Plasma kinins Plasma kinins Kallidin and Bradykinin Involved
Plasma kinins
- - Plasma kinins Kallidin and Bradykinin Involved in edema, pain, erythema and fever of inflammation Highest levels in many clinical situations e. g traumatic shock, pancreatitis, peritonitis, Carcinoid syndrome…etc Low levels in certain patients with essential hypertension
n Synthesis and catabolism of plasma kinins: Kallikrein (plasma) HMW kininogen bradykinin aminopeptidase kininases I & II* inactive metabolites LMW kininogen kallidin Kallikrein (tissues, glands, kidney) *kininase II is identical with ACE
Renin-angiotensin-aldosterone axis Angiotensinogen Renin Angiotensin I ACE Angiotensin II Aldosterone
Pharmacological and physiological effects to kinins: Mediated through interaction with at least 2 different types of receptors Mechanisms involved: - ↑ Prostaglandin production - ↑ NO production - ↑ c. AMP, c. GMP, IP 3, DAG n
Effects of kinins : - B. V’s: Relaxation → dilatation → ↓ S & D B. P ↑ permeability → edema - Heart: Reflex ↑ H. R & CO - Stimulation of sensory nerve endings → initiation of pain signals - Bronchi: Constriction → distress in n asthmatics, dry cough
Therapeutic considerations: A. Conditions associated with low kinin levels e. g essential hypertension - Synthetic kinin analogs Not available (under evaluation) - Inhibition of metabolism ACE inhibitors - Kallikrein synthetic analogs Padutin ( pancreatic kallikrein ) orally effective Use in high B. P, ♂ infertility n
B. Conditions associated with high kinin levels e. g septic, anaphylactic, traumatic and hemorrhagic shock, pancreatitis, peritonitis, fat embolism syndrome, hyperfibrinolytic hemorrhage, inflammations… - Kinin antagonists Not available (under evaluation) - Kallikrein inhibitors Aprotinin Given I. V Plasmin inhibitor frequently used to stop preor postoperative bleeding
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