Antiplatelets * Anticoagulants Flashcards
Clotting Cascade
Antiplatelet - Reasons for use
Prevention of MI
Post stent placement
Ischemic stroke
TIA
Anticoagulant
Prevention of thromboembolism
DVT
Prevent embolic stroke in A fib
prosthetic valve
Post MI
Post stent
Acetylsalicylic Acid
- MOA: prevents formation of thromboxane A2 (thromboxane synthase
promotes platelet aggregation) - Effect may last up to 8 -12 days (lifespan of platelet)
- AEs: risk of GI bleed due to gastric erosions
- Tinnitus = sign of toxicity
clopidogrel (Plavix)
- MOA: blocks ADP (adenosine diphosphate) receptors on platelet (ADP is a
platelet aggregator) - Prodrug substrate for CYP 450 2C19 enzymes (thus, they need CYP 2C19 to become active)
- CYP 2C19 inhibitors may decrease efficacy
- PPIs: (except pantoprazole (Protonix)
- fluoxetine (Prozac)
- 14% of population poor CYP 2C19 producers
prasugrel (Effient)
- MOA: ADP (adenosine diphosphate) receptor inhibitor
- More effective than clopidogrel (Plavix), but greater risk of bleeding
- Do NOT give if prior stroke or TIA (bleeding/stroke risk outweighs benefit)
- Avoid use in elderly (older than 75 yo)
- Not as affected by 2C19 inhibitors
dipyridamole/ASA (Aggrenox)
MOA: ADP receptor inhibitor
* Some vasodilation (coronary arteries) properties
* Better than ASA alone to prevent stroke after TIA
* Expensive $85/month
* Use if patient had TIA or CVA while on ASA
warfarin (Coumadin) PO
- MOA
- inhibits conversion of prothrombin to thrombin
- interferes with hepatic synthesis of vitamin K dependent coagulation factors (factors II,
VII, IX,X) - Long Half-Life 42 hrs and variable
- Initiate at 5-10 mg daily dose
- 2.5 mg daily dose if:
- Weigh less than 110 lb
- Over age 75
- Increased risk of bleeding
warfarin labs
- MOA
- inhibits conversion of prothrombin to thrombin
- interferes with hepatic synthesis of vitamin K dependent coagulation factors (factors II,
VII, IX,X) - Long Half-Life 42 hrs and variable
- Initiate at 5-10 mg daily dose
- 2.5 mg daily dose if:
- Weigh less than 110 lb
- Over age 75
- Increased risk of bleeding
warfarin concerns
- Narrow therapeutic index
- CYP 1A2 and 2C9 metabolism
- Antibiotics, antifungals, herbal products may affect INR levels
- Highly protein bound (95-99%; inactive), but low affinity (easily displaced or “knocked
off”) - Aspirin
- Protocols for dosage adjustment
- Ex: if INR high, then lower weekly dose by 10%* Be consistent with amount of vitamin K in diet
- Green leafy vegetables, tomatoes, fish, liver, cheese, egg yolks, red meats
- Pregnancy category X
- Safe with lactation
- Usually stop 5 days prior to surgery and restart 12-24 hours after surgery
**Antidote: vitamin K
warfarin concerns
- Narrow therapeutic index
- CYP 1A2 and 2C9 metabolism
- Antibiotics, antifungals, herbal products may affect INR levels
- Highly protein bound (95-99%; inactive), but low affinity (easily displaced or “knocked
off”) - Aspirin
- Protocols for dosage adjustment
- Ex: if INR high, then lower weekly dose by 10%* Be consistent with amount of vitamin K in diet
- Green leafy vegetables, tomatoes, fish, liver, cheese, egg yolks, red meats
- Pregnancy category X
- Safe with lactation
- Usually stop 5 days prior to surgery and restart 12-24 hours after surgery
**Antidote: vitamin K
Heparin
: potentiates action of antithrombin III
* (antithrombin III binds to/inactivates thrombin)
* No new clots are formed
* Short half-life
* Must be given SC (not absorbed in GI tract)
* Monitoring:
* UFH (unfractioned heparin) – aPTT (activated partial thromboplastin time)
* aPTT = increased 1.5-2.5 times normal
Pregnancy - Cat C
enoxaparin (Lovenox)
LMWH
potentiates action of antithrombin III (antithrombin III binds to/inactivates thrombin) AND
inactivates factors Xa and IIa
* Uses: DVT prophylaxis and tx
* SC
* Weight based (1mg/kg)
* BID
* Often used for 5 days to bridge the gap awaiting therapeutic warfarin INR levelsPregnancy category B
* Does not cross the placenta or cause teratogenicity or fetal bleeding
* First line drug for antithrombotic therapy during pregnancy
* Safely used during breastfeeding
* Less variation in bioavailability than heparin
* Monitoring: none
Anticoagulant; Thrombin Inhibitors
synthetic thrombin inhibitor (thrombin is required for the conversion of fibrinogen to fibrin)
* does not require antithrombin III
* reversibly binds to thrombin active site
dabigatran (Pradexa) PO
Thrombin Inhibitor* Indicated for stroke & embolic risk reduction in non-valvular a-fib
* DVT/PE treatment
* DVT/PE prophylaxis
* No CYP 450 implications
