Gastroesophageal reflux disease and diaphragmatic hernia (pharmacology)

Question 1

Explain which cells secrete gastric acid, how is it controlled/regulated and the phases involved

Answer 1

Gastric acid is secreted from parietal cells by a proton pump (H+/K+ ATPase)

It is controlled by:
- CNS
- Reflexes involving the stomach wall
- Hormones of the digestive tract

Phases:
Basal phase
Cephalic phase
Gastric phase
Intestinal phase

Question 2

Explain the basal phase of gastric acid secretion

Answer 2

10% of total acid is continiously secreted and is unrelated to feeding
Peaks at midnight and decreases at around 7am
Under autonomic control (enteric nervous system - Parasympathetic mediated by histaminic stimulation)

Question 3

Explain the cephalic phase of gastric acid secretion

Answer 3

30% of total gastric acid
Stimulated by anticipation of eating food and smell or taste
Signalling occurs from higher brain centers through vagus nerve
Generally only lasts a short period

Question 4

Explain the gastric phase of gastric acid secretion

Answer 4

50% of total acid
Begins when food enters the stomach
Stimulated by distention of the stomach and food amino acids
Stretch reflex increases myenteric stimulation
Submucosal plexus:
- Stimulates parietal and chief cells
- Stimulates G cells to produce Gastrin

May continue for several hours

Question 5

Explain the intestinal phase of gastric acid secretion

Answer 5

10% of acid is secreted
Stimulated by distention of the small intestine
Mostly inhibitory controls slowing gastric emptying
- Enterogastric reflex inhibits gastrin production
- Secretin, CCK, gastric inhibitory peptide reduce gastric activity

Ensures efficient intestinal functions

Question 6

Explain the regulation and mechanism of acid secretion

Answer 6

Gastric acid secretion is stimulated by:
- histamine (activation of adenylyl cyclase)
- Gastrin (induces increase intracellular Ca2+)
- Acetylcholine (induces increase intracellular Ca2+)
Leads to activation of protein-kinases that stimulates H+/K+ ATPase proton pump to secrete hydrogen ions inexchange for K+

Gastric acid secretion is inhibited by:
- Protaglandin E2 and I2 (inhibits adenylyl cyclase)
- Somatostatin (inhibits adenylyl cyclase)

Question 7

What is the etiology of reflux

Answer 7

• Decreased lower oesophageal sphincter tone
• Delayed gastric emptying
• Increased intra-abdominal pressure
• Motor failure of oesophagus - loss of peristalsis
• Iatrogenic injury to LOS

Question 8

What are the classic GORD symptoms

Answer 8

Heartburn
Regurgitation

Question 9

What are the predisposing and risk factors for GORD

Answer 9

• LOS function: Hiatal hernia, Bile reflux and gall stones
• Impaired oesophageal peristalsis: Scleroderma, systemic sclerosis
• Increased intragastric and abdominothoracic pressure: obesity, pregenancy
• Excess gastric acid secretion: Acid and Pepsin hypersecretory states, Hypercalcemia
• Eating and lifestyle

Question 10

What is a hiatal hernia

Answer 10

Protrusion of the gastrointestinal junction and stomach parts towards the diaphragm

When the muscle surrounding the oesophageal sphincter weakens it can cause the upper part of the stomach to bulge through the diaphragm

Question 11

What are the diagnostic tests for GORD

Answer 11

Barium swallow
Endoscopy
Ambulatory 24hr pH monitoring
Oesophageal manometry

Question 12

Whata re the principles of management of GORD

Answer 12

Eliminate the symptoms
Heal oesophagitis
Manage or prevent complications
Maintain remission

Question 13

What are the non-pharmacological treatment approaches to GORD

Answer 13

Elevation of head of bed 4-6 inches in those with nocturnal symptoms
Avoid eating within 2-3 hours before bed
Lose weight if overweight
Stop smoking
Modify diet - eat more frequent but smaller meals, avoid fatty foods

Question 14

Whata re examples of Proton pump inhibitors

Answer 14

Omeprazole
Lansoprazole
Rabeprazole
Pantoprazole
Esomeprazole

Question 15

What are examples of H2-receptor Antagonists

Answer 15

Cimetidine
Ranitidine
Famotidine
Nizatidine

Question 16

What is the MOA of PPI

Answer 16

Inhibit irreversible H+/K+ ATPase proton pump seppressing secretion of hydrogen ions into the gastric lumen

Most potent suppressors f gastric acid secretion
- Effect 1-2hours after 1st dose
- Effective for 2-3 days
- Preferred over H2 antagonists

Question 17

What are the indications for PPI

Answer 17

• Short term medication for Peptic ulcer disease and GORD
• Long term prevention or relapse of GORD
• H. Pylori eradication in combination with antibiotics
• Treatment of Zollinger-Ellison syndrome
• Treatment and prevention of NSAID-associated erosions and ulcers
• Erosive esophagitis
• IV PPI useful for high risk bleeding peptic ulcers

