ANTI-INFLAMMATORY

DRUGS
RICHA SINGH
M.PHARM(Ist yr)
PHARMACOLOGY
HYGIA INSTITUTE OF PHARMACEUTICAL
EDUCATION AND RESEARCH,LUCKNOW
 DEFINITION OF
INFLAMMATION
 Inflammation is defined as the local response
of living mammalian tissues to injury due to
any agent.
 It is a body defense reaction in order to
eliminate or limit the spread of injurious
agent as well as to remove the consequent
necrosed cells and tissues.
 CAUSES OF INFLAMMATION
 The agents causing inflammation may be as
under :-
1. Physical agents like heat, cold, radiation,
mechanical trauma.
2. Chemical agents like organic and inorganic
poisons.
3. Infective agents like bacteria, viruses and
their toxins.
4. Immunological agents like cell-mediated
and antigen-antibody reactions.
THE INFLAMMATORY RESPONSE
 The inflammatory response is a normal
(desirable) defense mechanism.
 The side effects are undesirable.
 Normal inflammatory response has an on/off
switch.
 In chronic inflammation something has gone
wrong with the OFF switch.
 Therefore we need drugs to control the
inflammatory reaction.
CARDINAL SIGNS OF ACUTE
INFLAMMATION

Heat Redness Swelling Pain Loss of fun ction

Celsius (30 BC) Virchow (1902)
MEDIATORS OF INFLAMMATION
MAJOR PATHWAYS
 EICOSANOIDS
Eicosanoids – a family of compounds that are the
products of three main pathways which use
oxygen as a major co substrate.
The three pathways are:
 the cyclooxygenase pathway.
 the lipoxygenase pathway.
 the epoxygenase pathway.
 COX 1 AND COX 2
 The key enzyme in the cyclooxygenase
pathway is the enzyme cyclooxygenase
(COX).
 There are two forms of cyclooxygenase,
COX1 (the predominant form) and COX2.
 COX 1 is a constitutive, housekeeping
enzyme involved in tissue homeostasis.
 COX 2 is induced in inflammatory cells and
produces the prostanoid mediators of
inflammation.
 CLASSIFICATION OF ANTI
INFLAMMATORY DRUGS
 Nonselective COX inhibitors (traditional NSAIDs)
1. Salicylates : Aspirin.
2. Propionic acid derivatives : Ibuprofen,
Naproxen, Ketoprofen, Flurbiprofen.
3. Anthranilic acid derivative : Mephenamic acid.
4. Aryl-acetic acid derivatives : Diclofenac,
Aceclofenac.
5. Oxicam derivatives : Piroxicam, Tenoxicam.
6. Pyrrole-pyrrole derivative : Ketorolac.
7. Indole derivative : Indomethacin.
8. Pyrazolone derivatives : Phenylbutazone,
Oxyphenbutazone.
 Preferential COX-2 inhibitors
Nimesulide, Meloxicam, Nabumetone.
 Selective COX-2 inhibitors

Calecoxib, Etoricoxib, Parecoxib

 Analgesic-antipyretics with poor antiinflammatory
action
1. Paraaminophenol derivative : Paracetamol
(Acetaminophen).
2. Pyrazolone derivatives : Metamizol(Dipyrone),
Propiphenazone.
3. Benzoxazocine derivative : Nefopam.
 MECHANISM OF ACTION
Non-steroidal anti-inflammatory drugs (NSAIDs)
 All NSAIDs inhibit the cyclooxygenase required for
conversion of arachidonic acid to endoperoxide
intermediate (PGG2 and PGH2).

 NSAIDs inhibit prostaglandin and thromboxane

synthesis, they are potent inhibitors of cyclooxygenase
and eliminate all prostaglandins and thromboxanes in
every cell they reach.

