Episode 6 Flashcards
Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of thrombi
Anticoagulants
Substances that promote the destruction of already formed blood clots or thrombi ( i.e. – lyse thrombi) by disrupting the fibrin mesh
Thrombolytics/Fibrinolytics
Drugs that reduce the adhesion and aggregation of platelets
Antiplatelets
Drugs that promote the formation of clots and prevent excessive bleeding
Antifibrinolytics
Anticoagulants are generally divided into
- Indirect thrombin inhibitors (HEPARIN)
- Coumarin Anticoagulants (basically WARFARIN)
- Direct Thrombin Inhibitors
- Direct Active Factor X (Xa) Inhibitors
three most common preparations or Heparin are
- Unfractionated heparin (UFH) – Heparin Sodium
- Low-molecular-weight heparin (LMWH)
- Fondaparinux
Heparin: How Does It Work?
stimulates antithrombin- III, which in turn, neutralizes the activity of factor X
Without factor Xa, prothrombin cannot be converted into thrombin
Unfractionated Heparin can have a varied response per individual. The dose and response can be tricky we need to monitor with…
aPTT
UFH treats
Acute thromboembolic disorders (e.g. pulmonary embolism, dear vein thrombosis, disseminated intravascular coagulation)
UFH prophylaxis when?
Prevent clotting in surgery
Blood transfusions
Renal Dialysis
Blood sample collection
Normal APTT is approximately_____, and Therapeutic levels of UFH will prolong that ______ times of normal value.
25-36s
2-2.5
UFH adverse effects?
Spontaneous bleeding
HIT = heparin-induced thrombocytopenia (Type 1 25%, Type 2 5%)
Reversal of UFH Action by…
PROTAMINE SULFATE
Unfractionated Heparin (UFH) Limitations
Binds to a variety of cells and plasma proteins, leading
to unpredictable effects
Difficult to predict dose
aPTT monitoring required
Short half-life (approx. 90 min
Increased risk of heparin-induced thrombocytopenia
(HIT)
How are Low Molecular Weight Heparins (LMWHs) Different than UFH?
inactivation of factor X than inactivation of thrombin
T or F LMWHs need APTT testing.
F they don’t need APTT testing
Why els are LMWHs better more ideal than UFH
Longer duration of action
Fewer cases of HIT
Do not cross Placental barrier
Prevent ischemic complications of unstable angina or NSTEMI
Low Molecular Weight Heparins (LMWHs)
A synthetic low molecular weight heparin (LMWH)
Fondaparinux (Arixtra)
The only major coumarin anticoagulant in the USA
warfarin (Coumadin)
Warfarin Pharmacokinetics
oral 100% bioavailable
Liver metabolizes
Onset slower than Heparin (8-12hr) may take 3-5 days.
Effects wear off slow 3-5 days.
Monitoring Warfarin Therapy is…
international normalized ratio (INR)
Dose adjusted to INR of 2.0-3.0.
Warfarin should never be used in
pregnancy (category X under the old FDA pregnancy categories)
Fetal warfarin syndrome
Warfarin has many drug interactions that may disrupt its effects by inhibiting its metabolism, most common are…
Many antimicrobials
Cimetidine (Tagamet)
Acetaminophen (Tylenol)
Warfarin has many drug interactions that may enhance its effects most common are…
Synthetic thyroid hormones cephalosporins Tetracyclines SSRIs Herbs Corticosteroids
Warfarin has many drug interactions that may enhance its effects by stimulating its metabolism, most common are…
- Griseofulvin
- Rifampin
- Anti-thyroid agents (methimazole, PTU)
Directly antagonizes the effect of warfarin on clotting factor synthesis and is used to treat severe hemorrhage caused by warfarin overdose (in addition to withholding warfarin or decreasing its dose)
Phytonadione (vitamin K1)
LOTS of patients are being switched from warfarin to…
dabigatran
Antidote for patients treated with dabigatran
idarucizumab (Praxbind)
Dabigatran is Contraindicated in patients with active pathological bleeding or…
a mechanical prosthetic heart valve
Direct Active Factor X (Xa) Inhibitors
Rivaroxaban (Xarelto) First one
Apixaban (Eliquis)
Edoxaban (Savaysa)
All are administered orally and do not require frequent blood tests for INR
The main classes of antiplatelet agents are:
- Cyclooxygenase Inhibitors (mainly aspirin)
- Thienopyridines (ADP Inhibitors)
- GP IIb/IIIa Inhibitors
Aspirin acts on platelets by
inhibiting the synthesis of TXA2
These drugs act by preventing the binding of ADP to its receptors (ADP-P2Y12 receptors) on platelets, thereby inhibiting an important pathway that leads to platelet aggregation.
ADP Inhibitors
ADP Inhibitors Examples
- Clopidogrel (Plavix)
- Prasugrel (Effient)
- Ticagrelor (Brilinta)
- Ticlopidine
The blockage of ADP-P2Y12 receptors on platelets does 2 things:
• Reduces the attraction of platelets to the scene of injury
• Inhibits the expression of GP IIb/IIIa
receptors
Contraindications Ticlopidine only
severe neutropenia that must be monitored via CBC
Contraindications Clopidogrel
action can be enhanced by CYP2C19 inhibitors (most notably PPIs)
Contraindications Ticagrelor
avoid taking with CYP3A4 inhibitors or inducers
GP IIb/IIIa Inhibitors Examples include:
- Abciximab (ReoPro) – irreversible inhibitor
- Tirofiban (Aggrastat) – reversible inhibitor
- Eptifibatide (Integrilin) – reversible inhibitor
GP IIb/IIIa Inhibitors These agents are administered..,
IV, typically with an initial bolus (loading dose) followed by constant (maintenance) infusion
derived from southeastern pygmy rattlesnake (Sistrurus miliarius barbouri; found in SE US)
Eptifibatide
Thrombolytics / Fibrinolytics Examples include:
• Streptokinase (from streptococci) • Urokinase (from neonatal kidney cells) • Synthetic (recombinant) tPA alteplase (Activase), reteplase (Retavase), tenecteplase (TNKase)
is “clot-specific” – in other words, it has a low affinity for free plasminogen, as it only activates plasminogen associated with fibrin
Recombinant tPA
are drugs that promote the formation of clots and/or prevent excessive bleeding
anti-fibrinolytics
Antifibrinolytic prevents plasmin from binding to fibrin
tranexamic acid
is used in dentistry in the form of a 5% mouth rinse after extractions or surgery in patients with prolonged bleeding time
tranexamic acid
Antifibrinolytic which prevents plasminogen activation to plasmin
aminocaproic acid
What is Warfarin’s mechanism of action?
inhibits the vitamin K-dependent synthesis of biologically active forms of the calcium-dependent clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S
Direct Thrombin Inhibitors
Desirudin
Bivalirudin
Hirudin