Question 18

What are the adverse effects of PPI

Answer 18

Hypomagnesemia
Increased risk of fracture
Headaches and skin rashes
Raised liver functio tests
Diarrhoea
Drowsiness and impaired concentration
Not reccomended in pregnancy

Question 19

Drug interactions of PPI

Answer 19

Omeprazole inhibits CYP450: Thus inhibits metabolism of warfarin, phenitoin, diazepam, cyclosporine, digoxin
Other PPI’s do not have interactions
Prolonged use may lead to Vit B12 deficiency
Incomplete absorption of calcium carbonate products

Question 20

What is the mechanism of action of H2-receptor antagonists

Answer 20

Reduces gastric acid secretion by reversibly blocking the action of histamine at the H2 receptors in the parietal cells of the stomach

Question 21

What are the indications for H2 receptor antagonists

Answer 21

Largely replaced by PPI’s

• Peptic ulcers, esophagitis
• Gastric and duodenal ulcers
• Acute stress ulcers
• GORD
• Prevention and treatment of heartburn
• Hypersecretory states (Zollinger-Ellison syndrome)
• In anaesthesia before emergency surgery to prevnet aspiration

Question 22

What are the adverse effects of H2-receptor antagonists

Answer 22

Headaches, dizziness, diarrhoea, musclular pain
CNS - confusion, hallucinations, slurred speech
Anti-adrogenic effect (esp cimetidine
- Impotence
- Gynaecomastia
- Galactorrhoea

Not reccomended in pregnancy

Question 23

What are the drug interactions for H2-receptor antagonists

Answer 23

Cimetidine: Inhibits P450 enzyme
- Warfarin, theophylline, phentoin, amiodarone, quinidine, fluorouracil, metformin, diazepam, imipramine (increased effect)
- Ketoconazole (increased absorption)

Ranitidine
- Less potential for drug interactions
- Doesnt cross BBB

Question 24

What are the MOA of Prostaglandins

Answer 24

Inhibits secretion of HCl, stimulates secretion of mucus and bicarbonate and causes vasodilation in the submucosa

Question 25

What are the indications for Prostaglandins

Answer 25

NSAID induced ulcers

Question 26

What are the adverse effects of Prostaglandins

Answer 26

Uterine contractions - contraindicated with pregnancy
Nausea and diarrhoea

Question 27

What are examples of Mucosal protective agents

Answer 27

Sucralfate
Bismuth subcitrate
Aliginates

Question 28

What is the MOA, Indications, Side effects and drug interactions of Sucralfate

Answer 28

MOA:
- Forms paste-like gel when in contact with HCL leads to local protective action on ulcer base
- Directly absorbs bile and pepsin

Indications:
- Management of benign gastric and duodenal ulceration
- Chronic gastritis

Side effects:
- Low incidence of systemic side effects
- May cause reduction in serum phosphorous
- Raised calcium levels

Drug interactions:
- Interferes with absorption of: Tetracyclins, Phentoins, Anticoagulants, Digoxin, Cimetidine

Question 29

What are the MOA and adverse effects of Bismuth subcitrate

Answer 29

high affinity for damaged tissue, forming a visible coating in ulcer base protecting it against acid and pepsin digestion

Adverse effect:
- Blackening of the tongue, teeth and stools
- Renal failure in prolonged treatment

Question 30

What are the MOA and indications for Alginates

Answer 30

Increases viscosity and adherence of mucus to the oesophageal mucosa forming a protective barrier

Used in:
- Dyspepsia
- Symptomatic relief in peptic ulcer or oesophageal reflux
- Pregnancy

Question 31

What are examples of antiacids

Answer 31

Aluminium hydroxide
Calcium carbonate
Magnesium
Sodium bicarbonate

Question 32

What are the MOA of antiacids

Answer 32

Directly neutralise intraluminal acid
Reduce the delivery of acid into the duodenum after a meal
Doesnt block production

Question 33

What is the MOA, Side effects, and indications for Aluminium hydroxide

Answer 33

Absorbs pepsin and binds bile
Forms complexes with phosphorous

Common side effect is constipation

Useful as a phosphate binding agent in renal impairment

Question 34

What is the MOA, side effets and indications of Magnesium

Answer 34

Forms magnesium chloride in stomach

Side effects:
- Nausea and vomiting
- Diarrhoea
- ECG changes
- Respiratory depression

Question 35

What is the MOA and side effects of Calcium antacides

Answer 35

Neutralise gastric acid, binds phosphate

Side effects:
- May cause rebound acid hyper secretion
- Milk-alkali syndrome (Burnetter syndrome): Hypercalcaemia leading to metastatic calcifications and renal failure