Pharmacology of Immunomodulary Drugs Flashcards
adrenocorticosteroids
steroids released by the adrenal cortex
*3 main categories
1. glucocorticoids (metabolic and immune activity - cortisol)
2. mineralocorticoids (salt-retaining activity - aldosterone)
3. androgenic or estrogenic activity
normal glucocorticoid secretion
*cortisol secreted normally in low stress conditions
*stimulated by ACTH (pituitary hormone)
*highest in early morning - circadian rhythm
glucocorticoids - big picture - mechanism of action
*most effects are from ALTERING GENE EXPRESSION, leading to changes in protein synthesis
*this takes time
mechanism of action - glucocorticoids (detailed)
- steroid dissociated from CBG (corticosteroid-binding globulin)
- intracellular glucocorticoid receptors (GR) are bound to chaperone proteins (including Hsp90)
- binding of steroids to GR causes release of chaperone proteins
- steroid-GR complex dimerizes and enters nucleus
- steroid-GR complex binds to glucocorticoid response element (GRE) on regulatory region of the gene (repressing or stimulating that gene)
metabolic effects of glucocorticoids
*increase serum glucose levels (various ways) and increase insulin secretion
*activates lipolysis (increases insulin resistance)
*promote protein breakdown
*breaking down bones (increases risk of fractures)
long-term results of metabolic effects of steroids
*decreased muscle mass
*buffalo hump (fat at back of neck)
*moon face (facial fat)
*osteoporosis
*thinning of the skin
*hyperglycemia/worsening of diabetes
anti-inflammatory effects of steroids
*INHIBIT phospholipase A2 (decreases prostaglandins)
*DECREASE expression of COX-2 (decreases prostaglandins)
effects of steroids on blood cells
*increases neutrophil concentration in circulation (reduces other WBCs)
*reduced ability of macrophages to fxn
*reduced production of inflammatory cytokines
other effects of steroids
*neurologically (initially, insomnia and euphoria; long-term, depression)
*peptic ulcers
*increases platelets and RBCs
names of synthetic glucocorticoids (steroids)
-hyrdocortisone
-cortisone
-prednisone
-prednisolone
-methylprednisone (SOLU-MEDROL)
-triamcinolone
-betamethasone
-dexamethasone (DECADRON)
short-term adverse effects of synthetic steroids
*neuro (insomnia, behavior changes, hypomania, acute psychosis)
*increased glucose
*increased appetite
*peptic ulcers
*GI upset
*mask signs of infection
long-term adverse effects of synthetic steroids
*fat redistribution
*increased hair on face
*acne
*muscle wasting
etc
adrenal suppression with synthetic steroids
-after ~14 days, the cortisol-producing cells are suppressed
*therefore, need to give them increased steroids if in “stressful situation” (sepsis)
*need to gradually taper off therapy rather than discontinuing abruptly
what must you do prior to starting a pt on long-term steroids
RULE OUT TUBERCULOSIS
immunosuppressant: rituximab (rituxan)
*depletes CD20 B lymphocytes
*used in oncology
*ADE: rash
