NSAIDs MOA
inhibit COX enzymes leading to decreased prostaglandin synthesis
NSAIDs therapeutic uses
anti inflammatory (reduce swelling)
analgesia (reduce pain)
antipyretic (reduce fever)
prostaglandins cause pain, attract WBC to site of inflammation, stimulates fever
NSAID absorption, metabolism, and elimination
well absorbed w minimal food impact
CYP pathways in the liver
renal and biliary excretion
NSAID adverse effects
GI - dyspepsia to bleeding (black box warning for all NSAIDs except ASA)
increased risk of bleeding (antiplatelet effect)
renal effects
increased risk for cardiovascular effects (black box warning all NSAIDs except ASA)
NSAIDs GI mucosa COX inhibition
COX-1
NSAIDs kidney COX inhibition
COX 1 & 2
NSAIDs cardiovascular COX inhibition
COX-2 greater than COX-1
selective COX-2 inhibitors advantages
reduced GI toxicity, lack of platelet inhibition
Celecoxib only available agent
selective COX-2 inhibitors disadvantages
increased cardiovascular risks, inhibit vasodilation
acetaminophen MOA
inhibits prostaglandin synthesis in the CNS for fever and pain relief
adrenocortical hormones
glucocorticoids: cortisol
-intermediary metabolism and immune function
mineralocorticoids: aldosterone
-salt-retaining activity
androgens: dehydroepiandrosterone (DHEA)
glucocorticoids MOA
- bind to intracellular receptors
- regulate gene transcription
- effects: physiologic, anti inflammatory, immunosuppressive
glucocorticoids physiologic effects
direct (cellular actions) or indirect (homeostatic responses)
influence nearly all cells in the body
permissive effects
maintain glucose levels, immune balance
glucocorticoids pharmacologic (high dose) effects
suppress inflammation and immunity
alter metabolism (hyperglycemia, lipolysis)
glucocorticoids anti-inflammatory and immunosuppresion
inflammation pathway inhibited, neutrophils increase but lymphocytes and monocytes decrease
inhibit macrophages and other APCs by decreasing cytokines
reduce expression of COX-2
adverse effects of glucocorticoids
short term (less than 2 weeks): usually well tolerated but can have transient symptoms of insomnia, behavioral changes, acute peptic ulcers, hyperglycemia, fluid retention, acute pancreatitis
long term: adrenal suppression, Iatrogenic Cushing syndrome (hypercortisolism)
