Pharmacology 18 - NSAIDs Flashcards
1
Q
How widely used are NSAIDs in England?
A
- Widely prescribed (16 million annual prescriptions)
- 6% patients experienced possible adverse drug reactions
- Available over counter
2
Q
What are the risks of NSAIDs?
A
Increased risk of GI and CVS deaths
3
Q
What are NSAIDs used for?
A
- Relief of mild to moderate pain (toothache, headache, menstrual pain) ANALGESIC
- Reduction of fever (influenza) ANTIPYRETIC
- Reduction of inflammation (rheumatoid arthritis, osteoarthritis, soft tissue injuries, gout) ANTI-INFLAMMATORY
4
Q
How do NSAIDs work?
A
- Inhibit prostaglandin and thromboxane synthesis
- Lipid mediators derived from arachidonic acid
- COX enzymes are inhibited (arachidonic acid to prostaglandin H2 which is later converted to thromboxane A2 and prostaglandins D2, F2a and E2)
- Widely distributed
- Receptor mediated
5
Q
List the prostanoid receptors. Describe their qualities.
A
- DP1, DP2, EP1, EP2, EP3, EP4, FP, IP1,IP2, TP
- Naming based on agonist potency
- Prostanoids have both G protein-dependent and -independent effects
- Physiological and pro-inflammatory
6
Q
List the unwanted actions of PGE2
A
- Increased pain perception
- Increased body temperature
- Acute inflammatory response
- Immune response
- Tumorigenesis
- Inhibition of apoptosis
7
Q
How does PGE2 increase pain?
A
- Lowers threshold for pain by sensitising nociceptors, both acutely and chronically
- cAMP mediated.
- Activates P2X3 nociceptors in the periphery.
- During inflammation, there is increased PGE2 production and increase in cAMP
- Also activates Epac (exchange pathway activated by cAMP) pathway to recruit more nociceptors
- May also affect neurones in the spine, or increase beta-endorphin in the spine
8
Q
List the desirable physiological actions of PGE2
A
- Bronchodilation
- Renal salt and water homeostasis
- Gastroprotection
- Vasoregulation (can cause dilation and constriction depending on receptors activated)
9
Q
Why should asthmatics not take NSAIDs?
A
- 10% asthma patients experience worsening symptoms with NSAIDs
- COX inhibition favors production of leukotrienes (bronchoconstrictors)
10
Q
Compare actions of PGE2 and NSAIDs in kidney
A
- PGE2 increases renal blood flow
- COX-1 and COX-2 are distributed throughout the kidney
- NSAIDs can cause toxicity via constriction of afferent renal arteriole, reduction in GFR and renal artery flow
11
Q
What is the role of PGE2 in gastric cytoprotection?
A
- Downregulates HCl secretion
- Stimulates mucus and bicarbonate secretion
- Therefore, blocking PGE2 can increase risk of ulceration
12
Q
List the unwanted cardiovascular effects of NSAIDs
A
- Vasoconstriction
- Salt and water retention
- Reduced effect of antihypertensives
- Selective COX2 inhibitors have higher risk of cardiovascular disease (increase probability of atherosclerosis, heart failure, and BP)
13
Q
Describe risk benefit of NSAID use
A
Analgesic use
- Usually occasional and low dose
- Relatively low risk of side effects
Anti-inflammatory use
- Often sustained use
- Higher doses
- Relatively high risk of side effects (older patients aren’t as good at metabolising drugs)
14
Q
List the strategies to limit GI side effects of NSAIDs
A
- Topical application (muscle pain)
- Use COX2 inhibitors instead (although there is risk of CV events)
- Minimise NSAID use in patients with history of GI ulceration
- Treat H pylori if present
- If NSAID essential, administer with omeprazole or other proton pump inhibitor
- Minimise NSAID use in patients with other risk factors and reduce risk factors where possible (e.g. Alcohol consumption, anticoagulant or glucocorticoid steroid use)
15
Q
List the newer NSAIDs being developed
A
- Duel COX and LOX inhibitors (however cause liver injury)
- Nitric oxide or hydrogen sulphide releasing NSAIDS (NO and H2S are protective to GI and CVS)
- May be safer
