Gastro-oesophageal reflux disease Flashcards
Clinical presentation of dyspepsia
Epigastric pain/burning
Early satiation
Postprandial fullness
Belching, bloating, nausea, discomfort
Synonym for dyspepsia?
Indigestion
Epidemiology of dyspepsia
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
Heartburn
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
How many patients with GORD will present with chest pain?
50%
Which condition must be excluded in a patient with unexplained chest pain?
Ischaemic heart disease (acute MI, angina)
Only 0.6% of heartburn cause
Aggravating factors of GORD
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)
Heartburn/chest pain after eating/drinking combined with difficulty swallowing may indicate?
Oesophageal spasms
What are the symptoms that give warning when combined with dysphagia?
Weight loss
Proven anemia
Vomiting
Haematemesis
High risk factors accompanying dyspepsia?
> 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
Which symptoms require endoscopy in heartburn and indigestion?
Weight loss Haematemesis Melaenia Dysphagia Anemia
Which symptoms allow for empiric treatment w/o endoscopy in heartburn and indigestion?
No weight loss
No haematemesis
<45yo
Which cells in the gastric mucosa are responsible for gastric acid secretion?
Parietal cells
Parietal cells are stimulated by?
Acetylcholine
Histamine
Gastrin
How does acetylcholine stimulate the parietal cells to secrete gastric acid?
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
How does histamine stimulate the parietal cells to secrete gastric acid?
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
How does gastrin stimulate the parietal cells to secrete gastric acid?
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
Gastric acid secretion is diminished by?
Prostaglandin E2
Somatostatin
How does prostaglandin E2 diminish the secretion of gastric acid by the parietal cells?
Inhibits adenylyl cyclase -> protein kinases not activated
How does somatostatin diminish the secretion of gastric acid by the parietal cells?
Inhibits adenylyl cyclase -> protein kinases not activated
Causative factors of peptic ulcer disease
NSAIDs esp aspirin
Infection w/ H.pylori (90% duodenal; 70% gastric)
Increased HCl and pepsin secretion
Inadequate mucosal defence against gastric acid
Principles of peptic ulcer disease management
Symptomatic relief
Promoting ulcer healing
Prevention of recurrence once healing has occurred
Prevention of complications
Peptic ulcers may occur and disappear spontaneously
True or false?
True
Non-pharmacological approaches to peptic ulcer disease
Stop smoking Avoid ulcerogenic drugs Reduce caffeine intake Healthy diet Test for H.pylori
Name ulcerogenic drugs
Alcohol
NSAIDs
Glucocorticosteroids
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
Drug classes used to treat peptic ulcer disease
Antimicrobial agents Mucosal protective agents H2 histamine receptor blockers Proton pump inhibitors Antacids Prostaglandins
Antimicrobial agents used for peptic ulcer disease
Amoxicillin
Clarithromycin
Metronidazole
Tetracycline
Mucosal protective agents used for peptic ulcer disease
Bismuth subcitrate
Sucralfate
Alginates
H2 histamine receptor blockers used for peptic ulcer disease
Cimetidine
Ranitidine
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
Antacids used for peptic ulcer disease
Aliminium hydroxide
Calcium carbonate
Magnesium
Sodium bicarbonate
Prostaglandins used for peptic ulcer disease
Misoprostol
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
Which proton pump inhibitor is in danger of drug interactions?
Omeprazole (inhibits CYP450) Warfarin Phenitoin Diazepam Cyclosporine Digoxin
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
Amelioration of GORD/PUD symptoms may delay diagnosis of…?
Gastric carcinoma
Which drug class is indicated for short term PUD and GORD management
PPI
Which drug class is indicated for long term GORD relapse prevention
PPI
Which drug class is indicated for H.pylori eradication in combination w/ ABs
PPI
Which drug class is indicated for Zollinger-Ellison syndrome treatment
PPI
Which drug class is indicated for NSAID-associated erosions + ulcers treatment and prevention
PPI
Which drug class is indicated for high risk bleeding peptic ulcers?
PPI
Increasing gastric pH stabilises the ulcer clot -> reduced rebleeding risk
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)
Which drugs will have inhibited metabolism with omeprazole use?
Warfarin Phenitoin Diazepam Cyclosporine Digoxin
Clinical presentation of hypomagnesemia?
Weakness Muscle cramps Cardiac arrythmias Confusion Seizures Hallucinations
What can prolonged proton pump inhibitor use result in?
Low vitamin B12
Acid required for absorption
Proton pump inhibitors cause … of calcium carbonate products?
Incomplete absorption
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
H2-receptor antagonists are very efficient with what type of secretion?
Nocturnal acid secretion
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
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
Cimetidine drug interactions
Inhibits P450
Increases effects of - warfarin, theopylline, phenytoin, amiodarone, quinidine, fluorouracil, metformin, diazepam, imipramine
Increases absorption of - ketoconazole
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
Mechanism of action of prostaglandins
Inhibit secretion of HCl + stimulate mucus and bicarbonate secretion + submucosa vasodilation
Less effective than PPIs/H2 receptor agonists
In what cases are prostaglandins routinely used?
NSAID induced ulcers
Adverse effects of prostaglandin use
Uterine contractions
Nausea
Diarrhoea
In which patients is prostaglandin use in peptic ulcer disease contraindicated?
Pregnancy
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
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)
Side effects of sucralfate use
Constipation Diarrhoea Vomiting Serum phosphorus reduction (binds phosphorus) Raised calcium levels
Drug interactions of sucralfate?
Tetracycline
Phenytoin
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
Adverse effects of bismuth subcitrate
Blackening of tongue, teeth + stools Renal failure (prolonged treatment)
Mechanism of action of alginates
Extracted from algae
Increase viscosity and adherence of mucus to oesophageal mucosa -> protective barrier
Indications for alginate use
Dyspepsia
Symptomatic peptic ulcer relief
Symptomatic oesophageal reflux relief
Used in pregnancy
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
At what pH does peptic enzyme activity stop?
5
Which ulcers are antiacids more effective with?
Duodenal ulcers (>gastric ulcers)
Which antacids must you use with caution
Na+ containing antacids w/ cardiovascular disorders
Does adding local anaesthetic add advantage to antacid efficacy?
No
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
Magnesium (hydroxide + trisilicate) antacid
Mechanism of action
Forms magnesium chloride in the stomach
Mg2+ poorly absorbed from gut -> does not cause systemic alkalosis
Aluminium hydroxide antacide
Side effects
Constipation/faecal impaction
Safe in pregnancy if renal fx normal
Can cause haemorrhoids
Magnesium (hydroxide + trisilicate) antacid
Side effects
Hypermagnesemia in severe renal impairment (accumulation) N+V Diarrhea ECG changes Respiratory depression Safe in pregnancy
Calcium antacid
Mechanism of action
Neutralises gastric acid + bonds phosphate
Calcium antacid
Side effects
Rebound acid hypersecretion
Milk-alkali (Burnette) syndrome - hypercalcaemia causing metastatic calcification + renal failure
Bones, stones, groans + moans
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.
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.
Sodium bicarbonate
Side effects
Systemic alkalosis
Belching + flatulence due to released CO2
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)
