Aspirin Flashcards
Rev Edward Stone
Has “epiphany” while relaxing under a willow tree
Bitter taste of bark reminds him of quinine used for malaria
salicin
breaks down into salicylic acid and a sugar in the intestine and liver
Spiraea ulmaria
Meadowsweet
Gaultheria procumbens
Wintergreen
Hippocrates (Greece)
uses willow leaf to ease the pain in child birth
Swiss pharmacist Johann Pagenstecher and later by German research Karl Jacob Lowig
found salicin in meadowsweet flower
Felix Hoffman (Bayer)
finds that addition of an acetyl group to salicylic acid reduces its irritant properties; Bayer patents the process
Aspirin in modern history
Used to treat hypertension with the greatest benefit seen in preventing heart attacks.
primary-prevention tool to reduce the risk of stroke increasing risk of heart attack or death from cardiovascular causes
reduces risk of colorectal, stomach and esophageal cancers
What does Asprin stand for?
“A” = Acetyl group
“Spir” = is derived from Spiraea ulmaria (meadowsweet)
“In” = was a common suffix used for drugs at the time of the first stable synthesis of acetylsalicylic acid
Elevated SA accumulation
mpk4
If this is knocked out - dysregulation of the system - SA is produced all the time
Reduced SA accumulation
eds1, pad4, sid1, sid2
All of these enzymes are important for the production of SA
If these are knocked out - no SA (eds1/pad4) or very little amount
Bifunctional enzymes
includescyclooxygenase and peroxidase activity
COX-1
Located in the kidney, stomach and platelets
COX-2
Located in macrophages, leukocytes and fibroblasts
Low doses inhibit COX-1 for the lifetime of the platelet
Platelets cannot synthesize new enzyme enabling low dose ASA to be an effective antiplatelet drug
Higher doses inhibits both isoforms of COX
The combination of COX-1 and (at higher doses) COX-2 inhibition are the molecular basis for aspirin’s analgesic (pain), antipyretic (fever) and anti-inflammatory (swelling) effects
PGH2
most common precursor for the five principal prostaglandins
Important biological roles of Prostaglandins
Aggregation of platelets
Induction of labor
Regulate cell growth
Regulate fever
Von euler
Thought that the acidic lipid was produced in prostate
Called them: Prostaglandins
Vane, Bergstorm and Samuelsson
Find the effect is from several closely related compounds
Elucidated structures of PGE1 and PG F2a from sheep
Bergstorm
Biosynthesis of PGE2 from Arachidonic Acid
Medicinal 5’-Lipoxygenase Inhibitors
Baicalein:
Root - Scutellaria Lateriflora
Caffeic acid:
Bark - Eucalyptus globulus
Freshwater fern - Salvinia molesta
Mushroom - Phellinus linteus
Curcumin: Curcuma longa (Tumeric)
Hyperforin: Hypericum perforatum (St. John’s Wort)
NSAIDS
Targeted inhibition of COX1/2 synthesis of prostaglandins (anti-inflammatory capabilities)
Pain reducing and anti-inflammatory
Acetaminophen
Targeted inhibition COX2/3 synthesis of prostaglandins (no anti-inflammatory effects)
Alkaloid
Pain reducing only (can be used by pregnant women)=
