Clinical Therapeutics for GI Diseases Flashcards
(59 cards)
1
Q
What is the main action of Proton-Pump Inhibitors (PPIs)?
A
irreversibly bind to H⁺/K⁺-ATPase pumps and decrease acid production (basal + stimulated) by 80–95%
2
Q
What are key characteristics of PPIs?
A
- all PPIs have similar efficacy
- require H⁺ for activation
- have a short half-life
- are often enteric-coated or delayed-release to improve oral bioavailability
3
Q
What are PPIs mainly used to treat?
A
- peptic ulcer disease (PUD)
- GERD (especially if H2R antagonist fails)
- H. pylori infections
- Zollinger-Ellison syndrome
4
Q
What are the key A.D.M.E insights for PPIs?
A
- require 2–5 days to reach full effect
- metabolized by CYP2C19 and CYP3A4
- mainly eliminated by the liver
5
Q
What are common side effects of PPIs?
A
- nausea
- abdominal pain
- constipation
- flatulence
- diarrhea
6
Q
What are important drug interactions with PPIs?
A
PPIs inhibit elimination of warfarin, diazepam, methotrexate; long-term use may decrease absorption of vitamin B12.
7
Q
What is nocturnal acid breakthrough and how is it managed?
A
- acid production that occurs at night despite PPI use
- may need twice-a-day dosing or H2 receptor antagonist at night
8
Q
What is rebound acid hypersecretion and how is it managed?
A
- excess acid secretion after stopping PPIs due to elevated gastrin
- managed with tapering the drug
9
Q
What are long-term risks of chronic PPI use?
A
- bone fractures
- *** infections ( C. diff, CA pneumonia)
- hypomagnesemia
- kidney disease
- dementia
10
Q
What is the mechanism of action of H2R antagonists and how do they differ from PPIs?
A
block histamine action on H₂ receptors in parietal cells, lowering cAMP and reducing H⁺/K⁺-ATPase pump activity
* reversible and less potent than PPIs
11
Q
What are the clinical uses and limitations of H2R antagonists?
A
- used to promote mucosal healing in ulcers (H. pylori-related), treat uncomplicated GERD, and prevent stress ulcers
- tolerance and rebound acid hypersecretion may develop with long-term use
12
Q
What are the A.D.M.E characteristics of H2R antagonists?
A
- rapid oral absorption (1–3 hours)
- excreted by kidneys via filtration and secretion
- 10–35% metabolized by liver
13
Q
What are key adverse effects of H2R antagonists?
A
- generally well tolerated
- may cause diarrhea, headache, fatigue
- IV use in elderly can lead to confusion, delirium, slurred speech, hallucinations
14
Q
What are important drug interactions of H2R antagonists?
A
- Cimetidine inhibits CYP1A2, CYP2C9, and CYP2D6, increasing drug levels
- Famotidine has fewer CYP effects
- Slight increases in blood alcohol concentration may occur
15
Q
What is the overall role of cytoprotective agents in the GI tract?
A
promote prostaglandins or somatostatin to increase bicarbonate secretion, mucus production, and inhibit acid secretion
16
Q
What is Misoprostol used for and how does it work?
A
a PGE₁ analog that prevents NSAID-induced mucosal injury by binding to EP₃ receptors on parietal cells to stimulate Gi pathway
- increases mucin, bicarbonate, and mucosal blood flow
17
Q
What are the adverse effects and contraindications of Misoprostol?
A
- diarrhea (≤30%)
- worsen inflammatory bowel disease
- is contraindicated in pregnancy due to risk of inducing uterine contractility
18
Q
How does Sucralfate work and what is it used to treat?
A
- forms a sticky acid buffer by reacting with HCl to form cross links and acts as a protective barrier
- used short-term for duodenal ulcers
19
Q
What are key considerations and side effects of Sucralfate?
A
- Must be taken during fasting
- Can cause constipation, aluminum overload (especially in renal disease), block drug absorption, and impair lipid absorption (→ steatorrhea)
20
Q
What is Octreotide and when is it used?
A
- somatostatin analog inhibits intestinal/pancreatic secretions and hormones like GH, glucagon, insulin, gastrin, CCK, and VIP
- Used for severe diarrhea in carcinoid tumors, acromegaly, variceal bleeding, GI fistulas, and acute pancreatitis
21
Q
How do antacids work and what are their limitations?
A
- neutralize gastric acid and inhibit pepsin activity
- act rapidly but don’t last long
- may also increase urinary pH (alkalinization of urine) and are less commonly used due to lower efficacy
22
Q
What are the main side effects of antacids?
