GI Tract Drugs Flashcards
what are the drug classes in controlling gastric acid?
H2 Blockers
Proton Pump Inhibitors
Anti-muscarinics
Cytoprotectives
Receptors of Gastric Parietal Cell HCl Secretion?
HK ATPase on luminal side, carbonic anhydrase intracellular rxn making H+
M3 receptor- vagus (parasym) stimulates, Gq, IP3/Ca, HK ATPase
CCK receptor- Gastrin stimulates, Gq, IP3/Ca, HK ATPase
H2 receptor- Histamine stimulates, cAMP, HK ATPase
PG and Somatostatin- Gi, decreased cAMP, inhibits HK ATPase
H2 blockers?
Cimetidine
Ranitidine
Famotidine
Nizatidine
Most imp’t mechanism of control gastric acid secretion?
Vagal or gastrin stimulation of enterochromaffin like cells (ECL) leads to histamine release
H2 Blockers MOA and USE
Directly inhibit histamine binding to H2 receptors on parietal cells
use: Gastric and Duodenal ulcers, ZE syndrome
available OTC in low doses bc of H2 receptors in heart and vasculature
Cimetidine Tox/Drug interaction
Inhibits cyp450, anti-androgenic activity with increase prolactin secretion–>gynecomoastia
PPI drugs?
Omeprazole Lansoprazole Rabprazole Pantoprazole Esomeprazole
PPI MOA
Inhibit HK ATPase on luminal side
can effective inhibit 100% of secretion
superior to H2 blockers and misoprostol in healing of NSAID ulcers
PPI Tox
- rebound effect- suppression of acid leads to increased gastrin release
- bone fracture, osteoporosis- long term use affects Ca absorbtion
- increase likelihood of infection
- Mg-deficiency
Anti Muscarinic Drugs?
atropine
glycopyrrolate
Anti-Muscarinic MOA
block pathway stimulated by vagus to parietal cells, decreased acid
Misoprostol MOA
Analog of PGE1, stimulates PGE1 receptors leading to increased mucus, bicarb secretions at luminal surface
decrease cAMP and HCL secretion
ONLY effective with NSAID-derived ulcers
Misoprostol Tox
Dose sependent diarrhea
contraindicated in pregnancy
Sucralfate MOA
under acetic conditions, polymerizes into sticky gel, affinity for exposed protein in craters
inhibits back diffusion of H+ and reduces pepsin activity
Physical protection against acid
Drug combo’s against H. pylori infection (2)
Bismuth subsalicylate, metronidazole, tetracycline for 14 days
omeprazole and clarithromycin 14 days
Antacids
AlOH3, CaCO3, Mg(OH)3
Mg and Al antacids often combined to offset laxative and constipation effects
Problem with antacids?
impractical b/c of amount you need to take for effect, should only be used occaisinally before starting another treatment
Prokinetic Drugs?
Metoclopramide, Cisapride
Prokinetic MOA
increase release of Ach from myenteric plexus
gets everything moving in right direction without backflow
ascending neurons contract behind bolus
descending neurons innervate inhibitory motor neurons releasing NO
prokinetic use
diabetic gastroparisis
GERD
metoclopramide MOA
increase Ach release- increase LES pressure, increase contraction of stomach, relax pyloric sphincter, does NOT stimulate secretions
metoclopramide Tox
Blocks D2 receptor- antiemetic and EPS side effects
Cisapride MOA
same effects as metoclopramide with increased effect on colon AND does not block D2 receptors
Cisapride Tox
restricted use due to TORSADES
headaches, abdominal cramps, thrombocytopenia
Laxative- Osmotic Drugs
Magnesium Citrate Polyethylene glycol Lactulose Sorbitol Pulls water into intestine and loosens stool, need to hydrate to avoid dehydration and electrolyte imbalances
Anti-Diarrheal Drugs
Diphenoxylate
Loperamide
Bismuth subsalicylate
Diphenoxylate MOA
meperidine like, acts at mu receptors on enteric neurons to increase absorption and slow peristalsis, increasing transit time
Atropine added for anticholinergic side effects to prevent abuse
Loperamide MOA
mu receptor opioid agonist that increases transit time and absorption
DOES NOT CROSS BBB
Bismuth Subsalicylate (Pepto)
SAlicylate- anti-motility, anti-secretory, anti-inflammatory
Bismuth- antibacterial against ETEC
Tox: discoloration of stool, tinnitus, Reye’s warnings for kids
