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Plasma kinins

Learn about plasma kinins – kallidin and bradykinin, their role in inflammation, highest and low levels in clinical situations like shock, pancreatitis, hypertension, and their synthesis, catabolism, and physiological effects. Explore therapeutic considerations including synthetic kinin analogs, ACE inhibitors, and kallikrein inhibitors.

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Plasma kinins

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  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

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