Pharmacology of Non-Opiates Flashcards
NSAIDs by structure
-salicylates (aspirin)
-arylpropionic acids (ibuprofen, naproxen)
-arylacetic acids (indomethacin and -acs)
-enolic acids (-oxicams)
Analgesic applications of NSAIDS
-chronic post-surgery pain (potentially inhibit bone healing)
-myalgias and arthralgias/sprains/strains
-inflammatory pain
-dysmenorrhea (specific PGE effect)
Anti-inflammatory uses of NSAIDs
-bursitis and tendonitis
-osteoarthritis
-rheumatoid arthritis
-gout/hyperuricemia
-rib fractures
Other applications of NSAIDs
-antipyretic (fever)
-aspirin t antiplatelet effect
Inflammatory reponse to injury
-acute (vasodilation)
-subacute (infiltration)
-chronic (proliferation)
Eicosanoids
-arachidonic acid metabolites!
-prostaglandins
-thromboxanes
-leukotrienes
-cytokines
-recruitment contributes to pain
COX inhbition MOA
-inhibits arachadonic acid from breaking down into prostanoids
-COX-1: TXA2, GI mucosa
-both PGE2 and PGI2
-COX-2: more nociceptors
Aspirin MOA
-IRREVERSIBLE binds COX1/2 by acetylation
-modifies COX2 activity = produce lipoxins
-duration of effect corresponds to time required for new protein synthesis
non-aspirin NSAID MOA
-competitive REVERSIBLE inhibitors of COX1/2
-some arylacetic acids also inhibit leukotriene sysnthesis = antiinflamatory (indomethacin and diclofenac)
Aspirin use
-freq used as prophylactic for anti-coagulation
-no tolerance development to analgesic effects
-Reye’s syndrome risk in children w viral fever
Absorption of aspirin (salicylates)
-rapid
-passive diffusion of unionized acid aat gastric pH
-delayed by food
Distribution of aspirin/salicylates
-throughout most tissues and fluids
-competes w many drugs for protein binding sites
Metabolism and excretion of aspirin/salicylates
-aspirin t1/2 15min (hydrolysis)
-salicylate t1/2 6-20h! dose dependent (saturated)
-active secretion and passive reabsorption in renal tubule
-inc excretion w increased urinary pH (IV bicarb)
Asprin poisonin
-vertigo, tinnitus, hearing probs
-N/V, sweating, fever
-stimulation followed by depression
-delirium/confusion/psychosis
-RESPIRATORY ALKALOSIS (caused by hyperventilation)
-METABOLIC ACIDOSIS (lower blood pH)
Aspirin poisoning tx
-reduce aspirin load
-inc urinary excretion (dextrose, sodium bicarbonate)
-trap in urine pKa of aspirin is 3 = ionized in urine = can’t go back
-correct metabolic imbalance
Arylproponic acids (ibuprofen, naproxen)
-REVERSIBLE cox
-ib: 2h t1/2
-nap: 14 t1/2
-better tolerated than aspirin
-interpt variation in response
Arylacetic acids
-Diclofenac
-Indomethacin
-Sulindac
Diclofenac
-gel
-good alt to ibuprofen/nap
-inc risk of peptic ulcer and renal probs
-arthrotec for chronic use (misoprostol = PGE1 analog)
Indomethacin
-one of most potent reversible inhibitors of PG synthesis
-high incidence and severity of side effects long-term
-use for acute gouty arthritis, akylosing spondylitis
Sulindac
-less toxic derivative of indomethacin
-still significant side effects
-rheumatoid arthritis and ankylosing spoloditis
Enolic acid MOA (meloxicam)
-COX-2 at low doses
-long t1/2
-meloxicam: 20h
-Piroxicam: 57h
-tx arthritis
-great joint penetration
-less GI effects
Adverse effects of NSAIDs
-renal function
-inc bleed risk (GI) (inhibit platelet aggregation)
-inhibit uterine motility
-gastrointestinal distress/ulceration
Renal function and NSAIDs
-inhibition of renal PGE2 sunthesis = inc Na reabsorption = peripheral edema!
-higher risk w longer t1/2 and long-term use
Inhibition of uterine mobility of NSAIDs
-therapeutic use for delaying preterm labor
