Pharmacologic Treatment of Coagulopathies Flashcards
What do Anticoagulants do?
inhibit the action or formation of clotting factors
Name some Oral Anticoagulants
Warfarin (Coumadin, Jantoven)
Dabigatran (Pradaxa)
Apixaban (Eliquis)
Rivaroxaban (Xarelto)
Describe Warfarin (Coumadin)
is the most widely used oral anticoagulant.
Mechanism of action: Inhibition of vitamin K dependent coagulation factors II, VII, IX, X
Also inhibits Protein C and S
How long does it take for Warfarin to reach therapeutic effect
36-72 hours
Normal clotting factors need to clear from the circulation
What is Warfarin used for?
to prevent further clot formation.
Indications for use of Warfarin
Venous and arterial thromboembolism Pulmonary embolus Stroke prevention in atrial fibrillation Thrombus prevention in cardiac valve replacement Stroke Transient ischemic attacks Prevention of clots
Dosing is based on what?
PT/INR
Normal INR is 1.0
Not therapeutic until INR is 2.0
For most indications the INR range is 2.0-3.0
How soon should the INR be checked after each dose change?
3rd day
What level should we start dosing Warfarin?
5 mg nightly
What things can dosing be dependent on?
Chronic dose will vary depending on the patient and their other medications
Chronic dose will also vary depending on the patient’s genotype
Adjust dose as need to achieve desired INR
What drugs can interact with Warfarin?
Just assume that EVERY drug interacts with warfarin - LOOK IT UP JACKASS!!!
Major interactions: cholesterol lowering meds (statins), most antibiotics, NSAIDs, drugs cleared through the liver
Food interactions that can decrease the INR
Vitamin K containing foods (dark leafy greens, green tea) decreases INR
Smoking/tobacco decreases INR
Alcohol increases the INR
Purple Toe Syndrome
Skin/tissue necrosis leading to gangrene
Usually occurs 3-8 days after starting
Purple toe syndrome (3-8 weeks after starting
Treatment of Purple Toe Syndrome
stop the coumadin and switch to another anticoagulant.
Same treatment for skin necrosis.
Management of an elevated INR
No bleeding and INR < 5 -Hold warfarin Bleeding or INR > 5 -Hold warfarin -Oral or IV or subQ vitamin K Life threatening bleeding -Vitamin K -Factor VII -Fresh frozen plasma or Prothrombin concentrate
Dosing patients on Warfarin with vitamin K, How and when is it dosed?
Sub Q variable
IV 1-2 hours later give slowly or they DIE!
Oral 24-48 hours later
Avoid IM
Note:: affects warfarin for up to a week after administration
Patient education needs to include
indication, dosing, monitoring, side effects, drug interactions, diet, alcohol, birth defects if appropriate
How often should the INR be checked after each dose change?
2-3 days
How long should warfarin be held when anticipating a surgical/invasive procedure?
5 days
Name 2 reasons it might be best to take this medication at night.
Not as much food reaction, For adjusting doses
Why is bridging with heparin important for initiation of therapy and for patients that may need procedures?
As a procoagulant state, to avoid necrosis. Patients with abnormal heart rhythm and a clot
Newer oral anticoagulants
Dabigatran (Pradaxa)
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Dont have to check INR
Major pros of new oral anticoagulants as compared to warfarin
No need for routine lab monitoring
Not affected by foods
Not as many drug interactions
Major cons of new oral anticoagulants as compared to warfarin
No antidote
No way to monitor anticoagulation
Dose adjustments likely needed for renal patients
Not for use in valvular heart disease
Parenteral Anticoagulants
Unfractionated IV heparin Heparin Low-Molecular weight heparin Enoxaparin (Lovenox) Dalteparin (Fragmin) Fondaparinux (Arixtra)
How do you monitor Heparin
PTT
How do you monitor Warfarin
PT/INR
Heparin mechanism of action
Potentiation of the action of antithrombin III and inactivating thrombin, IX, X, XI, XII, and plasmin
Prevents the conversion of fibrinogen to fibrin
Unfractionated Heparin is used to prevent clot formation in what disorders?
