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Copy of HIghlights of NSAIDs Misuse

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Christian Oliver Marzo

on 5 July 2013

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Transcript of Copy of HIghlights of NSAIDs Misuse

Highlights of NSAIDs Misuse
Mayyada Wazaify, PhD
Analgesics, Anti-inflammatory, Antipyretic
Inhibit COX1 & COX2
Some are selective COX2-Inhibitors

Treatment of:

e.g. sport injuries, dysmenorrhea
e.g. rheumatoid arthritis
There is NO BEST NSAID for ALL!
Choice requires balance of: efficacy, cost effectiveness and other personal factors
All NSAIDs, including aspirin, are about equally efficacious with a few exceptions:
tolmetin seems not to be effective for gout, and aspirin is less effective than other NSAIDs (eg, indomethacin) for ankylosing spondylitis.

E.g. the gastrointestinal and renal side effects of ketorolac limit its use.
Indomethacin, tolmetin, and meclofenamate

the greatest toxicity,
while salsalate, aspirin, and ibuprofen are least toxic.

Allergy: urticaria, edema, SOB, shock
Side Effects: N&V, C&D, edema, HA, dizziness
Most serious: Nephrotoxicity, Gastrotoxicity, Cardiotoxicity, asthma exacerbation, Reye’s Syndrome (aspirin)
Problems associated with NSAIDs
Take Home Messages!
In a recent report of rheumatoid arthritis patients receiving NSAIDs for at least 3 months with or without concurrent therapy with bisphosphonates, GI ulcers occurred in 17% of patients on NSAIDs without concurrent bisphosphonates, and in 31% of patients receiving bisphosphonates with NSAIDs.

Conversely, some other studies looking at upper GI bleeding or other GI adverse effects did not find an increase in GI toxicity when bisphosphonates were combined with NSAIDs, compared with NSAIDs alone. Explain !!!
For patients with low or moderate gastrointestinal risk but high cardiovascular risk (e.g., history of cardiovascular event, diabetes, hypertension, hyperlipidemia, obesity) taking aspirin, choose naproxen. These patients will also require a proton pump inhibitor or misoprostol.

Patients with high risk of both gastrointestinal and cardiovascular risk should not receive an NSAID (including celecoxib).
[Evidence level A; high-quality meta-analyses].
Indomethacin the highest risk of NSAIDs-induced renal ischemia, where as
aspirin the lowest risk.
Naproxen, ibuprofen, piroxicam and diclofenac are considered intermediate
Sulindac may offer a “renal sparing” effect. Sulindac is a prodrug that is converted to its active sulfide metabolite by the liver and then becomes reversibly oxidized back to its parent compound in the kidney; renal prostaglandin synthesis is essentially unaltered by sulindac. Cases of sulindac-induced renal dysfunction have been reported when the drug was administered to patients with cirrhosis and ascites.
Renal Risk
In patients on long term NSAIDs without acute or chronic renal failure, subclinical renal dysfunction such as reduced Clcr and impaired urine concentrating ability has been shown to be present

Although this sub-clinical dysfunction is reversible on withdrawal of NSAIDs, some reports have suggested a persistent residual dysfunction.

Even with a wide range of NSAIDs at our disposal, a renal safe NSAID is yet to be discovered.
Mechanism: NON-SPECIFIC block of cyclooxegenase leading to vasoconstriction and reversible mild renal impairment in volume contracted states (those with CHF, liver disease, the elderly, or dehydrated patients).

When unopposed, this may lead to acute tubular necrosis and acute renal failure
Interstitial nephritis w/wo nephrotic syndrome
Acute RF ------>>>> CRF
NSAIDs: 2nd most common cause of GU after H.pylori infection

Different NSAIDs confer different gastrointestinal risk.

Risk is high with some of the longer acting NSAIDs (e.g., piroxicam [57 hours], ketorolac [up to ten hours], and sustained-release formulations), perhaps due to longer mucosal exposure.

Ibuprofen seems to have the lowest risk of gastrointestinal events. This might be because low doses are typically used, or because it has a short half-life (two hours)
Gastric Erosion and Bleeding

Dangers of prophylactic NSAIDs use
Many athletes use NSAIDs prophylactic ally and presumably for prolonged periods of time blocking pain before it occurs!

Sydney 2000 Olympics: ¼ of players reported using NSAIDs before matches
FIFA: 2006 World cup > 10% of players used NSAIDs before every match

Prophylactic use by atheletes

Overuse toxicities: either dosage, frequency or duration

Disregard proper administration, cautions, contraindications and interactions
NSAIDs Misuse
‘to make bad use of…’

The use of OTC medicines for a non medical reason. e.g. to achieve high or lose weight.

Example: opioids, antihistamines, laxatives
Misuse Abuse
‘to use incorrectly…’
(Webster Dictionary, 2002)

The use of OTC medicine for a medical purpose, but to use it incorrectly in terms of dosage or duration of use.
Any medicine can be abused
94% know that all forms of oral NSAIDs should be taken with food,
35% know that NSAIDs can cause GIT upset,
22% know that NSAIDs can cause GIT ulcerations,
and only 11% know that NSAIDs can adversely affect kidneys function.
212 patients interviewed in 4 pharmacies
Diclofenac was most used (61%) followed by Ibuprofen (26%)
Upon getting NSAIDs from pharmacies only 16% of users received counseling from a pharmacist, 9% received their counseling from other sources (neighbor, friend, leaflet), and 14% did not receive any counseling.
Jordanian population and NSAIDs
Use of OTC analgesics and NSAIDs
3443 males and females in the USA
Almost everyone (97.0%) had taken OTC analgesic/NSAIDs
Only 28% read label last time they took pills
66% Never read label
American College of Emergency Physicians (ACEP) Survey (2009):
Many patients taking bisphosphonates, such as alendronate, ibandronate, and risedronate, for osteoporosis may also be taking various nonsteroidal antiinflammatory drugs (NSAIDs) for arthritis or other disorders. Whereas both of these drug classes can separately cause gastrointestinal (GI) toxicity, it is important to determine if the combination can have additive negative effects on the GI tract.
NSAIDs seem to increase the risk of cardiovascular events (heart attack, stroke, death) to varying degrees, even in healthy people.


Selective COX-2 inhibitors: Highest risk
The selective COX-2 inhibitor celecoxib (Celebrex) is associated with about a 20% lower risk of bleeding compared to traditional NSAIDs.
But this benefit is negated in patients who take aspirin concomitantly.
Furthermore, celecoxib does not seem to be safer than non-selective NSAIDs past six months of use.
Trends among users of OTC pain relievers
American College of Emergency Physicians (ACEP) Survey:

physiologic production of prostanoids “house-keeping enzyme”- regulates normal cellular processes (gastric epithelial cytoprotection, platelet aggregation, vascular homeostasis and kidney function)
elevated production of prostanoids in that occurs in sites of disease and inflammation (e.g. oxidative stress, injury, ischemia, seizures, neuro-degenerative diseases)
NSAIDS are effective and safe drugs if used correctly
They are liable for misuse which may cause different toxicities
There is NO ONE BEST NSAID for all
Choice depends on balanace between safety, efficacy and cost-effectiveness
NSAID-Drug Interactions
NSAID# Antihypertensive drugs
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