***Anti- inflammatory drugs Flashcards
What are the roles of chemical mediators inflammation?
What are the 2 chemical mediators of inflammation?
· During inflammation, chemical mediators work to produce vasodilation which ensures an influx of fluids containing neutrophils and phagocytes and the initiation of tissue repair
· These chemical mediators are; prostaglandins and leukotrienes
· In inflammation, two main things happen; vasodilation and increased vessel permeability
How are the mediators of inflammation made?
Arachidonic acid -> Phospholipase ->
COX -> prostaglandins
Lipoxygenase -> Leukotrienes and lipoxins
Describe leukotrienes
· They are released from mast cells, basophils and eosinophils and cause inflammation
· They also secret mucous and cause broncho-constriction
· Mediators of the inflammatory process in Asthma
· 5-lipoxygenase is what releases leukotrienes
· Can either inhibit via binding to the actual leukotriene or by inhibiting leukotriene synthesis by blocking 5- lipoxygenase
Name two types of anti- inflammatory drugs
- Non- steroidal anti- inflammatory drugs
* Steroid anti- inflammatory drugs
Describe how non- steroidal anti- inflammatory drugs work and their 3 functions.
How it works
· NSAIDS block the action of cycloxygenase non-specifically, inhibiting prostaglandin formation
· They relieve; pain, fever and inflammation
3 functions
· Anti-inflammatory: They can decrease vasodilation (by decreasing PGs) and also indirectly oedema ( caused by vasodilation and permeability of post-capillary venules)
· Anti-pyretic: IL-1 released from macrophages in response to pathogens is an inducer of PG E-types that mess with the “thermostat” in the hypothalamus
· Analgesic: Decrease of peripheral PGs that sensitise nociceptors to inflammatory mediators like Bradykinin
Describe Aspirin
· Non-specific COX inhibitor, inhibition of COX-1 results in GIT side effects; Reduces the production of PGs that maintain the GI mucosa.
· Inhibition of Cox-1 and hence Thromboxane A results in decrease in platelet aggregation and blood clotting, hence cardiovascular benefits
· Aspirin results in an irreversible inhibition of COX, therefore has a long-lasting effect on platelets.
Describe NSAID like drug, paracetamol
- Also known as “Acetaminophen”
- Only weakly inhibits COX-2, might exert its effects through some other pathways.
- Does not serve as an anti-inflammatory but very good to treat pain and fever
Describe specific inhibitors of COX-2: COXIBS
- These drugs are specific COX-2 inhibitors; Celecoxib, is used against rheumatoid arthritis and osteoarthritis
- They have analgesic, anti-pyretic and anti-inflammatory effects
- However, some COXIBs (like Rofecoxib) lower the amount of PGs that inhibit clot formation via platelet aggregation
- So as a side effect, they result in thrombosis, and myocardial infarction
- A number of specific COX-2 inhibitors have been withdrawn from the market because of this adverse effect
Describe the mechanism and regulation of steroid anti-inflammatory drugs
- Produced naturally from adrenal glands which sit on top of kidneys
- Glucocorticoids exert a majority of their effects by altering gene expression
- When a corticosteroid binds to a glucocorticoid receptor, it activates it.
- It enters the cell, then binds to the glucocorticoid response element, it; enhances expression of anti-inflammatory genes (and something called lipocortin) and down regulates the production of inflammatory cytokines/ mediators and inhibit proinflammatory cytokines (IL-1 and TNF-a)
- Lipocortin inhibits phosolipase A enzymes, preventing the formation of arachidonic acid
Describe the functions and clinical use
- Anti-inflammatory: Multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, psoriasis, eczema
- However, they are also immune-suppressive
Describe side effects of glucocosteroids
· Osteoporosis
· Myopathy: GCs can affect muscle tone by direct catabolic effect through activation of GC receptor
· Hyperlipidemia
· Increase glucose production, hyperglycemia
· Gastrointestinal: gastritis, peptic ulceration and gastrointestinal hemorrhage.
Describe anticytokine drugs and other biopharmaceuticals
· Main targets: inflammatory mediators IL-1 and TNF-α
· TNF-α: Adalimumab, Etanercept, Infliximab (bind both membrane-bound and free form, might induce complement-induced cell lysi)
· IL-1 Anakinra
IL-2 receptor blockage and repression of T-cell proliferation
Describe antagonists of histamine
· Antagonists exist for all three H1,2,3 receptors. Anti-histamines usually refer to H1 antagonists
· 1st (able to cross blood-brain barrier- have sedating actions) and 2nd (don’t cross BBB) generation
· Cetrizine, Fexofenadine: used in allergic reactions, rhinitis (hay fever)
· Cyclazine: prevention of motion sickness
· Promethazine: sedation
