2. INTRODUCTION.
โข Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug
class which reduces pain, decreases inflammation, decreases fever, and prevents
blood clots. Side effects depend on the specific drug, its dose and duration of use, but
largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack,
and kidney disease.
3. โข The term non-steroidal distinguishes these drugs from steroids, which
while having a similar eicosanoid-depressing, anti-inflammatory action,
have a broad range of other effects. First used in 1960, the term served
to distance these medications from steroids, which were particularly
stigmatized at the time due to some connotations with anabolic
steroid abuse.
โข NSAIDs work by inhibiting the activity of cyclooxygenase enzymes
(COX-1 or COX-2). In cells, these enzymes are involved in the
synthesis of key biological mediators, namely prostaglandins, which are
involved in inflammation, and thromboxanes, which are involved
in blood clotting.
Coated 200 mg ibuprofen tablets
4. โข There are two general types of NSAIDs available: non-selective, and COX-2
selective. Most NSAIDs are non-selective, and inhibit the activity of both
COX-1 and COX-2. These NSAIDs, while reducing inflammation, also inhibit
platelet aggregation and increase the risk of gastrointestinal ulcers and
bleeds. COX-2 selective inhibitors have fewer gastrointestinal side effects, but
promote thrombosis, and some of these agents substantially increase the risk
of heart attack. As a result, certain older COX-2 selective inhibitors are no
longer used due to the high risk of undiagnosed vascular disease. These
differential effects are due to the different roles and tissue localizations of
each COX isoenzyme. By inhibiting physiological COX activity, all NSAIDs
increase the risk of kidney disease and through a related mechanism, heart
attack. In addition, NSAIDs can blunt the production of erythropoietin,
resulting in anemia, since hemoglobin needs this hormone to be produced.
5. โข The most prominent NSAIDs
are aspirin, ibuprofen, and naproxen; all
available over the counter (OTC) in most
countries. Paracetamol (acetaminophen) is
generally not considered an NSAID because it
has only minor anti-inflammatory activity.
Paracetamol treats pain mainly by blocking COX-
2 and inhibiting endocannabinoid reuptake
almost exclusively within the brain, but not much
in the rest of the body.
6. โข NSAIDs are often suggested for the treatment of acute or
chronic conditions where pain and inflammation are
present. NSAIDs are generally used for the symptomatic
relief of the following conditions:
โข Osteoarthritis
โข Rheumatoid arthritis
โข Mild-to-moderate pain due to inflammation and tissue
injury
โข Low back pain
โข Inflammatory arthropathies (e.g., ankylosing
spondylitis, psoriatic arthritis, reactive arthritis)
โข Tennis elbow
โขHeadache
โขMigraine
โขAcute gout
โขDysmenorrhea (menstrual pain)
โขMetastatic bone pain
โขPostoperative pain
โขMuscle stiffness and pain due
to Parkinson's disease
โขPyrexia (fever)
โขIleus
โขRenal colic
โขMacular edema
โขTraumatic injury
7. CHRONIC PAIN AND CANCER RELATED PAIN.
โข The effectiveness of NSAIDs for treating non-cancer chronic pain and
cancer-related pain in children and adolescents is not clear. There have
not been sufficient numbers of high-quality randomized controlled trials
conducted.
8. INFLAMMATION.
โข Differences in anti-inflammatory activity between the various individual
NSAIDs are small, but there is considerable variation in individual
patient response, and tolerance to these drugs. About 60% of patients
will respond to any NSAID; of the others, those who do not respond to
one may well respond to another. Pain relief starts soon after taking the
first dose, and a full analgesic effect should normally be obtained within
a week, whereas an anti-inflammatory effect may not be achieved (or
may not be clinically assessable) for up to three weeks. If appropriate
responses are not obtained within these times, another NSAID should
be tried.
9. SURGICAL PAIN.
โข Pain following surgery can be significant, and many
people require strong pain medications such as opioids.
There is some low-certainty evidence that starting
NSAID painkiller medications in adults early, before
surgery, may help reduce post-operative pain, and also
reduce the dose or quantity of opioid medications
required after surgery. Any increase risk of surgical
bleeding, bleeding in the gastrointestinal system,
myocardial infarctions, or injury to the kidneys has not
been well studied. When used in combination with
paracetamol, the analgesic effect on post-operative pain
may be improved.
