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Gastro-oesophageal reflux disease Flashcards

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1
Q

Clinical presentation of dyspepsia

A

Epigastric pain/burning
Early satiation
Postprandial fullness
Belching, bloating, nausea, discomfort

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2
Q

Synonym for dyspepsia?

A

Indigestion

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3
Q

Epidemiology of dyspepsia

A 
Common worldwide (42%)
Only 5% will go to GP
1% referred for endoscopy

40-50% have functional/non-ulcer dyspepsia
40% have GORD
10-13% have some form of ulcer
1-3% have oesophageal/gastric cancer

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4
Q

Heartburn

A

A major symptom of GORD
Burning sensation in the chest just behind sternum/in epigastrium -> pain often rises in the chest and may radiate to the neck, back, shoulder, throat or angle of jaw

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5
Q

How many patients with GORD will present with chest pain?

A

50%

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6
Q

Which condition must be excluded in a patient with unexplained chest pain?

A

Ischaemic heart disease (acute MI, angina)

Only 0.6% of heartburn cause

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7
Q

Aggravating factors of GORD

A

After eating or at night
Worse when lying down/bending over
Common in pregnancy
Consuming food in large quantities or specific foods (certain spices, high fat content, high acid content)

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8
Q

Heartburn/chest pain after eating/drinking combined with difficulty swallowing may indicate?

A

Oesophageal spasms

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9
Q

What are the symptoms that give warning when combined with dysphagia?

A

Weight loss
Proven anemia
Vomiting
Haematemesis

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10
Q

High risk factors accompanying dyspepsia?

A

> 55yo pt

  • onset of dyspepsia <1y previously
  • continuous symptoms since onset
  • family history of upper GI cancer in > 2 1st degree relatives
  • Barrett’ oesophagus
  • pernicious anemia
  • peptic ulcer surgery >20y previously
  • palpable Virchow’s node
  • jaundice
  • upper abdominal mass
  • longstanding change in bowel habit
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11
Q

Which symptoms require endoscopy in heartburn and indigestion?

A 
Weight loss
Haematemesis
Melaenia
Dysphagia
Anemia
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12
Q

Which symptoms allow for empiric treatment w/o endoscopy in heartburn and indigestion?

A

No weight loss
No haematemesis
<45yo

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13
Q

Which cells in the gastric mucosa are responsible for gastric acid secretion?

A

Parietal cells

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14
Q

Parietal cells are stimulated by?

A

Acetylcholine
Histamine
Gastrin

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15
Q

How does acetylcholine stimulate the parietal cells to secrete gastric acid?

A

Induces increase in intracellular calcium -> activation of protein kinases -> stimulate H+/K+ ATPase proton pump to secrete H+ ions in exchange for K+ into stomach lumen

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16
Q

How does histamine stimulate the parietal cells to secrete gastric acid?

A

Activation of adenylyl cyclase -> activation of protein kinases -> stimulate H+/K+ ATPase proton pump to secrete H+ ions in exchange for K+ into stomach lumen

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17
Q

How does gastrin stimulate the parietal cells to secrete gastric acid?

A

Induces increase in intracellular calcium -> activation of protein kinases -> stimulate H+/K+ ATPase proton pump to secrete H+ ions in exchange for K+ into stomach lumen

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18
Q

Gastric acid secretion is diminished by?

A

Prostaglandin E2

Somatostatin

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19
Q

How does prostaglandin E2 diminish the secretion of gastric acid by the parietal cells?

A

Inhibits adenylyl cyclase -> protein kinases not activated

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20
Q

How does somatostatin diminish the secretion of gastric acid by the parietal cells?

A

Inhibits adenylyl cyclase -> protein kinases not activated

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21
Q

Causative factors of peptic ulcer disease

A

NSAIDs esp aspirin
Infection w/ H.pylori (90% duodenal; 70% gastric)
Increased HCl and pepsin secretion
Inadequate mucosal defence against gastric acid

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22
Q

Principles of peptic ulcer disease management

A

Symptomatic relief
Promoting ulcer healing
Prevention of recurrence once healing has occurred
Prevention of complications

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23
Q

Peptic ulcers may occur and disappear spontaneously

True or false?

