Article 16. A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly. Aging and Disease 2018. (fini)

Question 1

Quel est le rôle général des AINS?

Answer 1

• In addition to their anti-inflammatory effect, NSAIDs have antipyrexic and analgesic properties.
• These medications inhibit Cyclooxygenases (COXs) enzymes, which are rate-determining enzymes for prostaglandins and other prostanoids synthesis, such as thromboxanes.

Question 2

Quel est la différence entre Cox-1 et Cox-2?

Answer 2

Pharmacodynamics and Pharmacokinetics of NSAIDs

• The major therapeutic actions of NSAIDs are primarily enacted by their ability to block certain prostaglandins (PGs) synthesis through the cyclooxygenase enzymes (COX-1 and COX-2) inhibition.
• COX-1 produces prostaglandins and thromboxane A2 which control mucosal barrier in GI-tract, renal homeostasis, platelet aggregation and other physiological functions.
• COX-2 produces PGs that related to inflammation, pain and fever.
• COX-1 is expressed in normal cells, while COX-2 is induced in inflammatory cells [6-8].
• COX-2 inhibition most likely represents the desired effect of NSAIDs’ anti-inflammatory, antipyretic and analgesic response; while COX-1 inhibition plays a major role in the undesired side effects such as GI and renal toxicities

Question 3

Quels sont les effets secondaires des AINS ?

Answer 3

Question 4

Qui métabolise normalement les AINS?

Answer 4

• NSAIDs are highly bound to plasma proteins. NSAIDs are usually metabolized in the liver and excreted in the urine. Common NSAIDs drug have a variable half-life; they can be anywhere from 0.25-0.3 hours such as aspirin or 45-50 hours such as piroxicam

Question 5

Recommandation importante

The American Geriatric Society updated the Beers Criteria in 2015. They recommended that the chronic use of all NSAIDs, including high dose aspirin, should be avoided because of the risk of gastrointestinal bleeding.

High-risk groups include:

• age above 75 years
• corticosteroid use
• current use of anticoagulants or antiplatelet agents

Question 6

Quels sont les effets des AINS sur les reins?

Answer 6

• Renal side effects of NSAIDs are considered uncommon.
• NSAIDs cause inhibition of prostaglandin and thromboxane synthesis leading to renal vasoconstriction and consequently reduced renal perfusion and aberrant renal function.
• Clinical manifestations of NSAID induced nephrotoxicity includes electrolyte imbalance such as hyperkalemia, reduce glomerular filtration rate, nephrotic syndrome related to drug induced minimal change disease, chronic kidney disease, acute interstitial nephritis, sodium retention, edema, and renal papillary necrosis
• The American Geriatric Society (AGS) recommends that all NSAIDs should be avoided in patients with stage IV and V CKD (creatinine clearance less than 30 mL/min)

Question 7

Quels sont les effets des AINS sur le système gastro-intestinal ?

Answer 7

• NSAID use increases the risk of GI bleeding in the elderly four folds
• The mechanism underlying NSAIDs induced GI adverse effects lies in the fact that these medications inhibit prostaglandin synthesis, causing weakening of the protective GI mucosal barrier, predisposing one to bleeding.

Solution possible:

• NSAIDs-induced gastroduodenal ulcers can be prevented by the use of GI protective agents, such as, Misoprostol, H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI)
• Another strategy to minimize GI adverse effects is to substitute nonselective NSAIDs with COX-2 selective NSAIDs. Multiple studies have revealed that COX-2 inhibitors, such as lumiracoxib, celecoxib, and rofecoxib, caused less damage to GI mucosa compared to non-selective NSAIDs. However, there are increase risks of cardiovascular adverse effects with the use of COX-2 inhibitors

Question 8

Quels sont les effets des AINS sur le système cardiaque?

Answer 8

Since rofecoxib and valdecoxib, were withdrawn from market in 2004 and 2005 respectively, due to adverse cardiovascular events such as edema, myocardial infarction, thrombotic events, stroke and hypertension, concerns regarding all COX-2 inhibitors potential for cardiovascular adverse effects have been raised

Question 9

Quels sont les effets des AINS sur la tension?

Answer 9

• Non-selective NSAIDs are known to attenuate the antihypertensive effect of some specific blood pressure medications, such as ACE inhibitors.
• However, no similar effect was observed with COX-2 inhibitors
• In general, NSAIDs can increase blood pressure by 5 mmHg in average.

Mécanisme:

• related to the inhibition of prostaglandin synthesis, which leads to an interference of renal vasculature which manipulates the regulation of blood pressure. In addition, NSAIDs themselves can cause elevation of serum aldosterone, leading to sodium retention and hypertension

Question 10

Chez les personnes âgés, les AINS aiderait l‘incontinence urinaire

They found significant improvement in term of frequency and volume of nocturia. This finding highlights the treatment benefits of NSAIDs in overactive bladder.

Question 11

Est-ce que les AINS peuvent augmenter le risque de faire un ACV ?

Quel est celui qui aurait moins de risque ?

Answer 11

OUI

• NSAIDs can increase the risk of stroke, and the risk varies with different types of NSAIDs
• Population-based case-control study by Garica-Posa et al. revealed that certain NSAIDs including diclofenac (OR = 1.53; 95% CI, 1.19–1.97) and aceclofenac (OR = 1.67; 1.05–2.67) increase the risk of stroke. However, they found no association with naproxen or ibuprofen [59].
• Compared with naproxen, the least harmful NSAID for cardiovascular outcomes, valdecoxib was associated with the highest risk of stroke (adjusted HR 1.41, 95% CI 1.04, 1.91).

There are several potential mechanisms of NSAIDs associated with stroke. NSAIDs can interfere with vasoconstriction and sodium excretion causing hypertension, a major risk factor of stroke. Also, these medication can induce platelet aggregation and increase thrombus formation

Question 12

Les AINS ont des interractions médicamenteuses. Avec quelles médicaments ?

Answer 12

Question 13

Conclusion

In order to provide comprehensive care of the elderly, knowing the mechanism of action, current guidelines, adverse drug reaction, and the pleiotropic effects of common drugs is important. NSAIDs are one of the most commonly prescribed drugs in the elderly. These medications should be prescribed for the shortest duration possible in the lowest effective dose, and with careful surveillance to monitor GI, renal, and cardiovascular toxicity. This is especially true for elderly patients who are very susceptible to the side effect profiles of NSAIDs. There is some evidence to support the role of NSAIDs in dementia prevention, improve muscle performance, improve urinary incontinence, and decrease the risk of some specific cancers. However, NSAIDs can also increase the risk of falls, increase geriatric psychiatric events, and increase the risk of stroke. Thus, these risks and benefits should be balanced carefully in individual patients to optimize overall outcomes, especially in the elderly.