Important GIT Drugs

Subclass Mechanism of Action Clinical Applications Pharmacokinetics Toxicities, Drug

Interactions
Drugs used in acid-peptic diseases
Proton pump Irreversible blockade of H+/ K+ ATPase Peptic ulcer, GERD, Half-lives much Low toxicity; reduction of
inhibitors (eg, in active gastric parietal; long-lasting erosive gastritis shorter than duration stomach acid may reduce
omeprazole) reduction of stimulated and nocturnal of action absorption of some drugs
acid secretion and increase that of others
 

 Other proton pump inhibitors: Esomeprazole, lansoprazole, pantoprazole, rabeprazole

H2-receptor blockers: Cimetidine, famotidine, nizatidine, ranitidine reduce nocturnal acid but less effective against stimulated secretion; very
safe, available over the counter (OTC). Cimetidine, but not other H 2 blockers, is a weak anti-androgenic agent and a potent CYP enzyme inhibitor
Sucralfate: Polymerizes at site of tissue damage and protects against further damage; very insoluble with no systemic effects; must be given 4
times daily
Antacids: Popular OTC medication for symptomatic relief of heartburn; not as useful as proton pump inhibitors and H 2 blockers in peptic diseases
Prokinetic agents
Metoclopramide D2 receptor blocker; increases gastric Gastric paresis (eg, Oral and parenteral Parkinsonian symptoms
emptying and intestinal motility in diabetes); formulations due to block of CNS D2
  antiemetic receptors
 
Domperidone: Like metoclopramide but less CNS effect; not available in United States
Cholinomimetics: Neostigmine used for colonic pseudo-obstruction in hospitalized patients
Macrolides: Erythromycin useful in diabetic gastroparesis but tolerance develops
Drugs for irritable bowel syndrome (IBS)
Alosetron 5-HT3 antagonist of high potency and Severe diarrhea- Oral Rare but serious
duration of binding; reduces smooth predominant IBS in constipation; ischemic
muscle activity in gastrointestinal (GI) women colitis; bowel infarction
tract
 
Anticholinergics: Nonselective action on GI activity; associated with typical antimuscarinic toxicity
Chloride channel activator: Lubiprostone is useful in constipation-predominant IBS in women
Antiemetics
5-HT3 antagonists (eg, 5-HT3 block in GI and CNS Prevention of Oral and parenteral May slow colonic transit
ondansetron)   chemotherapy- formulations
  induced and
postoperative
nausea and
vomiting
Other 5-HT3 antagonist antiemetics: Dolasetron, granisetron, palonosetron;
Corticosteroids: Mechanism not known but useful in antiemetic IV cocktails;
Antimuscarinics (eg, scopolamine): Effective in emesis due to motion sickness; not other types;
Phenothiazines: Act primary through block of D2 and muscarinic receptors;
Cannabinoids: Dronabinol is available for use in chemotherapy-induced nausea and vomiting, but is associated with CNS marijuana effects
Aprepitant: A neurokinin 1 (NK1) antagonist available for use in chemotherapy-induced nausea and vomiting; associated with fatigue, dizziness,
diarrhea, and CYP interactions
Laxatives
Magnesium Osmotic agents increase water Simple Oral Magnesium may be
hydroxide, other content of stool constipations; absorbed and cause
nonabsorbable salts bowel prep for toxicity in renal
and sugars endoscopy impairment
(especially PEG
solutions)
Bulk-forming: Methylcellulose, psyllium, etc; increase volume, stimulate evacuation
Stool surfactants: Docusate, mineral oil; lubricate stool, ease passage
Stimulants: Senna, cascara; stimulate activity; may cause cramping
Chloride channel activator: Lubiprostone, prostanoic acid derivative, stimulates chloride secretion into intestine, increasing fluid content
Opioid receptor antagonists: Alvimopan, methylnaltrexone, block intestinal -opioid receptors but do not enter CNS, so analgesia is maintained
5-HT4 agonists: Tegaserod; activates enteric 5-HT4 receptors and increases intestinal motility
Antidiarrheal drugs
  Loperamide Activates -opioid receptors in enteric Nonspecific, Oral Mild cramping but little or
nervous system and slows motility noninfectious no CNS toxicity
with negligible CNS effects diarrhea
Diphenoxylate: Similar to loperamide, but high doses can cause CNS opioid effects and toxicity
Colloidal bismuth compounds: Subsalicylate and citrate salts available as over-the-counter products; have some value in travelers' diarrhea due
to absorption of toxins
Kaolin + pectin: Adsorbent compounds available OTC