Block 2: Adrenal Steroids and Immunopharm Flashcards
synthesis of aldosterone is controlled by what?
angiotensin II and plasma potassium
what are the effects of adrenal steroids on carbohydrate and protein metabolism and what receptor mediates these effects?
enhances liver gluconeogenesis, increases plasma glucose, stimulates amino acid mobilization, increases liver glycogen,
glucocorticoid receptor
what are the effects of adrenal steroids on mineral and electrolyte metabolism and what receptor mediates these effects?
increases sodium reabsorption, increases potassium excretion,
mineralocorticoid receptor
4 actions of adrenal steroids on immune system?
- inhibition of cytokines
- inhibition of phospholipase A2
- inhibition of COX-2
- inhibition of cell adhesion molecule expression
what is the biggest fear in prescribing steroid drugs?
abrupt discontinuation may be life-threatening due to adrenal insufficiency
name 5 steroid drugs
cortisol, dexamethasone, prednisone, fludrocortisone, aldosterone
uses of steroid drugs
adrenal insufficiency, rheumatoid arthritis, osteoarthritis, allergic disease, inflammatory disease, cerebral edema, transplantation, liver and renal diseases
name 3 adrenal steroid antagonists
mifepristone, spironolactone, eplerenone
mifepristone: what is it, uses
competitive antagonist at progesterone and glucocorticoid receptor
uses: termination of pregnancy, Cushing’s disease
spironolactone and eplerenone: what are they, therapeutic uses
aldosterone antagonists
uses: diuretics, hypertension, cardiac hypertrophy and heart failure
IL-1: cellular source, actions
source: macrophages
actions: activates lymphocytes, promotes differentiation of plasma cells, endogenous pyrogen
IL-2: cellular source, action
source: T cells
action: growth factor for T cells, enhances tumoricytic activity of lymphocytes
TNF-alpha inhibitors (2), uses
etanercept and infliximab
uses: rheumatoid arthritis and Crohn’s disease
prednisolone: what is it, therapeutic uses
synthetic glucocorticoid
uses: used in combination with other drugs in autoimmune diseases and to prevent graft rejection; adrenal cortical insufficiency (have both mineralocorticoid and glucocorticoid activity)
name 3 cytotoxic agents
azathioprine, cyclophosphamide, methotrexate
azathioprine: mechanism, therapeutic uses, toxicity
inhibits de novo and salvage purine biosynthesis (DNA synthesis)
uses: inhibit rejection of transplanted organs, rheumatoid arthritis
toxicity: bone marrow depression, GI and hepatic toxicity
cyclophosphamide: mechanism, therapeutic uses, toxicity
alkylating agent that results in cross-linking of DNA, suppresses B cells/humoral immunity
uses: autoimmune disease
toxicity: bone marrow depression
methotrexate: mechanism, therapeutic use, toxicity
inhibitor of dihydrofolate reductase necessary for purine synthesis = inhibits DNA synthesis
use: autoimmune disease
toxicity: hepatotoxicity
mycophenolate mofetil: mechanism, uses, toxicity
inhibits IMP dehydrogenase necessary for de novo purine synthesis, selectively toxic for lymphocytes, inhibits lymphocyte proliferation
uses: used with cyclosporine and corticosteroids to prevent renal allograft rejection; rheumatoid arthritis
toxicity: contraindicated in pregnancy
cyclosporine: mechanism, therapeutic uses, toxicity
binds to cellular receptor and inhibits calcineurin –> blocks IL-2 synthesis
uses: prevent organ rejection
toxicity: nephrotoxicity and hepatotoxicity
tacrolimus: mechanism, therapeutic uses, unique aspects
binds FK binding protein, inhibits calcineurin and therefore reduces IL-2 synthesis (same as cyclosporine)
uses: prevent organ rejection (same as cyclosporine)
unique aspects: 50-100 times more potent than cyclosporine, less nephro- and hepatotoxicity
sirolimus: mechanism, therapeutic uses
binds FK binding protein –> inhibits mTOR involved in cell cycle progression = inhibits downstream effects of IL-2 (T cell activation, proliferation)
uses: prevents organ rejection (same as cyclosporine and tacrolimus)
what 2 drugs can you prescribe for adrenal insufficiency?
prednisolone, cortisol
