1
Q
Anticoag Rxs
A
- Heparin/enoxaparin/fondaparinux
- Warfarin
- RivaroXaban, apiXaban
- DabigaTran/Argatroban/Desirudin/Bivalrudin
2
Q
Antiplatelet Rx
A
- Aspirin, clopidogrel, prasugrel
* Abciximab / tirofiban / eptifibatide
3
Q
Thombolytic
A
Alteplase
4
Q
DOWN Clot formation Rxs
PROPHYLAXIS
A
Anticoagulants
Antiplatelets
5
Q
UP Clot dissolution Rxs
A
Thrombolytic
6
Q
Antithrombin catalysts
A
Heparin
Enoxaparin
Fondaparinux
7
Q
Block clotting factor synthesis
A
Warfarin
8
Q
Direct Xa inhibitors
A
RivaroXaban
ApiXaban
9
Q
Direct thromibn (IIa) inhibitors
A
DabigaTran
Argatroban
Desirudin
Bivalrudin
10
Q
Block platelet activation (G2b/3a activation)
A
Aspirin
Clopidogrel
Prasurel
11
Q
Block glycoprotein 2b/3a function
A
Abciximab
tirofiban
Eptifibatide
12
Q
Plasminogen activator
A
Alteplase
13
Q
Red clot Tx
A
Anticoags
14
Q
White clot Tx
A
Anticoags + antiplatelets
15
Q
Just anticoag needed - Red clots
Hypercoaguable states
A
- stasis
- Afib
- immobility (DVT/PE)
- Foreign objects
- extracorporeal devices
- vascular access devices (heparin lock/central venous line)
16
Q
White clots from
A
*Atherosclerosis ACS -->UA, MI CVD -->TIA, CVA PVD *Foreign objects (PCI, heart valve)
17
Q
Treat ischemic CVA w/
A
Anticoag
18
Q
Treat Hemorrhagic CVA w/
A
NO anticoag
19
Q
Anticoags/antiplatelets
Physiology
A
Inhibit prevent clot growth
20
Q
Anticoag/antiplatelet
Rx interaction
A
Many
Herbals
21
Q
Anticoags/Antiplatelets
Contraindications
A
- Bleeding
- Impending surgery (ex. Spinal anesthesia/puncture–>hematoma–>paralysis)
- Hypersensitivity
22
Q
Anticoags
Indirectly affect clotting factors UNFINISHED
A
Antithrombin catalys
-Heparin
23
Q
What starts extrinsic pathway?
A
Tissue factor
24
Q
What starts intrinsic pathway?
A
Intravascular trigger
25
What starts common pathway?
Factor 10
26
Which factor is prothrombin/thrombin?
II/IIa
27
Goal of anticoagulation?
Diminish activity of Factors 10a +/- 2a (common pathway)
28
What type of enzymes are clotting factors?
Zymogens (proenzymes)
29
Heparin
Bio characteristics
* polysaccharide
* glycosaminoglycan
* VERY suflated, VERY acidic
30
Unfractionated heparin
Chains?
Mixture of long chains
| Some have pentasaccharide/some don't
31
LMW Heparin
Mixture of short chains
| Some have pentasaccharide/some don't
32
Fondaparinux
Pure pentasaccharide
33
Antithrombin (AT)
Most potent anticoag in body
| Looks like xymogem - 10A attaches, irreversible, suicide anti-coag
34
Heparins catalyze what?
Antithrombin (AT)
| x1000
35
Heparin pentasaccharide mechanism for 10a + 2a?
10a - pentasaccharide increases at affinity for this
| 2a - long chain bridges this and AT, easier to bump into each other
36
Heparin antidote
Protamine = (+), binds with (-) heparin, inactive complax
| NO w/ short heparin chains
37
Heparin-induced Thrombocytopenia (HIT)
* Hypersensitivity
* Autoimmune (PF4-heparin complex activate platelet)
* Get clot- gangrene
38
HIT
Tx
NO treat with Heparin/LMW, warfarin
| *USE fondaparinux/argatoban (off-label)
39
LMW heparin/Fondaparinux
Future indications
Soon will include indications of unfractionated heparin
40
Heparin dosing
Read label carefully, don't overdose
41
Heparin in pregnancy/neonate
USE W NO preservative (benzyl alcohol) fetal death
42
Heparin bleeding time monitored with
aPPT
43
Where does clotting occur?
On platelet surfaces
| Not in solution
44
Warfarin blocks
Gla formation
| Factor can't attach to membrane
45
Vitamin K
Reduces Gla, then recycled by VKORC (nadh)
46
Warfarin blocks
VKORC regeneration of Vitamin K,
| Not enough Gla for factors (10a) to stick to surface
47
INR 1
Normal clotting activity
48
Warfarin effects delayed - why?
Waiting for clotting factors to be used up (10a/2a take forever), and to build up useless clotting factors
49
Initiating warfarin
Heparin-bridge while waiting warfarin to get to steady state (slow onset)
50
Warfarin
S.E.
* Bleeding
* Clotting ?!? = stopping Protein C + S early (BRIDGE!)
* DEAD BABY
* NO HIT
51
Warfarin
Physiology
*S enantiomer - CYP2C9 metab
*t 1/2 = 20-60 h (human variation)
-CYP2C9 (elimination)
-VKORC (efficacy)
MONITOR INR
52
Warfarin
Rx interactions
Many
| *need low Vitamin K (competitive inhibitor)
53
INR
```
HIGH = less clotting
LOW = more clotting
```
54
10a /2a inhibitors
NOT WITH Afib + ***heart valve***
55
If inhibit metabolism Rivaroxaban?
Up efficacy
56
Argatroban
MOA
Direct 2a (thrombin
inhibitor - blocks catalytic site)
*tx HIT
57
Hirudo medicinalis
Saliva - hirudin (anticoag) - surgery(reattaching fingers)
58
Hirudin derivatives
Desiruden (t1/2= 2-3 hrs)
Bivalirudin (t/12 = shorter)
*Direct thrombin (2a) inhibitors
59
COX 1 + ADP blocker
Synergistic effect
60
Aspirin
Irreversible COX inhibitor
| - if stop - takes awhile to regenerate platelets (1week)
61
What if clopidogrel given to non metabolizer?
No effect, clopidogrel is pre-drug, need metabolism to activate
62
W/ heart valves?
Now, only warfarin
63
Thombolytics
Atleplase - plasminogen-like (fibrin), works best on fresh clots
64
Thienopyridine Anti-platelet agents ("grels")
PRODRUG = Cyp metab to activate
65
Prasugrel
Thienopyridine Anti-platelet agents ("grels")
More bleeding than clopidogrel
66
Clopidogrel
Thienopyridine Anti-platelet agents ("grels")
Special metablolism consideration
CYP2C19 poor metabolizers = UP risk (MI/Ischemic Stroke/Death)
67
GP 2b/3a blocker Anti-platelet drugs
Block GP 2b/3a from binding fibrinogen, vWF+ others
68
Alteplase
GP 2b/3a blocker Anti-platelet drugs
Works best on fresh clots (less fibrin linking)
FOR ER CLOT BUSTING = T1/2 = 10 mins (shorter than Streptokinase)