DVT PE Dialysis machines Atrial fibrillation Myocardial infarction Arterial or venous throbosis
Contraindications and complications of Heparin
Contraindications: anaphylaxis and recent major surgery
Adverse effects: bleeding, hypersensitivity reactions, transaminitis(elevated liver enzymes), Heparin induced thrombocytopenia
Antidote available to reverse in the case of severe bleeding/overdose
Protamine sulfate to rapidly reverse heparin
Slow IV infusion needed to prevent anaphylactic reaction
Can be used for LMWH and UFH
Heparin Induced Thrombocytopenia
Can occur with unfractionated heparin and low molecular weight heparin
Most likely to occur with UFH
Characteristics of terrible patients for chronic anticoagulants
Increased fall risk Dementia Occupational Hazard Non-compliant patients History of Aneurysm Alcoholism PUD Old people Liver Disease Pregnancy
Diagnostic evaluation
Noted when platelets drop by 50% after initiation of therapy Platelet factor 4 antibody (PF4) Not specific but sensitive Serotonin release assay Specific and sensitive CBC, PLT, Urine for blood,
Complication of Heparin
Heparin induced thrombocytopenia (HIT)
Describe HIT
Creates a pro-thrombotic state
Antibodies bind: Platelet factor 4, heparin and platelets
Platelets are activated and destroyed
Occurs 4-5 days after initiation of therapy
Treatment of HIT
Stop Heparin
Give alternative anticoagulant (direct thrombin inhibitor)
No platelet transfusions
Do not give warfarin until platelet count increases
Direct thrombin inhibitors
Lepirudin,
Bivalirudin,
Hiruden,
Argatroban
Low Molecular Weight Heparin
Enoxaparin (Lovenox),
Dalteparin (Fragmin),
Fondaparinux (Arixtra)
LMWH has multiple advantages over UFH
Can be given subcutaneously once or twice daily without need for labs for daily monitoring
Lower risk of heparin induced thrombocytopenia
Home administration
Safer then UFH for extended administration
LMWH mechanism of action
Inhibits Xa and antithrombin III
Indirect thrombin inhibitor
LMWH more strongly inhibits Xa then UFH
Dosing LMWH
Once or twice daily administration
Time to effect is about 2 hours (SQ) with peak effect at 4 hours
Monitor drug concentration with lab for anti-Xa activity in those who are obese, pregnant or with poor renal function
What would be the advantages of IV over SubQ?
Speed
What do Antiplatelet drugs do?
inhibit platelet aggregation and prevent platelet plugs.
Name some Antiplatelet meds
Aspirin
P2Y12 antagonists
Clopidrogrel (Plavix), Prasugrel (Effient), Ticagrelor (Brilinta)
Dipyridamole
Used in combo with aspirin (Aggrenox)
GIIb/IIIa antagonists
Abiciximab (Reopro), Eptifibatide (Integrelin)
What does Aspirin do?
Acetylsalicylic acid (ASA)
Irreversible platelet inhibitor
Prevents the formation of clots by inhibition of the platelet plug
Rapid absorption with peak effects in 1 hr
Aspirin Dosing recommendations
Primary prevention of CVA/MI 81 mg daily Secondary prevention of CVA/MI Depends on the other meds Acutely 325mg daily for MI and CVA Acute coronary syndrome 325mg chewed X 1
What useful for those at risk for thromboemolism
Aspirin in addition to the primary and secondary prevention of CAD and MI
Major side effect of Aspirin
Bleeding
Other side effects of Aspirin
Always assess for GI bleeding
H2 blockers and proton pump inhibitors may decrease gastritis and GI bleeding
Administer with food to decrease GI disturbance
Tinnitus at higher doses
Resistance
Allergy
What is Clopidogrel (Plavix) and the other P2Y12 antagonists used for?
Treatment and prevention of acute coronary syndrome
Treatment and prevention of thromboembolic events
Irreversible inhibition of activation and aggregation is noted with which anticoagulants
Clopidogrel (Plavix)
-P450 system
Prasugrel (Effient)
Ticagrelor (Brilinta)
Adverse effects of plavix
Bleeding
Multiple drug interactions with Plavix
Stop 7 days prior to surgery
Dipyridamole
Secondary prevention in patients following stroke and TIA
Used often with aspirin in a single combination pill (Aggrenox)
What is the MOA of Dipyridamole
it inhibits ADP and phosphodiasterase
Dipyridamole causes what?
vasodilation and inhibit platelet aggregation
Abciximab (Reopro) and Eptifibatide (Integrelin) side effects
Bleeding
Thrombocytopenia
Allergy
Name some Fibrinolytics
tPA, Streptokinase, Urokinase
What do Fibrinolitics do
break down existing clots.
Convert plasminogen to plasmin to breakdown the fibrin strands
Indications for Fibrinolitics
For treatment of existing clots
- MI
- Stroke
- Massive PE
- Limb threatening ischemia
Side effects of thrombolytics
life threatening bleeding.