Test 2 Thrombolytics Flashcards
Acute Myocardial Infarction (AMI)
- affects 1.5 million each year in the US
- caused by coronary clot (thrombus)
coronary clots
aggregates of platelets, other blood cells and insoluble fibrin
Thrombolytics
lyse the fibrin in blood clot to produce fibrin degradation products which are soluble and thereby dissolve the clot
types of thrombolytics
Non Specific - Streptokinase - Urokinase Specific - Alteplase - Reteplase - Tenecteplase - Desmoteplase
What are the differences between specific and non-specific thrombolytics?
- non-specific: lyse platelet clots
- specific: senses just fibrin only when it’s activated
Alteplase
- First generation rThrombolytic agent
- recombinant human tissue-plasminogen activator
- promotes conversion of plasminogen to active plasmin
- degrades insoluble fibrin clot into soluble degradation products
Alteplase mechanism of action
- hydrolysis of Arg560 – Val561 peptide bond of plasminogen
- High affinity for fibrin; in presence of firbin -> enchance activation by 600 times
- strong activator of plasminogen
- clot specific -> causes fewer side effects
synthesis of Alteplase
- synthesized by vascular endothelial cells as a single chain polypeptide of 527 aa
- rt-PA is produced by cDNA cloning methodology
- DNA is obtained from mRNA of human melanoma cells and expressed in CHO cells
Therapeutic use of Alteplase
- Acute MI
- Reduction of incidence of CHF
- Acute massive pulmonary embolism
- Acute ischemic stroke
concerns of Alteplase
- bleeding
- increased risk of bleeding with use of anticoagulants
contraindications of Alteplase
in subjects with a history of:
- cerebrovascular accidents
- active internal bleeding
- intracranial neoplasm
- arteriovenous malformation,
- aneurysm or who have had recent intracranial/intraspinal surgery or trauma
reconstitution of Alteplase
incompatible with bacteriostatic water for injection
half life of Alteplase
5 minutes
What are the second generation rThrombolytic agents?
- Reteplase
- Tenecteplase
- Desmoteplase (discontinued)
- Lanoteplase (in clinical trials)
properties of second generation rThrombolytic agents
- Relatively higher thrombolytic efficacy compared to rt-PA
- longer half-life
- are variants of rt-PA that include domain deletions, glycosylation changes, or site-directed amino acid changes
Reteplase
- Retavase
- 355-aa deletion variant of t-PA
- Therapeutic use and contraindicated situations are similar to that of t-PA
- 15 min half life
- contraindicated in heparin
- Expressed in E. coli as a single chain, nonglycosylated polypeptide
Tenecteplase
- TNKase
- Three aa substitutions along with a few oligosaccharide substitutions in parent t-PA molecule
- Therapeutic use and contraindicated situations are similar to that of t-PA
- Expressed in CHO cells
- half life of 60-90min
Desmoteplase
- Under clinical investigation
- Putative benefits : prolonged half life, highly specific in action, lower risk of bleeding
arteriovenous malformation
when oxygenated blood gets mixed up with the de-oxygenated blood in the organ
aneurysm
ballooning and weakened area in an artery
