Pharmacology of inflammation Flashcards
What do NSAIDs stand for?
Non-steroidal anti-inflammatory drugs
How do NSAIDs work?
Inhibiting the activity of cyclooxygenase enzymes (COX-1 or COX-2).
What is the role of COX enzyme?
COX catalyzes the formation of prostaglandins and thromboxane from arachidonic acid
What is arachidonic acid generated from?
Phosphatidylinositol
How is arachidonic converted from phosphatidylinositol?
Via phospholipase A2
What are prostaglandins involved in?
Inflammation
What are thromboxane’s involved in?
Haemostasis
What are non-selective NSAIDs?
Ibuprofen, Naproxen, Diclofenac, Aspirin
What are COX2 selective NSAIDs?
Celecoxib, Rofecoxib
What coverts arachidonic acid to the leukotriene pathway?
Lipoxygenase
Why is aspirin taken by stroke vulnerable patients?
Reduced blood clotting
What is the role of thromboxane A2?
Thromboxane that is produced by activated platelets during haemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation.
What steroid drugs are used for inflammation?
Glucocoticosteroids
Why are glucocorticosteroids the most powerful anti-inflammatories?
Capable of inhibiting virtually all the components of inflammation.
What do glucocorticosteriods upregulate?
Annexin-1
What does annexin-1 do?
Suppresses phospholipase A2, thereby blocking eicosanoid production, and inhibits various leukocyte inflammatory events (epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst).
Why are glucocorticosteroids good for treating asthma but NSAIDs don’t have a huge effect?
Steroids target earlier in the AA pathway, inhibit prostaglandin and leukotriene production
What are the most prominent glucocorticoids?
Cortisol (hydrocortisone), Cortisone, Prednisone, Prednisolone, Methylprednisolone and Dexamethasone.
Side effects of glucocorticoids?
Immunodeficiency is the main side effect: increasing susceptibility to viral infection
Hyperglycemia due to increased gluconeogenesis, insulin resistance, and impaired glucose tolerance (“steroid diabetes”); caution in those with diabetes mellitus
Increased skin fragility, easy bruising
Steroid-induced osteoporosis: reduced bone density (osteoporosis, osteonecrosis, higher fracture risk, slower fracture repair)
Weight gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation; see corticosteroid-induced lipodystrophy
Hypertension through effects of fluid and electrolyte balance.
What is histamine synthesised from?
Decarboxylation of histidine
First generation antihistamines are..
Not specific to the H1 receptor, inverse agonists
Second generation antihistamines, are…, they were synthesised because..
Modifications of the First Generation Antihistamines to eliminate side effects resulted in the Second Generation Antihistamines
More selective for peripheral H1 receptors
What are side effects of first generation anti-histamines?
Because they can cross the BBB, they cause drowsiness, as H1 receptors are also involved in the CNS in the sleep-wake cycle.
Types of first generation anti-histamine
Ethylenediamines, Ethanolamines, Alkylamines - Chlorphenamine, Piperazines and Tricyclics.
Examples of second generation anti-histamines
Terfenadine, loratadine and cetirizine
What are DMARDs
Disease-modifying antirheumatic drugs
What is does methotrexate do?
Stimulates adenosine release from fibroblasts, reduces neutrophil adhesion, inhibits leukotriene B4 synthesis by neutrophils, inhibits local IL-1 production, reduces levels of IL-6 and IL-8, suppresses cell-mediated immunity, and inhibits synovial collagenase gene expression.
What are biological DMARDs?
Biologic DMARDs are highly specific and target a specific pathway of the immune system
Biological DMARD examples
Some biologic agents include infliximab (TNFalpha), adalimumab, etanercept, rituximab, abatacept, rituximab, tocilizumab (IL-6), tofacitinib, among others.