 Recall that prostaglandins and thromboxanes play

crucial roles in: Pain, Inflammation, Fever ,
Excessive blood clotting.
 PHARMACOLOGY OF
INDOMETHACIN
 It is a potent anti-inflammatory drug with prompt
antipyretic action. Indomethcin relieves only
inflammatory or tissue injury related pain. It is a
highly potent inhibitor of PG synthesis and
suppresses neutrophil motility. In toxic doses it
uncouples oxidative phosphorylation.
Pharmacokinetics-
Indomethacin is well absorbed orally, rectal
absorption is slow but dependable. It is 90% bound
to plasma proteins, partly metabolized in liver to
inactivate products and excreted by kidney.
Plasma t1/2 is 2-5 hours.
 Adverse Effects-
 A high incidence(up to 50%) of gastrointestinal and
CNS side effects is produced.
 Gastric irritation, nausea, anorexia, gastric
bleeding and diarrhoea are prominent.
 Frontal headache(very common), dizziness, ataxia,
mental confusion, hallucination, depression and
psychosis can occur.
 Increased risk of bleeding due to decreased
platelet aggregability.

Uses-
Because of prominent adverse effects,
indomethacin is used as a reverse drug in
conditions requiring potent anti-inflammatory
action like ankylosing spondylitis, acute
exacerbations of destructive arthropathies,
psoriatic arthiritis and acute gout that are not
responding to better tolerated NSAIDs.
COMPARISON OF SOME COMMON
NON-STEROIDAL ANTI-
INFLAMMATORY DRUGS AND COXIBS
Drug Type RD Gout MS PO Dys H&M Comments
Aceclofenac Phenyl • -
acetate
Aspirin Salicy • • • • • Mainly
late cardiovascular
usage
Celecoxib Coxib • Fewer
gastrointestin
al effects
Diclofenac Phenylacetate • • • • Moderate
potency
Etoricoxib Coxib • • -
Ibuprofen • • • • • Suitable for
Propionate
children
Indometacin • • • • Suitable for
Indole moderate to
severe disease
Mefenamic Fenamate • • • • Moderate
acid activity

Dys= dysmenorrhoea; H&M= headache and

migraine; MS= musculoskeletal disorders;
PO=postoperative pain; RD= rheumatic diseases
(e.g. rheumatoid arthritis and osteoarthritis.
DRUG INTERACTIONS
Drug Recommendati
Severity Adverse Effect
ons
ACE Inhibitors Moderate May decrease Monitor blood
(e.g. antihypertensiv pressure and
Benazepril e and cardiovascular
Hydrochloride) natriuretic function.
effects.
Probenecid Moderate May result in Avoid
reversal of the concurrent use
uricosuric of high-dose
effects of the aspirin with
other drug. probenecid.
Lithium Moderate May increase
lithium plasma
Monitor for
levels and
lithium
decrease its
toxicity.
clearance
renally.
Warfarin Monitor PT
May result in (prothrombin
an increased time) and INR
Moderate
risk of (international
bleeding. normalized
ratio).
Methotrexate Severe DO NOT
May result in
administer
increased risk
NSAIDs within
of
10 days of high
methotrexate
dose
toxocity.
methotrexate.
 SCREENING OF ANTI-
INFLAMMATORY DRUGS
 Carrageenin-Induced Edema
The animals were divided into four groups of six
animals each(n=6). The plant extract of at the dose
level of 250 and 500mg/kg body weight were
administered orally to the treated group and
Indomethacin at the dose level of 10mg/kg body
weight was administered orally to the satndard
group. At the same time the control gorup received
freshly prepared 0.3ml of normal saline(0.9% w/v
NaCl) orally. After 30 min paw edema was induced by
injection of 0.1ml of 1% freshly prepared suspension
of carrageenin in normal saline into the sub-planter
region of the left hind paw of the each groups of rat.
 The paw volume was measured immediately
and then at 1h, 2h, 3h, and 4h intervals after
the carrageenin injection by using a
plethysmometer.
 Histamine-Induced Edema
For the study of Histamine-induced edema the
animals were treated exactly the same method
as in carrageenin-induced method but instead
of carrageenin, here 0.1mL of 1% w/v
histamine in normal saline(mediators of
inflammation) was used.
 Dextran-Induced Edema
For the study of Dextran induced edema the
animals were treated exactly the same method
 as in Carrageenin induced method but instead of
carrageenin, here 0.1mL of 1% w/v Dextran in
normal saline was used as the edemagen.
 Cotton Pellets-Induced Granuloma
The animals were divided into four groups of six
animals each(n=6). After shaving the fur, the rats
were anaesthetized and 20mg of sterile cotton
pellets were implanted subcutaneously into both
sides of the groin region of each rat. The plant
extract of at the dose level of 250 and 500mg/kg
body weight were administered orally to the
treated group and Indomethacin at the dose
level of 10mg/kg body weight was administered
orally to the satndard group and control vehicle
as 0.3mL of normal saline(0.9% w/v NaCl) was
 administered orally for 7 consecutive days from the
day of cotton pellet implantation. On the eighth day
the animals were anaesthetized by chloroform and
cotton pellets were removed by surgically and made
free from extraneous tissues. The pellets were then
incubated at 370 for 24 hrs and finally dried at 600 to
constant weight. Increment in the dry weight of the
pellets was taken as measure of granuloma formation.
The anti-inflammatory effect of the plant extract was
calculated by the following equation-

