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NSAIDs on CV conditions
Mechanisms and Efficacy
Hasom (Rachel) Lee, Rong Shan Liu, Stephanie Li, Joshua-Ryan Wye-Yan Heung
PHM142 Fall 2015Coordinator: Dr. Jeffrey HendersonInstructor: Dr. David Hampson
What are NSAID’s?
Non-Steroidal Anti-Inflammatory Drugs
Common over the counter drug
Analgesic (painkiller), antipyretic (lower fevers), anti-inflammatory properties
http://www.mcbuzz.com/2011/seo-101-how-to-choose-keywords-a-lesson-from-bayer-aspirin/http://dccrossfit.com/2014/07/ibuprofen/http://www.cvs.com/shop/health-medicine/pain-fever/non-aspirin-pain-relief/aleve-all-day-strong-naproxen-sodium-tablets-220-mg-skuid-367001
NSAID
Traditional Uses
Osteoarthritis
Low back pain
Headache
Rheumatoid Arthritis
Mild pain relief
http://www.heartmdinstitute.com/health-topics/alternative-medicine/grounding-earthing/106-grounding-healthy-heart http://robertsontrainingsystems.com/blog/should-we-train-people-in-pain/
Aspirin for Cardiovascular Therapy
Anti-thrombotic drugs that prevent cardiovascular events
Dose: 75-325mg/day
Most common: 81mg/day
Adverse Reactions:
GI damage (major bleeding)
Associated with higher doses
Economic implications
http://samadimd.com/health-politics/aspirin-now-recommended-for-patients-at-high-risk-for-heart-disease
Mechanism of NSAIDs
Phospholipid
Arachidonic Acid
Prostaglandin H2
PGE2TXA2
COX (PGH synthase)
NSAID
NSAID Mechanism
Platelet Phase- Normal State
platelet
endothelium
Factor VIII and von Willebrand Factor (vWF)
Platelet Phase - Adhesion
platelet
exposed collagen
Platelet Phase - Activation
Activated platelet releases:
Fibrinogen (forms a mesh around the platelet as the scaffold for platelet binding)
ADP (binds to P2Y, increase in intracellular [Ca2+])
COX-1 synthesizes TXA2 (binds to thromboxane-prostanoid receptor)
Result:
Platelet shape change (disc to round with extensions)
Maturation of GPIIa/IIIa (fibrinogen receptor)
Net Result: platelet plug formation
COX-1 and COX-2
Clinical Evidence: Aspirin Therapy in the Secondary Prevention of Cardiovascular Disease
Study design: Meta-analysis
Number of studies included: 16 secondary prevention studies
Population: 17 000 individuals at high average risk
Results:
Decreased in risk of recurrent major coronary events: 20%
Decreased in risk of recurrent stroke: 19%
Adverse Effects to Consider in Aspirin Therapy● Aspirin therapy may not be right for you; always
consult a doctor first
● Possible adverse effects:
- Damage to the protective mucous layer in the GI tract
- Lead to increased risk of GI ulcers and bleeding
- How?
- No formation of prostaglandins
- Prostaglandins modulate many aspects of mucosal defense
inhibition inhibition
Comparison of NSAIDs (Aspirin) and Warfarin
Anticoagulant, extrinsic pathway, vitamin k antagonist
Indirectly targets clotting factor II, VII, IX, X
By competitively inhibiting vitamin K epoxide reductase and Vitamin K quinone reductase -> decrease in active vitamin KH2
Adverse effects : hemorrhage, necrosis of soft tissue, teratogenicity (birth defects)
Reverse adverse effects: stop giving warfarin, give vitamin K and prothrombin
Do not consume with NSAIDs
No magic bullet, different drugs for different patients
Why We (Future Pharmacists) Care? Many NSAIDS - such as aspirin - are over-the-
counter drugs
Help prevent people from purchasing aspirin to treat CV events unless a doctor have recommended it to them
Helps reduce the chance of adverse effects
Summary
NSAIDs: Non-Steroidal Anti-Inflammatory Drugs
NSAIDs exert their anti-inflammatory and anti-thrombotic effect through COX inhibition
Aspirin acetylates Ser 530 on COX. This covalent modification permanently blocks the enzyme.
Clinical evidence that support the use of daily aspirin associated with secondary prevention cardiovascular
Adverse effects of aspirin therapy: mucosal injury and bleeding
References
Antithrombotic Trialists' (ATT) Collaboration. (2009). Aspirin in the primary and secondary prevention of
vascular disease:collaborative meta-analysis of individual participant data from randomized trials. Lancet.
373: 1849-1860.
Casado-Arroyo, R., Sostres, C., & Lanas, A. (2013). Optimizing the use of aspirin for cardiovascular
prevention. Drugs. 73(8): 803-14.
Dorsam RT, Kunapuli SP. (2004). Central role of the P2Y12 receptor in platelet activation. J Clin Invest.
113(3):340-345.
Flower RJ. (2003). The development of COX2 inhibitors. Nat Rev Drug Discov. 2(3):179-191.
Gasparyan, A. Y., Watson, T., & Lip, G. Y. H. (2008). The role of aspirin in cardiovascular prevention. Journal of
the American College of Cardiology. 51(19): 1829-1843.
Iwamoto J, Yoshifumi S, Honda A, & Matsuzaki Y. (2013). Clinical features of gastroduodenal injury associated
with long-term low-dose aspirin therapy. World J Gastroenterol.19(11): 1673–1682.
Mayhew, M.S. (2010). Aspirin for preventing cardiovascular damage. Journal for Nurse Practitioners. 6(2):
147-148.
Sadler JE. (1998) Biochemistry and genetics of von willebrand factor. Annu Rev Biochem. 67:395-424.
(1994). Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in
Atrial Fibrillation II Study. Lancet. 343: 687-91.