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Integrated Drug Structure, Function, and Therapeutics Winter Term > Upper GI Disorders - DeLander > Flashcards

Upper GI Disorders - DeLander Flashcards

1
Q

What are some different ways that upper GI disorders can be managed?

A
  • Buffer acidity
  • Inhibit acid secretion (gastrin, ACh, histamine, proton pumps)
  • Enhance protection (prostaglandins, sucralfate)
  • Antibacterial therapy (H. pylori)
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2
Q

Terms: Inflammation of the lining of the stomach. How is it treated?

A

gastritis. Treated with behavioral modifications (avoid triggers like spicy foods, or take drugs to eat spicy foods)

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3
Q

Terms: acid coming back into the esophagus more than normal

A

GERD

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4
Q

Terms: Erosion of the stomach lining (an open wound), or a perforation where the stomach contents leak back into the stomach. How do you treat this?

A

Peptic ulcer. Treat with avoidance of triggers and drugs like H2 blockers.

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5
Q

Terms: Erosion of stomach lining due to sepsis or a side effects from another disease. Not emotionally related.

A

Stress ulcer.

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6
Q

Terms: Disorder where huge amount of acid is released due to gastrin.

A

Zollinger-Ellison syndrome

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7
Q

Terms: Extra secretions released in stomach not due to gastritis (different progression).

A

Gastric cancers

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8
Q

Are the cells in the esophagus and stomach the same?

A

No, the esophageal cells are epithelial, while those in the stomach are secretory.

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9
Q

Inside the stomach: What are the function of epithelial cells?

A

They secrete mucus and bicarbonate, which protects other cells from the acid.

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10
Q

Inside the stomach: What are the function of parietal cells?

A

They secrete acid

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11
Q

Inside the stomach: What are the function of chief cells?

A

They secrete enzymes to help break down food.

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12
Q

Inside the stomach: What are the function of neuroendocrine cells?

A

Enterochromaffin-like (ECL) secrete histamine
Gastrin is secreted by G cells
Somatostatin is secreted by D cells
(G cells and D cells are interlaced between parietal and epithelial cells)

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13
Q

What type of ion exchange happens in the stomach?

A

In the parietal cells, a proton pump (activated when phosphorylated) works to pump protons into the lumen of the stomach as it pumps potassium out. As it transfers the potassium ion, it is dephosphorylated. Carbonic anhydrase is an enzyme in the parietal cell that works to help.

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14
Q

What do antacids do?

A
  • They buffer acidity rapidly (change the pH)
  • Need frequent dosing
  • Possible chelation of some drugs (tetracycline possibly inactivated)
  • toxicity possible in really impaired
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15
Q

What effect on the bowels does aluminum have?

A

Constipation: “Al’s all backed up”

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16
Q

What effect on the bowels does magnesium have?

A

Diarrhea: “Let the magma flow”

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17
Q

What effect on the bowels does calcium have?

A

less effective

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18
Q

What effect does HCO3, CO3 have?

A

Belching, flatulence

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19
Q

What does gastrin do in the stomach?

A

The presence of food activates G cells to release gastrin, which then enters the blood stream. From there, gastrin acts two ways:

  1. Directly activates parietal cells to stimulate release of acid in the stomach
  2. Interacts with ECL receptors to release histamine (always).
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20
Q

G cells activates what other pathway?

A

The parasympathetic nervous system is activated, which turns on the enteric nervous system. (utilizes ACh and muscarinic receptors). This pathway when activated also turns on parietal cells and releases histamine.

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21
Q

What is the difference between gastrin and histamine?

A

Gastrin may stimulate the release of acid, but histamine is considered to be necessary. Histamine uses a cAMP dependent-pathway, which is necessary for the protein kinases to be activated and turn on the pump to secrete acid into the stomach.

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22
Q

Prostaglandins role in protecting the stomach:

A

Protective!!!

  1. Histamine turns on cAMP pathway, prostaglandins turn it off (turns off PP)
  2. Epithelial cell - the primary meditator that is turning on the secretion of mucus and bicarbonate is prostaglandins to protect. (cytoprotective mechanism)
  3. Cause vasodilation to ensure adequate blood flow to whisk away any toxins
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23
Q

D cell function:

A

Regulatory. When the acidity drops too much, then D cells are activated. D cells release somatostatin, which inhibit G cells.

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24
Q

H2 blockers do what?

A

They make it very hard to activate the pump. Don’t block it completely.

25
Q

What would be the enzyme to block in Zollinger-Ellison syndrome?

A

Gastrin. Somatostatin doesn’t hang around long enough to use.

26
Q

What can you use to treat Zollinger-Ellison syndrome?

A

Octreotide. It decreases gastrin release and gastrin motility. Somatostatin-mimic. Most uses are off-label, it is indicated for acromegaly (too much growth hormone). It can treat diarrhea caused by gastric tumors.

27
Q

What is a problem with using octreotide?

A

Involved in inhibiting thyroid-stimulating hormone. Decreases motility of gallbladder.

28
Q

PNS activation (by G cells) can do what? What is used to counter this? What is the US equivalent of this and is it effective?

A

Turns on the parietal cell. Pirenzapine is used to stop this. M1 antagonist. Belladonna is not effective because in therapeutic doses there are other problems.

29
Q

To get optimal secretion of acid, what is necessary?

A

Histamine

30
Q

H2 antagonists act how at receptors?

A

They are selective, competitive blockade of H2 receptors.

