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Flashcards in Anti-inflammatory Drugs Deck (18):

NSAID characteristics

analgesic, anti-inflammatory, anti-pyretic


NSAID mech of action

Inhibition of COX


Types of COX

COX-1: constitutive enzyme
COX-2 : Induced at site inflmmation


Why are newer NSAID's preferred

Selective for COX-2 v. older which is unselective and binds mainly to COX-1 -> less toxicity on GI track but cardiovascular side effects are a problem


Anti-pyretic effect of NSAIDS mec of action

1. exogenous pyrogens are engulfed by macrophages to make endogenous pyrogens e,g, IL1. TNFa
2. Endogenous pyrogen leads to PGE2 formation in hypothalamus
3. PGE resets body's thermostat to higher level
-> NSAIDS inhibit PGE2 -> normal level


How do NSAID's provide analgesisa?

Since PGE2 sensitises sensory nerves at site of inflammation -> lower pain threshold + CNS effect -> inhibit PGE2 = reverse


NSAID's inhibit formation of XYZ which does ABC

X = PGE2
Y = PGD2
Z = PGI2
A = Decrease HR
B = decrease rednesss
C = decrease oedema of inflammation


How does PGE2 interact with COX-1 and what happens when this is inhibited?

PGE2 from COX-1 in stomach inhibits gastric acid secretion + promotes protective mucus formation + bicarbonate release
-> when inhibited -> mucosa ulcerates + bleeds


Only natural steroid



Why might I use a synthetic compound over hydrocortisone?

1. improve potency
2. improve selectivity


Steroid examples

Prednisolene, betamethascine, glutocorticoids


Steroids general mech:

1. anti-inflammatory
i) early events: vaso D, oedema, leucocyte, infiltration + activation
ii) later) cell proliferation, macrophage activity, fibroblast activity, angiogenesis
2. Immunosppressive


Steroids also suppress

Production of autocoids e.g. PG's, LT's, TX's -> histamine release from basophil inhibited


Glucocorticords characteristics

Lipid soluble, easily cross cell membrane and binds GR which causes loss of hsp complex -> reveals translocation + DNA binding region on GR -> receptor enters nucleus


Once in nucleus, steroid mechanism of action:

1. Binds G regulatory element + activating gene transcription of anti-inflammatory proteins e.g. Lipocortin-1 (calcium reg. annexin), IKB
2. Binds GRE -> neg. regulate pro-infl. gene transcription e.g. IL-1
3. Transexpression of NFKB at DNA
4. Direct bind soluble TF's/ transactivators


Steroid effects:

1. Synthesis/ suppression of proteins - not immediate
2. Anti-inflammatory -> after hours
3. Decrease cox products
4. decrease lipocygenase products
5. decrease leucocyte infiltration + activation
6. decrease bronchoconstriction
7. decrease COX2, NOS, adhesion and cytokines


Tumour necrosis factor (TNFa) characteristics

- Cytokine ( 3 x 17KDa protein trimer)
- key regulatory in chronic inflammatory diseases


TNFa effects

1. Cytokine synthesism angiongenesis
2. Acute phase protein release - fibroblast
3. cytotoxic. cytostatic for cells
4. activates granulocytes + macrophages
5. bone metabsorption by osteoclasts
6. inhibits collagen synthesis + promotes breakdown
7. Activates endothelial cells