anti-inflammatory agents Flashcards
what is the HPA axis?
stress stimulates the hypothalamus. it releases CRH, which causes the pituitary to release ACTH. ACTH stimualtes the adrenal cortex to make cortisol. cortisol inhibits CRH and ACTH release.
How do glucocorticoids work?
bind to the glucocorticoid receptor in cytoplasm, which is sequestered by heat shock proteins. this leads to release of heat shock proteins and translocation to the nucleus. glucocorticoids act as transcriptional inducesrs by interacting with glucocorticoid response elements and inhibiting transcription.
inhibits transcription factors like NF-kB. also alters cytokine/chemokine production, cell trafficking, survival
when are glucocorticoids useful?
rapid control of acute inflammation chronic control of autoimmune disease topical application intra-articular injections spinal cord injury? stim of surfactant in pre-term babies
what should I know about dosing glucocorticoids?
high doses can be life saving and tolerated for short periods
long term use: requires titration to minimum dose
if given for more than 1 wk, titrate dose to avoid adrenal insufficiency
Side effects of glucocorticoids
edema and HTN, hyperglycemia and fat redistribution, incr. susceptibility to infection, osteoporosis and osteonecrosis, psychosis, peptid ulcers, cataracts and growth retardation in kids
NSAIDs: general mechanism, uses
inhibit prostaglandin synthesis by inhibiting cyclooxygenase enzyme. usually competittive. anti-inflammatory, analgesic, anti-pyretic
selective NSAIDs
COX-2 selective
maloxicam, celecoxib
How does aspirin work?
covalently modifies COX active site. inhibits COX1 and 2 at high doses; selective anti-platelet action at low doses.
general schematic of prostaglanding biosynthesis
PLA2 from membrane made to arachidonic acid. AA converted by COX1 to PGH2 for homeostasis (constitutive prostaglandins)
AA converted by COX2 to PGH2 to make acute responses.
adverse effects of NSAIDs
allergies, gastric irritation, ulcers, bleeding, slowed wound healing, renal effects (edema, HTN)
what do you see with aspirin overdose?
vomiting, tinnitus, metabolic acidosis, resp depression
what are the disadvantages of coxibs?
incr CV and thrombogenic risks, potentially
What factors increase or mitigate risks of liver toxicity seen in acetaminophen?
incr: EtOH
decr: give N-acetylcystein to try to reduce toxicities in ppl experiencing liver probs.
tx of acute gout
colchicine or indomethacin (potent NSAID for short term use)
chronic tx of gout
allopurino (inhibits xanthine oxidase) or uricosuric agents that block renal absorption of uric acid