10. ASPIRIN.
โข Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also
indicated for antithrombosis through inhibition of platelet aggregation.
This is useful for the management of arterial thrombosis, and
prevention of adverse cardiovascular events like heart attacks. Aspirin
inhibits platelet aggregation by inhibiting the action of thromboxane A2.
11. CONTRAINDICATIONS.
โข NSAIDs may be used with caution by people with the following
conditions:
โข Irritable bowel syndrome (IBS)
โข Persons who are over age 50, and who have a family history of
gastrointestinal (GI) problems
โข Persons who have had previous gastrointestinal problems from NSAID
use
12. โข NSAIDs should usually be
avoided by people with the
following conditions:
โข Peptic ulcer or stomach bleeding
โข Uncontrolled hypertension
โข Kidney disease
โข People that suffer with inflammatory
bowel disease (Crohn's disease or
ulcerative colitis)
โข Past transient ischemic
attack (excluding aspirin)
โข Past stroke (excluding aspirin)
โข Past myocardial
infarction (excluding aspirin)
โขCoronary artery
disease (excluding aspirin)
โขUndergoing coronary artery bypass
surgery
โขCongestive heart failure (excluding
low-dose aspirin)
โขIn third trimester of pregnancy
โขPersons who have
undergone gastric bypass surgery
โขPersons who have a history of
allergic or allergic-type NSAID
hypersensitivity reactions,
e.g. aspirin-induced asthma
14. ANTI-PYRETIC ACTION.
โข NSAIDs have antipyretic activity and can be used to
treat fever. Fever is caused by elevated levels
of prostaglandin E2, which alters the firing rate of
neurons within the hypothalamus that control
thermoregulation. Antipyretics work by inhibiting the
enzyme COX, which causes the general inhibition
of prostanoid biosynthesis (PGE2) within
the hypothalamus. PGE2 signals to the hypothalamus to
increase the body's thermal setpoint. Ibuprofen has
been shown more effective as
an antipyretic than paracetamol (acetaminophen). Arach
idonic acid is the precursor substrate for
cyclooxygenase leading to the production of
prostaglandins F, D, and E.
15. CLASSIFICATION.
โข NSAIDs can be classified based on their chemical structure or
mechanism of action. Older NSAIDs were known long before their
mechanism of action was elucidated and were for this reason classified
by chemical structure or origin. Newer substances are more often
classified by mechanism of action.
Burana 600 mg โ
ibuprofen package
16.
17.
18. PHARMACOKINETICS.
โข Most nonsteroidal anti-inflammatory drugs are weak acids, with a pKa of 3โ5.
They are absorbed well from the stomach and intestinal mucosa. They are
highly protein-bound in plasma (typically >95%), usually to albumin, so that
their volume of distribution typically approximates to plasma volume. Most
NSAIDs are metabolized in the liver by oxidation and conjugation to inactive
metabolites that typically are excreted in the urine, though some drugs are
partially excreted in bile. Metabolism may be abnormal in certain disease
states, and accumulation may occur even with normal dosage.
โข Ibuprofen and diclofenac have short half-lives (2โ3 hours). Some NSAIDs
(typically oxicams) have very long half-lives (e.g. 20โ60 hours).
19. One of the first
advertisements for
Bayer Aspirin,
published in The
New York Times in
1917
20. VETERINARY USE.
โข Research supports the use of NSAIDs for the control of pain associated
with veterinary procedures such as dehorning and castration of
calves. The best effect is obtained by combining a short-term local
anesthetic such as lidocaine with an NSAID acting as a longer term
analgesic. However, as different species have varying reactions to
different medications in the NSAID family, little of the existing research
data can be extrapolated to animal species other than those specifically
studied, and the relevant government agency in one area sometimes
prohibits uses approved in other jurisdictions.
โข For example, ketoprofen's effects have been studied in horses more
than in ruminants but, due to controversy over its use in racehorses,
veterinarians who treat livestock in the United States more commonly
prescribe flunixin meglumine, which, while labeled for use in such
animals, is not indicated for post-operative pain.
