Pharmacology of GORD Flashcards
What is the patient’s problem?
Abdominal pain
Pain from osteoarthritis limiting daily activities
What is the therapeutic objective for the patient?
Treat abdominal pain whilst maintaining pain relief for osteoarthritis ensuring OA pain is not interfering with daily living
Lessen pain to help sleep
Explain the mechanism of action of naproxen?
Target: COX enzymes (non-selective, inhibits COX1 and COX2)
Location: Peripheral nociceptive nerve endings (analgesia)
Effect: COX produces prostaglandins. PGs to no directly cause pain themselves but they sensitise peripheral nociceptors (bradykinin and histamine) which causes pain.
NSAIDS inhibit COX, pain receptors do not get sensitised and are not stimulated
Explain the mechanism of action for the adverse effects?
Target: COX I enxyme
Location: Gastric mucosal cells
Effect: Inhibition PG production and hence inhibition of PG mediated protection of gastric mucosa
Less protection of mucosa from acid
How do NSAIDS indirectly reduce pain?
Indirectly:
PGs mediate inflammation and hence NSAIDS will reduce inflammation
What is the role of PGs in the stomach?
Increase bicarbonate secretion
Increased Mucus production
Increases Blood flow
What was the miscommunication error?
Patient should not have been on both oral naproxen and topical diclofenac
What changes should the GP made to his prescription?
Stop the gel
Switch to ibuprofen
Stop NSAIDs complete
The patient is diagnosed with peptic ulcer, no active bleeding and H. pylori negative. What is the first line treatment?
Offer full-dose PPI therapy for 4 to 8 weeks to patients who are H pylori negative
The patient is diagnosed with peptic ulcer, no active bleeding and H. pylori negative. What is the first line treatment?
Where possible stop NSAID
Offer full-dose PPI therapy for 4 to 8 weeks to patients who are H pylori negative
What is the mechanism of action of PPIs?
Target: Irreversible inhibitors of H+/K+ ATPase in gastric parietal cells.
Location: Parietal cell (secretory membrane)
Effect: Inhibit basal and stimulated gastric acid secretion by >90%.
What is the key take home message when comparing the guidance for omeprazole treatment (and PPIs in general) with the data in figure 1?
Disconnect between treatment recommendations and what is happening in practice
Almost everyone is at the highest dose and still on it after 12 weeks
At 12 months around 40% of people are on their PPI
NB: Data refers to all PPI prescription e.g. for indigestion of dyspepsia
Why are PPIs not stopped appropriately?
Stopping causes rebound acid secretion
Causes same symptoms
Reach for PPIs
Why would he have been give a H2 antagonist if he had osteoporosis?
PPIs increase risk/worsen osteoporosis putting him at risk of fractures
H2 antagonist do not carry this same effect but are also used to treat peptic ulcer disease
Although slightly less effective
What is the mechanism of action of histamine?
Target: Histamine H2 receptor
Location: Cell surface of the parietal cell
Effect: Decreased acid production from parietal cell
Histamine receptors increase acid production via cAMP dependent activation of H+/K+ ATPase.
The damaged mucosal barrier leaves stomach wall expose to acid
Lower acid production lowers the corrosive environment
