Pharmacology Of Antithrombotic Agents Ii

Front 1

Can anticoaggulant drugs dissolve and already-formed clot?

Back 1

No

Front 2

HMW Heparin mechanism of action?

Back 2

causes conformational change in antithrombin III exposing its reactive site =

Catalyzes inhibition of clotting factors IXa, Xa and thrombin by greatly enhancing ATIII activity

Front 3

1. HMW heparin mode of administration?

2. Reason for the mode?

3. Pregnancy class of HMW Heparin

Back 3

1. IV or SC because it is not absorbed into the GI tract

2. large molecular weight (polysaccharide sequence)

3. Does not cross the placenta: therefore it is the drug of choice for anticoagulation during pregnancy.

Front 4

Clinical indications for HMW Heparin (7)?

Back 4

1. Venous thrombosis

2. pulmonary embolism,

3. angina,

4. acute MI

5. atrial fibrillation

6. vascular surgery

7. catheter implantation (A&V)

Front 5

Adverse effects of Heparin?

Back 5

Hemorrhage, osteoporosis and spontaneous fractures, 1–4% patients get heparin-induced thrombocytopenia (HIT) (systemic hypercoagulable state)

Front 6

HIT:

when does it occur

what is the mechanism

Back 6

1. Occurs 5-14 days after initiation therapy

2. 50% decrease in platelets

3. bound to platelet factor 4 (PF4), causes heparin-PF4-IgG complex that binds platelet IIa receptor causing platelet activation = Systemic hypercoagulation

Front 7

What route of administration requires monitoring via heparin?

Back 7

IV; monitored every 6 hours

Front 8

1. Why is HMW Hep monitored?

2. How is HMW heparin monitored?

Back 8

1.HMW Heparin has unpredictable bioavailability

2. Activated Partial Thromboplastin Time:

-normally 25-39s

-with HMWH it should be 2-2.5x normal (1-1:30ish)

SubQ is normally not monitored

Front 9

What are the LMW Heparins?

Back 9

Enoxaprin and Fondaparinux

Front 10

What is the mechanism of action of LMW Heparin?

Back 10

Also interact with AntiThrombin but preferentially inhibits factor Xa > thrombin b/c of small length

Front 11

What is the result of preferential Xa > Thrombin binding?

Back 11

Results in a multiplier effect by blocking earlier in the cascade

(upstream block)

Front 12

How does LMW compare to HMW in terms of:

1. half life and absorbtion

2. risk of side effects

3. administration

4. monitoring

Back 12

1. Longer half-life + faster absorption time
2. Much lower risk of thrombocytopenia and osteoporosis
3. Once daily SC injections administered in outpatient setting
4. Less frequent monitoring required due to more predictable pharmacokinetic response, no effect on aPTT

Front 13

In rare cases in which monitoring the anticoagulant effect is necessary (e.g., in patients with ____________), a ___________ is used.

Back 13

In pts with renal dysfunction--because LMWHs are cleared via the kidneys--a factor Xa inhibition assay is used

Front 14

Clinical indications for LMWH? (3)

Back 14

1. prophylaxis against deep venous thrombosis following hip, knee, or abdominal surgery

2.treatment of deep venous thrombosis (with or without pulmonary embolism)

3. management of acute coronary syndromes.

Front 15

toxcities of LMWH

Back 15

From what I can tell, the same as HMW just not as high of a risk for developing any of them:

Hemorrhage, osteoporosis and spontaneous fractures, 1–4% patients get heparin-induced thrombocytopenia (HIT) (systemic hypercoagulable state)

Front 16

Administration of fondaparinux

Back 16

administered SC once a day because of long half life

Front 17

Does fondaparinux interfere with platelet actions? Does it cause HIT?

Back 17

no to both

Front 18

Warfarin mechanism of action?

Back 18

Blocks gamma-carboxylation of glutamate in prothrombin and factors VII, IX, and X

Front 19

_____________, the enzyme that catalyzes the carboxylation reaction, is inhibited by therapeutic doses of warfarin

Back 19

vitamin K epoxide reductase

Front 20

How does warfarin differ from heparin in terms of their effects on clotting factors

Back 20

Heparin direclty inactivates coagulation factors that exist already

warfarin inhibits synthesis of NEW coag factors

Front 21

1. Onset of action for warfarin?

2. when does warfarin reach maximal effect?

