ANTI -INFLAMMATORY AND

IMMUNOSUPPRESSANT DRUGS
Non-Steroidal Anti-Inflammatory Drugs
( NSAIDs)
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 Non-Steroidal Anti-Inflammatory Drugs
( NSAIDs)

■ Are among the most widely used drugs of all therapeutic agents .
■ They are frequently prescribed for rheumatic musculoskeletal
complaints .and for minor aches and pain .

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Mechanism of action of NSAID
■ All of the NSAI effects are due to the primary action of the drugs –
inhibition of the arachidonate cyclooxygenase and thus inhibition of
the production the prostanoids (prostaglandine and thromboxane).
■ Some drugs have actions other than those on inflammation which
occur by different mechanisms.

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 Phospholipids
Phospholipase A2
PLA2
Arachidonate
Cyclo oxygenase
COX
Prostanoids

Postaglandines Thromboxane
PGI2 TXA2

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Cyclooxygense COX enzymes :
■ There are three enzymes COX 1 , COX2 and COX3
■ COX -1 is a con stitutive ,house keeping enzyme involved in tissue
homeostasis .
■ COX -2 is induced in inflammatory cells and produce the prostanoid
mediators of infllamation
■ COX-3 has recently been described
■ These enzymes metabolize arachidonic acid and initiate the
biosynthesis of prostaglandiens and thromboxane

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■ Most traditional NSAID are inhibitors of both iso enzynes .COX-1, COX-2
■ The anti inflammatory action of NSAID is mainly due to inhibition of
COX-2 and their un wanted effects are largely a result of COX-1
inhibition .
■ Drugs with a selective action on COX-2 are now in clinical use.

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Pharmacological actions of NSAID:
■ NSAI include a variety of different agents of different classes . Most of
these drugs have three major types of effects :
1- Anti –inflammatory effect
2- Analgesic effect
3- Antipyretic effect

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Antipyretic effect
■ The normal body temperature is regulated by the a centre in the
hypothalamus called the hypothalamic thermostat.
■ It ensure a balance btn heat loss and heat production
■ The antipyretic effect is partially due to the inhibition of production of
mediator prostaglandin PGE2 responsible for elevating the
hypothalamic set point for temperature control.

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Analgesic effect:
■ NSAID are mainly effective against pain associated with inflammation
or tissue damage
■ They decrease prostaglandin generation ,that sensitize nociceptive
receptors in nerve endings ,sensitive to inflammatory mediators
bradykinin and histamine ,leading to relief from pain.

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Anti-inflammatory effect :
■ There are many chemical mediators of the inflammatory and allergic
response.
■ They facilitate the responses : vasodilatation
Increased vascular permeability, cell accumulation and etc .
■ Those inflammatory mediators play a significant part mainly :
■ vasodilatation , odema and pain
■ NSAID reduce those components of inflammation and immune
response by inhibiting cox enzyme .

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General un wanted effects :

■ Owing to inhibition of constitutive housekeeping enzyme COX1 ,

they are common particularly in elderly and they include :
■ 1 – Dysepsia ,nauseia and vomiting : also gastric damage in
chronic users , with the risk of haemorrhage resulting from
reduction of protective effect of PG on gastric mucosa .
■ 2- skin reactions

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3- reversible renal insufficiency
4- analgesic –associated nephropathy
5- liver disorder bone marrow depression and these are less common
6-bronchospasm in asprin sensitive asthmatics

7- central nervous system: headache, tinnitus,

dizziness
8- cardiovascular: hypertension, edema
9- hematologic: neutropenia, aplastic anemia

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 Classifications
■ Salicylates (SELECTIVE COX INHIBITORS)
Aspirin (acetylsalicylic acid)
Salicylic acid and other salicylates

■ Propionic acid derivatives (NON SELECTIVE COX INHIBITORS)

Ibuprofen
Naproxen
Ketoprofen

■ Acetic acid derivatives (NON SELECTIVE COX INHIBITORS)

Indomethacin
Sulindac
Diclofenac

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■ Enolic acid (Oxicam) derivatives (NON SELECTIVE COX
INHIBITORS)
Piroxicam
Meloxicam

■ Anthranilic acid derivatives (Fenamates ) (NON

SELECTIVE COX INHIBITORS)
Mefenamic acid
Flufenamic acid

■ Selective COX-2 inhibitors (Coxibs)

Celecoxib (FDA alert)

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Some important NSAID:
Asprin( Acetylsalycilic acid ):
■ It causes irreversible inactivation of COX1 and COX2
■ In addition to it anti inflammatory actions , in low doses asprin inhibits
platelet aggregation and its main clinical importance is the therapy of
myocardial infarction and it decrease the incidence of transient
ischemic and unstable angina.

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Unwanted effects :
■ With therapeutic doses: some gastric bleeding is
common
■ With large dose :
dizziness ,deafness and tennitus, salicylism
compensated respiratory alkalosis may occur
 Aspirin given during viral infections has been
associated with an increased incidence of Reye’s
syndrome, an often fatal hepatitis with cerebral
edema, especially in children (should be given
acetaminophen instead of aspirin)

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 Panadol (acetaminophen)
■ It has a potential analgesic and anti pyretic action but rather weaker
anti inflammatory effects .
 inhibits PG synthesis in the CNS; this explains their
antipyretic and analgesic properties
 Has less effect on COX in peripheral tissues, which
accounts for their weak anti-inflam activity
■ lacks many of the side-effects of aspirin
It is the drug of choice for children with viral infection

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■ It does not antagonize the uricosuric
agents probenecid and therefore may
be used in patient with gout who are
taking this drug.
■ Its given orally and metabolized in liver Paracetamol and its
metabolites are excreted in urine

■ Toxic doses causes nausea and vomiting ,then after

24 hours ,potentially liver damageAdministratn of N-
acetylcysteine can be life-saving if administered
within 10 hrs of the overdose

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 Diclofenac sodium

■ Is a COX inhibitor.
■ Is approved for long-term use in the treatment of
rheumatoid arthritis, ankylosing spondylitis, and
osteoarthritis
■ Found in forms of “sodium Na” “potassium K”
■ Diclofenac udergoes hepatic metabolism, and the drug and
its metabolites are eliminated via urine.
■ Its toxicities are similar to those of the other NSAIDs.

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 Propionic acid derivatives:

■ E.g., ibuprofen, naproxen

■ They possess anti-inflam, analgesic and antipyretic activity
and have gained wide acceptance in the chronic treatment
of rheumatoid and osteoarthritis because their GI effects
are generally less intense than that of aspirin.
■ Are reversible inhibitors of the COXs and inhibit PGs
synthesis all are well absorbed on oral administration
■ Undergo hepatic metabolism and are excreted by the
kidney.

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 Naproxen
Uses:
■ Headache

■ Migraine

■ Menstrual pain

■ Toothache

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 Agents selective for COX2:

• Two agents selective for COX2 are know availabole for

clinical use Celecoxib and rofecoxib
• Use :
• Both are effective antiarthritic agents and have shown
analgesic efficacy in pain caused by:
• -dysmenorrhoea and after dental orthopaedic surgery
• Bothare metabolised in the liver

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