Transcript alert_21_circ_2005_112_759

Molecular pathways for formation
of eicosanoids and prostanoids
E.M. Antman, Circulation 2005; 112: 759-770
The 9 chemical groupings of NSAIDs are shown, along
with key compounds in each class. Relative degree of COX-1
vs COX-2 selectivity is shown at the bottom of the figure
E.M. Antman, Circulation 2005; 112: 759-770
Comparison of COX-1 and COX-2 Enzymes
E.M. Antman, Circulation 2005; 112: 759-770
Structural determinants of inhibition
of arachidonic acid binding to COXs
E.M. Antman, Circulation 2005; 112: 759-770
Consequences of
COX inhibition for
prostacyclin and
thromboxane A2
production in
normal and
atherosclerotic
arteries
Endothelial cells are shown as
a source of prostacyclin
(PGI2)
and platelets as a source of
thromboxane A2 (TxA2)
E.M. Antman, Circulation 2005; 112: 759-770
Relationships between vascular eicosanoids
and NO under normal conditions (A) and
in inflammatory states (B)
E.M. Antman, Circulation 2005; 112: 759-770
Biostatistical considerations in a trial of a
coxib vs placebo. Left, Main findings of the
APC trial
Right, A 2x2 table is used to arrange the data
for the calculation of statistical tests of
treatment effect
E.M. Antman, Circulation 2005; 112: 759-770
Detection of harm with coxibs. Factors
related to trial design (top) and to the patient
and drug being investigated (bottom) are
shown
E.M. Antman, Circulation 2005; 112: 759-770
Number needed to harm
E.M. Antman, Circulation 2005; 112: 759-770