Kinins

Pharmacology, Bradykinins, Kallidins

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 :- Kallidin (decapeptide) Bradykinin (nonapeptide) Discovered around 1950, during hypotensive activity investigation of urine & snake venom

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

5. Kinins receptors Two types of receptors:- B 1 receptors (des-Arg metabolites) B 2 receptors (Kallidin & Bradykinin) Both are GPCRs B 1 receptors Mediate kinin action in inflamed tissue Cause contraction of veins, large vessels, enhance PG synthesis, etc B 2 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 & PGI 2 ) ; 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,8 th Edition

11. THANK YOU