1. Evaluation of the anti-inflammatory activity of NSAIDs and glucocorticoids Dr. Raz Mohammed

2. Inflammation is a normal, protective response to tissue injury caused by physical trauma, noxious chemicals, or microbiologic agents.
Inflammation is the body's effort to inactivate or destroy invading organisms, remove irritants, and set the stage for tissue repair.
When healing is complete, the inflammatory process usually subsides.

3. Inflammatory responses occur in three phases:
1. An acute phase characterized by transient local
vasodilatation and increased permeability.
2. A delayed, sub acute phase characterized by
infiltration of leukocytes and phagocyte cells.
3. A chronic proliferative phase, in which tissue
degeneration and fibrosis occur.

4. Types of Inflammation
1. Acute Inflammation:  is the initial response of the body to harmful stimuli.
Is usually of short duration and sudden onset.
characterized by an initial vasodilatation, increased vascular endothelial permeability, exudation of fluid and plasma proteins, and transmigration of leukocytes from vessels into the injured tissues.
The vasodilatation gives rise to heat and redness
The exudation and leukocyte infiltration give rise to swelling
Pain and loss of function are associated with increased pressure on nerves as a result of tissue edema.
All these signs are collectively called cardinal signs of inflammation
Increased vascular permeability occurs as a result of release of chemical mediators like histamine from mast cells,
bradykinin, PGs and serotonin (5-HT) from injured cells.

5. 2. Chronic Inflammation
Chronic inflammation is a long lasting type of changes that may persist for weeks, months or even years, and brought on by acute inflammation or may be the result of an autoimmune disease.

6. Anti inflammatory drugs
Non steroidal anti inflammatory drugs:
(inhibit COX-1 and COX-2)
Steroidal anti inflammatory drugs (corticosteroids)

7. Nonsteroidal Anti-Inflammatory Drugs
The NSAIDs have three major therapeutic actions:
antipyretic,
analgesic, and
anti-inflammatory activities.
Mechanism of action: They act primarily by inhibiting the cyclooxygenase enzymes, this leads to decreased prostaglandin synthesis.

9. Prostaglandins
 Prostaglandins are synthesized by cyclooxygenase enzyme at sites of tissue damage or infection, where they cause inflammation, pain and fever as part of the healing process.  
High levels of prostaglandins are produced in response to injury or infection and cause inflammation, which is associated with the symptoms of redness, swelling, pain and fever.  This is an important part of the body’s normal healing process.
However, this natural response can sometimes lead to excess and chronic production of prostaglandins which may contribute to several diseases by causing unwanted inflammation. 

10. NSAIDS diclofenac ibuprofen naproxen celecoxib mefenamic acid
indometacin
Aspirin
Meloxicam

11. Adrenal hormones The adrenal gland consists of cortex & medulla.
The cortex synthesizes glucocorticoids.
Glucocorticoids control carbohydrate, fat and protein metabolism, and have anti-inflammatory properties and a number of other mechanisms.

12. Several semisynthetic derivatives of the glucocorticoids have been developed:
Short acting (1-12 hrs): Hydrocorisone
Intermediate acting (12-36 hrs): prednisolone, methylprednisolone, triamcinolone
Long acting (36-55 hrs): Betamethasone, dexamethasone.

13. Mechanism of action
Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways.
They interact with specific intracellular receptor proteins leading to synthesis of new proteins.
Such proteins include lipocortin, a protein known to inhibit phospholipase A2  and thereby block the synthesis of prostaglandins and other inflammatory mediators.
2. Lowering and inhibition of peripheral lymphocytes and macrophages
3. Reduce the amount of histamine that is released from basophils and mast cells.

17. Procedure
Using fresh egg’s albumin to induce edema in rats to produce acute inflammation
Three groups are treated with either
...diclofenac 5mg/kg
...Dexamethazone 1 mg/kg
…Acetaminophine 100 mg/kg
Measure the paw thickness of the rat using vernier caliper at zero time
All drugs are administered I.P 30 minutes before inducing inflammation by injecting 0.1ml of fresh undiluted egg albumin to the right paw of the rats.
The increase in paw edema as a result of inflammation was measured by using the vernier caliper.
The paw thickness should be measured using vernier caliper before and 1hr after induction of inflammation.