Pharm Treatment of Clotting Disorders

Question 1

Anticoagulants inhibit the ____ or ____ of clotting factors.

Answer 1

action or formation

Question 2

Examples of oral anticoagulants

Answer 2

Warfarin (coumadin, jantoven) *most widely used

Dabigatran (pradaxa) (IIa) (new)
Apixaban (eliquis) (Xa) (new)
Rivaroxaban (xarelto) (Xa) (new)

Question 3

Warfarin
MOA
Time to achieve full therapeutic effect

Answer 3

Inhibits the synthesis of vitamin K dependent coagulation factors II, VII, IX, X and Protein C and Protein S.

*it doesn’t block them, it block the PRODUCTION of them

36-72 hours
-Normal clotting factors need to clear from the circulation

Question 4

What is Warfarin used for?
Indications
Why must the patient be monitored closely
What is dosing based on

Answer 4

Used to prevent further clot formation

• venous and arterial thromboembolism
• pulmonary embolism
• stroke embolism
• stroke prevention in A. fib
• thrombus prevention is cardiac valve replacement
• stroke
• TIA
• prevention of clots

Must be monitored closely because of the narrow therapeutic range

Dosing based on PT/INR

Question 5

What is normal INR?

What is the INR range for most warfarin indications?

Answer 5

1.0 normal

Warfarin INR- 2.0-3.0

Question 6

How soon should the INR be checked after each dose change?

Answer 6

2-3 days

Question 7

When should a pt take warfarin?

Answer 7

dosing depends on everything (pt, meds, etc.)

start with 5mg nightly

• -eating could disrupt absorption
• -can test in the am with little interactions

-warfarin is highly protein bound which leads to many drug interactions

Question 8

What are the major drug interactions of warfarin that can lead to life threatening bleeding (LTB)?

Answer 8

Just assume that every drug interacts with warfarin.

• Statins (cholesterol lowering)
• most antibiotics
• NSAIDs
• drugs cleared through the liver

Question 9

Food interactions with warfarin that lower the INR?

Answer 9

• vitamin K containing foods (dark leafy greens, green tea)
• smoking/tobacco

-Alcohol INCREASES

Question 10

Warfarin

adverse events

Answer 10

LTB*
Skin necrosis* (leading to gangrene)
–purple toe syndrome (cholesterol emboli to the feet)
bleeding!

Question 11

How to manage a pt with elevated INR:
5
LTB

Answer 11

5- hold warfarin and oral, IV or SQ Vitamin K

• SQ absorption is variable
• IV 1-2 hours later
• Oral 24-48 hours later

LTB- vitamin K, factor VII, and FFP/ prothrombin concentrate

Vitamin K is the antidote.

Question 12

Do anticoagulation clinics exist?

Answer 12

yep

Question 13

How long should warfarin be held when anticipating a surgical or invasive procedure?

Answer 13

5 days

Question 14

Why is “bridging” with heparin important for initiation of therapy and for patients that may need procedures?

Answer 14

Use heparin for 3-5 days when starting warfarin to prevent coagulation. Warfarin initially inhibits Protein C and S and ATIII (which help stop clotting) making you hypercoaguable.

Question 15

Pros and Cons to new oral anticoags (compared to warfarin)

Answer 15

Pros

• no need for routine labs
• not affected by food
• not as many drug interactions

Cons

• no antidote
• no way to monitor anticoagulation
• dose adjustments likely needed for renal pts
• not for use in valvular heart disease

Question 16

Examples of parenteral anticoagulants

Answer 16

Unfractionated Heparin (UFH)
-Heparin

Low molecular weight heparin (LMWH)

• enoxaparin (lovenox)
• dalteparin (fragmin)
• fondaparinux (arixta)

Question 17

Heparin

MOA

Answer 17

• Potentiation of the action of antithrombin III and inactivating thrombin, IX, X, XI, XII, and plasmin
• prevents the conversion of fibrinogen to fibin

Question 18

Why is frequent monitoring needed in heparin pts?
What test monitors?
Resistance can be seen in?
Dosing?

Answer 18

• due to a narrow therapeutic window
• PTT
• seen more commonly in acute illness with antithrombin III deficiency
• bolus followed by IV drip

Question 19

Heparin
Indications
CI
Adverse effects

Answer 19

• DVT
• PE
• A fib
• MI
• Arterial or venous thrombosis

CI- anaphylaxis and recent major surgery or ongoing bleeding

AE- bleeding, hypersensitivity rxns, transaminitis (bump in liver enzymes), heparin induced thrombocytopenia

Question 20

What is the antidote for heparin?