A
- nausea, belching, flatulence, and metabolic alkalosis
- aluminum-only antacids can cause constipation, while magnesium-only antacids can cause diarrhea
- may also interfere with drug absorption and contain aspirin
23
Q
What is the role of PPIs in H. pylori testing and treatment?
A
- may cause false-negative urease test results, so they should be stopped 2 weeks before testing
- treatment of H. pylori involves a 14-day regimen, often with quadruple therapy due to clarithromycin resistance
24
Q
What is the mechanism of action of antibiotics used for H. pylori?
A
- Amoxicillin: Inhibits cross-linkage of peptidoglycan chains
- Clarithromycin: Binds 23S rRNA on 50S ribosome, blocking protein synthesis
- Tetracyclines: Inhibit protein translation by binding 30S subunit
- Metronidazole: Inhibits nucleic acid synthesis via nitroso radicals
25
What causes Zollinger-Ellison Syndrome and how is it treated?
gastrin-releasing tumors (gastrinomas) → increased gastric acid → ulcers in unusual places (e.g., jejunum)
- Treated with surgery; PPIs or octreotide may also be used
26
How is octreotide useful in Zollinger-Ellison Syndrome?
binds gastrinomas and can be used for imaging and slowing tumor progression
27
What increases the risk of esophageal cancer in chronic GERD?
- chronic reflux
- Barrett’s esophagus
- smoking
- alcohol
-Cancer typically affects the lower third of the esophagus
28
What is gastroparesis and its common symptoms?
- delayed gastric emptying often due to diabetes, GERD, or surgery
- causes nausea, postprandial abdominal distention, and vomiting
29
What drug classes are used to treat gastroparesis (prokinetics)?
1. Dopamine antagonists
2. Macrolide antibiotics (erythromycin)
3. Cholinomimetics / AChE inhibitors
30
How does erythromycin help gastroparesis and what is a risk?
- acts as a motilin mimetic, used short-term for mod/severe gastroparesis
- can prolong QT interval and cause tolerance
31
What is the MOA for bethanechol and neostigmine and when should they not be used?
- Bethanechol (M3 agonist) and neostigmine (AChE inhibitor) increase GI smooth muscle tone
- should not be used in bowel obstruction or IBD
32
How do dopamine antagonists affect GI motility and what are the adverse effects?
- block dopamine, which inhibits upper GI motility
- anxiety, dystonia, tardive dyskinesia,
- elevated prolactin→ galactorrhea, gynecomastia, amenorrhea, impotence
33
What are the 6 drug classes used to treat Upper GI diseases and examples?
- Proton Pump Inhibitors: Omeprazole, Pantoprazole
- H2R Antagonists: Cimetidine, Famotidine
- Cytoprotectives: Misoprostol, Sucralfate, octreotide
- Dopamine Antaginists: Domperidone, Metoclopramide
- Macrolides: Erythromycin
- Cholinomimetics/AchE inhibitors: Bethanechol, Neostigmine
34
what are the different types of diarrhea and their causes?
- Decreased surface area: less absorption --> Crohn's, surgery
- Osmotic diarrhea: due to disaccharide malabsorption (lactose); fasting helps
- Secretory diarrhea: caused by toxins (cholera, C. diff)
35
Why is oral rehydration solution important for diarrhea?
- It replaces glucose and electrolytes lost during diarrhea
- In secretory diarrhea caused by bacteria, it’s crucial to allow clearance of the organism—avoid opioids early on
36
When are antibiotics risky or helpful in diarrhea?
- Avoid antibiotics in enterohemorrhagic E. coli ---->↑ risk of hemolytic uremic syndrome
- Stop antibiotics if possible in C. difficile
- traveler’s diarrhea, use fluoroquinolones, azithromycin, or rifaximin
37
What is Bismuth subsalicylate used for, and what are its effects?
- Used for traveler’s diarrhea and gastroenteritis
- Has anti-secretory, anti-inflammatory, and antimicrobial effects
- Can cause black stool/tongue and, rarely, Reye syndrome
38
How can probiotics help with diarrhea and what are the effective strains?
- restore gut flora in antibiotic-associated diarrhea
- Lactobacillus and Saccharomyces boulardii
39
How do opioids treat diarrhea and what are the risks?
- reduce intestinal motility, absorption and secretion via MOR and DOR receptors
- Use cautiously to avoid toxic megacolon
40
What other drugs can be used for diarrhea?
- Octreotide, telotristat (for secretory causes)
- Bulk-forming agents (bind toxins/salts)
- Bile acid sequestrants
- Crofelemer (used in HIV/AIDS; blocks chloride channels)
41
What are antispasmodics and what are they used for?
