GI Pharmacology Flashcards

1
Q

What are some of the symptoms of GORD?

A
  • Painful heart burn
  • Cough
  • Larygntitis
  • Astha
  • Dental erosion
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2
Q

What are some of the complications of GORD?

A
  • Oesophagitis
  • Ulceration
  • Haemorrhage (anaemia)
  • Stricure formation
  • Barret’s oesophagus
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3
Q

What medications can exacerbate the symptoms of GORD?

A

Anything that relaxes smooth muscle

  • alpha bockers
  • anticholinergics
  • benzodiazepines
  • beta blockers
  • CCBs
  • NSAIDs
  • Nitrates
  • Theophylline
  • TCAs
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4
Q

What are some risk factors for developing GORD?

A
  • Older age
  • Hiatus hernia (lower oesophageal sphinter into thorax)
  • Obesity
  • Pregnancy
  • Smoking
  • Alcohol consumption
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5
Q

What lifestyle changes would you recommend for someone experiencing GORD symptoms?

A
  • Weight loss
  • Avoid trigger food
  • Eat smaller meals
  • Eat earlier in the day
  • Reduce alcohol/ caggeine intake
  • Stop smoking (limited evidence)
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6
Q

What are the pharmacological steps for treating GORD?

A
  • Introduce proton pump inhibitor first line
  • If unsuccessful- add in H2 Receptor Antagonist
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7
Q

Name 2 proton pump inhibitors

A
  • Omeprazole
  • Lansoprazole
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8
Q

What is gastritis?

A

An inflammatory change in the gastric mucosa

Can be erosive/ non-erosive. Acute / chronic

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9
Q

What are some of the symptoms of gastritis?

A
  • Burning epigastric pain
    • Food may increase or decrease pain
  • Nausea
  • Vomiting
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10
Q

What are some of the risk factors for developing gastritis?

A
  • H. pylori infection
  • Chronic NSAID use
  • Bile reflux
  • Chronic alcohol use
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11
Q

How do you manage erosive gastritis?

A
  • Remove irritant (NSAID, alcohol, bile)
  • Add PPI or H2 Receptor antagonist
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12
Q

How do you eradicate H. pylori?

A

Triple therapy

  1. PPI
    • Amoxicillin
    • Clarithromycin or Metronidazole (effectove but has side effects)
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13
Q

How do PPIs work?

A
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14
Q

How do H2 receptor antagonists work?

A
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15
Q

Name a H2 receptor antagonist

A

Ranitidine

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16
Q

What is peptic ulcer disease?

A

A defect in the gastric or dueodenal mucosa that exptends through the muscularis mucosa

17
Q

What are some the symptoms of peptic ulcer disease?

A
  • Epigastric pain after meals
    • soon after meals (gastric ulcer)
    • 2-3 hours after (duodenal)
18
Q

What are some of the risk factors for developing peptic ulcer disease?

A
  • H pylori infection
  • NSAIDs
19
Q

How do manage peptic ulcer disease that is H.pylori negative?

A
  • Stop NSAIDs
    • consider switching to COX-2 selective NSAID e.g. celecoxib
    • doesn’t effect COX-1 prostaglandin synthesis which is protective for the GI tract
  • Add PPI (+ H2 RA if unresponsive)
20
Q

How do you test for H.pylori?

A
  • Carbon 13 urea breath test
  • Or stool antigen test
21
Q

What are the 2 different isoforms of COX enzymes and where are they distributed throughout the body?

A

COX-1

  • high concentration in platelets, vascular endothelial cells, stomach and kidney
  • produces prostaglandings necessary to maintain endocrine, renal function, gastric mucosa integrity and haemostasis

COX-2

  • normal conditions, very low levels
  • rapdily increases at time of tissue damage
22
Q

What are the benefits and disadvantages of COX-2 inhibitors

A

Benefit:

  • Gastric protection

Disadvantage:

  • not good for CVS if given long term
  • High levels of TXA2 → pro-thrombotic
23
Q

What factors of the stomach offer protection against mucosal injury?

