The document presents information on kinins, which are vasoactive polypeptides formed from plasma kininogen through proteolytic reactions and have important roles in inflammation and pain sensation through their actions on B1 and B2 receptors. It discusses the generation and metabolism of kinins, their receptors, physiological actions including vasodilation and increased capillary permeability, pathophysiological roles in inflammation and angioedema, and bradykinin antagonists used to treat conditions like hereditary angioedema.

1. A PRESENTATION ON
KININS
Submitted to : Dr. Harikrishna Reddy
M. Pharm, PhD
Assistant Professor
Department of Pharmacology
Prepared by: Raja Babu
Reg. No. : 21mpclgy10
M. Pharm (Pharmacology)
1st semester

2. CONTENT
• Kinins
• Generation & Metabolism of kinins
• Receptors of kinins
• Actions of kinins
• Pathophysiological roles of kinins
• Bradykinin antagonist

3. Kinins
• Vasoactive polypeptides
• Formed from a plasma globulin Kininogen
• Enzymes involved Kallikreins
• Generated by proteolytic reactions triggered by tissue injury, inflammation,
allergic reactions, etc.
• Important kinins are :-
1. Kallidin (decapeptide)
2. Bradykinin (nonapeptide)
Discovered around 1950, during hypotensive activity investigation of urine
& snake venom

4. Generation and metabolism of kinins
(t1/2)Kinins < 1 min

5. Kinins receptors
Two types of receptors:-
B1 receptors (des-Arg metabolites)
B2 receptors (Kallidin & Bradykinin)
Both are GPCRs
B1 receptors
• Mediate kinin action in inflamed
tissue
• Cause contraction of veins, large
vessels, enhance PG synthesis, etc
B2 receptors
• Mediate kinin action in noninflamed
tissue
• Visceral smooth muscle contraction
(intestine, uterus, airway)
• Vascular endothelium (NO release, VD,.)
• Sensory nerves (acute pain)

6. Actions of Kinins
• Blood vessels:
Potent vasodilator (via endothelial NO & PGI2) ; arterioles
Large arteries, most veins and vessels with damaged endothelial are
constricted
Increased capillary permeability due to separation of endothelial cells
No direct effect on heart; reflex stimulation due to fall in BP (IV)
• Smooth muscles:
Slow contraction of intestine
Bronchoconstriction in guineapigs & asthmatic patients

7. • Neurones
Strongly stimulates nociceptive afferents and produces burning
sensation
Bradykinin produces intense, transient pain so used in analgesic
testing
Increase permeability BBB (IC)
• Kidney :
Increase renal blood flow
Facilitates water and salt excretion

8. Pathophysiological roles of Kinins
• Mediation of inflammation
All signs of inflammation (redness, exudation, pain, leukocyte mobilization)
 Via B1 receptor (IL-1, TNF-, etc)
• Mediation of pain
By stimulating pain nerve ending & increasing PG production
• Major role in development of angioedema
• Hereditary angioedema
Due to deficiency of complement (C1) esterase inhibitor
bradykinin level increases

9. Bradykinin antagonists
• Icatibant
Synthetic
Bradykinin B2 receptor antagonists
Resistant to kinin degrading enzymes
Duration of action = 6hrs.
Reverse symptoms of Hereditary angioedema

10. Reference
• Tripathi KD, Essential of Medical Pharmacology,8th Edition

11. THANK
YOU