pharm - 9-24- Thrombolytics

Question 1

4 Plasminogen Activators

B: MOA

Answer 1

1. [Tissue Plasminogen Activator - tPA] 3 types
2. Urokinase
3. [Streptokinase Anistreplase]
4. Factor 12A

B: [Plasminogen Activators] cleaves Plasminogen at the [Arg 560 - Val] bond —> Plasmin

Question 2

Name the 4 Physiologic [Plasminogen Activator INHIBITORS]

B: Give brief description of each

Answer 2

1) [PAI-1] = RAPID Plasminogen Activator Inhibitor
2) A2-antiplasmin = binds to [Plasmin’s Serine Site] OR Fibrin
3) TAFI (Thrombin activatable fibrinolytic inhibitor) = Modifies Fibrinogen so Plasmin CAN’T digest it
4) A2-macroglobulin

Question 3

A: Fibrinogen can be dissolved by _____ into what 4 things? This is the ____ state.

vs.

B: FIBRIN is dissolved by ______ into _____ / _____ / _____ which are all _______. This is the ____ state.

C: These Degradation products are Coagulative or ANTI-Coagulative?

Answer 3

A: Fibrinogen can be dissolved by Plasmin into [Fragments Y / D / E / X]

vs.

B: FIBRIN is dissolved by Plasmin into [DDE] / [YD/DY] / [YYE] = D-DIMERS!

C: Fibrinogen and FIBRIN degradation products are ANTI-COAGULANTS = PREVENT FURTHER CLOTTING!

Question 4

Name all the factors that PROMOTE Fibrinolysis (6)

Answer 4

• Plasminogen direct incorporation into thrombus via fibrin binding
• Clot retraction
• Local release of t-PA by endothelial cells
• Binding of t-PA to fibrin
• INC [t-PA or urokinase] activity in the presence of fibrin
• Protection of bound plasmin from [A2-antiplasmin]

Question 5

3 Main Factors that LIMIT Fibrinolysis

Answer 5

1. Fibrin crosslinking/stabilization by [Factor 13A] (tPA has to be administered within 30 min of the incident)
2. Binding of α2-antiplasmin to fibrin
3. PAI1 INC

Question 6

Name the 3 current t-PA drugs and briefly describe them

B: Which is the MOST Fibrin Specific?

C: List the Indications for t-PA (3)

Answer 6

1. Alteplase (Recombinant form of Human t-Pa)
2. Reteplase (Mutant nonglycosylated form of human t-

Pa, more fibrin specific and l_onger half life_

3. Tenecteplase (Mutant form of human t-Pa with HIGH fibrin specificity and longer half life

C:

• Stroke
• MI
• Thrombolysis

Question 7

3 Complications of Thrombolytic Therapy

Answer 7

1. Bleeding
2. Re-Occulsion
3. Hemorrhagic Stroke

Question 8

Systemic Lytic State

Answer 8

Side Effect of [Thrombolytic OD] —> Degradation of plasma Fibrinogen by circulating plasmin

Question 9

Which 2 medications are used for [peripheral arterial occlusion] dissolution?

B: What were they initially used for?

C: Which medicaiton is NOT used for [Pulmonary Embolism] Tx

Answer 9

Urokinase and Streptokinase

B: Initially used for DVT tx

C: t-PA is NOT used in PE

Question 10

A: What are the 2 ABSOLUTE Contraindications to using Thrombolytic Therapy

B: Are Thrombolytics safe for Pregnant Women?

C: Name the 3 Antagonist that Reverse Thrombolytic Effects.

C2: List their Side Effects

C3: What Route of Administration should you use for these?

Answer 10

Pt with…

(x) INTRACRANIAL BLEEDING

OR

(X) MASSIVE HEMORRHAGE

B: No

C: ALL Administered IV:

1) [EACA AMICAR] (Epsilon Amino Caproic Acid) –> hypOtension
2) [TAA - Tranexamic Acid AMCHA] –> Retinopathy
3) [Aprotonin Trasylol] –> Graft Thrombosis

Question 11

A: Snake Venom contains LARGE amounts of _____—> Can Digest _____

B: List an example drug and its indication

Answer 11

A: Snake Venom contains LARGE amounts of [Plasminogen Activators] —> Can Digest Fibrinogen

B: Ancrod is being tested for Stroke

Question 12

What are the 3 Types of Coronary Stents?

Answer 12

• Bare metal stents
• Drug eluting stents
• Disposable stents

Question 13

A: Indications for Urokinase (4)

B: Route of Administration

Answer 13

• Stroke
• MI
• PE
• Thrombolysis

B: Administered IV