detailed study of anti inflammatory drugs

1. ANTI -INFLAMMATORY DRUGS
PRESENTED BY,
MANJUNATH D
GUIDED BY,
Prof. K. KEMPARAJU

2. Introduction
 Inflammation is a protective immunovascular
response that involves immune cells, blood vessels, and
molecular mediators.
Can be CAUSED by numerous stimuli including:
•Antigen-antibody interaction
•Thermal and physical injury
•Microbial invasion
•Physical damage
•Immune reactions

3. Signs of inflammation
Redness –due to vasodilation of capillaries to
increase blood flow.
Heat - due to effect on thermoregulatory site of
the brain.
Swelling – due to Increased vascular permeability
and influx of plasma proteins and
phagocytic cells into the tissue spaces
Pain – due to
-Hyperalgesia, sensitization of nociceptors
-local release of pain inducers and
-increased tissue pressure

4. Inflammatory responses occur in
three distinct phases:
1. An acute transient phase, characterized by:
– local vasodilation and its resulting increased blood flow
causes the redness (rubor) and increased heat (calor)
– Increased permeability of the blood vessels results in the
leakage of plasma proteins and fluid into the tissue (edema),
which manifests itself as swelling.
2. A delayed phase, most prominently characterized by:
– infiltration of leukocytes and phagocytic cells to the
injured /inflammed tissue
3. A chronic proliferative phase, in which:
– tissue degeneration and fibrosis occur

5. Mediators of the inflammatory response
 Histamine – Secreted from mast cell .Histamine
causes dilation and increased permeability of
capillaries.
 Prostaglandins
PGE2 - promote Vasodilation,Directly Cause Pain and
Induces Fever
PGI2 - increase vascular permeability, enhance pain
producing properties of bradykinin.
Plasma proteases (Bradykinin)- A vasoactive protein
which is able to induce vasodilation, increase vascular
permeability, cause smooth muscle contraction, and
induce pain.
Bradykinin
(C5H9N3)
C50H73N15O11

6.  Leukotrienes
- increase vascular permeability and leakiness.
- increase mobilization of endogenous mediators of inflammation
 Thromboxane A2 (TXA2)- Thromboxane is a member of the
family of lipids known as eicosanoids. The two major thromboxanes
are thromboxane A2 and thromboxane B2.
cause platelets to aggregate
causes vasoconstriction
causes smooth muscle contraction
enhances function of inflammatory cells.
C20H32O5

7. Types of anti-inflammatory drugs
Steroidal anti-
inflammatory drugs
Non-steroidal anti-
inflammatory drug
- Cortisone
- Hydrocortisone
- Acetaminophen
- Aspirin

8. Steroidal anti-inflammatory drugs
(SAIDs)
 The steroids are compounds with glucocorticoid activity, and
are more powerful drugs than NSAIDs.
 - Containing steroid moiety in their structure.
 Derived from cholesterol.
Glucocorticoids (GC)
CortisoneHydrocortisone C21H28O5C21H30O5

9. Glucocorticoids (GC)
Mechanism of Action :
They act by indirect inhibition of the enzyme phospholipase A2
which activate synthesis of arachidonic acid with subsequent
formation of prostaglandins.
They induce synthesis of a protein “lipocortin-1” which has
the inhibitory effect on phospholipase A2.
They enter in to the cell and reach nucleus.

10. phospholipase A2
GC inhibition

11. Hyperglycemia due to increased gluconeogensis, insulin resistance,
and impaired glucose tolerance ("steroid diabetes");
Redistribution of body fat: moon face, buffalo hump and truncal
obesity.
 Muscle breakdown (proteolysis),weakness; reduced muscle mass.
 Increased plasma amino acids, increased urea formation;
Growth failure,
Adrenal insufficiency.
 Glaucoma due to increased cranial pressure.
Side Effects :

12. Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) are a chemically
heterogeneous group of compounds that provide unmistakable and
significant health benefits in the treatment of pain and inflammation.
The NSAIDs can be sub-classified on the basis of chemical structure
as follows:
 Salicylates
 Propionic Acids (Profens)
 Aryl and Heteroarylacetic Acids
Oxicams (“Enol Acids”)
Anilides
In general, NSAIDs structurally consist of an
carboxylic acid, enols attached to a planar,
aromatic functionality.

