Test 2 Thrombolytics

Question 1

Acute Myocardial Infarction (AMI)

Answer 1

• affects 1.5 million each year in the US

- caused by coronary clot (thrombus)

Question 2

coronary clots

Answer 2

aggregates of platelets, other blood cells and insoluble fibrin

Question 3

Thrombolytics

Answer 3

lyse the fibrin in blood clot to produce fibrin degradation products which are soluble and thereby dissolve the clot

Question 4

types of thrombolytics

Answer 4

Non Specific 
- Streptokinase
- Urokinase
Specific 
- Alteplase
- Reteplase
- Tenecteplase
- Desmoteplase

Question 5

What are the differences between specific and non-specific thrombolytics?

Answer 5

• non-specific: lyse platelet clots

- specific: senses just fibrin only when it’s activated

Question 6

Alteplase

Answer 6

• First generation rThrombolytic agent
• recombinant human tissue-plasminogen activator
• promotes conversion of plasminogen to active plasmin
• degrades insoluble fibrin clot into soluble degradation products

Question 7

Alteplase mechanism of action

Answer 7

• 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

Question 8

synthesis of Alteplase

Answer 8

• 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

Question 9

Therapeutic use of Alteplase

Answer 9

• Acute MI
• Reduction of incidence of CHF
• Acute massive pulmonary embolism
• Acute ischemic stroke

Question 10

concerns of Alteplase

Answer 10

• bleeding

- increased risk of bleeding with use of anticoagulants

Question 11

contraindications of Alteplase

Answer 11

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

Question 12

reconstitution of Alteplase

Answer 12

incompatible with bacteriostatic water for injection

Question 13

half life of Alteplase

Answer 13

5 minutes

Question 14

What are the second generation rThrombolytic agents?

Answer 14

• Reteplase
• Tenecteplase
• Desmoteplase (discontinued)
• Lanoteplase (in clinical trials)

Question 15

properties of second generation rThrombolytic agents

Answer 15

• 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

Question 16

Reteplase

Answer 16

• 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

Question 17

Tenecteplase

Answer 17

• 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

Question 18

Desmoteplase

Answer 18

• Under clinical investigation

- Putative benefits : prolonged half life, highly specific in action, lower risk of bleeding

Question 19

arteriovenous malformation

Answer 19

when oxygenated blood gets mixed up with the de-oxygenated blood in the organ

Question 20

aneurysm

Answer 20

ballooning and weakened area in an artery