Anticoagulants Flashcards
(38 cards)
1
Q
Primary Hemostasis
A
- Platelet Adhesion
- platelets stick to damaged epithelial wall of blood vessels
- Granule Release
- Aggregation & Consolidation
2
Q
Platelet Granule Release
A
Lead to
- ADP, epinepherine, & collagen activation
- increased GPIIb/IIIa expression
- phospholipase A2 cleavage of arachidonic acid (AA) from phospholipid
- AA converted by cycloolygenase (COX) enzyme to thromboxane A2 (TXA2)
- 5-hydroxytryptamine (5HT) also produced & released
**Stimulate Platelet Aggregation
3
Q
Primary Hemostatic Plug
A
reversible
bridging molecule between molecule is fibrinogen, which binds GPIIb/IIIa receptors
4
Q
White Thrombus
A
mostly platelets
can form in high pressure arteries
can reduced blood flow
5
Q
Red Thrombus
A
can form around a white thrombus
in low pressure veins
coloring is from RBCs
6
Q
Secondary Hemostasis
A
activation of coagulation casacade
concurrent with platelet aggregation
Aims:
- generate fibrin
- produce thrombin
- direction platelet aggregation action
- helps sustain aggregation
- makes irreversible secondary hemostatic plug
7
Q
Thrombin
A
avtivator of many steps in coagulation cascade
most important is the transformation of fibrinogen to fibrin
8
Q
Partial Thromboplastin Time
A
aPTT
measurement of the intrinsic coagulation pathway
think of PTT blood test in blue tube
9
Q
Prothombin Time
A
PT
measurement index for the extrinsic coagulation pathway
PT test in blue blood tube
10
Q
Prostacyclin
A
PGI2
arachidonic acid metabolite secreted by endothelium
antiaggregtory
increases cAMP in platelets
11
Q
Antithrombin III
A
ATIII
inhibits factor VIIa, factor IXa, factor Xa, & thrombin
activated by intact endothelium
NOT very active on its own, only in complex coagulation factor (thus stopping them from their purpose)
12
Q
Proteins C & S
A
negative feedback to prevent excessive enlargement of fibrin clot
protein C & S work together to inactivate facotrs Va & VIIIa
protein C is activated by binding to thrombomoldulin with thrombin when thrombin levels are in excess
13
Q
Thrombomodulin
A
enzyme that binds both thrombin and protein C
binds both together to activate protein C when thrombin is in excess
14
Q
Tissue Factor Pathway Inhibitor
A
TFPI
activated by TF:VIIa complex
part of negative feedback mechanism to inactivate TF:VIIa complex & prevent excessive activation of factors IX & X
15
Q
Predisposition for Thrombus (clot) Formation
A
- endothelial injury
- blood vessel damage
- abnormal blood flow
- usually in arrythmia patients
- hypercoagulability
- RA
- Lupus
- mutations of protein C & S
16
Q
Unfractionated Heparin
A
- Other names:
- Uses:
- DVT
- prevent propagation of PEs (rapid onset)
- post MI to prevent venous thromboembolism
- initially in unstable angina
- maintain patency in vascular catheters
- Mechanism:
- binds to antithrombin III (ATIII) conformationally changing it
- new complex has higher affinity for clottin facotrs
- prolongation of aPTT
- Contraindications: none mentioned
- Adverse Effects:
- bleeding
- heparin-induced thrombocytopenia
- long term use can cause osteoporosis
- excessive anticoagulation can be treated by discontinuation or protamine sulfate
- Other:
- negatively charged sulfated mucoplysaccharide found naturally in mast cells
- MUST monitor aPTT
17
Q
Low Molecular Weight Heparins
A
- Names: Enoxaparin (Lovenox), Dalteparin, Tinzaparin
- Uses:
- DVT
- acute coronary syndromes (Enoxaparin & Dalteparin only)
- Mechanism:
- less anti-thrombin activity
- equal amount of anti-factor X activity/molecule
- prolongation of aPTT
- Contraindications: renal insufficient patients
- Adverse Effects:
- bleeding
- heparin-induced thrombocytopenia
- long term use may cause osteoporosis
