Pharmacology of non-opiate analgesics Flashcards
amine autocoids
histamine
serotonin
lipid derived autocoids
prostaglandins
leukotrienes
peptide hormones
bradykinin
angiotensin
non classified class of autocoids
cytokines
timeline of non-opioids for pain
aspirin acetaminophen paracetamol ibuprofen indomethacin diclofenac naproxen piroxicam
Salicylates class of NSAIDs
aspirin
Arylpropionic acids class of NSAIDs
ibuprofen
naproxen
Arylacetic acids class of NSAIDs
indomethacin
diclofenac
ketorolac
etodolac
Enolic acids class of NSAIDs
piroxicam
meloxicam
2nd class of non-opioid that isn’t NSAID
p-Aminophenols
Only drug of p-aminophenols
acetaminophen
NSAIDs for analgesic
> headache: tylenol
chronic postsurgical pain: tylenol + opioid
myalgias/arthralgias/sprains/strains: ibuprofen
inflammatory pain: ibuprofen
dysmenorrhea(specific PGE effect): ibuprofen
NSAIDs for antipyretic
> fever: acetaminophen
NSAIDs for anti-inflammatory
bursitis and tendonitis osteoarthritis RA including ankylosing spondylitis gout and hyperuricemia rib fractures
5 symptoms of inflammation
rubor: redness
tumor: swelling
calor: heat
dolor: pain
…and loss of function
3 phases of inflammation
acute; vasodilation and increased permeability
subacute; infiltration
chronic; proliferation
mediators that recruit inflammatory cells
eicosanoids > arachidonic acid metabolites > PG; redness, heat > thromboxanes > leukotrienes; swelling > cytokines; pain
main function of NSAIDs; inhibit what and what pathway
cox inhibitors in the arachidonic pathway
cox-1 produces
prostanoids from arachadonic acid
prostanoids metabolites include
TXA2
PGE2
PGI2
function of TXA2
> prothombotic; increase platelet activation and clotting via gp2b3a
vasoconstriction
inhibitor acts as blood thinner
function of PGE2 and PGI2
> protect stomach lining cox 1 GI expression
inhibit acid secretion
promote mucus secretion
inhibition can lead to stomach ulcers
cox-1 expressed where
platelets, kidneys, stomach
function of PGI2 in vasculature
vasodilation
reduce platelet aggregation
cox-2 expressed where
brain
spinal cord
function of cox-2
> induced in setting of inflammation
> induced by cytokines and inflammatory mediators
MOA of aspirin
irreversibly inhibits cox-1 and modifies cox-2 by acetylation
Aspirin and cox-2
modified by acetylation to turn off its ability to produce PGE and activate its ability to produce protective lipid mediators
Arylacetic acids that inhibit leukotriene synthesis
indomethacin
diclofenac
Absorption of salicylates
> rapidly absorbed from stomach and jejunum
passive diffusion of free acid; gastric pH
delayed by presence of food
distribution of salicylates
> throughout most tissues and fluids
readily crosses placenta
competes with many drugs for protein binding sites
metabolism and excretion of salicylates
> aspirin t1/2 15min
salicylate t1/2 12hrs
active secretion and passive reabsorption in renal tubule
increased excretion with increased urinary pH
absorption of non-salicylate NSAIDs
> well absorbed from GI tract
metabolism of non-salicylate NSAIDs
> little first pass metabolism
> oxidation, demethylation, conjugation for metabolism
excretion of non-salicylate NSAIDs
> drugs and metabolites excreted primarly as conjugates
> active secretion of parent drug in renal tubule
Aspirin general use
> analgesia, antipyresis, anti-inflammatory
main use of anti-coagulation
no tolerance development
risk in treating children; Reye’s syndrome(rash, vomitting, liver necrosis)
Arylpropionic acids half life
Ibuprofen: 2hr
Naproxen: 14hr
NSAID for coronary artery disease
safest is naproxen
Diclofenac use
gel for arthritic pain
risk of diclofenac
> increased risk of peptic ulcer and renal dysfunction with prolonged use
Arthrotec description
> diclofenac/misoprostol mix
> misoprostol = PGE1 analog
indomethacin MOA
potent reversible inhibitors of PG biosynthesis
use for indomethacin
acute gouty arthritis, ankylosing spondylitis, pericarditis
ketorolac
> should not be given longer than 5 days
> available as IV
Use of enolic acids(Meloxicam, Piroxicam)
> treat arthritis
great joint penetration
one of the least GI side effects
Half lives of enolic acids
> Meloxicam: 20hrs
Piroxicam: 57hrs
low dose meloxicam is cox-2 selective
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