Regal- Thrombolytics, Anticoagulants, and Antiplatelet Drugs

Question 1

When do we interfere w/ hemostasis?

Answer 1

Prevent and treat thrombosis

1. Venous thrombosis
2. Arterial thrombosis–platelet activation is central

Question 2

What agents do we use to control blood fluidity?

Answer 2

Antiplatelet agents
Parenteral anticoagulant heparin and its derivatives (Thrombin inhibitors direct/indirect)
Oral Coumadin anticoagulants (inhibitors of vit K)
Fibrinolytic agents to lyse pathological thrombi

Question 3

What does aspirin do mechanistically?

Answer 3

It is an irreversible inhibitor of COX

Question 4

Do platelets have Cox2?

Answer 4

NO

Question 5

Can platelets make more COX

Answer 5

NO they don’t have a nucleus

Question 6

What does aspirin do clinically?

Answer 6

Antipyretic, analgesic, anti-inflamatory

Question 7

What are the adverse effects of aspirin?

Answer 7

Bleeding
GI disturbances
Tinnitus

Question 8

What is the difference between low and high doses of aspirin?

Answer 8

LOW- antiplatelet

HIGH- inhibits COX1 and 2 in epithelial cells (anti-inflammatory)

Question 9

What are the three ADP receptor antagonists?

Answer 9

Clopidogrel
Ticlopidine
Prasugrel

Question 10

How do ADP antagonists work?

Answer 10

Irreversible ADP receptor antagonists that prevent activation of ADP receptor that would ultimately lead to platelet aggregation

Question 11

How long do ADP receptor antagonists last?

Answer 11

days

Question 12

When are ADP receptor antagonists commonly used?

Answer 12

Stenting

Recommended for pts that don’t tolerate aspirin

Question 13

What are the adverse effects of ADP receptor antagonists?

Answer 13

BLEEDING

nausea, diarrhea, rash
severe leukopenia
TTP (very rare–ticlodipine)

Question 14

Which ADP R Antag has the worst side effects?

Answer 14

Ticlodipine

Question 15

Which ADP drug requires activation?

Answer 15

Clopidogrel via CYP2C10

**drugs that impair this isoform should be used w/ caution (omeprazole)

Question 16

What does dipyridamole do?

Answer 16

Increases cAMP and inhibits platelet activation by inhibiting PDE3 (preventing the break down of cAMP) and inhibiting platelet uptake of adneosine, thus increasing adenosine interaction w/ adensoine receptor and increasing cAMP

PDE 3 inhibitor

Question 17

What adverse effect is associated w/ dipyridamole?

Answer 17

Headache

b/c it’s a vasodilator

Question 18

How is dipyridamole commonly prescribed? Why?

Answer 18

In combination w/ aspirin or warfarin

No beneficial effect by itself

Question 19

What do GPiiB/IIIa receptor inhibitors do?

Answer 19

Prevent binding of adhesive glycoproteins such as fibrinogen and vWF to activated platelets

Question 20

How do abciximab, eptifibatide and tirofiban differ?

Answer 20

abciximab-Humanized MAB a against receptor
eptifibatide- fibrinogen analoguse
tirofiban- non-peptide competitive inhibitor

Question 21

What are the three GPIIb/IIIa receptor inhibitors?

Answer 21

abciximab
eptifibatide
tirofiban

Question 22

What is the one disadvantage of GpIIb/IIIa receptor inhibitors?

Answer 22

they have to be given IV

Question 23

What are GpIIb/IIIa receptor inhibitors commonly used for?

Answer 23

w/ aspirin and heparin during angioplasty

for acute coronary syndromes

Question 24

What are the adverse effects of GpIIb/IIIa receptor inhibitors?

Answer 24

Bleeding

thrombocytopoenia

Question 25

What are the two types of thrombin inhibitors?

Answer 25

Direct and indirect?

Question 26

What are the 4 types of direct thrombin inhibitors?

Answer 26

Lepirudin Bivalirudin Agratroban Dabigatran (ORAL)

Question 27

What are the three types of indirect thrombin inhibitors?

Answer 27

Unfractionated heparin LMW heparin Fondaparinux

Question 28

What do lepirudin, bivalirudin and argatroban and dabigatran do? How is dabigatran different?