Anti-inflammatory activity(%)=[(1-D/C)*100]
Where , D=percentage difference in paw volume
after the administration of drugs to rats.
C=percentage difference of volume in the
control groups.
ADVERSE EFFECTS OF NSAIDS
The two main adverse drug reactions, associated
with NSAIDs relate to gastrointestinal effects and
renal effects of the agents. These effects are
dose-dependent, and in many cases severe enough
to pose the risk of ulcer perforation, upper
gastrointestinal bleeding, and death, limiting the
use of NSAID therapy.
 Gastrointestinal – Gastric irritation,erosions,
peptic ulceration,gastric bleeding/perforation,
esophagitis.
 Renal – Na+ and water retention, chronic renal
failure,interstitial nephritis, papillary necrosis
(rare).
 Hepatic – Raised transaminases, hepatic failure
(rare).
 CNS – Headache, mental confusion,
behavioural disturbances, seizure
precipitation.
 Haematological – Bleeding, thrombocytopenia,
haemolytic anaemia, agranulocytosis.
 Others – Asthma, exacerbation, nasal
polyposis, skin rashes, pruritis, angioedema.
 PRECAUTIONS &
CONTRAINDICATIONS
NSAIDs cannot be used (are contraindicated)
in the following cases:
 Allergy to aspirin or any NSAID.
 Aspirin should not be used under the age of 16
years.
 During pregnancy.
 During breast feeding.
 On blood thinning agents (anticoagulants).
 Suffering from a defect of the blood clotting
system (coagulation).
 Active peptic ulcer.
 USES
NSAIDs are usually indicated for the treatment of
acute or chronic conditions where pain and
inflammation are present. Nonsteroidal anti-
inflammatory drugs are powerful analgesics,
especially for nociceptive pain. NSAIDs also are
effective in some neuropathic pain syndromes when
used with other analgesics. NSAIDs are generally
indicated for the symptomatic relief of the following
conditions:
 Rheumatoid arthritis. The common use of these drugs
is for arthritis. NSAIDs are particularly useful in the
inflammatory forms of arthritis (such as rheumatoid
arthritis) and, sometimes, in the more severe forms of
osteoarthritis.
 Osteoarthritis.
 Acute gout.
 Inflammatory arthropathies (e.g. ankylosing
spondylitis, psoriatic arthritis, Reiter's syndrome).
 Dysmenorrhoea (painful menstruation).
 Headache and migraine.
 Postoperative pain.
 Mild-to-moderate pain due to inflammation and
tissue injury.
 Back pain and sciatica.
 Sprains, strains, and rheumatism. Dental pain.
 Pain from kidney stones (renal colic).
 To reduce fever.
 Other painful conditions, especially where there is
inflammation.
THANK YOU