ATPase proton pump do?
Move acid from the parietal cell into the gastric lumen
What is the energy source for the The H+/K+ ATPase proton pump?
ATP
Where do the protons that the the H+/K+ ATPase proton pump pumps out come from?
Carbonic anhydrase which removes the proton from bicarbonate
What are the three important controls of acid release?
- Acetylcholine on M3 receptors
- Histamine on H2 receptors
- Gastrin on CCKb receptors
What do G cells in the antrum respond to?
Intraluminal dietary peptides
What do G cells released when stimulated by peptides?
Gastrin
What does Gastrin bind to?
- CCK receptors on parietal cells
* Enterochromaffin cells (H cells)
How does Gastrin affect enterochromaffin cells (H cells)?
Causes them to release histamine which bind to histamine receptors (H2) on parietal cells
What does the vagus nerve stimulation of postganglionic neurons do in the stomach?
Stimulates postganglionic neurons of the enteric system to release acetylcholine
What does acetylcholine released by postganglionic fibers of the enteric nervous system do?
Binds to muscarinic receptors on parietal cells
What kind of G receptors are CCK receptors?
Gq
How do the CCK receptors affect parietal cells?
They increase secretion
How does the increase of intraluminal acid affect D cells?
Increase in acid causes D cells to release somatostatin
What does Somatostatin released by D cells do?
Inhibits gastrin release from G cells
What are Antacids?
Weak bases that neutralize stomach acid by reacting with protons in the lumen of the gut
What are the Popular antacids?
- Magnesium hydroxide
* Aluminium hydroxide
What is one of the effects of magnesium hydroxide?
Strong laxative effect because it traps water in the gut
What is another effect of aluminium hydroxide?
It has constipating action because it precipitates phosphate to produce salt which dries things out
What are Proton pump inhibitors?
Lipophilic weak bases that diffuse into the parietal cell and inactivate the H+/K+ ATPase transporter
What can prolonged use of Proton Pump inhibitors lead to?
Hypergastrinemia
Why do PPIs lead to Hypergastrinemia?
Because acid secretion inhibits gastric release
How do PPIs affect other drugs?
They decrease the bioavailability of vitamin B12 and other drugs that require acidity for absorption
How does the stomach ensure vitamin B12 remains uncharged?
By creating a very low pH allowing B12 to accept a proton
What is the active ingredient in Peptobismol?
Bismuth Subsalicylate
What happens to Bismuth Subsalicylate in the gut?
It hydrolyzes to form Bismuth oxychloride and salicylic acid
What does Salicylic Acid form from Bismuth Subsalicylate do in the gut?
Is a COX2 inhibitor and has anti-inflammatory properties
What are the effects of Bismuth salts?
They have bactericidal effects and can bind to toxins
What drug treats motion sickness?
Dimenhydrinate
What it the action of Dimenhydrinate at the receptors?
It is a competitive antagonist at the H1 receptor
How does Dimenhydrinate work?
It blocks histamine activity in the vestibular system from sending signals to the medulla
What is Gastric motility controlled by?
Intrinsic neural plexuses (enteric nervous system)
What can modulate activity of the Gut?
Central nervous system input via parasympathetic and sympathetic system
What happens if autonomic control is removed from the gut?
It results in disorganized gastric activity however over time gastric activity will return to normal
What does the Myenteric Plexus do?
Provides motor innervation to the muscular layer of the gut
What does the Submucosal Plexus provide?
Secretomotor innervation to the mucosa
What do the neurons of the plexus usually release?
Acetylcholine, serotonin and dopamine
What do all-preganglionic neurons release?
Acetylcholine
What do Postganglionic parasympathetic neurons release?
Acetylcholine
What do Postganglionic sympathetic neurons release?
Noradrenaline
How does acetylcholine affect the muscle of the GI tract?
Causes contraction of the muscle
What G receptors are the adrenergic receptors linked to in the gut?
Gi
What is constipation usually caused by?
Diet low in fiber and water
What are laxatives?
Substances loosen stool or stimulate bowel movement
What are the four kinds of laxatives?
- Bulk forming
- Osmotic
- Lubricant
- Stimulant
How do Bulk forming laxatives work?
They contain plant fiber like psyllium and methylcellulose that draw water into the stool to make them larger and easier to pass
How do Osmotic laxative work?
They contain ingredients like polyethylene glycol or magnesium that draw fluid into the bowel from nearby tissue
How do Lubricant laxatives work?
They coat the surface of stools or anus to make it easier for stools to pass
How do stimulant laxative work?
Contain ingredients like senna and bisacodyl that cause bowels to squeeze stools out (enhance smooth muscle)
What are the most common diarrhea medications?
- Loperamide
* Bismuth subsalicylate
How does Loperamide work at a receptor?
It is a mu opioid agonist
Where are Mu opioid receptors located?
On the myenteric plexus
How does Bismuth Subsalicylate work to help diarrhea?
Its COX2 inhibition reduces inflammation and irritation
What other effects does Loperamide have?
It has weak analgesic effects
Why isn’t Loperamide rewarding or addictive like morphine or codeine?
Because it is a substrate of P-glycoprotein of the BBB and P-glycoprotein pumps drugs out of the brain
What is P-hp inhibited by?
Tricyclic antidepressants
