Acid Suppression Flashcards
Outline the process of acid secretion.
Parietal cells
On cell surface there are receptors:
- CCK-B (stimulated by gastrin; raise [Ca2+]i)
- M3 (stimulated by ACh, raise [Ca2+]i)
- H2 (stimulated by histamine, raise c.AMP)
Proton pumps on cannaliculi exchange H+ for K+
- luminal K+ stimulates dephosphorylation
- inactive in empty stomach
H+ reacts with CO2 to form HCO3-
HCO3- moves out of cannaliculi, Cl- moves in
= HCl secreted by cannaliculi into gastric lumen
note: blocking one receptor up-regulates the others
Gives some examples of proton pump inhibitors. Describe the pharmacokinetics of these drugs. Give examples of ADRs associated with their use.
e.g. omeprazole, lansoprazole
Pharmacokinetics:
- inhibits proton pump in parietal cell canaliculi (resultant reduction in [H+] causes increased secretion of gastrin via negative feedback)
- taken with meals (proton pump inactive when stomach is empty)
- delayed action (not all pumps are active all of the time; max efficacy is 2-3 days)
- de novo synthesis of new pumps following cessation of treatment takes 2-3 days
- available OTC
ADRs:
- GI disturbances = N&V, abdo pain, flatulence, diarrhoea, constipation
- concern that resultant increase in gastrin would cause gastrinomas (does not seem to be the case)
- ?increased risk of infection due to increased pH
- ?risk of osteoporosis due to reduced Ca2+ absorption
Give some examples of H2 receptor antagonists. Describe the pharmacokinetics of these drugs. Give some examples of ADRs associated with their use.
e.g. cimetidine, ranitidine
Pharmacokinetics:
- short half life (can be taken as required but BD dosage required to cover the whole day)
- still advisable to eat after dose
ADRs:
- cimetidine is a CYP450 inhibitor —> gynaecomastia, galactorrhoea, etc.
- GI disturbances
- headache
- dizziness
Outline the epidemiology of Helicobacter pylori and its involvement in peptic ulcers.
West: 1% increase/yr in risk of infection with H. pylori (but reduced risk of gastric cancer due to accidental eradication by antibiotics)
Asia/Africa: 60%-80% of 20yrs infected (increased risk of gastric cancer, but not seen due to reduced life expectancy)
Gastric ulcers: 75% are H. pylori +ve (H. pylori -ve cases include gastric cancer and NSAID-induced gastritis)
Duodenal ulcers: 96% are H. pylori +ve
Give some examples of antacids. Describe their mechanism of action.
e.g. Rennies, Gaviscon
Short-term relief
Buffer solutions e.g. HCO3-
Give an example of an alginate. What is their mechanism of action?
e.g. sucralfate
Form viscous layer above exposed GI surfaces
What is GORD? What are the differing principles in treatment in primary and secondary care?
Motility disorder (GOJ dysfunction preventing full closure)
Primary care = symptom control (STEP-UP)
- Lifestyle (reduce alcohol, alter position in bed)
- Antacids/alginates
- H2 receptor antagonists
- PPIs
Secondary care = healing of oesophagitis (increased risk of gastric cancer) + endoscopy (STEP-DOWN)
- PPI
- H2 receptor antagonists
- Antacids/alginates
- Lifestyle
What is the treatment for oesophagitis? What are some potential complications?
Acid suppression to promote healing and maintenance
Grade 1-2 = start on PPI, step down to H2 antagonist
Grade 3+ = long-term PPI to prevent complications
Complications:
- Barrett’s oesophagus
- peptic stricture
- GI cancer
What are the surgical options for treating peptic ulcers and GORD?
Peptic ulcers: highly selective vagotomy (removal of vagus nerves supplying the stomach —> achlorhydric stomach)
GORD: reinforce GOJ by using fundus of stomach
What is the pharmacological management of peptic ulcers?
- stop NSAIDs where possible
- 6wks of PPI/H2 receptor antagonists (92% heal)
- H. pylori eradication (Leicester): 1wk of clarithromycin + amoxicillin + lansoprazole
note: clarithromycin replaces metronidazole (high incidence of resistance in Leicester due to OTC use in S. Asia)
What are the aggressive and defensive factors affecting the gastric mucosa?
AGGRESSIVE FACTORS:
- acid
- Helicobacter pylori
- drugs (esp. NSAIDs —> vasoconstriction of arterioles in crypts —> ischaemia of gastric mucosa)
DEFENSIVE FACTORS:
- epithelial integrity
- cell replication and restitution (via supply of stem cells)
- mucous membrane barrier
- vascular supply
How can H. pylori be detected?
Urea breath test
Give examples of genetic disorders which may mimic GORD.
FAP - colorectal cancers
Zollinger-Ellison syndrome (gastrinoma) = severe peptic ulceration + gastric acid hypersecretion
Give some differentials for dysphagia. How may dysphagia be investigated?
INTRINSIC OBSTRUCTION:
- strictures (GORD)
- post-cricoid web
- foreign body
EXTRINSIC OBSTRUCTION:
- GIT tumour (progressive/unusual dysphagia +/- weight loss)
ACHALASIA:
- liquids more of a problem than solids
Investigations:
- OGD (2wk wait)
- barium swallow/video fluoroscopy (liquids problem)
- oesophageal pH (GORD)
Give some examples of complications of GORD.
Barrett’s oesophagus
Oesophageal strictures
GI disturbances
Increased risk of C. difficile in hospitalised patients
Chronic cough
