Episode 6

Question 1

Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of thrombi

Answer 1

Anticoagulants

Question 2

Substances that promote the destruction of already formed blood clots or thrombi ( i.e. – lyse thrombi) by disrupting the fibrin mesh

Answer 2

Thrombolytics/Fibrinolytics

Question 3

Drugs that reduce the adhesion and aggregation of platelets

Answer 3

Antiplatelets

Question 4

Drugs that promote the formation of clots and prevent excessive bleeding

Answer 4

Antifibrinolytics

Question 5

Anticoagulants are generally divided into

Answer 5

• Indirect thrombin inhibitors (HEPARIN)
• Coumarin Anticoagulants (basically WARFARIN)
• Direct Thrombin Inhibitors
• Direct Active Factor X (Xa) Inhibitors

Question 6

three most common preparations or Heparin are

Answer 6

• Unfractionated heparin (UFH) – Heparin Sodium
• Low-molecular-weight heparin (LMWH)
• Fondaparinux

Question 7

Heparin: How Does It Work?

Answer 7

stimulates antithrombin- III, which in turn, neutralizes the activity of factor X

Without factor Xa, prothrombin cannot be converted into thrombin

Question 8

Unfractionated Heparin can have a varied response per individual. The dose and response can be tricky we need to monitor with…

Answer 8

aPTT

Question 9

UFH treats

Answer 9

Acute thromboembolic disorders (e.g. pulmonary embolism, dear vein thrombosis, disseminated intravascular coagulation)

Question 10

UFH prophylaxis when?

Answer 10

Prevent clotting in surgery
Blood transfusions
Renal Dialysis
Blood sample collection

Question 11

Normal APTT is approximately_____, and Therapeutic levels of UFH will prolong that ______ times of normal value.

Answer 11

25-36s

2-2.5

Question 12

UFH adverse effects?

Answer 12

Spontaneous bleeding

HIT = heparin-induced thrombocytopenia (Type 1 25%, Type 2 5%)

Question 13

Reversal of UFH Action by…

Answer 13

PROTAMINE SULFATE

Question 14

Unfractionated Heparin (UFH) Limitations

Answer 14

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)

Question 15

How are Low Molecular Weight Heparins (LMWHs) Different than UFH?

Answer 15

inactivation of factor X than inactivation of thrombin

Question 16

T or F LMWHs need APTT testing.

Answer 16

F they don’t need APTT testing

Question 17

Why els are LMWHs better more ideal than UFH

Answer 17

Longer duration of action
Fewer cases of HIT
Do not cross Placental barrier

Question 18

Prevent ischemic complications of unstable angina or NSTEMI

Answer 18

Low Molecular Weight Heparins (LMWHs)

Question 19

A synthetic low molecular weight heparin (LMWH)

Answer 19

Fondaparinux (Arixtra)

Question 20

The only major coumarin anticoagulant in the USA

Answer 20

warfarin (Coumadin)

Question 21

Warfarin Pharmacokinetics

Answer 21

oral 100% bioavailable
Liver metabolizes
Onset slower than Heparin (8-12hr) may take 3-5 days.
Effects wear off slow 3-5 days.

Question 22

Monitoring Warfarin Therapy is…

Answer 22

international normalized ratio (INR)

Dose adjusted to INR of 2.0-3.0.

Question 23

Warfarin should never be used in

Answer 23

pregnancy (category X under the old FDA pregnancy categories)
Fetal warfarin syndrome

Question 24

Warfarin has many drug interactions that may disrupt its effects by inhibiting its metabolism, most common are…

Answer 24

Many antimicrobials
Cimetidine (Tagamet)
Acetaminophen (Tylenol)

Question 25

Warfarin has many drug interactions that may enhance its effects most common are...

Answer 25

``` Synthetic thyroid hormones cephalosporins Tetracyclines SSRIs Herbs Corticosteroids ```

Question 26

Warfarin has many drug interactions that may enhance its effects by stimulating its metabolism, most common are...

Answer 26

* Griseofulvin * Rifampin * Anti-thyroid agents (methimazole, PTU)

Question 27

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)

Answer 27

Phytonadione (vitamin K1)

Question 28

LOTS of patients are being switched from warfarin to...

Answer 28

dabigatran

Question 29

Antidote for patients treated with dabigatran

Answer 29

idarucizumab (Praxbind)

Question 30

Dabigatran is Contraindicated in patients with active pathological bleeding or...

Answer 30

a mechanical prosthetic heart valve

Question 31

Direct Active Factor X (Xa) Inhibitors

Answer 31

Rivaroxaban (Xarelto) First one Apixaban (Eliquis) Edoxaban (Savaysa) All are administered orally and do not require frequent blood tests for INR

Question 32

The main classes of antiplatelet agents are:

Answer 32

* Cyclooxygenase Inhibitors (mainly aspirin) * Thienopyridines (ADP Inhibitors) * GP IIb/IIIa Inhibitors

Question 33

Aspirin acts on platelets by

Answer 33

inhibiting the synthesis of TXA2

Question 34

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.

Answer 34

ADP Inhibitors

Question 35

ADP Inhibitors Examples

Answer 35

* Clopidogrel (Plavix) * Prasugrel (Effient) * Ticagrelor (Brilinta) * Ticlopidine

Question 36

The blockage of ADP-P2Y12 receptors on platelets does 2 things:

Answer 36

• Reduces the attraction of platelets to the scene of injury • Inhibits the expression of GP IIb/IIIa receptors

Question 37

Contraindications Ticlopidine only

Answer 37

severe neutropenia that must be monitored via CBC

Question 38

Contraindications Clopidogrel

Answer 38

action can be enhanced by CYP2C19 inhibitors (most notably PPIs)

Question 39

Contraindications Ticagrelor

Answer 39

avoid taking with CYP3A4 inhibitors or inducers

Question 40

GP IIb/IIIa Inhibitors Examples include:

Answer 40

* Abciximab (ReoPro) – irreversible inhibitor * Tirofiban (Aggrastat) – reversible inhibitor * Eptifibatide (Integrilin) – reversible inhibitor

Question 41

GP IIb/IIIa Inhibitors These agents are administered..,

Answer 41

IV, typically with an initial bolus (loading dose) followed by constant (maintenance) infusion

Question 42

derived from southeastern pygmy rattlesnake (Sistrurus miliarius barbouri; found in SE US)

Answer 42

Eptifibatide

Question 43

Thrombolytics / Fibrinolytics Examples include:

Answer 43

``` • Streptokinase (from streptococci) • Urokinase (from neonatal kidney cells) • Synthetic (recombinant) tPA  alteplase (Activase), reteplase (Retavase), tenecteplase (TNKase) ```

Question 44

is "clot-specific" – in other words, it has a low affinity for free plasminogen, as it only activates plasminogen associated with fibrin

Answer 44

Recombinant tPA

Question 45

are drugs that promote the formation of clots and/or prevent excessive bleeding

Answer 45

anti-fibrinolytics

Question 46

Antifibrinolytic prevents plasmin from binding to fibrin

Answer 46

tranexamic acid

Question 47

is used in dentistry in the form of a 5% mouth rinse after extractions or surgery in patients with prolonged bleeding time

Answer 47

tranexamic acid

Question 48

Antifibrinolytic which prevents plasminogen activation to plasmin

Answer 48

aminocaproic acid

Question 49

What is Warfarin's mechanism of action?

Answer 49

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

Question 50

Direct Thrombin Inhibitors

Answer 50

Desirudin Bivalirudin Hirudin