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
aminopeptidase kininases 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
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