exam 1: NSAIDS, DMARDS, Flashcards
(56 cards)
3 phases of inflammation
acute inflam
immune response
chronic inflam
what mediator do we really want to target
Prostaglandins
Stimulus –> Phopholipids –> arachidonic acid via phospholipase a2 –> leukotrienes via lipoxygenase or PG, TXA2, Prostacylcin via cyclooxygenase
*what inhibits where
Steroids inhibit Phospholipase
NSAIDS/ASA inhibit cyclooxygenase
Lipoxygenase inhibitors inhibit Leukotriene formation
ASA actions
Nonselective irreversible inhibitor of COX1,2
- antiinflam
- antipyretic
- analgesic
- anti platelet (irreversible)
PK of ASA
simple organic acid good fast oral absorption
- Wide distribution, crosses placenta, slowly crosses BBB
- concentration may reach value 20x higher in mucosal cell than lumen of stomach
- Rapid hydrolysis in plasma, liver and RBC
- binds plasma proteins, competes with other acids for binding sites
Metabolism of ASA
low dose = first order high dose (above 600 mg body burden) = zero order
*renal excretions (thus alkalinization of urine promotes excretion)
Uses for ASA
mild to moderate pain antipyresis anti-inflamm (NSAID) MI, thrombosis prophylaxis long term use decreases colon CA
Adverse effect of ASA related to a/b balance
ASA is an acid, makes pH more acidic resulting in increased resp (stimulation). This increases O2 whil CO2 decreases ultimately resulting in resp alkalosis. Resp alkalosis will cause resp depression ultimately resulting in resp acidosis
At toxic doses: resp acidosis combined with metabolic acidosis (ASA is an acid), K loss, dehydration and cardiovascular collapse
How does ASA effect platelets and bleeding. What caution should be taken
ASA (no Na salicylate) inhibits plt aggregation thus increasing bleeding time (single dose 650 mg doubles)
- effect may last 8-10 d
- avoid ASA use in pt with:
1. hypoprothrombinemia
2. Vit K def
3. Hemophilia
4. Severe hepatic damage - avoid 1 wk before surgery and prior to labor (last three months of preg)
How does ASA effect Uric acid levels
at low dose (1-2 g) ASA decreases excretion (higher plasma urate)
At large doses (>5g), ASA is uricosuric (but these high doses often have bad GI SE)
What effects does ASA have on heart and lungs?
Heart - minimla in reg dose
Lungs: ASA asthma bc ARACHIDONIC acid is shunted to form leukotrienes
How does ASA affect the GI and how can this be addressed
GI upset, gastritis, ulcer, bleeding
*use buffered form, take with food, take combined with misoprostol
How does ASA affect kidneys?
Renal damage, acute renal failure, interstitial nephritis
- NSAIDS inhibit PG synthesis leaving actions of vasoconstricitors (Ang II, Catecholamines, vasopressin) unopposed
- PG synthesis normally antagonizes intrarenal effects of vasoconstrictors
What effects does ASA have on skin
Salicylic acid (not ASA) destroys epithelial cells, a keratolytic effect used for wart removal, corns, fungal infection and dermatitis (note that salts of salicylic acid have no effect on unbroken skin)
Methyl salicylates (oil of wintergreen) is irritating to skin and mucosa
which effects does ASA have first (at therapeutic dose).. simultaneous complications?
antiplt –> antipyretic –> analgesic –> uricosuric –> antiinflammatory
*SE: gastric intolerance, bleeding, hypersensitivity reactions, impaired hemostasis
ASA should be decreased during long term tx with…
oral anticoagulants, hypoglycemic agents etc
ASA should be avoided in pt with
gastric ulcer, severe hepatic damage, hypoprothrombinemia, vit K def, hemophilia, hypersens
What are fatal/poisonous doses of ASA
Fatal dose 20 g (10-30) of ASA
For methyl salicylate (oil of wintergreen) 4-5 mL
What is Reyes syndrome
cerebral edema in children with viral infections, NO ASA, the DOC is acetaminophen
What are the nonacetylated salicylates
Mg choline salicylate
Na salicylate
Salicyl Salicylate
*effective antiinflamm, less analgesic, NOT IRREVERSIBLE
What is Diflunisal
Salicylic acid derivative, no antipyretic
What is Celecoxib (celebrex) and indicated use? SE? CI?
reversible COX2 inhibitor, less GI adverse effects, oral admin
SE: Increased risk for cardiovascular disease
CI: GI dz (active PUD), asthma, breast feeding, preg, renal failure
What does COX 1 do? COX2?
COX-1: promotes inflam, protects against gastric irritation, promotes plt agg (TXA2), vasoconstriciton (TXA2)
COX2: inflam, protects GI, Inihbits platelet agg (PGI2), vasoDILATION (PGI2)
*this is why selectively inhibiting COX 2 increases risk heart dz (platelet aggregation and vasoconstriction uninhibited)
General overview of nonspecific reversible inhibitors of COX1 and 2
various chemical structures, similar effect of asa but are reversible *variable SE freq but basically the same *varible PHK DOC: Ibuprofen bc best SE profile Worst: indomethacin, phenylbutazone
