Coagulation Theaputics

Question 0

Unfractionated heparin

Answer 0

• MOA: combines to antithrombin III -> thrombin, Xa, IXa, XIa, and XIIa
• indication: DVT’s, acute coronary syndrome, anticoagulant ion during heparin, maintaining catheter patency

Question 1

Anticoagulants e.g.

• Heparins (3)
• factor Xa inhibitors (3)
• direct thrombin inhibitors (3)
• K antagonists (1)

Answer 1

• Heparins (unfractionated/low mol. Weight)
  ~ LMWHs: endoxaparin, delteparin, tinzaparin
• factor Xa inhibitors (fondaparinux, rivaroxaban, apixaban)
• direct thrombin inhibitors (leporudin, desirudin, argatroban)
• vitamin K antagonists (warfarin)

Question 2

Low molecular weight heparin

Answer 2

• Enoxaparin, dalteparin, tinzaparin
• MOA: same as unfractionated
• indications: allows for outpatient DVT Rx

Question 3

UF heparin vs. LMW heparin

Answer 3

• UF much wider range of PK/PD effects
• LMW better for outpatient
• both are parenteral only

Question 4

Heparin Black Box Warning

Answer 4

• Increased risk of spinal epidermal hematoma with neuraxial anesthesia

Question 5

Parenteral Factor Xa inhibitor

Answer 5

• Fondparinux
  ~ MOA: combines and activates ATIII -> selectively inhibits Xa
  ~ indication: DVT, PE

Question 6

Oral direct Xa inhibitors

Answer 6

• rivaroxaban, apixaban
  ~ MOA: binds factor Xa’s active site
  ~ prevention of stroke in Afib and DVT prophylaxis
• Sx: acute renal failure

Question 7

Direct thrombin inhibitors MOA and indication

Answer 7

• MOA: bind active site of thrombin
• parenteral indication: acute coronary syndrome, treatment of HIT (heparin induced thrombocytopenia)
• oral indication: prevention of stroke in DVT

Question 8

Direct thrombin inhibitor Sx

Answer 8

• bleeding

- interaction with dabigatran

Question 9

Warfarin

Answer 9

• MOA: inhibits vitamin K (epoxied reductase)
  ~ inhibits factors in intrinsic path factor (typically about 24 hrs) and protein C at about 9 hours
• indication: prevention of stroke in Afib, trt of DVT, PE
• Sx: cat X, bleeding, purple toe syndrome, skin necrosis
• warfarin paradox
• Category X

Question 10

Warfarin monitoring

Answer 10

• PT pt/PT control = INR
• target 2.5
• OD: Vitamin K admin, FFP, factors

Question 11

Thrombolytics (streptokinase, recombinant TPA, tenecteplase)

Answer 11

• MOA: activates plasmin
  ~ streptokinase: converts plasminogen
  ~ TPA et al: fibrin in fresh clot -> conformational change
• indication:
  ~ ischemic stroke (TPA)
  ~ ST-elevation MI (MI)
  ~ PE (TPA, streptokinase)
• Cind: bleeding risk, STK - previous exposure (anapalaxis)

Question 12

Anti platelet agents classes

Answer 12

• cox inhibitors (aspirins)
• adp inhibitors (theinopyradines, ticargrelor)
• GPIIa/IIIb inhibitors (eptifibatide, abciximab, tirofiban)
• phosphodiesterase inhibitor (dipyridamole)

Question 13

Cox inhibor: aspirin MOA and Cind

Answer 13

• decrease TXA-2, decreases PLT granule release and aggregation
• contraindication: ASA allergy, Reyes (encephalitis in kids with viral illness)

Question 14

ticlopidine, clopedigrel, prasugrel (theinopyradines)

Ticargrelor

Answer 14

• ADP inhibitors
• MOA: prodrugs; inhibition of ADP P2Y12 -> agg inhibition
  ~ thienos: irreversible
  ~ ticargrelor: reversible and higher binding affinity
• Cind:
  ~ prasugrel: 75+ y/o
  ~ ticargrelor: use of > 100g ASA, 3A4 inhibition
• Sx:
  ~ ticlopidine: hemeotoxic not used
  ~ bleeding: clopedigrel lowest risk
  ~

Question 15

GPIIb/IIIb inhibitors

Answer 15

• MOA: blocks cross linking of platelets via fibrinogen
• e.g. Eptifibatide, abciximab (percutanous only), tirofiban
• indication: acute coronary syndrome
• Cind: history if stroke, tcytopenia
• Sx: bleeding, tcytopenia (more common with abciximab)

Question 16

dipyridamole

Answer 16

• MOA: phosphodiesterase inhibitor
  ~ decreases (weakest of all the classes) aggregation and
  vasodilates
• indication: stroke prevention (w/ aspirin)
• Sx: bleeding, coronary steal, HA

Question 17

Clotting facilitators

Answer 17

- vitamin K (oral or IV) 2-6 hr onset
    ~ req bile salts for absorption 
- factors: 7,8 and 9
- desmopressin acetate
- prothrombin complex concentrate 
- cryoprecipitate (contains fibrinogen)

Question 18

Fibrinolytic inhibitors

Answer 18

• lysine analogues: aminocaproic acid (amicar), transexamic acid
• MOA: bind and inhibit plasmin and plasminogen
• indications:
  ~ transexamic: menorrahgia
  ~ aminocaproic: prevention of rebleeding after surgery

Question 19

P2Y12

Answer 19

• target for clopedigrel, ticlopidine, prasurgel
• irreversible
• ticargrelor: reversible

Question 20

Trt of heparin induces thrombocytopenia

Answer 20

• direct thrombin inhibitors

- leporudin, desirudin, argatroban

Question 21

Heparin antidote

Answer 21

Protamine sulfate

Question 22

Depotentiators of warfarin

Answer 22

C- cholestyramine 
R- rifampin 
A- anti-seizure meds
K- K vitamin
D- diuretics