A

True

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24
Q

Non-pharmacological approaches to peptic ulcer disease

A 
Stop smoking
Avoid ulcerogenic drugs
Reduce caffeine intake
Healthy diet
Test for H.pylori
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25
Name ulcerogenic drugs
Alcohol NSAIDs Glucocorticosteroids
26
Pharmacological approaches to peptic ulcer disease
``` Eradicate H.pylori infection - antimicrobial therapy + PPI Reduce gastric acid secretion - PPI - H2 receptor antagonists Protect the gastric mucosa - misoprostol - sucralfate - alginates - bismuth Neutralize gastric acid with non-absorbable antacids ```
27
Drug classes used to treat peptic ulcer disease
``` Antimicrobial agents Mucosal protective agents H2 histamine receptor blockers Proton pump inhibitors Antacids Prostaglandins ```
28
Antimicrobial agents used for peptic ulcer disease
Amoxicillin Clarithromycin Metronidazole Tetracycline
29
Mucosal protective agents used for peptic ulcer disease
Bismuth subcitrate Sucralfate Alginates
30
H2 histamine receptor blockers used for peptic ulcer disease
Cimetidine | Ranitidine
31
Proton pump inhibitors used for peptic ulcer disease
``` Esomeprazole Lanzoprazole Omeprazole Pentoprazole Rabeprazole ``` Most potent suppressors of gastric acid secretion - begins 1-2hrs after 1st dose - effect for 2-3 days because of accumulation in gastric canaliculi - preferred to H2 antagonists
32
Antacids used for peptic ulcer disease
Aliminium hydroxide Calcium carbonate Magnesium Sodium bicarbonate
33
Prostaglandins used for peptic ulcer disease
Misoprostol
34
Mechanism of action of proton pump inhibitors in peptic ulcer disease
Irreversibly inhibit the K+/K+ ATPase proton pump -> hydrogen ion secretion into gastric lumen suppressed
35
Which proton pump inhibitor is in danger of drug interactions?
``` Omeprazole (inhibits CYP450) Warfarin Phenitoin Diazepam Cyclosporine Digoxin ```
36
Indication for proton pump inhibitor use?
Short term PUD and GORD management Long term GORD relapse prevention H.pylori eradication in combination w/ ABs Zollinger-Ellison syndrome treatment NSAID-associated erosions + ulcers treatment and prevention IV PPI in high risk bleeding peptic ulcers
37
Amelioration of GORD/PUD symptoms may delay diagnosis of...?
Gastric carcinoma
38
Which drug class is indicated for short term PUD and GORD management
PPI
39
Which drug class is indicated for long term GORD relapse prevention
PPI
40
Which drug class is indicated for H.pylori eradication in combination w/ ABs
PPI
41
Which drug class is indicated for Zollinger-Ellison syndrome treatment
PPI
42
Which drug class is indicated for NSAID-associated erosions + ulcers treatment and prevention
PPI
43
Which drug class is indicated for high risk bleeding peptic ulcers?
PPI | Increasing gastric pH stabilises the ulcer clot -> reduced rebleeding risk
44
Adverse effects of proton pump inhibitors
``` Hypomagnesemia (prolonged use) Increased fracture risk Headaches Skin rashes Raised LFTs Diarrhoea (C.difficile) Drowsiness + impaired concentration (aggravated in CNS depressant use) ```
45
Which drugs will have inhibited metabolism with omeprazole use?
``` Warfarin Phenitoin Diazepam Cyclosporine Digoxin ```
46
Clinical presentation of hypomagnesemia?
``` Weakness Muscle cramps Cardiac arrythmias Confusion Seizures Hallucinations ```
47
What can prolonged proton pump inhibitor use result in?
Low vitamin B12 | Acid required for absorption
48
Proton pump inhibitors cause ... of calcium carbonate products?
Incomplete absorption
49
H2-receptor antagonists | Mechanism of action
Reversibly block the action of histamine at H2 receptors in parietal cells of stomach -> reduce intracellular cyclic adenosine monophosphate concentration -> reduced gastric acid secretion Gastric acid secretion in response to secretagogues e.g Ach, gastrin also reduced
50
H2-receptor antagonists are very efficient with what type of secretion?
Nocturnal acid secretion
51
Indications for H2-receptor antagonists use?
Largely replaced by PPIs Peptic ulcers Oesophagitis Effective in healing gastric + duodenal ulcer but high recurrence >60% Acute stress ulcers GORD Heartburn prevention + treatment (50% effective) Hypersecretory states e.g Zollinger-Ellison syndrome Prevent aspiration during anasthesia before emergency surgery e.g Mendelson's syndrome
52
Adverse effects of H2-receptor antagonists
``` Antiandrogenic effect esp cimetidine (0.1-0.2%) - impotence - gynecomastia - galactorrhoea Headache Dizziness Diarrhoea Muscular pain Confusion Hallucinations Slurred speech ```
53
Cimetidine drug interactions
Inhibits P450 Increases effects of - warfarin, theopylline, phenytoin, amiodarone, quinidine, fluorouracil, metformin, diazepam, imipramine Increases absorption of - ketoconazole