Answer 20

Protamine sulfate

• in the event of severe bleeding or overdose
• slow IV infusion to prevent anaphylactic rxn
• can be used for both LMWH and UFH

Question 21

Heparin Induced Thrombocytopenia (HIT)
What type of heparin is it most likely to occur with?
What is is?

Answer 21

Most likely to occur with UFH but can occur with both UFH and LMWH

HIT is a serious complication of Heparin therapy

• creates a pro-thrombotic state
• antibodies bind: platelet factor 4 antibodies bind to heparin and platelets
• platelets are activated and destroyed
• occurs 4-5 days after the initiation of therapy

Question 22

HIT
Dx criteria
Labs

Answer 22

Noted when platelets drop by 50% after initiation of therapy

Labs

• platelet factor 4 antibody
• serotonin release assay (high=aggregation)

Question 23

HIT

tx

Answer 23

1st- STOP HEPARIN

• give alternative anticoag like a direct thrombin inhibitor
• no platelet transfusion
• do not give warfarin until platelet count increases

Question 24

Advantages to LMWH

Answer 24

• can be given SQ once or twice daily without need for labs for daily monitoring
• lower risk of HIT
• Safer than UFH for extended administration

Question 25

LMWH MOA Dosing depends on? Time to effect?

Answer 25

- inhibits Xa and accelerate ATIII - indirect thrombin inhibitor - LMWH more strongly inhibits Xa that UFH Dosing varies depending on the indication, renal function, and drug 2 hours with peak effect at 4 hours *if you need to know drug levels, you can check with a lab for anti-Xa activity

Question 26

Antiplatelet drugs inhibit ______ _____ and prevent _____ _____. Examples?

Answer 26

inhibit platelet aggregation and prevent platelet plugs Aspirin P2Y12 antagonists (plavix, effient, brilinta) Dipyridamole (aggrenox, used in combo with ASA) GIIb/IIIa antagonists (reopro, integrelin)

Question 27

``` Aspirin reversible or irreversible? MOA Peak effects? Used for the prevention of? ```

Answer 27

Irreversible platelet inhibitor Prevents the formation of clots by inhibition of the platelet plug rapid absorption with peak effects in 1 hour Thromboembolism

Question 28

ASA Dosing SE

Answer 28

Primary prevention- 81mg daily secondary prevention- depends, 81-325mg daily acute coronary syndrome- 325 mg chewed SE - bleeding - administer with food to decrease GI disturbance, H2 and PPIs may decrease gastritis and GI bleeding - tinnitus at higher doses - resistance - allergy - stop 4 days prior to surgery

Question 29

Clopidogrel (Plavix) and other P2Y12 antagonists Used for the treatment and prevention of? MOA reversible or irreversible? Adverse Effects

Answer 29

acute coronary syndrome and thromboembolic events The binding of ADP to the (type 2 purinergic) receptor (P2Y12) is blocked and prevents the activation of GPIIb/IIIa complex therefore preventing platelet aggregation. -Basically it blocks the receptor site. The receptor normally allows the platelet bridge to form and aggregate. IRREVERSIBLE inhibition of platelet activation and aggregation is noted AE - bleeding - multiple drug interactions with plavix - stop 7 days prior to surgery

Question 30

Dipyridamole indications MOA

Answer 30

Indications - secondary prevention in patients following stroke and TIA - used often with aspirin in a single pill called aggrenox MOA -causes an accumulation of adenosine, c-AMP (these mediators cause vasodialation and inhibit platelet aggregation

Question 31

GPIIb/IIIa antagonists: (Reopro, Integrelin) Indications SE

Answer 31

* most powerful platelet inhibitor * decrease platelet bridge formation Indication - acute coronary syndrome - clot prevention during percutaneous coronary intervention SE - bleeding - thrombocytopenia - allergy

Question 32

``` Thrombolytic drugs AKA Examples MOA Indications SE ```

Answer 32

Fibrinolytics tPA, streptokinase, Urokinase Breakdown existing clots. Convert plasminogen to plasmin to facilitate breakdown of the fibrin strands Indications - MI if >90 min to PCl - Stroke within the first few hours - massive PE with unstable hemodynamics - limb threatening ischemia SE - massive LTB - use hospital checklist prior to administration **these are very dangerous drugs. We don't give these.