A
  • Acid - innate defence against bacterial invasion
  • Mucus - lubricates, traps bacteria, barrier against pepsin (protease that can auto-digest stomach)
  • Epthelial replaced 2-4 days
  • Good mucosal blood flow- if epithelium damaged rapid repair can occur
24
Q

What are the two types of gastric prostalandins and what are their effects?

A

PGE2 & PGI2

  • Potent vasodilators
  • Decrease acid secretion (at high levels)
  • Stimulate mucus and bicarb secretion in stomach
  • Reduce permeability of epithelium to backflow of acid
  • Reduce release of inflammatory mediators
  • Promote ulcer healing
25
Explain how parietal cells change from non-secreting state to secreting states
* **Non-secreting state:** Proton pumps are in membrane bound compartments (**tubovesicles)** * **​**lack K+ permeability blocking H-K ATPase activity * **Apical membrane** of parietal cell has involutions called **canaliculi** - v. acidic, have K+ channels * **Secreting state:** tubulovesicles **fuse** with canalicular membrane * proton pumps move to a position where they can exchange H+ for K+ * Requires a lot of **energy**
26
Proton pump inhibitors are pro-drugs. Explain how they are activated
* Activated by the **acidic conditions** of the parietal cell canaliculus * PPIs are **weak bases** so accumulate in the acidic space of secreteory canaliculi * Gives them a high concentration in the luminal surface of parietal cell
27
Explain the MoA of proton pump inhibitors
* Bind **covalently** to the gastric H+/K+ ATPase to irreversibly block function * Prolonged and nearly complete suppression of acid secretion * Have long effect- takes time for de novo synthesis to produce more enzyme
28
What are some of the side effects of proton pump inhibitors?
* Generally well tolerated * Headache, nausea, GI tract issues, abdo pain * May decrease effectiveness of clopidogrel (anti-platelet) * Increased risk of infections if used in hosptials * Leads to an increased production of **gastrin** due to parietal cell and ECL hyperplasia
29
Explain how H2 receptor antagonists work
* Competitively and reversibly inhibit the binding of histamine to H2 receptors on patietal cells * Indirectly block the effects of gastrin and ACh on the parietal cell * Activate PKA to change **shape** of parietal cell → create cannaliculi
30
What are some of the side effects of H2 receptor antagonists?
* Diarrhoea * Constipation * Musche ache and fatigue
31
Why is the H2 receptor antagonists Cimetidine not used as frequently?
* Inhibitis several Cytochrome P450s * Decreases metabolism of lidocaine, phenytoin theophylline and warfarin * Potentially results in toxic levels
32
Give an example of prostaglandin analogue
Misoprostol
33
Explain how misoprostol works
* Prostaglandin analgoue * Acts on PGE2 affecting similar pathway to H2 RA * Eventually inhibits PKA so there is **no conformational change** of parietal cell
34
What are some of the side effects and contraindications of misoprostol?
**Side effect:** * Diarrhoea * Abdominal pain * Often result in non-compliance **Contra-indicated:** * Pregnant women * Causes uterine contractions * useful in post-partum haemorrhage
35
How to antacids work?
* Neutralise HCl in stomach * React with acid to form water and salt
36
Name 2 commonly used antacid preparations
Alginic acid Aluminium hydroxide
37
What is step up vs step down therapy for treating GORD?
**Step up:** Start on H2 RA then progress to PPI if necessary (more economical) **Step down:** start on PPI and lower to H2 RA to see if they can maintain symptoms Continuous PPI therapy is the most effective
38
What properties of helicobacter pylori mean it thrives in the upper GI tract?
* Microaerophillic (stomach has perfect amount of O2) * Has flagellae- allows movement through mucus layer * Can attach to gastric epithelia * Produces urease. Converts urea→ ammonia + CO2
39
How does helicobacter pylori damage the gastric epithelium
* Promotes strong immune response * Ammonium hydroxide is toxic to gastric epthelia * Produces endotoxins