Antiplatelets, Anticoagulants, Thombolytics

Question 0

What is platelet activation?

Answer 0

• Platelet cell membranes are covered with a variety of receptors that respond to different body chemicals.
• Platelets are activated when certain substances bind to these membrane receptors. Exposed collagen: Platelets will stick to any exposed collagen. Collagen triggers platelets to release a substance called ADENOSINE DIPHOSPHATE (ADP). ADP causes more platelets to stick to the developing aggregate.
• Collagen & ADP activate the arachidonic acid cascade. One metabolite of the arachidonic acid cascade is Thromboxane A2. This requires an enzyme called cyclooxygenase.

Question 1

What are the normal responses to vascular trauma?

Answer 1

*Platelets normally circulate throughout the blood stream in inactive form
*Stage 1: Once activated, they will stick to damaged vessel tissue & aggregate together. forming a platelet plug. Some drugs inhibit platelet aggregation- such drugs are called antiplatelet drugs.
Stage 2: Activation of the coagulation cascade, which involves many chemical reactions and coagulation factors.
»Contact activation pathway (intrinsic pathway)
»tissue factor pathway (extrinsic pathway)
Both pathways converge at Factor Xa; common steps end in fibrin formation. Some drugs inhibit parts of the coagulation cascade–such drugs are called anticoagulants.
*Keeping homeostasis under control is important so that you don’t have over-production of clots; thus, there are a multitude of negative inhibitory feedback mechanisms built into platelet aggregation and the coagulation cascade.

Question 2

What is Thromboxane A2?

Answer 2

Activated platelets stimulate the synthesis of Thromboxane A2 which causes platelet clumping & activation of other platelets.

Question 3

what is the antidote for warfarin?

Answer 3

Vitamin K, also known as phytonadione

Question 4

what is some good patient education for warfarin?

Answer 4

• suggest wearing a medical alert bracelet
• Avoid foods high in vitamin K
• Should not use aspirin but if needed no more than 81 mg/day
• Do not skip doses
• Avoid pregnancy
• Do not drink alcohol

Question 5

what is the mechanism of action for Warfarin (Coumadin)?

Answer 5

• Onset of clinical effectiveness is delayed (3-5) days. Why? Warfarin inhibits synthesis of new clotting factors only. It takes 3-5 days for existing clotting factors to be depleted.
• Drug interactions are numerous (98% protein bound, liver metabolism, interactions with other drugs that increase bleeding risk)
• Very narrow therapeutic window

Question 6

what are the therapeutic uses of warfarin?

Answer 6

*Prophylaxis against DVT or PE in patients with:
»a recent DVT or PE, continue x 3-6 months
»chronic atrial fibrillation, unstable angina, acute MI
»after bypass, orthopedic, or other major surgeries
»Tissue valves or valvular disease or mechanical prosthetic valves
»Prevention of transient ischemic attack (TIA) and recurrent MI

Question 7

what are the adverse effects of warfarin?

Answer 7

• Minor bleeding is fairly common, major bleeding (hemorrhage) is more rare
• Loss of appetite, nausea, vomiting, stomach cramps, diarrhea, and hair loss

Question 8

What are the contraindications of warfarin?

Answer 8

• Pregnancy- it will cross the placenta
• Alcoholism, liver disease, vitamin K deficiency
• Recent surgery where risk of bleeding is high
• Uncontrolled bleeding
• Active peptic ulcer disease

Question 9

What is the dosing for warfarin?

Answer 9

• Once daily, start at 2-5 mg/day
• Adjusted based on INR
• Genetic variations: VKORC1, CYP2CP variants requires dose reduction

Question 10

How do you monitor warfarin therapy?

Answer 10

• as with heparin, actual serum levels are not monitored
• Although we expect a lag time in the onset of clinical effectiveness–shown in the INR, we still monitor daily initially.
• Typical INR in someone not taking warfarin is 1.0. Therapeutic INR is usually 2.0-3.0 depending on what is being treated. Elevated INR is associated with increased risk of bleeding.

Question 11

What drug class is warfarin (Coumadin)?

Answer 11

Oral Anticoagulants

Question 12

what drug class is dabigatran?

