36 - Fibronolytics + Hemostatic Drugs Flashcards
Coagulation Inhibitors
APC
Activated protein C
MoA + Indications
Common & Intrinsic Pathway
- *Factor 8_ + _Factor 5a**
- *Phospholipids**
- *SEVERE SEPSIS**
- WITHDRAWN from Market*
Coagulation Inhibitors
AT3
Antithrombin 3
MoA / Indication
Targets:
Factor 7a + 2 = Thrombin
AntiThrombin = 7-2
Indication:
AT3 Deficiency + Hereditary
Coagulation Inhibitors
TFPI
Tissue Factor Pathway Inhibitor
MoA / Indication
Targets:
Factor 10** + **7a
TFPI = 10-7
- *Severe Sepsis also**
- off market , failed to reduce mortality*
Fibrinolytics
SK = Streptokinase
1st Drug
MoA / Improvements
MoA
Binds to fibrin-bound & circulating Plasminogen
Produces Activator complex** –> **PLASMIN
INDIRECT ACTIVATION
IMMUNE RELATED REACTIONS
Fibrinolytics
UK = Urokinase
1st gen
MoA / Improvements
MoA
- *Non-specific Plasminogen Binding**
- fibrin bound & circulating*
DIRECT ACTIVATION
No PAI-1 Resistance
2 min half life
No Immune Related Reactions
Fibrinolytics
rt-PA = ALTEPLASE
2nd Gen
MoA / Improvements
MoA
SPECIFICALLY binds to FIBRIN bound to plasminogen
Direct + More Fibrin Specific
No Immune Related Reactions
Only Fibrinolytic indicated for:
ACUTE ISCHEMIC STROKE
also indicated for:
PE + Centra Venous Catheter Occlusion
Fibrinolytics
r-PA = RETEPLASE
3rd Gen
MoA / Improvements
MoA
- NONSPECIFIC* Plasminogen Binding
- fibrin bound + circulating*
- *15 min half life**
- NOT a great improvement > ACTIVASE*
Fibrinolytics
TNK-t-PA = TENECTEPLASE
3rd Gen
MoA / Improvements
MoA
Increase Specificity to FIBRIN BOUND plasminogen
reduced drug clearance / increased BV + AUC
+++ MOST FIBRIN SPECIFIC +++
Has PA1 Resistance
25 min half life
- *Hemostatic Drugs**
- *INDICATION**
- *PREVENT_ or _STOP**
- *MAJOR BLEEDING:**
Fatal Bleeding
Bleeding causing a ↓ Hgb level > 2 g/dL
or leading to:
transfusion of 2+ Whole Blood or RBC
Symptomatic Bleeding** in a **Critical Area/Organ
GI TRACT / BRAIN / Pericardial
spinal / ocular / retroperitineal
Hemostatic Drugs
Anti-Fibronolytic Drugs
Stops Fibrinolysis along with Aprotinin
MoA / Use
Tranexamic Acid = TA // E-aminocaproic Acid = EACA
Affinity for Plasminogen:
TA > EACA
not clinically significant
*PREVENT* binding of FIBRIN
Bind at the
LYSINE binding site of PLASMINOGEN
REVERSIBLE
Hemostatic Drugs
Aprotinin
Stops Fibrinolysis along with Aprotinin
MoA / Indication
- *Non-Specific SERINE protease Inhibitor**
- *Trypsin > Plasmin > Kallikrein** > elastase > urokinase > thrombin
REVERSIBLE
Indication:
- *Cardiopulmonary Bypass Operation**
- REMOVED FROM MARKET*
Hemostatic Drugs
Packed Red Blood Cell (PRBC) vs Platelets
Contents / Use
PRBC used for:
OXYGEN SUPPLY
Increase hemoglobin 10 g/L and hematocrit 3%
Platelets used for:
HEMOSTASIS
Increase platelet count 5,000–10,000/μL
Hemostatic Drugs
FPP = Fresh Frozen Plasma
Contents / Use
- *200-250mL** –> HYPERvolemia is an issue
- *Fursomide addded**
Plasma proteins:
Coagulation Factors
Protein C + S
AntiThrombin
Hemostatic Drugs
Cryoprecipitate
Contents / Use
Cold-insoluble plasma proteins
FIBRINOGEN
FVIII = 8 & vWF
topical fibrin “glue” + 80iu factor 8
Hemostatic Drugs
DESMOPRESSIN
MoA / Use
↑Factor 8** & **vWF
by 2-6 times, last 8-10 hours
Response within -60 min
tachyphylaxis issue
Insication:
- *UREMIC BLEEDING**
- *vWF disease / Factor 8 deficiency**