13. General Mechanism of NSAID Action
The primary action of NSAIDs is the inhibition of the COX enzyme,
by inhibiting this enzyme the production of prostaglandins are also
inhibited. The COX enzyme synthesised prostaglandins from fatty
acids such as arachidonic acid.
Most NSAIDs inhibit both major forms of the COX enzyme, however
all are still considered toxic. Newer drugs which are believed to be
COX-2 specific are relatively safer in chronic use.

15. Besides from the inhibition of the COX enzyme, other actions
include:
Inhibit superoxides (toxic) and free radicals.
Inhibit Bradykinin production (A Peptide which dilates
blood vessels, lowering blood pressure)
 Inhibits metalloproteinases (Proteolytic enzymes whose
catalytic mechanism involves a metal)
 Antagonises interleukin-1 and tumour necrosis factor.
Other Actions of NSAIDs

16. Commonly Used NSAIDs and their
properties
Aspirin (Acetylsalicylic acid)
Aspirin is a potent anti-inflammatory drug with
mild central analgesic and antipyretic actions. It is
readily absorbed from the stomach and small
intestine, an acid drug is well absorbed in an acidic
environment. It is metabolised by tissue /plasma
esterases. Aspirin may also be used in low doses,
daily to prevent platelet aggregation.
Aspirin
C9H8O4

17. Aspirin and nonselective NSAIDs produce inhibition of platelet
function via their inhibition of COX1. In the case of aspirin, the
inhibition is irreversible, so the effect on platelet function
continues for the life of the affected platelet
Action of aspirin
Aspirin-like drugs act by inhibiting
the activity of the cyclooxygenase
(COX) enzyme.
COX-1 are implicated in the
maintenance of normal physiological
function and have a 'cytoprotective'
action in the stomach. COX-2
expression is normally low but is
induced by inflammatory stimuli and
cytokines.
Mechanism

18. Phenylbutazone is the most widely used NSAID in equine
medicine; however it is extremely toxic in humans. Due to
the acidity of the drug, it is readily absorbed from the
stomach or duodenum. Phenylbutazone metabolites are
weak acids and therefore preferably excreted in alkaline
urine.
Phenylbutazone
Meloxicam
Meloxicam is a similar drug, but with a shorter half-life (30-
40 hours). It is thought to have greater potency for COX-2
than COX-1 therefore side-effects may be less. It is also
thought to be chondroprotective (The slowing of
degradation of articular cartilage)
Phenylbutazone
Meloxicam
C19H20N2O2
C14H13N3O4S2

19. Meclofenamic acid is a potent anti-inflammatory, anti-
pyretic analgesic. It is more potent than aspirin but similar in
effect. As well as inhibiting COX enzymes it has found to be a
prostaglandin antagonist, interacting with prostaglandin
receptors. It therefore prevents the action of prostaglandin
already present possibly exerting a more rapid reduction of
inflammation.
Meclofenamic Acid
Carprofen is a potent anti-inflammatory drug, but is a weak
inhibitor of COX. Its mode of action is not yet known but it
significantly inhibits neutrophil migration. Due to weak
inhibition of COX, toxicity of Carprofen tends to be low.
Carprofen
All this anti-inflammatory drugs have similar mechanism as aspirin.
Meclofenamic Acid
Carprofen
C14H11Cl2NO2
C15H12ClNO2

20. Mild to moderate inflammatory lesions and
associated pain
 Acute inflammation and pain
 Joint inflammation and pain
Suppression of pulmonary oedema
 Endotoxaemia
 Anti-thrombic
When to Use NSAIDs

21.  Gastric irritation and ulceration
 Vomiting and diarrhoea
 Hepatotoxicity
 Renal papillary necrosis, chronic nephritis
 Bone marrow disturbance
 Skin rashes
 Respiratory distress
Side Effects of NSAIDs

22. Conclusions
 Anti inflammatory drugs plays pivotal role in preventing
inflammation either by affecting inflammatory mediators or
by modifying enzymes required for the synthesis of these
mediators.
 The understanding of the pivotal role of inflammation in
seemingly unrelated diseases has resulted in the use and
development of new anti-inflammatory agents.