Gastroesophageal reflux disease and diaphragmatic hernia (pharmacology) Flashcards
Explain which cells secrete gastric acid, how is it controlled/regulated and the phases involved
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
Explain the basal phase of gastric acid secretion
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)
Explain the cephalic phase of gastric acid secretion
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
Explain the gastric phase of gastric acid secretion
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
Explain the intestinal phase of gastric acid secretion
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
Explain the regulation and mechanism of acid secretion
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)
What is the etiology of reflux
- Decreased lower oesophageal sphincter tone
- Delayed gastric emptying
- Increased intra-abdominal pressure
- Motor failure of oesophagus - loss of peristalsis
- Iatrogenic injury to LOS
What are the classic GORD symptoms
Heartburn
Regurgitation
What are the predisposing and risk factors for GORD
- 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
What is a hiatal hernia
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
What are the diagnostic tests for GORD
Barium swallow
Endoscopy
Ambulatory 24hr pH monitoring
Oesophageal manometry
Whata re the principles of management of GORD
Eliminate the symptoms
Heal oesophagitis
Manage or prevent complications
Maintain remission
What are the non-pharmacological treatment approaches to GORD
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
Whata re examples of Proton pump inhibitors
Omeprazole
Lansoprazole
Rabeprazole
Pantoprazole
Esomeprazole
What are examples of H2-receptor Antagonists
Cimetidine
Ranitidine
Famotidine
Nizatidine
What is the MOA of PPI
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
What are the indications for PPI
- 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
What are the adverse effects of PPI
Hypomagnesemia
Increased risk of fracture
Headaches and skin rashes
Raised liver functio tests
Diarrhoea
Drowsiness and impaired concentration
Not reccomended in pregnancy
Drug interactions of PPI
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
What is the mechanism of action of H2-receptor antagonists
Reduces gastric acid secretion by reversibly blocking the action of histamine at the H2 receptors in the parietal cells of the stomach
What are the indications for H2 receptor antagonists
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
What are the adverse effects of H2-receptor antagonists
Headaches, dizziness, diarrhoea, musclular pain
CNS - confusion, hallucinations, slurred speech
Anti-adrogenic effect (esp cimetidine
- Impotence
- Gynaecomastia
- Galactorrhoea
Not reccomended in pregnancy
What are the drug interactions for H2-receptor antagonists
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
What are the MOA of Prostaglandins
Inhibits secretion of HCl, stimulates secretion of mucus and bicarbonate and causes vasodilation in the submucosa
What are the indications for Prostaglandins
NSAID induced ulcers
What are the adverse effects of Prostaglandins
Uterine contractions - contraindicated with pregnancy
Nausea and diarrhoea
What are examples of Mucosal protective agents
Sucralfate
Bismuth subcitrate
Aliginates
What is the MOA, Indications, Side effects and drug interactions of Sucralfate
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
What are the MOA and adverse effects of Bismuth subcitrate
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
What are the MOA and indications for Alginates
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
What are examples of antiacids
Aluminium hydroxide
Calcium carbonate
Magnesium
Sodium bicarbonate
What are the MOA of antiacids
Directly neutralise intraluminal acid
Reduce the delivery of acid into the duodenum after a meal
Doesnt block production
What is the MOA, Side effects, and indications for Aluminium hydroxide
Absorbs pepsin and binds bile
Forms complexes with phosphorous
Common side effect is constipation
Useful as a phosphate binding agent in renal impairment
What is the MOA, side effets and indications of Magnesium
Forms magnesium chloride in stomach
Side effects:
- Nausea and vomiting
- Diarrhoea
- ECG changes
- Respiratory depression
What is the MOA and side effects of Calcium antacides
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
