WEEK 3: PHARMACOLOGY OF ANT-INFLAMMATORIES. Flashcards
What is inflammation?
Inflammation is the body’s effort to inactivate or destroy invading organisms, remove irritants and set stage for tissue repair.
NORMAL PROTECTIVE RESPONSE TO TISSUE INJURY CAUSED BY PHYSICAL TRAUMA, NOXIOUS CHEMICALS OR MICROBIAL AGENTS.
Outline the 5 classical signs of inflammation caused by eicosanoids.
1.Redness
2.Heat
3.Pain
4.Loss of function
5.Swelling
What are eicosanoids?
Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are around 20 carbon units in length.
When healing is complete, the inflammatory process usually subsides.
Inappropriate activation of the immune system can result in inflammation, leading to immune diseases such as rheumatoid arthritis.
How are these treated?
Treatment is with anti-inflammatory and immunosuppressive agents.
Describe the MOA of NSAIDS.
They are COX inhibitors.
Describe the MOA of ASPIRIN.
Prototype
Irreversibly acetylates cyclooxygenases.
Inhibits both COX1 and COX 2
Antiplatelet, analgesic, antipyretic, anti-inflammatory
Outline the adverse effects of Aspirin.
*Gastrointestinal irritation: Too much unregulated HCL due to less prostaglandins
- Renal insufficiency: The risk of renal failure may increase with cumulative lifetime doses or with the combination of aspirin.
- Prolonged bleeding time:
- Exacerbation of asthma: But blocking COX-1 decreases anti-inflammatory chemicals called prostaglandins. It also increases pro-inflammatory chemicals called leukotrienes. This can lead to acute asthma and allergy-like reactions.
- Salicylism: Aspirin poisoning, is the acute or chronic poisoning with a salicylate such as aspirin. The classic symptoms are ringing in the ears, nausea, abdominal pain, and a fast-breathing rate. CAUSED BY HIGHER DOSES OF ASPIRIN.
- Reye syndrome: Reye syndrome is a very rare disorder that damages many parts of the body, especially the brain and the liver.
It could be due to an abnormal response to aspirin or aspirin-containing products taken during a viral illness.
Other NSAIDS.
*Reversible & Non-selective COX inhibitors
Ketorolac (Moderate-severe pain)
Ibuprofen, Diclofenac, Naproxen (Mild to moderate pain)
Celecoxib (COX-2 selective inhibitor
State the metabolic effect of cortisol.
Stress hormone
Favors gluconeogenesis through increasing amino acid uptake by the liver and kidney and elevating activities of
gluconeogenetic enzymes.
Stimulate Proteolysis and lipolysis.
Provide the body with energy to combat stress caused by
trauma, fright, infection etc.
Describe the secretions of the Adrenal gland.
*The adrenal cortex secretes glucocorticoids, mineralocorticoids, and androgens.
*The adrenal medulla secretes epinephrine and norepinephrine. CATHECOLAMINES.
Describe the anti-inflammatory effects of cortisol.
It inhibits the PHOSPHOLIPASE A2 WHICH RESULT IN NO production of eicosanoids.
Outline the immunosuppressive effects of cortisol.
*Decrease release of pro-inflammatory cytokines in lymphocytes
- Decreases phagocytosis
- Decrease production
Describe the MINERALOCORTICOID EFFECT of cortisol.
*Cortisol also acts on mineralocorticoid receptors.
*It increases reabsorption of sodium and water from the kidneys.
Describe the synthetic glucocorticoids.
*Less rapidly inactivated
- Minimal salt-retaining
properties - More potent than cortisol
Outline the adverse effect of using Glucocorticoids.
Glucocorticoid treatment may cause adrenal insufficiency via feedback suppression of CRH and ACTH, eventually inducing adrenocortical hypoplasia and atrophy, and rendering the HPA axis unable to produce an adequate cortisol response to stress.