Answer 28

bind directly to thrombin and inhibit the enzyme dabigatrin is ORAL

Question 29

Which indirect thrombin inhibitors interact w/ antithrombin and enhance/accelerate its inactivation of Factors Xa?

Answer 29

Heparin LMWH Fondaparinux

Question 30

Which indirect thrombin inhibitors enhance/accelerate antithrombin's inactivation of thrombin (IIa)?

Answer 30

Heparin and LMWH

Question 31

What is the end effect of indirect thrombin inhibitors?

Answer 31

Factor Xa and thrombin IIa don't work so clotting doesn't happen

Question 32

Unfractionated heparin requires close monitoring of...?

Answer 32

aPTT--activated partial thromboplastin time

Question 33

Does LMW heparin require monitoring?

Answer 33

No, it has more predictable pharamacokinetics

Question 34

What are the adverse effects of indirect thrombin inhibitors?

Answer 34

Bleeding | Heparin induced thrombocytopenia

Question 35

What causes Heparin induced thrombocytopenia?

Answer 35

Probably the development of IgG antibodies against complexes of heparin w/ platelet factor 4 **twice as likely in women than men

Question 36

Which indirect thrombin inhibitors only targets Xa?

Answer 36

Fondaparinux

Question 37

Which indirect thrombin inhibitors has no antidote effect?

Answer 37

Fondaprinux LMWH has only parital Heparin is full

Question 38

What does protamine do?

Answer 38

Combines w/ negatively charged heparin to form a stable complex that lacks anticoagulant activity

Question 39

What does protamine do to LMWH?

Answer 39

incompletely reverses its activity

Question 40

What are the two oral anticoagulant drugs?

Answer 40

Warfarin | Vitamin K

Question 41

What does Warfarin do?

Answer 41

Inhibits conversion of oxd vit K epoxide into it's reduced form, vit K hydoquinone> this inhibits vit K dependent gamma carboxylation of factors II, VII, IX and X and Prot C

Question 42

What's important to know about the pharmakokinetics of warfarin?

Answer 42

Delayed hypothrombic effect | narrow TI--need enough so that you don't clot and not enough that you don't bleed all over

Question 43

What are the adverse effects of warfarin?

Answer 43

Bleeding flatulence and diarrhea cutaneous necrosis chondrodysplasia

Question 44

What is the difference between R and S warfarin and which is the more active enantiomer?

Answer 44

S is more active enantiomer S- metabolized by cyp2c9 R- metabolized by cyps1a1, 1A2, 3A4

Question 45

What is one of the worst things about warfarin?

Answer 45

It interacts with MANY drugs

Question 46

What are the effects of warfarin pharmacokinetically?

Answer 46

Inhibition of cyt450 Metabolism-> more warfarin Decreased plasma protein binding

Question 47

What are the effects of increased warfarin on pharmacodynamics?

Answer 47

decreased platelet/clotting factor function | Decreased availabilty of vit K-->warfarin increases

Question 48

What are the effects of decreased warfarin pharmacokinetically and pharmacodynamically?

Answer 48

pharmacokinetically- induction of CYT p450 metabolism, decreased absorption pharmacodynamically- increased clotting factor/vit K concentrations

Question 49

What do you do if a pt has been given TOO much warfarin and is bleeding uncontrollably?

Answer 49

STOP the drug | Add vit K--so enzyme can do it's thing and make the right clotting factors (phytonodione)

Question 50

What are urokinases?

Answer 50

kidney enzymes that directly converts plasminogen to plasmin

Question 51

What are the three tPAs?

Answer 51

Alteplase reteplase tenecteplase

Question 52

What do tPAs do?

Answer 52

Preferentially activate plasminogen that is bound to fibrin which confines it to the thrombus rather than systemic activation.

Question 53

What do Fibrinolytic Drugs do?

Answer 53

Dissolve EXISTING life threatening thrombi | activate plasminogen

Question 54

How are fibrinolytic drugs given?

Answer 54

IV | Narrow spectrum of use

Question 55

What are the adverse effects of fibrinolytic drugs?

Answer 55

Bleeding | cost

Question 56

What is the MOA of alteplase, reteplase, tenecteplase?

Answer 56

Selective activation of fibrin bound plasminogen