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LCRS Pharma > Peptic Ulcers > Flashcards

Peptic Ulcers Flashcards

1
Q

what is a peptic ulcer?

A

an area of damage to the inner lining of the stomach (gastric ulcer) or the upper part of the duodenum (duodenal ulcer).

prevalent in developed countries

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2
Q

how do the timings of the symptoms differ and how can you therefore tell which type of ulcer it is?

A

 Gastric ulcer – pain at mealtimes when the acid is secreted. Epigastric

 Duodenal ulcer – pain relieved by a meal as the pyloric sphincter closes (pain starts after 2-3 hours

duodenal ulcers are more common

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3
Q

what are the 3 protective elements of the GI barrier?

A

o Mucus :
-from gastric mucosa creates a gastrointestinal mucosal barrier.

o HCO3- ions :
- trapped in the mucous and generate a protective pH of 6-7 at the mucosal surface.

o Locally produced
prostaglandins :
- stimulate mucus and bicarbonate production (paracrine action), inhibit gastric acid secretion and facilitate a good blood supply to the stomach.

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4
Q

what are the main cells involved in damaging the mucosal barrier because of the products they make?

A

o Parietal cells
– acid secretion from parietal cells of the oxyntic glands in the gastric mucosa.

o Chief cells
– pepsinogens which erode the mucous layer.

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5
Q

what factors contribute to mucosal damage?

A 
o Increased acid or decreased HCO3-.
o Decreased thickness of mucosal layer.
o Increase in pepsin type 1.
o Decreased mucosal blood flow.
o Infections with H. pylori. 
o Risk factors – genetics, stress, diet (alcohol, smoking).
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6
Q

what is the aim of the treatment of peptic ulcers?

A
  • treat the underlying cause (reduce acid secretion and bacteria)
  • promote healing/eleviate symptoms
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7
Q

what is a rapid test that can be done to establish H.pylori infection? what other test can be done?

A

carbon urea breath test

[H.pyloric converts urea to ammonia and carbon dioxide using urease]

along with peptic stool antigen test

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8
Q

what effect does H.pylori (urease) have on the mucous layer?

A

it dissolves it leading to increased risk of epithelial cell damage via exotoxins & inflammation

increases gastric acid formation via gastrin stimulation and inhibition of somatostatin

ulcer forms due to metaplasia due to acid exposure

defence mechanisms like bicarbonate ions and epidermal GF are down regulated

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9
Q

what is the standard treatment for peptic ulcer involving H.pylori?

A

triple therapy:

  • Amoxicillin (penicillin)
  • clarithromycin (macrolide antibiotic) /metronidazole
  • PPI e.g. omeprazole
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10
Q

what is used to eliminate H.pylori?

A

Antibiotics as part of triple therapy

~100% of duodenal ulcers and 80-90% of gastric ulcers are infected with H. pylori.

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11
Q

describe H.pylori:

  • gram?
  • risk factors for contraction
A 
generally commensal 
gram -ve
motile 
microaerophilic 
risk factors for acquiring: 
- Socioeconomic conditions.
- Contact with animals and contaminated faeces.

50-80% are worldwide chronically infected

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12
Q

what gives H.pylori its virulence?

A

1) enzyme urease:
- converts urea to ammonia and carbon dioxide (hence carbon urea breath test)
- evokes immune response

2) virulence factors: produce CagA (antigenic) or VacA (cytotoxic) – more intense tissue inflammation

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13
Q

what are the inhibitor drugs of gastric acid secretion?

A

o Proton pump inhibitors. e.g. Omeprazole

o H2 receptor antagonists. e.g. Cimetidine, Ranitidine.

o Anti-muscarinics.

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14
Q

How is acid production triggered and continued?

A
  1. Presence/smell of food can trigger acid production.
  2. In the fundus, there are acid-secreting parietal cells.
    - PNS can act on H-cells to stimulate histamine production in respond to acid
  3. In the antrum, amino-acids can trigger the g-cells to secrete gastrin.
    - Gastrin triggers more histamine release or can simply trigger more acid production directly (CCKB receptors).
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15
Q

what transporter mediates the production of acid?

what increases it activity and what is the effect of its activity?

A

H+/K+ exchanger (proton pump)

via cAMP:

  • Histamine acts on H2 receptors on parietal cells
  • trigger activation of these exchangers via a cAMP-pathway.
  • [Ca2+]i goes up leading to increased cAMP
  • -> translocation of secretory vesicles to parietal cell apical surface
  • ->H+ secretion
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16
Q

which cells provide the protective bicarbonates that mix with the mucous?

A

Superficial epithelial cells

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17
Q

what is considered for therapy use when there is a chronic H.pylori infection?

A

Consider quinolone, tetracycline (bismuth sucralfate) to reduce acidity

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18
Q

what is the simple function of PPIs?

A

Inhibits basal and stimulated gastric acid secretion by >90% via:

irreversible inhibition of the H+/K+ ATPase exchanger (found in parietal cells)

19
Q

when does a PPI become inactive? where does it accumulate?

A

inactive at neutral pH

accumulates at the canaliculi as it is a weak base so concentrates action at the canaliculi.

20
Q

what are the uses of PPIs?

A

o Peptic ulcers resistant to H2-receptor antagonists.
o Triple therapy component.
o GERD and oesophagitis.
o Prophylaxis of peptic ulcers in intensive care, high-risk patients prescribed aspirin, NSAIDs, antiplatelets and anti-coagulants.

21
Q

where are proton pumps found and what happens to them in disease?

