GI Pharm

• Antacids
• H2 Receptor Antagonists
• Proton Pump Inhibitors

• Na bicarbonate
• Ca carbonate
• Mg hydroxide
• AI hydroxide

• Cimetidine
• Ranitidine
• Famotidine
• Nizatidine

• Omeprazole
• Iansoprazole
• Rabeprazole
• Pantoprazole
• Esomeprazole

• Sucralfate
• Misoprostol
• Bismuth subsalicylate

• Weak acids
• MOA: decreases intragastric acidity by reacting with gastric HCl to form a salt and water
• Clinical uses: dyspepsia, acid-peptic disorders
• Side effects: belching and metabolic alkalosis (CO2), diarrhea (Mg) or constipation (Al)
• Fluid retention (NaCl), hypercalcemia, decreased absorption of other medicines

• Competitive inhibition at the parietal cell H2 receptor (decreased cAMP)
• Effective at inhibiting nocturnal acid secretion (stim by histamine) but have a modest impact on meal-stimulated acid secretion (stim by gastrin, Ach and histamine)

• GERD (longer duration than antacids)
• Peptic ulcer disease (replaced by PPI)
• Prevention of bleeding from stress-related gastritis

• Side effects:
• <3%: diarrhea, HA, fatigue, constipation
• Cross placenta and is secretedin breast milk
• Blocks cardiac H2 receptor (rapid IV bradycardia/hypotension)
• CNS (confusion, hallucination, agitation)
• Cimetidine: gynecomastia, impotence, galactorrhea

• Cimetidine and rantidine: inhibit p450 drug metabolism
• Inhibit gastric first-pass metabolism of alcohol, esp in women (except for famotidine)

• Cimetidine: 1
• Ranitidine: 4-10x
• Nizatidine: 4-10x
• Famotidine: 20-50x

• Lipophilic weak bases administered as inactive prodrugs.
• Enteric-coated for delayed release.
• Omeprazole is a racemic mixutre of R- amd S- isomers
• Esomeprazole is the S-isomer (active) of omeprazole

• MOA: prodrugs are protonated and concentrated in parietal cell canaliculus; converted to the active thiophilic sulfonamide cations which inactivate H+/K+ ATPase irreversibly
• They should be taken 30 minutes before meals

They inhibit both fasting and meal-stimulated secretion becasue they inhibit the final common pathway

• GERD (most effective)
• Peptic ulcer disease
• H.pylori 'triple therapy' (w/ clarithromycin & amxoicillin or metronidazole)
• Prevention of stress-related mucosal bleeding
• Gastrinoma and other hypersecretory conditions

• Safe (1-5% diarrhea, HA, abdominal pain)
• Decreased oral vitamin B12 absorption
• Respiratoy and enteric infections
• Increased serum gastrin

• All PPIs are metabolized by hepatic p450 cytochromes
• Altered intragastric acidity affects other drug bioavailability

• Mucosal protective agent- negatively charged
• A salt of sucrose and sufated Al hydroxide
• MOA: Forms a viscous paste that selectively binds to ulcers or erosions
• Clinical uses: decreases GI bleeding
• Side effects:
• no systemicadverse effects
• Constipation
• May bind to other meds

• Mucosal protective agent
• MOA: non-competitive inhibition of histamine-mediated cAMP production in parietal cells
• Clinical uses: NSAID-induced peptic ulcer
• Side effects: diarrhea, cramping abdominal pain, stimulate uterine contractions

• MOA:
• - Bismuth: coats ulcers and erosions
• - Salicylate: inhibits intestinal prostaglandin & CI secretion
• Clinical uses: dyspepsia, acute diarrhea
• Side effects: Black stool (bismuth), dark tongue. Salicylate toxicity- nausea, vomiting, sweating, rapid breathing, ringing in ears, fever

• Cholinomimetics
• Dopamine D2 receptor antagonists
• Macrolides
• Chlorine channel activator

• Cholinomimetic agent
• Stimulates GI motility
• Stimulates M3 receptors on muscle cells and myenteric plexus synapses
• Long duration- resistant to acetylcholinesterase

• Cholinomimetic agent
• Stimulates GI motility
• Acetylcholinesterase inhibitor
• Enhances gastric, intestinal and colonic emptying
• Useful in acute colonic pseudo-obstruction (AKA Ogilvie syndrome)
• Side effects: cholinergic effects (salivation, nausea, vomiting, diarrhea, bradycardia)

Given with atropine

• Dopamine D2 receptor antagonists
• Stimulate GI motility
• MOA: block the activity of dopamine receptor (activation of dopamine receptors in GI inhibits cholinergic smooth muscle stimulation)
• Clinical uses: Anti-nausea/anti-emetic (act on D2 receptors in medulla), GERD, impaired gastric emptying, nonuclear dyspepsia,

• Dopamine inhibits prolactin
• Galactorrhea, gynecomastia, impotence (increased prolactin)

Domperidone does not cross the BBB

Metoclopramide: CNS syndromes (restlessness, drowsiness, insomnia, anxiety, agitation), extrapyramidal effects (dystonia, parkinsonian)- avoid long term use!

• Macrolide
• Stimulate GI motility
• Stimulate motilin receptors on GI smooth muscle
• Used in patients with acute upper GI hemorrhage to promote gastric emptying of blood prior to enoscopy

• Chloride channel activator
• Stimulates GI motility
• Increases secretion of chloride-rich fluid which promotes bowel movement
• Treats idiopathic chronic constipation
• Side effects: nausea (30%), diarrhea, headache