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GI Pharmacology B&B Flashcards

1
Q

name 4 OTC antacids

A
  1. sodium bicarbonate (Alka Seltzer)
  2. calcium carbonate (Tums)
  3. aluminum hydroxide
  4. magnesium hydroxide
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2
Q

what are the potential side effects of sodium bicarbonate (Alka Seltzer), and why does this make sense? (3)

A
  1. bloating/belching - via CO2 production
  2. alkalosis - via bicarb (duh)
  3. fluid retention - via NaCl production

NaHCO3 + HCl <> NaCl - H2O + CO2

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3
Q

what are the potential side effects of calcium carbonate (Tums), and why does this make sense? (6)

A
  1. bloating/belching - via CO2 production
  2. alkalosis - via bicarb
  3. constipation - via Ca2+ (decreases GI motility)
  4. hypercalcemia - would really need to take a lot, but can be used for tx of hypocalcemia
  5. milk alkali syndrome (historic, if taken for ulcers): hypercalcemia + metabolic alkalosis + renal failure
  6. acid rebound - acid surge once antacid leaves stomach

CaCO3 + 2HCl <> CaCl2 + H2O + CO2

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4
Q

what are the potential side effects of aluminum hydroxide (antacid), and why does this make sense? (2)

A
  1. constipation - aluminum decreases GI motility.
  2. hypophosphatemia (would have to take a lot) - due to aluminum binding phosphate, which can be used in renal failure

Al(OH)3 + 3HCl <> AlCl3 + 3H2O

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5
Q

in which patients might you see aluminum toxicity, and why? how does it present? (3)

A

renal failure patients are sometimes given aluminum hydroxide (antacid) because aluminum binds phosphate - can be used to reduce hyperphosphatemia seen in renal failure

aluminum toxicity causes bone pain/muscle weakness/osteomalacia, dementia, ”iron resistant anemia” (microcytic anemia, does not improve with iron supplementation)

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6
Q

Pt w/ PMH of renal failure presents w/ fatigue and muscle weakness. PE is notable for pallor. Iron studies indicate a microcytic anemia. They are given iron supplements, but their condition does not improve. What is the cause of their “iron deficient” anemia?

A

aluminum toxicity: renal failure patients are sometimes given aluminum hydroxide (antacid) because aluminum binds phosphate - can be used to reduce hyperphosphatemia seen in renal failure

aluminum toxicity causes bone pain/muscle weakness/osteomalacia, dementia, ”iron resistant anemia” (microcytic anemia, does not improve with iron supplementation)

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7
Q

what are the potential side effects of magnesium hydroxide (antacid)? (2)

A
  1. osmotic diarrhea - poorly absorbed, sometimes used as osmotic laxative (“milk of magnesia”)
  2. hypermagnesemia (would need to take a lot) - hypotension, bradycardia

Mg(OH)2 + 2HCl <> MgCl2 + 2H2O

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8
Q

name 4 drugs that exhibit poor absorption in patients taking antacids

A
  1. tetracycline
  2. fluoroquinolones
  3. isoniazid
  4. iron supplements

this is because they bind the metals in antacids

[think of the metal ribbons in the Sketchy vids!]

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9
Q

name 4 histamine H2 receptor blockers

A
  1. famotidine
  2. ranitidine
  3. nizatidine
  4. cimetidine

[Famous Cinemas Ran Nicely]

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10
Q

what are the side effects of cimetidine that caused its disuse in the modern era? (4)

A

H2 blocker

  1. potent P450 inhibitor
  2. anti-androgen —> gynecomastia, impotence, prolactinemia
  3. cross BBB —> dizziness, confusion, headache
  4. reduces creatinine excretion
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11
Q

name 4 PPI

A
  1. omeprazole
  2. pantoprazole
  3. lansoprazole
  4. esomeprazole

[the OMElet in the PAN LANded SOMEwhere]

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12
Q

name 3 potential adverse effects of omeprazole, pantoprazole, lansoprazole, and esomeprazole

A
  1. Clostridium difficile infection - due to loss of H+ protection
  2. pneumonia - due to more pathogens in upper GI tract, due to loss of H+ protection
  3. malabsorption - Mg2+, Ca2+, B12, iron, vitamin C
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13
Q

what are the clinical uses of bismuth salicylate? (2)

A

aka Pepto-Bismol/ Kaopectate

  1. gastric ulcers/erosions - most effective in H. pylori ulcers (“quadruple therapy” instead of triple therapy)
  2. diarrhea - salicylate inhibits prostaglandins —> decreased mucus secretion into stool

note, bismuth reacts with hydrogen sulfide in the colon, forming black-colored stools (can look like GI bleeding)

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14
Q

what is the clinical use of sucralfate?

A

sucralfate = sulfated polysaccharide + aluminum hydroxide

negative charge binds to positively charged H+ in ulcers —> ulcer healing

side effects are rare because it is not absorbed

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15
Q

name 7 osmotic laxatives (there are others)

A
  1. magnesium hydroxide (milk of magnesia)
  2. magnesium citrate
  3. polyethylene glycol (Miralax)
  4. sodium polystyrene sulfonate (Kayexalate)
  5. sorbitol (sugar alcohol)
  6. sodium phosphate
  7. lactulose
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16
Q

what is the clinical use (2) of sodium polystyrene sulfonate (Kayexalate)?