- MUST monitor aPTT
- Other:
- more expensive
- more favorable benefit to risk ratio
18
Q
Lepirudin
A
- Other names: none mentioned
- Uses: patients that develop heparin-induced thrombocytopenia
- Mechanism: inactivates thrombin in thrombi
- Contraindications: renal insufficiency
- Adverse Effects: bleeding
- Other:
- monitored by PTT
- cleared by kidneys
19
Q
Bivalirudin
A
- Other names: none mentioned
- Uses: percutaneous coronary angioplasty (balloon sx) & unstable angina
- Mechanism: inactivates thrombin in thrombi
- Contraindications: none mentioned
- Adverse Effects: bleeding
- Other: monitored by PTT
20
Q
Argotroban
A
- Other names: none mentioned
- Uses: heparin-induced thrombocytopenia in renal insufficient patients
- Mechanism: inactivates thrombin in thrombi
- Contraindications: none mentioned
- Adverse Effects: bleeding
- Other:
- monitored by PTT
- cleared by liver
21
Q
Warfarin
A
- Other names: Coumadin
- Uses: in conjunction with heparin for longer term
- DVT
- PE
- systemic embolism post MI or Afib
- Mechanism: blockade coupled to metabolism of vitamin K, which aides in prothrombin formation
- Contraindications: none mentioned
- Adeverse Effects:
- readily crosses the placenta & can cause hemorrhagic fiver in fetus
- serious birth defects by abnormal bone formation
- cutaneous necrosis in first few weeks
- rarely can cause clotting
- Other:
- class of delayed-acting anticoagulants
- others in class include: dicumarol & phenindione
- monitored by PT
- 36h half life (long)
- highly bound to albumin
- 8-12hr delay bc of degradation rate of circulating vitamin K
22
Q
Warfarin Enhancers
A
- clopidogrel (Plavix)- decreases warfarin metabolism
- fluconazole (Diflucan- antifungal)- decreases earfarin metabolism
- broad spectrum antibiotics- reduces vitamin K availability
23
Q
Warfarin Diminishers
A
- Cholestyramine (lowers cholesterol)- inhibits warfarin absorption in GI tract
- Vitamin K- bypasses warfarin’s inhibition of epoxide reductase
24
Q
Fibrinolytic Drugs
A
- Use:
- lyse already existing clots in multiple PE & central DVT
- early treatment acute MI (must be less than 6 hours)
- Adverse Effect: may cause lysis of physiologically important fibrin clots
25
Streptokinase
1. Other names/class: none mentioned/ fibrinolytic drug
2. Uses:
* acute PE
* DVT
* acute MI
* arterial thrombosis
3. Mechanism:
* combines with proactivator plasminogen
* catalyzes the degradation of fibrinogen, factors V & VII
4. Contraindications: none mentioned
5. Adverse Effects:
* bleeding disorders
* systemic fibrinolysis
6. Other:
* protein synthesized from streptococci
* for MI, use w/in 4h & continue 1-3days thenuse heparin or oral anticoagulation
26
Urokinase
1. Other Names/ Class: n/m, fibrinolytic
2. Uses: severe PE & DVT
3. Mechanism: activates plasminogen, thus degrading both fibrin and fibrinogen
4. Contraindications:n/m
5. Adverse Effects: bleeding
6. Other:
* originally isolated from human urine
* obtained from human fetal renal cells
* more expensive than Streptokinase
* bc of human origin, will **NOT** cause allergic rxn
27
Tissue Plasminogen Activator
1. class of sering protease drugs
2. Uses:
* MI
* PE
* peripheral arterial thromboembolism
* stroke
3. Mechanism:
* rapidly binds to and activated plasminogen bound to fibrin in a thrombus or hemostatic plug
* low affinity for free plasminogen
* \*\*\*advantage: only lysing fibrin & no degredation of other proteins
4. Contraindications: recent hemorrhagic stroke
5. Adverse Effects: bleeding, including hemorrhagic stroke
6. Other:
28
Alteplase
1. Other names/class: nm/ t-PA (tissue plasminogen activator)
2. Uses:
* MI
* stroke
* PE
* peripheral arterial thromboembolism
3. Mechanism:
* fibrin selective
