Plasma kinins

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 syndromeetc
• 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.Vs 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