anti inflammatory drugs Flashcards

1
Q

how are glucocorticoids produced and what is the HPA axis

A

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)

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2
Q

what is role of HSD in steroid synthesis

A

HSD2 converts cortisol to cortisone

HSD1 converts cortisone to cortisol

cortisone acts as negative feedback for mineralocorticoid and glucocorticoid synthesis

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3
Q

what are the molecular actions of glucocorticoids

A

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

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4
Q

what are effects of lipocortins

A

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

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5
Q

how do glucocorticoids act immunosupressively

A

they inhibit induction and effector phases of immune response

anti inflammatory effect partly due to inhibition of autacoid production

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6
Q

what are unwated effects of glucocorticoid treatment

A

suppression of hypothalamic-pituitary-adrenal function

cushings syndrome if steroid treatment stopped

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7
Q

what are overall effects of glucocorticoids

A

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

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8
Q

what are examples of exogenous glucocorticoids used in steroid treatment

A

prednisolone, betamethasone

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9
Q

what are other treatments used for inflammation

A

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

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10
Q

what are benefits/ cons of steroids vs NSAIDs

A

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

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