* activates plasminogen in a thrombus of hemostatic plug
4. Contraindications: recent hemorrhagic stroke
5. Adeverse Effects: bleeding, including hemorrhagic stroke
6. Other:
* most common in t-PA family
* unmodified human t-PA
29
Reteplase
1. Other name/class: nm/ t-PA
2. Uses:
* MI
* PE
* peripheral arterial thromboembolism
* stroke
3. Mechanism:
* activates plasminogen bound fibrin in thrombus or hemostatic plug
4. Contraindications: recent hemorrhagic stroke
5. Adverse Effects: bleeding, including hemorrhagic stroke
6. Other:
* genetically engineered t-PA w/ several aminoacis deletions
* longer half-life due to increased specificity
30
Tenecteplase
1. Other names/Class: nm/ t-PA
2. Uses:
* MI
* Stroke
* PE
* peripheral arterial thromboembolism
3. Mechanism: plasminogen activator when bound to fibrin; fibrin lysis
4. Contraindications: recent hemorrhagic stroke
5. Adverse Effects: bleeeding, including hemorrhagic stroke
6. Other: similar to Reteplase
31
Anisetreplase
1. Other names/Class: nm/ t-PA
2. Uses:
* MI
* stroke
* PE
* peripheral arterial thromboembolism
3. Mechanism: activator of plasminogen bound to fibrin; lysis of fibrin
4. Contraindications: recent hemorrhagic stroke
5. Adverse Effects: bleeding, including hemorrhagic stroke
6. Other:
* complex of purified plasminogen & streptokinase
* long half-life \*\*sinlge bolus achieves reperfusion
32
Aspirin
1. Other Name/Class: ASA/?
2. Uses:
* antiplatelet therapy
* prevention of arterial thrombosis leading to MI & stroke
3. Mechanism: inhibition of COX enzyme through acetylation
4. Contraindication: nm
5. Adverse Effects:
* GI disturbances
* Renal toxicity (rare in low doses)
* prolonged bleeding time
6. Other:
* **low dose must be used **
* most often 81mg/day, but up to 325 mg/day
* high 1st pass effect
* higher doses may inhibit beneficial postacyclin production
33
Ticlopidine
1. Other names/Class: nm/ ADP receptor inhibitor
2. Uses:
* secondary prevention of thrombotic stroke (ASA intolerant pts)
* in combo with ASA to prevent stent thrombosis
3. Mechanism: ADP receptor inhibitor
4. Contraindications: nm
5. Adverse Effects: thrombocytopenia
6. Other: must monitor blood counts
34
Clopidogrel
1. Other names/Class: Plavix/ ADP receptor inhibitor
2. Uses:
* prevention in MI, stroke & vascular patients
* post coronary bypass
3. Mechanism: inhibits ADP receptors
4. Contraindications: nm
5. Adverse Effects:
* less than Ticlopidine
* GI disturbances
35
Dipyridamole
1. Other names/Class: phosphodiesterase inhibitor
2. Uses:
* w/warfarin: prevention of thrombosis in prosthetic heart valves
* w/ASA: patients w/ thrombotic diathesis (predisposed to blood clot)
3. Mechanism: inhibits phosphodiesterase by increasing cAMP & vasodilator of arteries
4. Contraindications: nm
5. Adverse Effects: bleeding
6. Other: \*\*\*no longer given\*\*\*
36
Abciximab
1. Other names/Class: nm/ GPIIb/IIIa antibody
2. Uses: acute coronary syndromes
3. Mechaninsm:
* GPIIb/IIIa inhibitor
* new class of platelet inhibitor
* directed against IIb/IIIa complex
4. Contraindications:
5. Adverse Effects: bleeding, especially when used with thrombolytics
6. Other:
* administered IV
* **humanized monoclonal antibody**
37
Eptifibatide & Tirofiban
1. Other names/class: GPIIb/IIIa inhibitor
2. Uses: acute coronary syndromes
3. Mechanism: they are fibrinogen analogs that reviersible inhibit binding of fibrinogen to receptor
4. Contraindications: nm
5. Adverse Effects: bleeding, especially when given with thrombolytics
6. Other: administered by IV
38
Post MI treatment
1. low dose ASA- reduces secondary coronary thrombosis
2. nitrates- reduce preload
3. beta blockers (do NOT use alone)
4. ACE inhibitors- reduces mortality after thrombolytics
