GI Drugs

Question 1

Antacids

Answer 1

• treatment of excess acid
• immediate relief
• weak bases
• NaHCO3 and CaCO3 (TUMS) produce CO2, which bloats the stomach and a lot can actually be harmful
• Mg(OH)2 and Al(OH)3 avoid production of CO2 gas but must be careful giving with Ciprofloxacin and Tetracyclines (aluminum and magnesium and other cations bind antibiotic in the digestive system and prevent absorption)

Question 2

Proton Pump Inhibitors

Answer 2

• treatment of excess acid
• longer term therapy

Omeprazole:
- prodrug; activated within parietal cell canaliculus
- inactivated by gastric acid so there must be a coating
- mechanism of action: irreversible inhibition of H/K ATPase pump found at the secretory surface of gastric parietal cells
forms a ring in the presence of acid –> further metabolism –> irreversibly combines with enzyme when enzyme is pumping out H+ –> enzyme-inhibitor complex
this must be done in the parietal cell canaliculi
- pharmacokinetics: short half life in plasma, extensive first pass and systemic hepatic metabolism; not dependent on renal clearance
- adverse effects: diarrhea, headache, abdominal pain, inhibition of B12 absorption, interferes with iron, calcium and zinc absorption

Question 3

H2-histamine antagonists

Answer 3

• treatment of excess acid (H2R = significant contributor to gastric acid secretion. works very well during the night, causes nocturnal gastric acid secretion)
• longer term therapy

Cimetidine

• mechanism of action: H2R antagonist. action of site: gastric mucosa
• pharmacokinetics: orally active, interferes with drug metabolism particularly Cimetidine (other drugs have less interactions)
• adverse effects: pretty mild; Cimetidine however can cause mental status changes and delirium in the elderly and puts with hepatic impairment

Question 4

Triple therapy for H pylori infection

Answer 4

Clarithromycin
Amoxicillin (or metronidazole)
PPI

treat for 14 days

Question 5

Quadruple therapy for H pylori infection

Answer 5

Bismuth subsalicylate (surfactant)
Metronidazole
Tetracycline
PPI or H2 blocker

treat for 14 days

Question 6

Mucosal protective agents

Answer 6

Sucralfate and Bismuth subsalicylate: coat the gastric mucosa, preventing H ions already in the lumen from affecting the mucosa as well as slow down the rate of movement of H ions from the parietal cells out to the lumen.
Potential interference with drugs absorbed mainly in the stomach and upper SI.

Misoprostol: prostaglandin; promotes secretion of mucous to protect the mucosa

Question 7

Prokinetic drugs

Answer 7

Metoclopromide: D2 receptor blocker; employed in GERD - prevents reflux of gastric fluid at the lower esophageal sphincter

Erythromycin: Motolin receptor agonist - treatment of gastroparesis (given at lower doses than the doses given for a bacterial infection)

Tegaserod: 5-HT4 agonist - treatment of IBS with chronic constipation; risk of cardiac arrhythmias

Question 8

Irritable Bowel Syndrome

Answer 8

Alosetron: for IBS with diarrhea
antagonist at 5HT3 receptors
inhibit unpleasant afferent sensation such as bloating, pain, and nausea
Another 5HT3 receptor antagonist: Ondansetron aka Zofran

Tegaserod: for IBS with constipation
agonist at 5HT4 receptors
promotes smooth muscle contraction in gut
prolongs the QT interval –> risk of cardiac arrhythmia, associated with CV deaths, not available

Question 9

IBD drugs

Answer 9

Aminosalicylates
Glucocorticoids
Immunomodulatory agents
Anti TNF-alpha antibodies

Question 10

Aminosalicylates

Answer 10

5-aminosalicylate (5-ASA, mesalamine)

Mechanism of action: anti-inflammatory action through inhibition of leukotriene and prostaglandin production

5-ASA is absorbed in the small intestine, doesn’t reach the colon
Prodrugs such as sulfasalazine are employed to expose the colon to 5-ASA

Mesalamine and Sulfasalazine are used to treat IBD Ulcerative colitis, not Crohn’s. Remission in 35-50% of patients with mild to moderate UC, only modest improvement in Crohn’s.

Adverse effects: NVD, headache/abdominal pain, nephrotixicity

Question 11

Glucocorticoids

Answer 11

Effective for both UC and Crohn’s

Adverse effects: HTN, edema, risk of infection, osteoporosis, impaired healing, insomnia, mood disorder, glaucoma, Cushing’s syndrome, hyperglycemia
–> limit systemic use only until acute inflammation is resolved. 70-80% response rate but relapse is common (not treating underlying disease, only the Sx)

Rectal steroids can be used as maintenance in Crohn’s disease

Question 12

Immunomodulatory agents

Answer 12

ex) Methotrexate, azathioprine, mercaptopurine, cyclosporine

Azathioprine inhibits de novo purine synthesis, resulting in anti-proliferative actions and induction of apoptosis in T lymphocytes. Remission rates 45-70%.

adverse effects: myelosuppression, NVD, hepatotoxicity, pancreatitis

Question 13

TNF-inhibitors

Answer 13

Infliximab, adalimumab, certlizumab pegol

For moderate to severe Crohn’s that has not responded to other drugs. infliximab is also approved for treatment of unresponsive UC.

Infliximab = monoclonal antibody that binds to membrane bound and soluble TNF-alpha, a pro-inflammatory cytokine. Efficacy = 40% remained symptom free for 30 weeks

adverse effects: risk of serious infections including TB. Reactivation of HBV has occurred. Risk of cancer, cytopenias, CHF, and demyelinating disorders have been reported.