GI Pharmacology Flashcards
Strength of ___ wave determines escape of chyme through ____
antral, pyloric sphincter
Gastric factors that determine stomach emptying?
DISTENSION
- STRETCH promotes motility of smooth muscle
- Simulates activity of INTRINSIC NERVE PLEXUSES
- Simulates VAGUS NERVE activity
- Stimulates GASTRIN release
Rate of emptying is proportional to?
Volume and consistency of chyme (causes distension)
Enterogastrones ____ contractile forces of stomach
decrease
Examples of enterogastrones?
Cholycystkinene, secretinin, gastric inhibitory peptides
Enterogastrones released inresponse to?
fatty hypertonic acidic chyme in duodenum
fatty hypertonic acidic chyme in duodenum will stimulate…
1) duodenal enterendocrine cells
2) chemoreceptors and stretch receptors (activate enteric neurones, inc. SNS activity dec. PNS activity)
These will inhibit contractile force and rate of emptying in stomach
D cells secrete ____ , this ____ HCL secretion. D cells are found in the ______ of the ______
SOMATOSTATIN, inhibits, mucosa, pyloric gland area
G cells secrete ____ , this ____ HCL secretion. G cells are found in the ______ of the ______
Gastrin, inhibits, mucosa, pyloric gland area
Enterochromaffin-like cells secrete ____ , this ____ HCL secretion. Enterochromaffin-like cells are found in the ______ of the ______
Histamine, stimulates, OXYNTIC MUCOSA, fundus and body
Parietal cells secrete ____ & _____. Parietal cells are found in the ______ of the ______
Hydrocholric acid, intrinsic factor, OXYNTIC MUCOSA, fundus and body
Chief cells secrete ____ . chief cells are found in the ______ of the ______
pepsinogen, OXYNTIC MUCOSA, fundus and body
What does intrinsic factor do?
Binds to vitamin B12 allowing it to be absorbed in terminal ileum
What does pepsinogen do?
Precursor of pepsin - an enzyme that breaks down proteins
What does HCL do?
Activates pepsinogen to pepsin
Denatures protein
Kills most (not all) micro-organisms ingested with food
What does oxyntic mean
secretory cells which produce hydrochloric acid in the main part of the stomach, or the glands which they compose.
How is HCL secreted from gasrtic parietal cells?
Water and C02 makes carbonic acid.
Carbonic acid breaks down releasing one H+ ion and hydrogen carbonate.
H+ leaves the cell via an antiporter which transfers K+ into the cell
hydrogen carbonate goes into an antiporter.
Antiporter allows entry of Cl- into cell
Cl- diffuses out of cell into lumen of gastric pit
H+ and Cl- become HCL
Which pumps are involbed in HCL secretion?
K+ channel Cl- channel Cl-/hydrogen carbonate antiporter H+/K+ ATPase (PROTON PUMP) Na+/K+ ATPASE
How is secretion of HCL regulated? Which receptors?
- Gastrin (CCk2) receptor - expressed on enterochromaffin like cell and parietal cells
- Muscarininc M1 or M3 Ach receptor expressed enterochromaffin like cell and PARIETAL CELLS
- Histamine H2 receptor expressed on PARIETAL CELLS
GASTRIN ACTS ON
Gastrin CCK receptor expressed on enterochromaffin like cell and parietal cells
Ach from postganglionic parasympathetics acts on
Muscarininc M1 or M3 Ach receptor expressed enterochromaffin like cell and PARIETAL CELLS
Histamine from ____ cells acts on ____, expressed on _____
enterochromaffin like, H2 receptor on parietal cells
T/F
Somatostatin inhibits gastrin sceretion between meals. This has the ffect of increasing HCL secretion
F
Somatostatin DOES inhibit gastrin sceretion between meals. This has the ffect of DECREASING HCL secretion
Prostaglandin inhibits ..?
The effect of stimulating Gastrin CCK2 receptors, M1, M3 and H2 receptors on parietal cells
Receptors M1,M2.H2 and G on parietal cells specifically stimulate the ____
K+/H+ antiporter!
Secretion from M1,M2.H2 and G on parietal cells results in (detail)
- Extended microvilli in cannaculi of pRIETAL CELL
- Release of protein kinases
- Protein kinases cause TRAFFICKING of K+/H+ antiporter from INSIDE cell to the surface of the extended microvillus
What are the three phases of gastric secretion?
- cephalic : sight/smell vagal stimulation acting on Parietal cells and G cells
- Gastric : mechanical and chemical factors (distensin and digestion products)
- Intestinal
Intestinal phase gastric secretion?
- less distension , less stimuli for secretion
- secretion of somatostatin resumes between miles
- factors from intestine switch off acid secretion
NSAIDS block _____, this is ____ binding, this ____ acid secretion
Cyclooxygenase ( stops creation of prostaglandin),
irreversible, increases
Ranitidine is a ____, it blocks _____
this is ____ binding, this ____ acid secretion
Histamine receptor antagonist, H2 receptor
competitive, decreases
Pirenzepine is a ____, it blocks _____
this is ____ binding, this ____ acid secretion
Muscarinic receptor anatgonis, M1 m3,
competitive, decreases
Omeprazole is a ____, it binds to _____
via ____ , this ____ acid secretion
proton pump (H+/K+) inhibitor, proton pump, covalent modification, decreases
Localle produced prostaglandins protect the mucosa from attack by HCl and pepsin by..
reduce acid secretion
increase mucus and bicarbonate secretion
increase mucosal blood flow
Gastric damage due to longterm NSAID use can be prevented with…
a stable PGE analogue - stimulates PGE receptors MISOPROSTOL
H Pylori causes peptic ulcer because…
Lives in mucus gel and secretes agents tht cause persistent inflammation
weakens mucosal barrier
Breakdown mucosal barrier exposed to pepsin and HCL
Drugs that reduce gastric acid secretion are used in the treatment of
- peptic ulcer
- GORD (inapprop relaxation of LOS, reflux gastric acid secretion)
- Acid hypersecretion (Zollinger-Ellison syndrome, Cushing’s)
How do PPIs respond to changes in pH?
- They are BASIC PRODRUGS
- Inactive at NEUTRAL pH
- Conformational chnage and ACTIVATION in LOW ph(strongly acidic)
T/F
Omeprazole’s full effect is only achieved after repeated dosing
T
T/F
Ranitidine has many common side effects
F
side effects rare
What is sucralfate?
MUCOSAL strengthener
How does sucralfate work?
- binds to the ulcer base (positively charged proteins) - forms complex gels with mucus
– provides a mucosal barrier against acid and pepsin
Increases mucosal blood flow, mucus, bicarbonate, prostaglandin
What are examples of Mucosal strengtheners?
Sucralfate
Bismuth chealate