Back 21

1. onset = 8-12 hours because existing clotting factors must be depleted

2. max effect in 3-5 days

Front 22

Indications for warfarin? (6)

Back 22

1. Acute DVT

2. pulmonary embolism

3. venous thromboembolism

4. following acute MI

5. prosthetic heart valve placement

6. chronic atrial fibrillation

Front 23

Adverse effects of warfarin (4)

Back 23

1. Hemorrhage; risk increases with intensity and duration of therapy
2. crosses the placenta, can cause hemorrhage at any time & developmental defects (abnormal bone formation) during 1st trimester
3. Cutaneous necrosis can occur during initiation of therapy (linked to reduced protein C activity)

4. drug interactions

Front 24

Drug interactions associated with warfarin

Back 24

Certain substances can increase the effect of warfarin while others can decrease it

Front 25

How is warfarin metabolized

Back 25

Metabolized by CYP2C9

– induction e.g. barbiturate = reduces effects
– inhibition e.g. metronidazole = increases effects

Isomers of warfarin are metabolized differently

Front 26

How do you monitor warfarin?

Back 26

Monitor with prothrombin time (PT) (time for plasma sample to clot) to calculate International Normalized Ratio (INR)

INR = PTpatient/PTnormal

Front 27

Normal INR and PTT?

Therapeutic goal for INR and PTT with warfaring

Back 27

1. Normal: INR = 1 PTT= 11-13.5s

2. Therapeutic INR = 2-3 times normal

2.5-3.5 for tilting disk heart valves (cool)

Front 28

1. What is the direct thrombin inhibitor?

2. What state is the drug in when it is administered?

Back 28

1. Dabigatran

2. Low molec weight prodrug

Front 29

Mechanism of action of Dabigatran?

Back 29

rapidly (approx. 1 hr) converted to active form from prodrug which binds to exosite 1 on thrombin preventing fibrinogen cleavage to insoluble fibrin

Front 30

Dabigatran is rapidly (approx. 1 hr) converted to active form from prodrug which binds to ______ on thrombin preventing ?

Back 30

binds to exosite 1 on thrombin preventing fibrinogen cleavage to insoluble fibrin

Front 31

Indications for dabigatran?

Back 31

Stroke prevention in patients with nonvalvular atrial fibrillation – equal efficacy to warfarin

Front 32

Adverse effects of dabigatran?

Back 32

Hemorrhage, heartburn, stomach upset, increase in risk of MI

Front 33

Advantages of dabigitran over warfarin

Back 33

1. No patient monitoring or titration

2. rapid onset of action

3. no adverse drug interactions

Front 34

What is the Oral Direct Xa Inhibitor?

Back 34

Rivaroxaban

Front 35

Rivaroxaban:

1. mechanism

2. administration and monitoring

3. onset

Back 35

1. Inhibits factor Xa

2. given as fixed dose (10mg/day), no monitoring
required

3. rapid onset of action.

Front 36

1. Indications for rivaroxaban

2. adverse effects?

3. contraindications?

Back 36

1. prevention of venous thromboembolism following hip or knee surgery

2. hemorrhage

3. Metabolized by kidney – issue in patients with reduced renal function

Front 37

Fibrinolytic agent? mechanism of action?

Back 37

Alteplase (an r-tPA) - Directly convert plasminogen to plasmin which then breaks down existing clots

Front 38

1. How is ateplase metabolized?

2. Half life?

3. administration

Back 38

1. metabolized by the Liver

2. 3-8 minutes

3. IV

Front 39

Indication for ateplase

Back 39

Effective only if used rapidly after onset of thrombosis:

• Acute ischemic stroke, acute MI, pulmonary embolism, severe deep venous thrombosis, ascending thrombophlebitis

Front 40

Side effects of ateplase

Back 40

hemorrhage, of which intracranial hemorrhage is the most serious