A

“cation exchange resin” - binds potassium

can be used as osmotic laxative or to treat mild hyperkalemia

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17
Q

what is the special use of the osmotic laxative lactulose?

A

lactulose = synthetic disaccharide used as osmotic laxative but also to treat hyperammonemia

bacteria in colon break down lactulose into fatty acids —> lowers colonic pH, favors formation of NH4+ (not absorbable) over NH3

NH4+ is trapped in colon —> decreased plasma ammonia

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18
Q

what is the clinical use of bisacodyl (Dulcolax), senna (Senokot), and docusate?

A

bisacodyl (Dulcolax) and senna (Senokot) = “stimulant laxatives” (increase GI motility)

docusate = stool softener (also laxative)

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19
Q

MOA and clinical use of ondansetron

A

ondansetron = 5-HT3 receptor antagonist used as anti-emetic, esp. in chemo patients

5-HT3 R found in vomiting center in medulla and vagal/spinal nerves to GI tract

side effects = headache + contraption

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20
Q

MOA and clinical use (2) of metoclopramide

A

metoclopramide (Reglan) = D2 receptor antagonist

  1. in GI: block D2 = block ACh —> increased gastric motility, tx gastroparesis (esp. diabetics)
  2. in CNS: block D2 = block chemo trigger zone in area postrema (medulla) —> anti-emetic (esp. patients with migraines)

note, D2 blockade can also cause extrapyramidal symptoms (restless, akathisia, dystopia, tardive dyskinesia)

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21
Q

3 clinical scenarios in which metoclopramide is contraindicated

A

aka Reglan: D2 receptor antagonist, treats gastroparesis (diabetics) and anti-emetic (migraines)

contraindicated:
1. seizure disorder - lowers seizure threshold
2. Parkinson’s - bc of dopamine blockade
3. bowel obstruction - increased GI motility would make this worse

22
Q

When is the effect of H2 receptor antagonists most pronounced? (ex: famotidine, ranitidine, cimetidine, nizatidine)

A

effect is most pronounced on nocturnal acid secretion, which largely depends on histamine

23
Q

When should proton pump inhibitors be administered?
(ex: omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, rabeprazole)

A

bioavailability is decreased half by food, so drugs should be administered on an empty stomach one hour before a meal

short half-life (0.5–2 hours), but acid inhibition lasts up to 24 hours due to irreversible in activation of H/K ATPase pump on gastric parietal cells

24
Q

MOA sucralfate

A

selectively binds and coats necrotic ulcer tissue – activation requires the acidic conditions in the gut (should not be taken together with H2 antagonist, PPIs, or antacids)

Acts as a barrier to acid, pepsin, bile, may also stimulate synthesis of prostaglandins (—> mucus, and bicarb secretion)

Effective in preventing and healing duodenal ulcers with minimal systemic affects due to lack of absorption

