lecture 75 Flashcards
li - pharmacology of non-opiate drugs
what are the structures associated with NSAIDs?
salicylate – ASA
arylpropionic acids – ibuprofen, naproxen
arylacetic acids – indomethacin, diclofenac, ketorolac, etodolac
enolic acid – prioxicam, meloxicam
what are the therapeutic usages of NSAIDs?
analgesic
anti-inflammatory
antipyretic (fever)
prophylactic to reduce risk of MI (ASA)
what are the phases of inflammatory response?
acute (vasodilation, increased permeability)
subacute (infiltration)
chronic (proliferation)
what eiconsanoids are recruited by mediators to the site of pain?
arachidonic acid metabolites
prostaglandins (causes redness, heat, pain)
thromboxanes
leukotrienes (causes swelling)
cytokines (causes pain)
what is the moa of ASA?
irreversible COX-1 and COX-2 inhibitor through acetylation and produces lipoxins
what is unique about indomethacin and diclofenac?
inhibit leukotriene synthesis and produce anti-inflammatory effects as a result
what are the pros and cons of aspirin?
pro – can be used as prophylactic for anti-cog; do not cause any tolerance to its analgesic effects
cons – can cause reye’s syndrome
what is the absorption of ASA?
rapidly absorbed through passive diffusion at gastric pH (delayed by food)
half life of 6-20 hours
what is the impact of urinary pH on ASA?
increased excretion with increased urinary pH (IV bicarb)
how does ASA poisoning (salicyclism) present?
vertigo
tinnitus
NV
respiratory alkalosis (hyperventilation)
metabolic acidosis
how should ASA poisoning be treated?
reduce ASA load by increasing urinary excretion through dextrose or sodium bicarb admin
correct metabolic imbalance
what are the half lives of ibuprofen and naproxen?
I - 2 hours
N - 14 hours
what is arthrotec?
combination product of diclofenac and misoprostol-PGE1 analog (used to reduce AE) that is used for chronic pain
what are the risks associated with diclofenac?
peptic ulcer and renal dysfunc
what are the risks associated with indomethacin?
one of the most potent reversible inhibitors of prostaglandin synthesis
high incidence and severity of SE when used long term
what is sulindac?
less toxic derivative of indomethacin used for RA and AS
what are key characteristics of meloxicam?
use – arthritis
selectivity – COX-2 at low doses
half life – 20 hours
what is the half life of piroxicam?
57 hrs
what are the AE of NSAIDs?
reduce renal func (particular for longer half life and longer use)
peripheral edema (due to increased Na reabsorption from inhibition of renal PGE2 synthesis)
bleeding
inhibition of uterine motility
GI distress/ulcers (increased risk if over 65y)
what is misoprostol used for?
to treat GI distress/ulceration secondary to NSAID use
why would acetaminophen be preferred over other NSAIDs?
no GI toxicity
no effect on platelet aggregation
no correlation with reye’s syndrome
can use in liver disease pts if under 2 g/day
why would acetaminophen not be used in comparison to NSAIDs?
little anti-inflammatory activity
risk of hepatic necrosis with OD
what are the AE of acetaminophen?
renal toxicity
papillary necrosis (due to vasoconstriction by PGE2 inhibition)
hepatic necrosis
what is the interaction between alcohol and acetaminophen?
alcohol increases CYP450 enzymes –> increase of NAPQI, which a toxic acetaminophen metabolite –> increases risk of hepatic necrosis