- Muscarinic antagonists use to reduce GI smooth muscle activity
- used to treat abdominal pain in IBS-D
42
What types of laxatives are used to treat constipation?
- Bulk-forming
- osmotic
- stimulant
- stool softeners
- surfactant agents
For chronic issues, use opioid antagonists and chloride channel activators
43
What are examples of bulk-forming laxatives and how do they work?
- Bran, psyllium, methylcellulose, calcium polycarbophil
- increase stool bulk by absorbing water; poorly fermentable ones should not be used in dehydrated patients
44
What are surfactant and emollient laxatives what do they do?
- docusate salts are anionic surfactants that lower surface tension
- mineral oil softens stool but can impair absorption of fat-soluble vitamins and may cause lipid pneumonitis if aspirated
45
What are stimulant laxatives and what are their risks?
bisacodyl,diphenylmethane derivative, requires endogenous esterases to stimulate motility but can damage mucosa and cause ischemia or an atonic colon with chronic use
46
What are the osmotically active laxatives and when are they used?
- Polyethylene glycol-electrolyte solutions (PEGs)
- Saline Laxatives (magnesium, phosphate)
- Nondigestible Sugars and Alcohols (Lactulose)
utilized in children with fecal impaction or prior to colonoscopy
47
What are the clinical indications fro saline and sugar/alcohol laxatives?
- Salines: oral phosphates should not be used in elderly patients with known bowel
pathology or renal dysfunction; avoid in patients on ACE inhibitors, ARBs, NSAIDs
- Lactulose: also used for hepatic encephalopathy by lowering ammonia levels
48
What is lubiprostone and what is it used for?
- activates EP4 receptors to activate Gs --> enhance Cl⁻ conductance and promote water secretion
- IBS-C and opioid-induced constipation
49
What are linaclotide and plecanatide and what are they used for?
- Guanylate cyclase activators that promote Cl⁻ and HCO₃⁻ secretion
- used in IBS-C and chronic constipation
*** Plecanatide is contraindicated in children <6 and not advised <18.
50
What is the treatment approach for opioid-induced constipation and what is a consideration for one of the drugs?
- Use peripheral MOR antagonists like methylnaltrexone, naloxegol, and alvimopan (for postoperative ileus)
- Alvimopan is restricted due to risk of MI.
51
What drug classes are used to treat Inflammatory Bowel Disease (IBD)?
- Anti-inflammatories (5-ASA, glucocorticoids, antimetabolites)
- Immunosuppressants (methotrexate, cyclosporine)
- Antibiotics (metronidazole, fluoroquinolones)
- Biologics (anti-TNF-α, integrins)
52
What is the first-line treatment for mild-to-moderate ulcerative colitis (UC)?
5-Aminosalicylic acids (ASAs) like sulfasalazine, mesalamine, olsalazine, and balsalazide ***Not used in Crohn’s
53
What are the MOAs and concerns with sulfasalazine?
- Inhibits IL-1/TNF-α, NF-κB, LOX pathway, PPAR-γ
- Inhibits folate absorption—folic acid should be supplemented, can be combined with glucocorticoids
54
When are glucocorticoids used in IBD and what are their risks?
- Used for moderate to severe IBD (UC & Crohn’s) ---> dexamethasone, prednisolone, budesonide
- Risks: cardiovascular events, adrenal insufficiency, cognitive effects
55
What are thiopurines and what are their risks?
Mercaptopurine & azathioprine are steroid-sparing agents used in Crohn’s, for fistulas (steroid resistant patients)
- Long onset ---> monitor blood counts due to risk of bone marrow suppression
56
How do methotrexate and cyclosporine work in severe IBD?
- Methotrexate: Inhibits dihydrofolate reductase (↓ purine & thymidine synthesis); give folinic acid to prevent macrocytic anemia
- Cyclosporine: Calcineurin inhibitor that blocks T-cell activation; used for Crohn’s fistulas
57
How do monoclonal antibodies like adalimumab help treat IBD?
neutralizes TNF-α, reduces inflammation, and is highly specific, avoids P450 metabolism, but increases risk of infection/reactivation (e.g., TB, hepatitis).
58
What does vedolizumab target and what is a concern for IBD treatment?
- blocks α₄β₇ integrin to prevent tissue adhesion and lymphocyte migration to inflamed GI sites (esp. in moderate to severe UC)
- reactivation of latent viruses is a concern.
59
What alternative therapies can help manage IBD?
may help reduce symptoms or prevent flare-ups
- diet modification
- avoidance of NSAIDs
- stress management
- probiotics
