GI Pharmacology 1 Flashcards
What are the three bases of therapy for acid-peptic disease?
Neutralize excess acid
Reduce gastric acid secretion
Enhance gastric mucous defense
How do we neutralize excess acid?
Antacids
How do antacids work?
They neutralize acid directly in the stomach
How are different antacids different from eachother?
They have different neutralizing capacity, different solubilities, and different palatability
Describe sodium bicarbonate
Baking soda
Quickly neutralizes acid
Produces sodium and alkali load
Can cause fluid retention, produce gas (belching)
Increased pH will increase gastrin release
Describe calcium carbonate
Works rapidly Moderate neutralizing ability CaCl2 - absorb 10-15% Increased kidney pH can cause kidney stones May induce rebound acid secretion Can cause constipation
Describe aluminum hydroxide
Amphogel Decreases phosphate absorption, increases stomach emptying which can increase acid secretion Cytoprotective effect on mucosa Can cause constipation Chelates other drugs Contraindicated in appendicitis
Describe magnesium hydroxide
Milk of Magnesia
Good neutralizing ability
MgCl2 - low solubility, some Mg absorption
Can cause diarrhea
Contraindicated in renal failure, appendicitis, intestinal obstruction
What two antacids are combined? How do they work?
Magnesium hydroxide + Aluminum hydroxide
Liquid suspension - insoluble
Used together counteracts the GI motility
Liquids better than tablets
Take 1-3 hours after meal and at bedtime for 6-8 weeks for peptic ulcer
Doesn’t control noctural acid secretion!
How do we reduce gastric acid secretion?
H2 receptor antagonists, proton pump inhibitors
How do H2 receptor antagonists work?
They decrease acid secretion by blocking H2 receptors on parietal cells
This blocks basal, nocturnal, AND stimulated acid secretion (so no rebound decrease in pH)
Reduces volume and H+ concentration in secretion
Also reduces pepsin so they will have effects on digestion
Describe the structure of antihistamines?
Structural analogs of histamine with a bulky side chain
Indications for H2 receptor antagonists
Peptic ulcer disease
GERD
Zollinger-Ellison syndrome
Describe the pharmacodynamics of H2 receptor antagonists?
Well absorbed from GI tract
Hepatic metabolism and secreted by renal tubules
Renal impairment dosage adjustment required
Adverse effects of cimetidine?
Headache CNS: Confusion, seizures***** Rash Diarrhea Decreased metabolism
Adverse effects of ranitidine?
Diarrhea
Constipation
Headache
Blood dyscrasias
Adverse effects of famotidine?
Headache Constipation Diarrhea Dizziness Blood dyscrasias
Adverse effects of Nizatidine?
Somnolence***** Fatigue Headache Rash***** Blood dyscrasias Tachycardia****
How to proton pump inhibitors work?
They are prodrugs activated by stomach acid
Irreversible inhibitors of proton pumps, they form sulfate bonds with the pumps
Acid secretion requires a new pump!
Up to 95% inhibition after 7 days
Indications for PPI’s?
Pts not controlled by H2 antagonists
Hypersecretory states - Zollinger Ellison, systemic mastocytosis
Severe GERD
Short term ulcers
Adverse effects of PPI’s?
Hyperplasia of parietal cells in experimental animals (not yet seen in humans, this could be risk for tumor)
Elevated stomach pH, bacterial infections, hypergastrinemia, decreased calcium absorption, rebound hypersecretion upon drug removal
What anticholinergics are used for gastric-peptic disease? How do anticholinergics work?
Pirenzepine, Telenzepine
M1 antagonists, they decrease basal secretion 40-50%
They have limited effects on stimulated pumps(?)
Toxicities with anticholinergics?
Worry about antimuscarinic side effects
True or False: Anticholinergics are approved for use in gastric-peptic disease in the US
False, only in Japan/Europe/Canada
What is Octreotide?
Gastrin inhibitor
It is a somatostatin analog that blocks gastrin release
What is Octreotide used for?
Gastrinomas
Zollinger-Ellison
Toxicities with Octreotide?
Severe diarrhea
How is Octreotide administered?
IV
What mucosal protecting agents do we have?
Sucralfate
Colloidal bismuth (Pepto bismol)
Misoprostol
Why do we use mucosal protecting agents?
They promote healing of epidermal layer damaged in ulcer disease
What is Sucralfate?
A mucosal protecting agent, an aluminum salt with sugars attached
Binds to ulcerated spots to form a protective layer/barrier to acid and pepsin
Also promotes PG synthesis
Toxicities with Sucralfate?
Can cause constipation
Avoid in renal failure
Patients at risk of aluminum overload
Can inhibit the absorption of other drugs
How does Colloidal bismuth work?
Coats the stomach lining
Enhances cytoprotective factors
Inhibits pepsin activity
Toxicities with colloidal bismuth?
Imparts black color to oral cavity and feces
Contains salicylates, can induce acid secretion
How does misoprostol work?
It is a PGE1 analog
It enhances mucous production
Decreases acid production
Indications for Misoprostol?
Ulcers caused by NSAIDs
Toxicities with Misoprostol?
Diarrhea
Abdominal cramps
CI in pregnancy
Use with caution in renal failure
What is Helicobacter pylori?
Causes inflammatory gastritis
Involved in 60% of peptic ulcers
Associated with gastric lymphoma, adenocarcinoma
Common, many asymptomatic - increases incidence with age
What is the H. pylori triple therapy regimen?
Proton pump inhibitor (or H2 antagonist) plus Clarithromycin 500 mg BID plus Amoxicillin (1g) or Metronidazole (500 mg)
Take for 14 days
What is the H Pylori quadruple regimen?
Proton pump inhibitor BID (or H2 antagonist)
Metronidazole (500 mg TID)
Tetracycline (500 mg QID)
Bismouth subsalicylate (525 mg QID)
