non-steroidal anti-inflammatory drugs (NSAIDs)

1. NSAIDs
By: ph Abeer Abd Elrahman

2. What are NSAIDs and how do they
work?
• They are anti-inflammatory drugs not
having a steroid nucleus (not cortisols).

3. NSAIDs mechanism of action:

5. Cox 1&2
•
• only COX-1 produces prostaglandins that
activate platelets and protect the stomach
and intestinal lining.
• It also causes afferent arteriolar VD
increasing GFL and thus salt and water
execretion.

6. Non-selective NSAIDs:
• Asprin - Diclofenac Na / k -Ibuprofen
• Ketoprofen
• Mefenamic acid (common with menstrual disorders)
• Indomethacin
• Ketrolac (strong NSAID common with kidney problems)
• Naproxin (only NSAID safe with cardiac patients)
• piroxicam

7. important side effects are:
• Stomach Ulcers
• prolonged bleeding after injury or surgery.
• kidney failure (primarily with chronic use).
• NSAIDs can cause salt & fluid retention
which can lead to edema, which is why
they are CI with hypertension.
• liver failure.

9. Selective cox II inhibitors
• the COX-2 inhibitors only block the COX-
2 enzyme.
• This shifts the pathway to increasing COX-1
activity.
• COX-1 produces prostaglandins that protect
the stomach and promote blood clotting.
• Therefore, they’ve been associated with a
higher risk of stroke and heart attack.

10. Examples for Selective cox II
inhibitors
• Celecoxib (celebrex)
• Meloxicam (mobitil / anticox-II)
• tenoxicam

11. Paracetamol (acetaminophen)
• Paracetamol is a simple analgesic and an
antipyretic.
• Despite it acts by inhibition of (COX-3),
unlike other (NSAIDs), paracetamol has
been demonstrated not to reduce tissue
inflammation.

13. Precautions:
• Use of aspirin in children and teenagers
under 18 with chickenpox or influenza has
been associated with the development of
Reye's syndrome, a serious and
sometimes fatal liver disease.

14. • Note: people with asthma should not take
any NSAID as they shift the pathway to
LOX producing more leukotriens which
worsens the case.
• Solution: paracetamol

15. NSAIDs effect on GI bleeding:

16. • NSAIDs increase the risk of potentially
fatal, stomach and intestinal adverse
reactions (for example, bleeding, ulcers,
and perforation of the stomach
or intestines.
• Solution:
1) Selective cox ll
2) Give NSAID with PPI

17. Renal toxicity
• sodium retention.
• increased BP and weight.
• hyperkalemia, and acute renal failure
• peripheral edema.

18. Pregnancy and lactation:
• Paracetamol is the most safe analgesic
and antipyretic.
• However, all NSAIDs should not be taken
after 29 weeks of pregnancy as these
medicines may cause serious harm to the
unborn baby.

19. Use with anticoagulant
• NSAIDs are strong displacers especially
(ibuprofen)

20. • Co-administration of NSAIDs especially
ibupofen with anticoagulants should be
avoided due to increased risk of bleeding.

21. NSAIDs and hypertension
• As mentioned previously NSAIDs will
cause salt and water retention leading to
increase in BP.

22. If necessary for hypertensive
patient to take NSAID:
• Paracetamol is the DOC.
• It is important to avoid use of any ACEI
(lisniopril, capropril..,) and ARBs
• As it causes reducing their anti-
hypertensive effects, as well as the
potential acute renal damage.

23. Other antihypertensive
medications
• NSAIDs have been found to interact with
β-blockers (eg, propranolol, oxprenolol,
atenolol), attenuating their
antihypertensive effects.
• With little or no effect on ca channel
blockers (verapamil and amlodipine).

24. NSAIDs and diabetes:
• NSAIDs inhibit ATP-sensitive potassium
channels (KATP) and thus increase insulin
secretion.
Insulin dependent

25. Non-insulin dependent
• Sulfonylureas (glibenclamide, gliclazide,
tolbutamide,..etc )

26. • Sulfonylureas are commonly listed as
having protein-binding drug interactions.
• NSAIDs (ibuprofen) are strong displacers
of sulfonylurea thus increasing the active
drug available.
• This would result in a reduction of plasma
glucose and possibly hypoglycemia

27. NSAIDs used in liver impairment
• Ibuprofen has the highest liver
safety profile among NSAIDs and showed
no severe liver injury in larger studies.
• Along with paracetamol (2-3g/d) and
aspirin.

28. References:
• https://www.youtube.com/watch?v=I1uHkbocRCw
• https://www.medicinenet.com/nonsteroidal_antiinflammat
ory_drugs/article.htm
• https://www.rxlist.com/cox-2_inhibitors/drug-class.htm
• https://www.drugs.com/drug-class/cox-2-inhibitors.html
• https://slideplayer.com/slide/6881232/
• http://tmedweb.tulane.edu/pharmwiki/doku.php/nsaid_sid
e_effects
• https://lecom.edu/nsaids-and-ace-inhibitors/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508078/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508078/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997980/