Cardiac enzymes 3 - Streptokinase Lecture No: 1st MBBS Dr Muhammad Ramzan

Streptokinase (SK) – the definition Is proteolytic Streptokinase (SK) is an enzyme secreted by several species of streptococci that can bind with and catalyze the : Conversion of  Plasminogen(PLG) to Plasmin SK is used as an  thrombolytic medication for MI , pulmonary embolism and deep vein thrombosis www. merrium - webster.com

Streptokinase – the background haemolytic streptococci β.C SK is fibrinolytic and prevents the unwanted clot growth and its complications like embolism SK is on the WHOs List of Essential Medicine. 1.5 million/vial It is a bacterial product can build up immunity SK may not be reused within 4 days 1.to prevent allergic reactions. 2. SK is ineffective if given within 4 days) www.science direct.com (ELSEVIER)

Plasminogen - PLG glycoprotein with 77 AAs PLG is a glycoprotein and is expressed in liver and kidneys PLG is encoded by its own gene and is secreted as Zymogen in blood as well as in ECF Genetic mutation in PLG gene may cause thrombophilia and Ligneous disease (Ligneous conjunctivitis) - PLG ranges from 10 - 16mg/dl in adults with a half life of 2.2 days www.plasminogen.com – www.emedicine.medscape.com. www.ncbi.nlm.nih.gov.

Fibrinolysis – resolves clots A Physiological process Fibrinolysis is the enzymatic breakdown of the fibrin in the blood clot that is formed in response to vascular injury. It is a physiological process and is catalyzed by the Plasmin Plasmin is a Protease enzyme present in the blood as its precursor – the Plasminogen The process clears fibrin deposits locally but does not cause systemic Fibrinolysis www.merrium- webster.com – www.medlineplus.gov.

Fibrinolysis

Fibrinolysis - Mechanism and significance Plasmin acts on its substrate , the Fibrin for its conversion to soluble fibrinogen degradation products. (FDPs) FDPs are unable to bind with PLG activators, so there is no further conversion of PLG to Plasmin Fibrinolysis 1. Removes thrombus, 2. prevents its growth and complications like embolism 3. It restores blood supply. www.merrium- webster.com – www.medlineplus.gov – www.basicmedicalkey.com

Vascular injury to Fibrinolysis

PLG to active Plasmin - the activators tPA is secreted in its inactive form The conversion of PLG to Plasmin is mediated by the tPA- 1 and Urokinase Plasminogen activator(uPA) Inactive tPA-1 is generated by the damaged vascular cells and is activated by the Urokinase Urokinase is produced in inactive form by epithelium of renal excretory ducts www.medicaldictionary.com

PLG to Plasmin – the inhibitors Major at 2 levels- tPAI and α2 antiplasmin PLG to Plasmin is inhibited by the Tissue Plasminogen activator inhibitor tPAI- 1-2- (for tPA-1) . 1 Generation of Plasmin is quickly inactivated by the main Inhibitor - α2- antiplasmin (alpha2- AP) 2 Congenital deficiency of α2- antiplasmin produces: .A rare bleeding disorder in females

PLG to Plasmin – activators and inhibitors

PLG to Plasmin – the inhibitors major at 2 levels

PLG - Secretion abnormalities Deficiency/Ligneous disease PLG can be secreted in excess or there can be its deficiency. Both can be congenital or acquired PLG Deficiency leads to the development of fibrin rich pseudo- membrane as Fibrin is not degraded normally) Fibrin gets deposited on various mucous membranes and tissues www.plasminogen.com

PLG deficiency – Ligneous disease PLG deficiency results in the failure of this mechanism, leading to deposition of fibrin that impairs: functions of the various body tissues PLG deficiency leads to Ligneous disease of body tissues The affected ones include eye; mouth (gums), respiratory and female reproductive organs www.plasminogen.com – Medical problems in dentistry by Scully,7th edition,2007

Ligneous conjunctivitis

Ligneous conjunctivitis

Ligneous gingivitis

SK and Thrombolysis - Mechanism of action PLG SK complex formation SK binds with the unbound PLG in blood clot to form : PLG Streptokinase complex - PLG SK complex The complex is activated by t-PA - 1 and Urokinase PLG SK complex then activates unbound PLG in the blood clot to form Plasmin

Mechanism of action of SK cont. Plasmin is a Serine Protease that degrades fibrin in blood clot to Soluble Degradation Products (FDPs) FDPS cannot bind with tPA-1 to activate PLG for Plasmin So there is no conversion of PLG to Plasmin Plasmin also degrades many Plasma proteins www.ahajournals.gov.

Mechanism of action of SK

Mechanism of SK action

Streptokinase – Major Indications SK can be given in the following conditions. Myocardial infarction Pulmonary thrombosis/embolism Deep vein thrombosis

SK – Contra indications CVS : severe/uncontrolled Hypertension CNS : stroke and Cerebral neoplasm/ haemorrhage Women : Pregnancy and delivery Age – children with PLG deficiency and allergy Recent surgery and trauma Recent history of peptic ulcer Previous history of SK. Allergy

Significance of SK - major Lyses of coronary, Pulmonary and deep vein thrombosis Reduction of the mortality rate with MI Reduction in infarct size and : improvement in ventricular/ lung function and : Restoration of blood flow

SK – the administration 1.5million U SK is given I/V in 60 mint. (100ml saline) as soon as possible after the ST elevation – best results within 4- 24hrs SK takes 90 minutes to be effective Dose should not be repeated within 4 days as It is ineffective within this period. May cause allergy Overdose is treated with amino Caproic acid or 150mg aspirin for 4 wks as adjuvant therapy after MI