1. Plasma kinins

2. 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

3. Synthesis and catabolism of plasma kinins: Kallikrein (plasma) HMW kininogen bradykinin aminopeptidasekininases I & II* inactive metabolites LMW kininogen kallidin Kallikrein (tissues, glands, kidney) *kininase II is identical with ACE

4. Renin-angiotensin-aldosterone axis Angiotensinogen Renin Angiotensin I ACE Angiotensin II Aldosterone

5. Pharmacological and physiological effects to kinins: Mediated through interaction with at least 2 different types of receptors Mechanisms involved: - ↑ Prostaglandin production - ↑ NO production - ↑ cAMP, cGMP, IP3, DAG

6. 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 asthmatics, dry cough

7. 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

8. 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 pre- or postoperative bleeding