25
MOA of bismuth subsalicylate / bismuth subcitrate?
**bismuth**: binds and coats necrotic ulcer tissue —> barrier to acid and pepsin and has direct anti-microbial activity against H pylori **salicylate**: inhibits intestinal prostaglandin, and chloride secretion —> reduces stool frequency and liquidity causes harmless blackening of the stool (can be confused for G.I. bleeding)
26
which prostaglandin analog is approved for prevention of NSAID-induced ulcers?
**misoprostol**: PGE1 analog, stimulates mucus/HCO3 secretion contraindicated in women with childbearing potential due to stimulate effect on the uterus
27
MOA of psyllium, methylcellulose, and polycorbophil
**bulk forming laxatives**: indigestible colloids that absorb water, forming a bulky gel in the G.I. tract that distends colon and promotes peristalsis —> useful for management of intermittent constipation in patients not responding to high-fiber diet bacterial digestion of plant fibers can lead to bloating and flatus
28
MOA docusate, glycerin suppository, and mineral oil?
**stool softeners**: enhance penetration of water and lipids into the stool Docusate used in hospitals to prevent constipation and minimize straining Long-term use can impair absorption of fat soluble vitamins (DAKE)
29
lavage solutions containing ______ are used for colonic cleansing prior to GI endoscopic procedures
**polyethylene glycol**: osmotic laxative soluble but non-absorbable, alters osmolarity of fecal water in the colon [bisacodyl (stimulant laxative) is also given in conjunction, orally or rectally]
30
MOA of bisacodyl, aloe vera, senna, and cascara sagrada?
**stimulant laxatives (cathartics)** - stimulate enteric nervous system and secretion of colonic electrolytes and fluid used for acute and chronic constipation, produce bowel movements within 6-12 hours when given orally or 0.5-2 hours when given rectally
31
MOA lubiprostone
fatty acid derived from **PGE1**, activates type 2 **chloride channels** in GI epithelial cells —> prosecretory agent treats **constipation** from chronic idiopathic constipation, IBS, opioid induced constipation Like LUBE for the GI tract
32
MOA linaclotide
peptide agonist of guanylate cyclase that **activates CFTR chloride ion channels** in GI epithelial cells —> treats **constipation** treats chronic idiopathic constipation and IBS lina[CL-]otide
33
which of the following does NOT cross the BBB: a. loperamide b. diphenoxylate
both are mu-opioid agonists in enteric nervous system, increase colonic transit time - **anti-diarrheal** **loperamide** does NOT cross BBB at high doses, diphenoxylate can cross BBB and has potential for dependence
34
which two mu opioid receptor agonists are appropriate for treatment of IBS with predominant diarrhea (IBS-D)?
1. eluxadoline 2. Loperamide Agonist at mu opioid receptors - anti-diarrheal antagonist at delta opioid receptors - analgesic properties to help with visceral pain
35
MOA eluxadoline
Agonist at mu opioid receptors - anti-diarrheal antagonist at delta opioid receptors - analgesic properties to help with visceral pain treats IBS with predominant diarrhea (IBS-D)
36
name three drug classes which are appropriate for treating IBS with predominant constipation (IBS-C) - indicate which is most effective
1. Chloride ion channel activators – most effective (lubiprostone) 2. Osmotic laxatives (polyethylene glycol) 3. Bulk forming laxatives (psyllium)
37
MOA of mesalamine, sulfasalazine, olsalazine, and balsalazide?
**aminosalicylates**: inhibit, inflammatory, mediators, derived from COX & LOX pathways First line for mild to moderate **ulcerative colitis** and **Crohn’s** disease involving colon or distal ileum Adverse effects include N/V, constipation, headache, myalgia, rash, altered liver enzymes
38
MOA of infliximab, adalimumab, and certolizumab
mAb that bind both soluble and membrane-bound **TNF** —> suppressed TH1 immune response approved for acute and chronic treatment of Crohn’s disease, infliximab approved for acute and chronic treatment of ulcerative colitis as well
39
MOA of natalizumab and vedolizumab
natalizumab: mAb against **alpha4 beta1** and **alpha4 beta7** integrins vedolizumab: mAb against alpha4 beta7 integrin inhibited integrins = inhibited migrating lymphocytes approved to treat Crohn’s disease and ulcerative colitis (in patients refractory to anti-TNF therapy) rare risk of *progressive multifocal leukoencephalopathy (PML) due to reactivation of latent HPV*
40
MOA aprepitant and netupitant?
**neurokinin 1 (NK1) receptor antagonists**: anti-emetic properties through central blockade in the area postrema used in combination with 5-HT3 receptor antagonist and corticosteroids for prevention of acute and delayed chemotherapy induced nausea/vomiting (CINV) note - inhibits the metabolism of drugs by CYP3A4
41
at which receptors do dimenhydrinate, meclizine, and diphenhydramine act?
**H1 antagonists** - weakly antiemetic, useful for prevention/treatment of motion sickness may cause sedation, dry mouth, urinary retention
42
name a drug which treat Crohn’s disease by inhibiting the function of integrins on circulating inflammatory cells
**natalizumab** - mAb of **alpha4 beta1/7** also vedolizumab
43
Name a drug which is a first line agent for ulcerative colitis and Crohn’s disease by inhibiting inflammatory mediators derived from COX & LOX
mesalamine, sulfasalazine, olsalazine, balsalazide
44
name a drug which treats constipation by activating type two chloride ion channels in G.I. epithelial cells
**lubiprostone**: fatty acid derived from PGE1 Produces a chloride rich fluid secretion that softens stool, increases motility, and promote spontaneous bowel movements Treats chronic idiopathic constipation, IBS with predominant constipation (IBS-C), and opioid induced constipation
45
name a D2 receptor antagonist that is both anti-emetic and prokinetic
**metoclopramide** - accelerates gastric emptying and also prevents vomiting
46
which of the following is an osmotic laxative? a. pysllium b. docusate c. polyethylene glycol d. bisacodyl
c. polyethylene glycol also Mg(OH)2 (milk of magnesium), sorbitol, lactulose
47
which of the following is a bulk-forming laxative? a. pysllium b. docusate c. polyethylene glycol d. bisacodyl
a. pysllium also methylcellulose, polycorbophil
48
which of the following is a stool-softener? a. pysllium b. docusate c. polyethylene glycol d. bisacodyl
b. docusate also glycerin suppository, mineral oil
49
which of the following is a stimulant laxative? a. pysllium b. docusate c. polyethylene glycol d. bisacodyl
d. bisacodyl also aloe vera, senna, cascara sagrada
50
name a drug used to treat irritable bowel disease (IBD) that carries a rare but serious side effect of progressive multifocal leukoencephalopathy (PML)
**natalizumab** or **vedolizumab** mAb to **alpha4 integrins** - prevent lymphocyte migration may (rarely) cause PML due to HPV reactivation

Gastrointestinal (25 decks)

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