Answer 12

Oral anticoagulants

Question 13

What drugs are in the class Thrombolytics?

Answer 13

“plase”
Alteplase
streptokinase
tenecteplase

Question 14

what is the mechanism of action for Thrombolytics?

Answer 14

*converts plasminogen to plasmin. Plasmin dissolves clots.

Question 15

What are the therapeutic uses of thrombolytics?

Answer 15

*Treatment of acute DVT, massive PE, MI, and acute ischemic stroke. Also used to clear clotted IV catheters.

Question 16

what are the adverse effects of thrombolytics?

Answer 16

Severe hemorrhage; re-thrombosis after initial lysis- sometimes busting up the clot causes little chunks of the clot to travel throughout the body to lodge in smaller vessels & activate more platelets. (Always follow up a clot-buster with heparin to prevent more clots from forming.)

Question 17

what are the absolute contraindications of thrombolytics?

Answer 17

*Active bleeding, aortic dissection, cerebral neoplasm (cancer) or aneurysm, history of recent intracranial hemorrhage, surgery, or trauma and others.

Question 18

what types of foods are high in vitamin K?

Answer 18

Green leafy veggies

lettuce

Question 19

what drug class is Heparin in?

Answer 19

Anticoagulants

Question 20

What is the mechanism of action of Heparin?

Answer 20

*binds to antithrombin III to inhibit fibrin formation. Liver metabolized. Quick onset of action and fairly short duration of action.

Question 21

What are the therapeutic uses of Heparin?

Answer 21

*Drug of choice in situations requiring rapid onset of anticoagulant effects.
»acute stroke, acute MI, DVT, PE
*Prevent DVT & PE following surgeries known to increase clot potential (e.g. hip, knee) and bedridden/immobile patients.
*Prevent clotting during renal dialysis & open-heart surgery.
*Central line IV flushes to prevent clotting

Question 22

What are the adverse effects of Heparin?

Answer 22

• Major and minor bleeding- i.e. cerebral, GI tract, urinary tract, nosebleeds
• Heparin induced thrombocytopenia (HIT)- immune mediated destruction of platelets

Question 23

What are the contraindications/ Precautions?

Answer 23

• Pre-existing thrombocytopenia, uncontrollable bleeding
• Avoid after surgeries/ procedures with a high risk of bleeding (e.g. eye, brain, spinal cord, lumbar puncture, & spinal epidural)

Question 24

How do you monitor Heparin?

Answer 24

*activated partial thromboplastin time (APTT)- measures the length of time it takes a clot to form.
Normal= 30-40 seconds.
Therapeutic= 1.3-2 times normal
* Continuous, infusion, weight-based regimens are commonly used in acute treatment of DVT, PE, & MI. During these situations, APTT monitoring generally occurs every 4-6 hours.

Question 25

what is the dosing for Heparin?

Answer 25

prescribed in “units” rather than “mg”

Question 26

What is the antidote for Heparin?

Answer 26

*infrequently used, protamine sulfate (binds to & inactivates heparin molecules)

Question 27

what are the drugs in the class Low Molecular Weight Heparins (LMWH)?

Answer 27

enoxaparin
dalteparin
tinzaparin

Question 28

What are the therapeutic uses of Low Molecular Weight Heparins?

Answer 28

similar to unfractioned heparin

Question 29

What are the adverse effects of LMWH?

Answer 29

• similar to unfractioned heparin except less thrombocytopenia.

Question 30

how do you monitor and whats the dosing for LMWH?

Answer 30

• fixed dosing in “mg” and dosing is based on patient weight.
• Given once or twice daily
• Routine use does not require monitoring. APTT is NOT monitored with the LMWHs.

Question 31

what drugs are antiplatelets?

Answer 31

Aspirin
Clopidogrel
prasugrel
ticagrelor
Extended release dipyridamole 200mg + Aspirin 25mg

Question 32

what drugs are anticoagulants?

Answer 32

heparin
enoxaparin
dalteparin
tinzaparin
fondaparinux
bivalirudin
lepirudin
desirudin
argatroban
warfarin (coumadin)
dabigatran
rivaroxaban