54
Why is ranitidine considered superior to cimetidine?
Structurally different to cimetidine but as effective Less CNS symptoms because does not cross BBB as easily Little/no anti-androgenic effect No effect on P450 therefore fewer drug interactions
55
Mechanism of action of prostaglandins
Inhibit secretion of HCl + stimulate mucus and bicarbonate secretion + submucosa vasodilation Less effective than PPIs/H2 receptor agonists
56
In what cases are prostaglandins routinely used?
NSAID induced ulcers
57
Adverse effects of prostaglandin use
Uterine contractions Nausea Diarrhoea
58
In which patients is prostaglandin use in peptic ulcer disease contraindicated?
Pregnancy
59
Mechanism of action of sucralfate
A sucrose hydrogen sulphate-aliminium complex that forms paste-like gel when in contact w/ HCl -> local protective action on ulcer base + protect ulcer epithelium from gastric acid and directly absorbs pepsin and bile
60
Indications for use of sucralfate
Benign gastric ulceration Benign duodenal ulceration Chronic gastritis Administer frequently and at least 2 hours apart from other medications (30min from other antacids)
61
Side effects of sucralfate use
``` Constipation Diarrhoea Vomiting Serum phosphorus reduction (binds phosphorus) Raised calcium levels ```
62
Drug interactions of sucralfate?
Tetracycline | Phenytoin
63
Mechanism of action of bismuth subcitrate
Precipitates at acid pH w/ high affinity for damaged tissue -> visible coating at ulcer base -> protection against acid + pepsin digestion AND mucous production stimulation
64
Adverse effects of bismuth subcitrate
``` Blackening of tongue, teeth + stools Renal failure (prolonged treatment) ```
65
Mechanism of action of alginates
Extracted from algae | Increase viscosity and adherence of mucus to oesophageal mucosa -> protective barrier
66
Indications for alginate use
Dyspepsia Symptomatic peptic ulcer relief Symptomatic oesophageal reflux relief Used in pregnancy
67
Mechanism of action of antacids
``` Directly neutralise intaluminal acid -> reduce acid delivery into duodenum after meal Doesn't block production May increase oesophageal sphincter tone May reduce oesophageal pressure Take 1hr after meal + at bedtime ```
68
At what pH does peptic enzyme activity stop?
5
69
Which ulcers are antiacids more effective with?
Duodenal ulcers (>gastric ulcers)
70
Which antacids must you use with caution
Na+ containing antacids w/ cardiovascular disorders
71
Does adding local anaesthetic add advantage to antacid efficacy?
No
72
Aluminium hydroxide antacid | Mechanism of action
Forms AlCl in stomach + raises pH to 4 -> absorbs pepsin + binds bile Increases phosphorus excretion (forms complexes) - useful as phosphate binding agent in renal impairment
73
Magnesium (hydroxide + trisilicate) antacid | Mechanism of action
Forms magnesium chloride in the stomach | Mg2+ poorly absorbed from gut -> does not cause systemic alkalosis
74
Aluminium hydroxide antacide | Side effects
Constipation/faecal impaction Safe in pregnancy if renal fx normal Can cause haemorrhoids
75
Magnesium (hydroxide + trisilicate) antacid | Side effects
``` Hypermagnesemia in severe renal impairment (accumulation) N+V Diarrhea ECG changes Respiratory depression Safe in pregnancy ```
76
Calcium antacid | Mechanism of action
Neutralises gastric acid + bonds phosphate
77
Calcium antacid | Side effects
Rebound acid hypersecretion Milk-alkali (Burnette) syndrome - hypercalcaemia causing metastatic calcification + renal failure Bones, stones, groans + moans
78
Burnett's syndrome
A far-advanced milk-alkali syndrome due to long-standing calcium and alkali ingestion. It is characterised by severe hypercalcaemia, irreversible renal failure, and phosphate retention. The patient is treated by withdrawal of excessive calcium and alkali intake.
79
Mendelson's syndrome
A chemical pneumonitis or aspiration pneumonitis caused by aspiration during anaesthesia, especially during pregnancy. Aspiration contents may include gastric juice, blood, bile, water or an association of them.
80
Sodium bicarbonate | Side effects
Systemic alkalosis | Belching + flatulence due to released CO2
81
H.pylori therapy
``` Triple therapy - 7-14 day regimen for eradication therapy - PPI plus 2 of the following a) Clarithromycin 500mg bd b) Amoxicillin 1g bd c) Metronidazole 400mg bd d) Tetracycline (resistance cases) Continue the PPI for 1 month or until ulcer has healed ``` Quadruple therapy - if PPI contraindicated - Ranitidine 300mg daily for 7 days plus bismuth subcitrate 120mg 6hrly for 7 days plus 2 of the following a) Clarithromycin 500mg bd b) Amoxicillin 1g bd c) Metronidazole 400mg bd d) Tetracycline (resistance cases)

Pharmacology (32 decks)

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