And Their Effect on Renal Function
1 Definition of the drugs & their categories
The inflammatory response & inhibition 2
3 Renal effects of inhibition
Nonsteroidal Anti-Inflammatory Drug
• A therapeutic agent which relieves pain and
fever by inhibiting the inflammatory
• These drugs are available over the counter
and by prescription.
• Some common examples include aspirin,
ibuprofen, Celebrex, and less commonly
Categories of NSAIDs
• There are two major categories for non-
steroidal anti-inflammatory drugs
• The first is non-selective anti-inflammatory
• The second is selective anti-inflammatory
drugs, COX-2 inhibitors.
The Inflammatory Response
• The body’s response to a stimuli which
causes pain and/or tissue damage.
• Physiologically capillaries become “leaky”
• The response is initiated by the chemical
• Prostaglandins were isolated from human
semen in 1936 by Ulf von Euler. He named
them Prostaglandins because he believed
they came from the prostate gland.
• The Swedish scientist received the Nobel
Prize in medicine in 1970 for this work.
• Since his work in this area it has been
determined that they exist and are
synthesized in almost every cell of the body.
• They are synthesized in the same cell on
which they act.
Biosynthesis of Prostaglandins
• The goal is to inhibit the biosynthesis of
prostaglandins in order to relieve the
symptoms caused by the inflammatory
• Prostaglandins are synthesized from
arachidonic acid in a pathway mediated by
the Cyclooxygenase enzymes.
COX Expression Function Inhibitors
organ pain, platelet
constitutively function, stomach NSAIDs including
COX-1 throughout the body aspirin
Inducible: inflammation, NSAIDs, COX 2
Inducible and pain, fever inhibitors including
COX-2 constitutively in brain, Constitutive: synaptic celecoxib
plasticity (Celobrex )
Constitutively, high in pain pathways, not acetaminophen
brain, heart inflammation pathways some NSAIDs
Effect of Prostaglandins on Renal Function
• Decreased reabsoprtion of chloride in the
proximal tubule. The proximal tubule re-
absorbs about 60% of water and solutes.
• Vasoconstriction via their effect on the anti-
diuretic hormone (ADH).
Inhibition of Prostaglandin Synthesis
• When COX-2 inhibitors are administered
absorption is altered in the proximal tubule.
• Also, because they enhance the effect of
ADH, vasoconstriction occurs reducing the
glomelular filtration rate (GFR).
• Any abrupt reduction in GFR can result in
acute renal failure.
No Need for Alarm
• For a normal healthy person, NSAIDs are
not going to cause renal failure. The kidney
adapts very well to changes in GFR in
• NSAIDs become a problem when they are
used for very long terms, and in patients who
already have a decreased GFR caused by
high blood pressure, congestive heart failure,
or chronic renal disease.