WK 4- ANTI-INFLAMMATORY DRUGS Flashcards
What are the 2 subclasses of NSAIDS
Non-Selective and COX-2 selective
What drug is an example of a Non-Selective NSAID
Ibuprofen
What drug is an example of COX-2 Selective NSAID
Celecoxib
What is the MOA of NSAIDS
-inhibit COX enzymes→ inhibit production of prostaglandins and thromboxanes → stop formation of local mediators of pain, fever and inflammation
What is the function of COX-1
-constitutive, expressed in most tissues, has a housekeeping role such as tissue homeostasis, production of prostaglandins that are gastric cytoprotective, cause platelet aggregation
What is the function of COX-2
-inducible during inflammation and is activated by cytokines (IL-1, TNF), causes production of prostaglandins
What are the adverse effects of non-selective NSAIDs
GI: Dyspepsia, nausea and GI damage due to suppression of gastroprotective PG, risk of haemorrhage (as antiplatelet)
- Cardio: increased risk of MI, stoke and hypertension
- Renal: reversible renal insufficiency in individuals with compromised renal function, compensatory PGE2-mediated vasodilatation is inhibited, Analgesic-associated nephropathy (decrease renal blood flow and GFR)
- Resp: bronchospasm in aspirin-sensitive asthmatics
What are the adverse effects of Selective COX-2 inhibitors
GI: increased risk of serious GI adverse events
Cardio: MI and stroke
Why is COX-2 selective inhibitors contraindicated in patients with CV history
-thromboxane A2 is formed in platelets through COX-1→ TXA2 causes vasoconstriction and increased platelet aggregation→ PG12 normally offsets this by causing vasodilation and restraining platelet activation→ COX-2 inhibits block production of PG12 and PGE2 but doesn’t inhibit TXA2→ causes hypertension, thrombosis and increased
What is the MOA of Corticosteroids/Glucocorticoids
-cross membrane and binds to intracellular glucocorticoid receptors and initiates transcriptional regulation of expression of genes involved in metabolic and inflammatory responses
What are the effects of inflammatory mediators cause by corticosteroids
- decrease in transcription for cell adhesion factors and cytokines
- decrease in activation of T helper cells
- reduced proliferation of T cells
- decrease in fibroblast function (decrease healing and repair)
- decreased activity of osteoblasts
- decreased expression of COX-2
- decrease in IgG production
What is the indication for NSAID use
symptomatic relief from fever, minor pain, inflammation
-acute inflammatory conditions and chronic joint disease eg osteoarthritis, rheumatoid arthritis
What is the indication for corticosteroid use
anti-inflammatory and immunosuppressant effects also used for replacement therapy in adrenal insufficiency- used in asthma, dermatitis, chrons disease, UC, RA
What are the adverse effects of corticosteroid use
Immune: decreased response to infection or injury / risk of opportunistic infection eg peptic ulceration, oral thrush
Ortho: osteoporosis and increased risk of fractures -alterations in calcium and phosphate metabolism -reduce osteoblast and increase osteoclast activity
Endo: hyperglycaemia -decreased glucose uptake / increased gluconeogenesis, muscle wasting and weakness, growth retardation in children, iatrogenic cushings syndrome
-CNS: euphoria, depression, psychosis
-Renal: sudden withdrawal after prolonged therapy may result in acute adrenal insufficiency via suppression of HPA axis
What are the 4 classes used as anti-rheumatic drugs
- 5aminosalicylates 2. TNF-alpha antagonist 3. Cytokine modulators 4. DMARDS (disease modifying antirheumatic drugs)
What is the MOA of sulfasalazine (5aminosalicylates)
Form a complex between sulfonainide and salycylate that scavenges toxic oxygen metabolites and blocks damage caused by ROS metabolites (produced by neutrophils)
What are the adverse effects of sulfasalazine (5aminosal..)
malaise, headache , GI disturbances
What is the MOA of TNF alpha antagonist (lol)
Bind to and block the action of TNF-alpha and stop it contributing to inflammation (stop chemotaxis and recruitment of other immune cells)
What are the adverse effects of TNF-alpha antagonists
immunosuppression, lymphoproliferative disorders, malignancies, infections, AutoAb
What patients should be reviewed before giving TNF-alpha antag (precautioned)
Demyelinating disorders, heart failure, serious infections
What is the MOA of rituximab (cytokine modulator)
chimeric anti-CD20 molecule that binds to CD20 molecules on B cells and causes destruction and lysis of the cell–> both unhealthy and healthy
-healthy cells will grow back
What is the MOA of abatacept (cytokine modulator)
Binds to B7 on APC and stop it binding to CD28 on T cell–> prevents costimulation of T cell, leaving it anergic and unable to secrete cytokines that cause inflammation
What adverse effects occur from cytokine modulators
infection, weakness, infusion related reactions
What is the mechanism of action of methotrexate in RA
Prevents the breakdown of purine (by inhibiting AICAR transforylase)-> causes build up of adenosine (anti-inflam)–> also cause increase of Fas expression (CD95), stop IL-1 binding, stop intracellular adhesion molecules/activation of T cells/B cells