A
  • they are found on parietal cells
  • upregulated in disease (more expression on apical surface)
  • leading to more acid secretion via the cAMP pathway involving G protein (increased vesicular translocation)
22
Q

describe the pharmacokinetics and side effects of PPIs

A

Oral and administered in an enteric coating.

Side effects – rare due to short term use

Long term and/or high dose –>enteric infections (C. diff), community acquired pneumonia, hip fracture.

23
Q

what is the simple function of H2 receptor antagonists?

A

Inhibits gastric acid secretion by parietal cells by ~60% (less effective than PPIs) via competitive H2-receptor antagonism (reducing cAMP)

e.g. Cimetidine, Ranitidine

24
Q

describe the pharmacokinetics and side effects of H2 receptor antagonists

A
  • Oral, well-absorbed
  • Ranitidine longer acting than cimetidine.
  • Relapses are likely after withdrawal from treatment (>90% recurrence within 1 year after healing) hence is part of triple therapy.

Side effects:
o Rare – headaches and dizziness.
o Fewer side effects with Ranitidine (available OTC).

25
Q

what is the use of anti-muscarinic drug in peptic ulcer treatment?

A

Little use as anti-ulcer drugs, more effective in combination therapies

26
Q

what kind of drugs are Sucralfate, Bismuth chelate, Misoprostol?

A

cytoprotective:
These drugs enhance mucosal protection and/or build a physical barrier over the ulcer

Bismuth chelate / Pepto-Bismol acts like Sucralfate

27
Q

what is the MoA of sucralfate? what does this result in?

what does sucralfate increase and decrease?

A

In an acid environment, it acquires a strong negative charge.
It binds to positive groups in large molecules resulting in gel-like complexes.
This coats and protects the ulcer, limits H+ diffusion and pepsin degradation of mucus.

•Increases
– prostaglandin, mucus and HCO3- production.
• Decreases
– number of H. pylori.

28
Q

what are the side effects of sucralfate?

A

Most orally administered Sucralfate remains in the GIT which may cause constipation or reduced absorption of other drugs (e.g. digoxin and antibiotics).

29
Q

what is misoprostol? when is it prescribed?

A

prostaglandin analogue (orally active)

  • co-prescribed with NSAIDs when used chronically as NSAIDs block the COX enzymes required for PG synthesis from arachidonic acid.
30
Q

what salts are used in antacids and how do they vary in action?

A

Salts of Na+, Al3+, Mg2+

Sodium bicarbonate has rapid effects whilst aluminium hydroxide and magnesium trisilicate have slower actions

31
Q

what do antacids do?

A

neutralise acid, raise gastric pH, reduce pepsin activity.

May be effective in reducing duodenal recurrence rates.
Administer orally – primarily used for non-ulcer dyspepsia,GORD (can become Barrett’s Oesophagus when chronic)

(OTC)

32
Q

what is the role of amoxicillin in triple therapy?

A

target anaerobic bacteria or protozoa / broad-spectrum.

33
Q

what is the role of clarithromycin in triple therapy?

A

Macrolide antibiotic – inhibits translocation of bacterial tRNA

34
Q

how does NSAID use contribute to the formation of peptic ulcer?

A
  • Directly cytotoxic (irreversible effects on COX)
  • Reduces mucus production
  • Increases likelihood of bleeding
  • increased gastric blood flow due to blood thinning effect

COX-1 inhibition reduces PGE2 levels that have GI protective effects
overall Increased acidity –>peptic ulcer

35
Q

what would the treatment option be for ulcers due NSAID used?

A

stopping use of the NSAID

but this can be difficult if used for other conditions e.g. heart conditions
give PPI or histamine receptor antagonist e.g ranitidine (H2)

36
Q

why are Histamine receptor antagonists used less?

A

they are not as effective as PPIs

37
Q

what is the effect of stimulating an H2 receptor?

A

increases acid secretion by activation of H+/K+ ATPase in parietal cells

38
Q

what are the 4 regulators of gastric acid production?

A

ACh (hence anti-muscarinics)
Prostaglandins (COX products)
Histamine (H2 receptors)
Gastrin (G cells)

39
Q

how does ACh regulate acid production?

A

(ACh) released from neurones (vagus / enteric) acts on muscarinic (M3) receptors to

increase [Ca2+]I

therefore proton pump expression

more acid

40
Q

how do prostaglandins regulate acid production?

A

(PGs) released from local cells act on EP3 receptors

↓ cAMP (–> reduced H+/K+ ATPase activity)

therefore less proton pump expression

less acid - explains how NSAIDs, that prevent PG production, exacerbate ulcers

41
Q

how does histamine regulate acid production?

  • where is it released from?
  • where does it act on?
  • what effect does that have?
A
  • released from enterochromaffin-like cells (ECL)
  • act on H2 receptors
  • increase cAMP
    therefore more proton pump expression
    more acid produced

therefore use H2 receptor antagonists like ranitidine

42
Q

how does gastrin regulate acid production?

A

released from G-cells, acts on cholecystokinin B receptors to

increase [Ca2+]I

therefore more proton pump expression

more acid produced

43
Q

what are the effects of increases calcium and cAMP?

A

translocation of secretory vesicles to parietal cell apical surface–> ↑ H+ secretion

the cAMP pathway activates H+/K+ ATPase when H2 receptor is stimulates by histamine

44
Q

what is the effect of somatostatin?

A

peptide that inhibits G-cells, ECL cells and parietal cells

G-cell produces gastrin
parietal cell produces HCl (regulated by gastrin)
ECL produces histamine

LCRS Pharma (32 decks)

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