anti-inflammatory drugs Flashcards
describe the mechanism of action of steroids
drug crosses plasma membrane and acts at glucocorticoid receptor.
receptor dimerizes and crosses the nuclear membrane to reduce the transcription of inflammatory genes and increase the transcription of anti-inflammatory genes.
they are preventative drugs and they do not reverse asthma attacks
describe the mechanism of action of leukotriene receptor antagonists
in response to activation by allergens, mast cells release leukotrienes.
the breakdown of arachidonic acid via the lipoxygenase pathway also releases leukotrienes
these leukotrienes act at the cysteine leukotriene receptors to stimulate mucous secretion, cause bronchoconstriction and have effects on airway remodelling (ex: increased smooth muscle mass, vascularity and thicker airway walls)
ex: montelukast and zafirlukast
give examples of steroid drugs
inhaled:
beclomethasone
budesonide
ciclesonide
fluticasone
mometasone
oral: prednisolone
IV: hydrocortisone
what is the difference between endogenous and synthetic steroids.
endogenous steroids have both mineralocorticoid and glucocorticoid action.
synthetic steroids are selective for either glucocorticoid or mineralocorticoid effects.
anti inflammatory asthma medications selective for glucocorticoid effects
(mineralocorticoid action effects water and electrolyte balances by increasing sodium reabsorption in kidneys)
what causes the anti-inflammatory effects of steroids
activation of:
annexin a1
B2 adrenoceptors
lkB gene (inhibits NF-kB)
MKP1 gene (inhibits map kinase)
cytokines IL-10/12
repression of:
cytokines IL2/3/6/ TNF a
chemokines
enzymes iNOS and COX-2
peptides like endothelin-1
what is annexin A1 action
antagonizes formyl peptide receptors to inhibit release of histamine from mast cells
binds to enzyme cytosolic PLA2 (which forms arachidonic acid) to prevent its translocation into cell membranes where it catalyses arachidonic acids formation from phospholipids. the arachidonic acid would initiate the production of prostaglandins and leukotrienes.
what are side effects of steroids
throat infections if inhaled (due to immune response dampening)
osteoperosis (due to adrenal supression)
Increases blood pressure due to water retention from adrenal supression
increases hyperglycemia (effects on carbohydrate metabolism)
resistance (patients with severe asthma or chronic inflammation from COPD have poor response to steroids) (due to increased efflux of drug, genetic resistance, receptor modifications, decreased nuclear translocation of receptor)
what are lipoxygenase inhibitors
block synthesis of leukotrienes ex: zileuton
what is omalizumab used for and what is its mechanism of action
used for severe allergic asthma that fails to respond to steroids
it is a monoclonal antibody that acts against free IgE antibodies to prevent them from binding to immune cells. this prevents allergen induced mediator release.
it is administered as a subcutaneous injection every 2-4 weeks
what are examples of bronchoconstriction due to adverse drug reactions
NSAIDs: Inhibition of COX pathway of arachidonic acid increases action of lipoxygenase pathway leading to more leukotriene production
B adrenoceptor antagonists: use of non selective and “selective” atenolol contradicted for asthma and COPD
drug allergy: ex: penicillin and cephalosporins
what are chromones likely mechanism of action
thought to prevent mast cell degranulation by enhancing action of Annexin A1 (inhaled)
ex: nedocromil
