NSAIDS AND DEMARDS Flashcards
1
Q
CLASSESS OF ANTI-INFLAMMATORIES AND USES
A
- NSAIDS-NON STEROIDAL ANTI-INFLAMMATORY DRUGS, target the inflammatory response by inhibiting production of inflammatory mediators, reducing inflammation. (aspirin, ibuprofen, paracetamol)
- DISEASE MODIFYING ANTI-RHEUMATIC DRUGS, used to slow down rheumatoid arthritis, they might halt or reverse the underlying disease, they have unrelated chemical structure with different mechanism of action (methotrexate, inliximab, sulfasalazine)
2
Q
ROLES AND SIGNS OF INFLAMATION
A
- MANIFESTATION OF BODY’S RESPONSE to tissue damage or infection
- SIGNS ARE : redness, swelling, heat, pain, loss of function
- can be local or systemic, can be inappropriately triggered, acute or chronic
3
Q
CYCLO-OXYGENASE PATHWAY AND FORMS OF COX
A
- 2 FORMS OF COX, cox 1 constitutively expressed and involved in normal homeostasis, cox 2, induced during inflammatory response,. they are not exclusively present, their concentration is predominant in either or the 2 scenarios
- cox enzymes have two endoperoxide synthase and peroxidase activity (PGG2 to PGH2)
- PGH2 IS the precursor of all prostanoids
- prostanoids have different effects and their actions terminate in uptake and degradation.
4
Q
BENEFITS OF NSAIDS
A
- INHIBIT COX 1 NAD COX 2 to reduce prostaglandins production
- antipyretic, inhibition of prostaglandin production in the hypothalamus and reduction of fever
- analgesic, inhibition of prostaglandins that sensitize nociceptors to inflammatory mediators like bradykinin
5
Q
S/E NSAIDS
A
- ⇓VASODILATION and Vascular PERMEABILITY
- ⇓platelet aggregation, TXA2 is more susceptible to aspirin because cox in platelets can’t be resynthesized like the cox from endothelium
- gastric irritation, inhibit cox 1 that produces PGE2 protective for gastric mucosa.
6
Q
examples of popular NSAID
A
- IBUPROFEN, weakly cox 1 selective antagonist, suitable for children
- DICLOFENAC, weakly cox 2 selective antagonist, moderate potency
- ASPIRIN, weakly cox 1 selective, common over the counter not suitable for children
7
Q
DEFINITION AND CHARACTERISTICS OF CYTOKINES
A
- PROTEIN MEDIATORS SECRETED BY MANY CELLS TYPE to elicit focal effect
- chemokines are chemotactic cytokines that attract cells into the tissue
- interleukins are signals between leukocytes
- secretion is brief and localized, they form interacting network, effects are mediated by high affinity receptors, effects mediated by changes in gene expression, stimulate leukocyte recruitment, activation and proliferation
- pro inflammatory mediators IL-1B, TNF, IL-8
8
Q
in rheumatoid arthritis, the immune activation is initiated by ______ that stimulates the production of _____ and they both release cytokine responsible for the inflammation process in the synovial fluid.
A
macrophage, Th1 T cells
9
Q
list source, trigger agents, and action of IL-1beta
A
- source macrophage
- triggered by microorganisms
- IL-1BETA links to receptor activating transcription factors and gene expressions such as the production of IL2 and COX2
- effects: vasodilatation, increased vascular permeability, fever, production of leukocyte cell adhesion molecules that stops the flowing immune cells in the area of inflammation, chemokines (promotes leukocyte migration into infected tissues), collagen and collagenase(tissue repair/remodeling), beneficial pro-inflammatory effect apart from RA.
10
Q
NAC OF IL-1RA
A
- NATURE, IL-1 receptor antagonist, recombinant synthetic form of the human interleukin-1 receptor antagonist
- action, competitively inhibits IL-1 binding to the IL-1 receptor (IL-1RI), inhibiting biological activity of IL-1BETA
- CONSEQUENCES, reduction of the inflammation process, s/e worsening of symptoms, nausea, vomiting, stomach pain, headache, give s.c daily at the same time for the circadian rhythm of the drug
11
Q
NAC OF AZATHRIOPRINE
A
- NATURE, inhibit clonal expansion of T and B cells in specific immune response (purine analog)
- ACTION, inhibit DNS synthesis, cell division, and proliferation( can target high proliferative tissues like endothelium)
- CONSEQUENCES, immunosuppressant used in organ transplant
12
Q
NAC OF METHOTREXATE
A
- NATURE, folic acid antagonist
- ACTION, unrelated to folic acid, blocks thymidylate synthesis which is essential for DNA synthesis and cell division
- CONSEQUENCES, stimulate hydrolysis of ATP to AMP, to produce anti-inflammatory adenosis and block adenosine uptake increasing the local concentration
- pharmacokinetics, give PO/IV/IM low solubility and doesn’t cross BBB< onset of action less than 24h
13
Q
NAC OF SULFASALAZINE
A
- NATURE, an inhibitor of cox and lipoxygenase pathways, reduces production of IL-8
- ACTION, stimulates hydrolysis of ATP and amp to produce anti-inflammatory adenosine,
- CONSEQUENCES as above
- uses and pharmacokinetics, complex of sulphonamide and salicylate as prodrug, activated by gut bacteria, used in RA/PA/JRA/UC, s/e GI disturbances, headache, malaise, skin reactions, reversible oligospermia
14
Q
NAC hydroxychloroquine
A
- NATURE, interferes with antigen presentation by macrophages and dendritic cells,
- ACTION, alter protein degradation, by acid hydrolases in the lysosome, assembly of macromolecules in the endosomes, and post-translation modification of proteins in the Golgi apparatus.
- CONSEQUENCES AND USES, used for malaria treatment, especially when pt in remission because of slow onset of action, s/e exacerbate skin lesions/rashes/headache/dizziness
15
Q
anti TNF therapies
A
- soluble TNF receptors, Etanercept, a recombinant protein that mimics TNF at the receptor by blocking its action
- neutralizing TNF antibodies, infliximab, binds to TNF and removes it from the system, prevents TNF signaling, works as a monoclonal antibody (humanized immunoglobulin), used for CD, RA, PA,s/e risk of infections, risk of cancer, development of anti-drug antibodies.
