💊Pharmacology💊 - GORD Flashcards
(31 cards)
What is diclofenac?
A very potent NSAID
What is the advantage of giving drugs topically (e.g. diclofenac as a gel)?
Attempts to confine drug effect to target area
Systemic effects to some extent are, however, inevitable
How do NSAIDs reduce pain?
Reduce prostaglandin synthesis
What is the mechanism by which NSAID’s reduce pain and inflammation?
Inhibit cyclooxygenase (mainly COX-2 but also COX-1) - decreased PG synthesis
Prostaglandins sensitize nociceptors → their reduction leads to decreased pain perception
Anti-inflammatory action → ↓ vasodilation, ↓ leukocyte infiltration, ↓ swelling → improved mobility
What adverse effects do NSAIDs have in the stomach?
COX-1 inhibition → ↓ protective gastric mucosal prostaglandins
Leads to reduced mucus and bicarbonate secretion, ↑ gastric acid secretion
Increased risk of gastritis, peptic ulcers, and GI bleeding → presenting as upper abdominal pain
How does decreased PG synthesis lead to a reduction in pain?
PGs do not directly cause pain themselves, but they sensitise peripheral nociceptors mediators (bradykinin and histamine) which causes pain
How can oral naproxen and topical diclofenac lead to adverse effects?
2 NSAIDs is a lot, especially when this potent
Topical drugs can still have systemic effects - hence combination with oral naproxen and the resulting abdominal symptoms
What can be co-prescribed with an NSAID to reduce risk of gastrointestinal pain?
Proton pump inhibitors (PPIs)
What should be given to a patient with a form of arthritis?
NSAID
Co-prescribe PPI
What should be given to someone who is elderly and in chronic pain?
NSAID and PPI
What should be prescribed to someone in chronic pain with a high risk of GI adverse effects?
COX-2 selective NSAID (e.g. etoricoxib, celecoxib)
PPI
What should be prescribed to someone in chronic pain with a moderate risk of GI adverse effects?
Specific COX-2 inhibitor
OR
NSAID + PPI
What should be prescribed to someone in chronic pain with a low risk of GI adverse effects?
Non-selective NSAID
What is the go-to treatment for peptic ulcer disease with no active bleeding and H. pylori negative?
For patients on NSAID, stop NSAID where possible.
Offer full-dose PPI therapy for 4 to 8 weeks
Several PPI options, one of which is omeprazole:20 mg orally once daily
What is the mechanism of action of PPIs?
Target: H⁺/K⁺-ATPase (proton pump) in gastric parietal cells.
Action: Irreversible inhibition → prevents final step of gastric acid secretion.
Effect: ↓ HCl production → increased gastric pH → ulcer healing & symptom relief.
What are the most notable potential adverse effects of NSAIDs?
Risks vary among individuals and are influenced by dose and duration of use
Cardiovascular and renal complications (uncommon)
All NSAID use associated with small increase risk of thrombotic events
Why should PPIs not be used in patients with osteoporosis?
Proton pump inhibitors are known to increase the risk of fracture
Theory - Change in pH induced by PPIs might be responsible for a reduction in absorption and decrease in calcium available for bone
What should be prescribed to patients with osteoporosis instead of a PPI?
Histamine (H2) receptor antagonist
What is the mechanism of action of Histamine (H2) receptor antagonists?
Target – Histamine H2 receptor
Location – Cell surface of the parietal cell
Effect – ↓ acid production from parietal cell
Histamine receptors ↑ acid production via cAMP dependent activation of H+/K+ ATPase
↓ acid production = ↓ corrosive nature of environment
What is the primary mechanism of action of NSAIDs?
Inhibit COX enzymes, and so prostaglandin synthesis
What is the primary mechanism of action of Proton pump inhibitors
Irreversible inhibitors of H+/K+ ATPase in gastric parietal cells
Inhibit gastric acid secretion by up to 90%
What is the primary mechanism of action of Histamine (H2) receptor antagonists?
Competitive antagonists of H2 histamine receptors
Inhibit stimulatory action of histamine released from enterochromaffin-like (ECL) cells in the gastric parietal cells
Inhibit gastric acid secretion by up to 60%
What is the primary mechanism of action of paracetamol?
Still unclear
Inhibits a peroxidase enzyme involved in converting arachidonic acid → prostaglandins - inhibition is weaker and reversible, especially in high-peroxide environments (e.g., inflammation)
Activates 5-HT₃ receptors, enhancing descending pain inhibition from the brainstem
Inhibits reuptake of endogenous cannabinoids, increasing CB receptor activation
What is the drug target of NSAIDs?
COX enzyme
