GI-Block 1 Flashcards
Acid-Peptic Diseases: Antacids
- Sodium Bicarb
- Calcium Bicarb
- Magnesium hydroxide
- Aluminum hydroxide
- Magnesium hydroxide + Aluminum hydroxide
Mech: Weak bases that neutralize gastric acid
CU: intermittent heartburn and dyspepsia
Prob: Sodium bicarbonate and calcium bicarbonate: -Gas from CO2 production -Higher doses, metabolic alkalosis -fluid retention (NaHCO3)
Magnesium hydroxide:
-diarrhea
Aluminum hydroxide:
-constipation, encephalopathy, myopathy
Cimetidine, Ranitidine, Famotidine
Mech: H2 antagonist (rev. compete)
CU: ulcers, GERD
Effectiveness:
-Very effective at inhibiting nocturnal acid secretion
Prob:
- tolerance occurs
- cimitidine inhibits CYP450
Sucralfate
Mech: Forms viscous paste through cross-linking that binds selectively to ulcers or erosions
CU: Limited (reduce upper GI bleed in critically ill patients, stress related bleeding)
Disadv: not as effective as H2 antagonists or PPIs
Prob: Few
Glucocorticoids:
Hydrocortisone, Methylprednisolone
Action: bind nuclear hormone receptor, translocate to nucleus, affect gene transcription
-Anti-emesis mech is unclear
Clinical Use:
moderate to severe IBD for short periods; not ideal for maintenance of remission –
-taper dose after patient has been stable for 2-4 weeks.
Of note: enhances anti-emetic efficacy of 5-HT3 receptor antagonists
Problems: See slide on powerpoint
Prochlorperazine
Mech: antagonist of D2 receptor
CU: emesis, particularly induced by chemotherapy
Prob: Antimuscarinic effects
Cannabinoids:
Dronabinol (delta-9 THC)
Action: stimulation of cannaboind receptors in vomiting center
Clinical Use:
- prophylactic in cancer chemotherapy,
- appetite stimulant (AIDS, anorexia)
Problems:
- central sympathomimetic activity (tachycardia, palpitations, bloodshot eyes)
- can experience paranoid reactions
Lubiprostone
Action: Stimulates chloride channels. Increase chloride-rich fluid secretion into intestine, thus stimulating intestinal motility
Clinical Use: constipation-predominant IBS (approved for women)
Problems: nausea
Opioid Receptor Antagonist:
Methylnaltrexone
Opioids produce constipation by decreasing intestinal motility thus prolonging transit time and increasing absorption of fecal water
-Methylnaltrexone blocks this
Unlike naloxone and naltrexone, methylnaltrexone does not readily cross BBB
Loperamide
Action: mu opioid receptor agonist
Clinical Use: diarrhea
Problems: torsades de pointes
Of note: available over-the-counter because it does not cross blood-brain barrier and thus has no potential for addiction
-Pt. should contact MD if after 48 hours if no benefit
Bismuth Subsalicylate
Action: salicylate inhibits formation of prostaglandins and chloride secretion to reduce stool frequency and liquidity, bismuth has antimicrobial effects
Clinical Use:
- diarrhea
- as part of 4-drug regimen for eradication of H. pylori
Problems: harmless blackening of stool and darkening of tongue may occur
Tricyclic Antidepressant (TCAs): Amitriptyline
Action: Inhibits reuptake of serotonin and norepinephrine
Clinical Use: low-doses for visceral pain associated with IBS
Problems:
- prolong QT interval
- high-risk medication for geriatric population due to antimuscarinic effects
Of note: analgesic dose lower than doses for depression
10 mg QHS (IBS pain) vs. 100 mg BID (depression)
Antispasmodic:
Dicyclomine and Hyoscyamine
Action: Block muscarinic cholinergic receptors in the enteric plexus and on smooth muscle
==>reduce colonic motility
Clinical Use:
- IBS on an as-needed basis (provide short-term symptom relief, no long term efficacy established)
- Pre-op anesthesia (hyoscyamine)
Problems:
- Low dose: minimal autonomic adverse effects
- Higher doses: antimuscarinic
Note: due to adverse effects and the lack of small/large bowel spasm contributing to IBS symptoms, these drugs are not first-line
Sulfasalazine (5-ASA)
Action: not completely understood
- Modulate inflammatory mediators derived from cyclooxygenase and lipoxygenase pathways.
- May also interfere with production of inflammatory cytokines
Clinical Use:
- Mild IBD.
- Induce remission in ulcerative colitis (may be >90% of patients)
Administration: many 5-ASAs are formulated for rectal administration (suppositories and enemas)
Problems:
Up to 40% may discontinue due to nausea, GI upset, headaches, arthralgias, myalgias, bone marrow suppression, malaise.
Azathioprine and 6-Mercaptopurine
Action: decrease lymphoid cell proliferation
Azathioprine: pro-drug of 6-mecaptopurine: purine pathway inhibitor
Clinical Use: IBD, immunosuppression of other autoimmune disorders, cancer chemotherapy
Problems:
Response may take weeks to months
Adverse effects can occur immediately: nausea, vomiting, bone marrow suppression (usually manifested as leukopenia), teratogenicity (avoid pregnancy)
Of note: 6-MP is inactivated by thiopurine methyltransferase (TPMT). 11% have reduced TPMT activity resulting in accumulation of 6-MP and potential for bone marrow toxicity and myelosuppression.
Monitoring: routine lab monitoring of complete blood count and liver function
Methotrexate
Action: inhibitor of dihydrofolate reductase thus inhibiting synthesis of tetrahydrofolate and subsequently thymidine and purine nucleotides
Clinical Use: Crohn’s (efficacy in ulcerative colitis not as clear), other autoimmune disorders, cancer chemotherapy
Advantages: potentially steroid sparing