31
Q

H2 Antagonists

A
  • Rapid onset
  • Decrease basal and stimulated proton secretion
  • Best for nocturnal dyspepsia
  • Side effects, especially cimetidine (2D6, 3A4, 1A2) with inhibition
  • Side effects can include confusion, especially elderly (remove elderly from H2 blocker and they become cognizant). B12, antifungals are some that are affected because they require an acidic environment for optimal bioavailability.
32
Q

PPIs

A
  • greatest efficacy
  • irreversible, selective inhibitor of K/h ATPase
  • takes several days for full effectiveness
  • needs to be given before food (50% decreased bioavailability with food)
  • potentially decreased absorption for acid-loving drugs
  • prodrug: absorbed into intestines, circulated, secreted into stomach and binds to proton pumps
33
Q

problems with high-dose therapy of PPI or H2 blocker?

A
  • possible reflex gastrin release
  • increased risk of C. dif
  • increased risk of hip fractures (osteoclasts also have proton pumps in repair sites. makes more fragile)
  • Recommended use not to exceed 60 days
34
Q

What are the three protective functions of prostaglandins?

A
  1. Inhibit cAMP-dependent pump activation
  2. Increase secretion of mucus and bicarbonate
  3. Increase blood flow to disperse acid or toxins
35
Q

What drug is a prostaglandin analog?

A

Misoprostol

36
Q

Misoprostol

A
  • Effective as an agent, don’t promote healing
  • Indicated for NSAID-induced ulceration or dyspepsia
  • SE’s: abdominal cramping/diarrhea. Not for pregnant women.
37
Q

Sucralfate

A
  • collection of substances that gel in pH <4. Binds to exposed tissue to form a protective barrier
  • SE: constipation
  • Take before meals, some malabsorption of other drugs, reduced dosing with kidney impairment
  • duodenal ulcer benefit from this
38
Q

Bismuth salicylate

A
  • increases mucus and bicarbonate production
  • some antibacterial action
  • helps in H. pylori management
  • Reacts with exposed tissue to form a barrier
  • SE: black hairy tongue, dark stools, reduced dosing with kidney impairment
39
Q

Heliobacter pylori

A
  • gram negative bacteria
  • Endemic in our guts (80% of us have it)
  • Causes an inflammatory response that can cause ulcerations
  • Almost always a contributor to peptic ulcers
40
Q

How do you treat H. pylori?

A

triple or quadruple therapy for 14 days. Short-term goal is to decrease distress, long-term is to decrease inflammation

41
Q

In terms of peristalsis, what does bethanechol do?

A

It stimulates peristalsis as an ACh mimetic.

42
Q

In terms of peristalsis, what does Dexpanthenol do?

A

It stimulates peristalsis as an ACh mimetic.

43
Q

In terms of peristalsis, what does Alosetron do?

A

It inhibits peristalsis as a 5-HT3 antagonist. (Zoran causes this a little)

44
Q

In terms of peristalsis, what does belladonna do?

A

It inhibits peristalsis as a muscarinic antagonist.

45
Q

In terms of peristalsis, what do cisapride and tegaserod do?

A

They stimulate peristalsis, as 5HT4 agonists. They prolong the QT interval, and are reserved for constipation unrelieved by other methods.

46
Q

In terms of peristalsis, what does Erythromycin do?

A

It mimics the action of motolin, and increases peristalsis.

47
Q

In terms of peristalsis, what do dopamine antagonists like metoclopramide do?

A

They stimulate peristalsis, even though it is counter by the 5HT4 antagonist

48
Q

In terms of peristalsis, what does octreotide do?

A

It inhibits peristalsis. It is a somatostatin agonist.

49
Q

What stimulant would you use if you were going to get aggressive with opioid-induced constipation? For mild constipation?

A

Aggressive - bisacodyl

Mild - Senna

50
Q

What do lubiprostone and Linaclotide do?

A

Lubiprostone is a chloride channel type 2 activator, and linaclotide is gunnel cyclase C agonist. They both have the same effect and chloride is dumped into the gut which causes massive diarrhea. You run the risk of dehydration when you use these, and only use if nothing else works.

51
Q

What could you use to treat motion sickness?

A

Antihistamines or antimuscarinics (diphenhydramine, scopolamine)

52
Q

What could you use to treat acute chemo- or endotoxin-induced nausea/vomiting?

A

D2 antagonists or 5HT3 antagonists.

53
Q

What are some D2 antagonists?

A

Metoclopramide, prochlorperazine, chlorpromazine, haldol

54
Q

What are some 5HT3 antagonists?

A

ondansetron, granisetron, palonisetron

55
Q

What are the NK-1 antagonists? What do they do?

A

Aprepitant, rolapitant. They can be used as an adjunct for delayed nausea/vomiting. Substance P is the natural ligand.

56
Q

What do the CB-1 agonists do?

A
  • Help with nausea/vomiting

- Dronabinol - efficacy not the same as 5HT3 antagonists

57
Q

How do corticosteroids help with nausea and vomiting?

A

Drugs such as dexamethasone can be used as an adjunct. Not a well-understood mechanism, boosts efficacy of other agents.

58
Q

What type of nausea and vomiting do benzodiazepines help with?

A

Anticipatory nausea. Usually lorazepam.

59
Q

What drug has a possible side effect of neutropenia?

A

The NK-1 antagonists

Integrated Drug Structure, Function, and Therapeutics Winter Term (18 decks)

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