anti inflammatory drugs Flashcards
how are glucocorticoids produced and what is the HPA axis
the hypothalamus secreted corticotropin releasing factor which acts on anterior pituitary to secrete adrenocorticotrophic hormone which acts on adrenal cortex to produce glucocorticoids and mineralocorticoids
the HPA axis the the pathway for glucocorticoid production, glucocorticoids act as negative feedback at both the hypothalamic and anterior pituitary stages
(see protein notes)
what is role of HSD in steroid synthesis
HSD2 converts cortisol to cortisone
HSD1 converts cortisone to cortisol
cortisone acts as negative feedback for mineralocorticoid and glucocorticoid synthesis
what are the molecular actions of glucocorticoids
glucocorticoid enters cell and binds to intracellular receptor site
drug receptor complex activates transcription in nucleus, mRNA is translated into effector protein
anti inflammatory effects of glucocorticoids are partly explained by the effector proteins; lipocortins
what are effects of lipocortins
they are calcium regulated phospholipid binding proteins
in presence of micromolar calcium concentrations lipocortins bind to phospholipids
they inhibit activity of phospholipase A2, result is reduced production of arachidonic acid and platelet activating factor
how do glucocorticoids act immunosupressively
they inhibit induction and effector phases of immune response
anti inflammatory effect partly due to inhibition of autacoid production
what are unwated effects of glucocorticoid treatment
suppression of hypothalamic-pituitary-adrenal function
cushings syndrome if steroid treatment stopped
what are overall effects of glucocorticoids
decreased;
migration of neutrophils in inflammation
activatoin of neutrophils and macrophages
activation of T lymphocytes and clonal expansion
fibroblast activation and osteoblast activation
they are anti-inflammatory and immunosuppressive
what are examples of exogenous glucocorticoids used in steroid treatment
prednisolone, betamethasone
what are other treatments used for inflammation
biologics: biomolecules used to target inflammatory mediators
benefit of biologics is that they are specific so less side effects
however they require a lot of RandD and pharmacokinetics are poorly understood
e.g anti TNFalpha antibodies
what are benefits/ cons of steroids vs NSAIDs
NSAIDs have anti-inflammatory actions, analgesic effects and anti-pyretic effects however can cause negative GI effects, renal effects and skin reactions, also non aspirin NSAIDs increase chance of thrombosis
steroids: cannot simply stop steroid treatment due to feedback mechanisms reducing HPA axis function (cushings syndrome), decreased healing response
