Final exam lecture 3 Flashcards
anatomy of stomach
Fundus is the top
two valves.
(pyloric valve and esophageal valve.)
Name the 4 kind of drugs affecting gastric secretion.
Antacids
H2 histamine receptor antaginists
PPIs
Protectants
drugs that increase GI motility
Laxatives
prokinetic drugs
Drugs that reduce GI motility
Antidiarrheal
Anti emetic
Explain the physiological control of GI secretions
We eat food
It activates G cells to make gastrin
gastrin acts on ECL to produce histamine
Histamine, AcH and gastrin act on parietal cells to activate proton pumps
Effect of parietal cells being acted upon by histamine, gastrin or Ach
Histamine, Ach and gastrin acidify the lumen of the stomach by activating parietal cells
how is the acid secretion is stomach halted
acid acts on D cells to produce somatostatin. Somatostatin feedsback and shuts down G cells.
What do D cells do?
Deaccelerate to shut down acid secretion via somatostatin.
mucus is produced by cells in stomach through
prostaglandins
How does aspirin cause ulcers of stomach
decrease prostaglandin production, decreasing mucus
Name 4 of the antacids
NaHCO3
CaCO3
AL(OH)3
MG(OH)2
What is the neutralizing capacity of the antacids
NaHCO3- High
CaCO3- moderate
AL(OH)3- High
MG(OH)2- High
Adverse effects of the antacids
NaHCO3- systemic alkilosis, fluid retention
CaCO3- hypercalcemia, nephrolithiasis, milk-alkali syndrome
AL(OH)3- constipation, hypophosphatemia
MG(OH)2- diarrhea
difference in side effects between AL(OH)3 and MG(OH)2
Al causes constipation
Mg causes diarrhea
Which cells produce histamine that acts on parietal cells
ECL cells
how do histamine receptor antagonists work? (H2RA)
They competitively inhibit H2 histamine receptors
H2RA drugs names
End with -tidine
(cimetidine, ranitidine, Nizatidine, Famotidine)
Mechanism of PPI inhibition of acid secretion
Directly binds and blocks ability of protein pump to exchange a proton for K+. Leading to profound inhibition of gastric acidification.
Leads to irreversible inhibition through disulfide bond.
PPI drug names
End with -prazole
(esomeprazole Purified S enantiomer), omeprazole S and R enantiomer)
Structure of PPI
Hexene next to 5 membered ring with two nitrogens
How are PPIs activated
By acidic PH in the parietal cells
What may occur during withdrawal of PPIs
Hypergastrinemia occurs and may result in rebound hypersecretion of gastric acid.
compare H2 blockade and PPI
H2 blockade damps down peaks in acid production.
PPI completely prevents acid producton
People who take PPIs chronically have
hypergastrinemia
Why does hypergastrinemia happen on PPIs
Reduced gastric acid removes somatostatin inhibition of gastrin secretion.
side effects of PPI
Increased risk of infection
Vit B12 deficiency
Decreased Ca 2+ absorption/ increased bone fractures (increased bone resorption)
What are the two mechanisms of PPI therapy causing fractures
1) decreased calcium absorption causes a decline in Ca.
causes secondary hyperparathyroidism, increasing bone resorption
2) Hypergastrinemia causes Parathyroid hyperplasia
______ are prodrugs that must be protonated to become active and form ______ bonds
PPIs, covalent disulfide bonds
MOA of sucralfate
It is an AlOH complex of sucrose. It polymerizes and forms a protective barrier at ulcer site. Acidic PH activates complex.
Name two mucosal protective agents
Misoprostol
Sucralfate
Misoprostol MOA
Semisynthetic PGE derivative. Instead of mimicking mucus, it stimulates gastric cells to produce their own
H. pylori combo treatment (with example)
BSS
Antibiotic (metronidazole, clarithromycin, tetracycline, amoxicillin)
H2 blocker or PPI
example- Metronidazole+ omeprazole+clarithromycin X 2 weeks
Example of bulk and osmotic laxatives
Psyllium (metamucil)
PEG 3350 (MiraLAX )
Methylcellulose (citrucel)
Lactulose (duphalac)
example of stimulant laxatives
Castor oil, bisacodyl (dulcolax), senna
What situations would prokinetic drugs be used
Gastroparesis
parkinsons
opioid induced constipation
What is Metoclopramide? What is it use for?
Metoclopramide is a dopamine receptor antagonist.
It is used for promotion of gastric emptying for post OP, diabetic, gastroparesis patients
name opioid receptor antagonists that cant cross BBB
Naloxegol (movantik)
Alvimopan (entereg)
naldemedine (SYMPROIC)
Opioid induced constipation can be avoided by ________
Biased agonists like olicerdine (instead of morphine)
How do Prucalopride (motegrity) and tegaserod (zelnorm) work
5HT4 agonists, leading to increased cAMP, PKA activation and release of ACH
What is prucalopride (motegrity) indicated for
Chronic idiopathic constipation in adults
WHat is tegaserod (zelnorm)indicated for
Indicated for treatment of IBS with constipation in women UNDER 65
Age range of zelnorm (tegaserod)
Under 65 and no prior heart conditions
How do chloride channel activators work?
Increases amount of Cl in gut, leads to increased Na+ and increased H20
Example of chloride channel activators
Lubiprostone (amatiza)
Linaclotide (linzess)
Plecanatide (Trulance)
What are chloride channel activators used for
IBS+constipation
how does Tenapanor work?
Inhibits Na/H exchanger in gut. This leaves more Na+ in lumen and h20 follows. Leads to increased movement in intestine
How do anti-diarrheals work
Slow peristalisis to increase water and electrolyte absorption
Name anti diarrheals
Diphenoxylate Active in CNS
loperamide (imodium)
both opiates, but loperamide poorly traverses BBB
