Summary Pharmacodynamics in a nutshell

BRADYKININ:

 Vasoactive peptides
 Kallidin is a closely related peptide (1 additional A/a residue)
 Formed by action of enzymes on protein substrates called KININOGENS

KININOGENS in liver (HMW) + Kallikrein  Bradykinin  Kallidin (lysyl-bradykinin)

Prekallikrein (plasma) = inactive precursor of proteolytic enzyme kallikrein

Kininogen (plasma alpa-globulin)  kallikrein  bradykinin

↑ Vascular permeability during inflammation (Hageman factor)

 Prekallikrein and kininogen leak out of vessels with plasma  bradykinin

PHARMACOLOGICAL ACTION of Bradykinin

 VasoDILATION
 Endothelial cell dependent
 Caused by NO production and accumulation of PLA 2
 Releasing PGI2

 ↑ vascular permeability
 Stimulation of:
 Pain nerve endings
 Epithelial ion transport/fluid secretion in airways and GIT
 Contraction of smooth muscle:
 Uterine
 Intestinal



INACTIVATION of Bradykinin

 By kininases (with related kinins)
 Kinininase 2 = active vasoconstrictor
Angiotensin 1  Angiotensin 2
 Inactivates a vasodilator
 Activated a vasoconstrictor




Kininogen