PathoPharm Test 2: Anticoagulant, Antiplatelet & Thrombolytic Drugs

1. Platelet plug - platelets adhere to collagen @ site of injury --> fibrinogen binds adjacent platelets via GP IIb/IIIa Rs (unstable) = Aggregation

2. Reinforcement of plug (fibrin) = coagulation
Fibrin created via coagulation cascade (intrinsic & extrinsic paths)
Xa turns Prothrombin --> Thrombin which creates Fibrin

Controls:
1) Antithrombin (forms complex with clotting factors, inactivating them
Heparin's target
2) Plasmin (digests fibrin)

VII, IX, X, Prothrombin

- Enhances Antithrombin activity (neutralizing Xa & Thrombin) --> less fibrin produced --> less coagulation --> hemostasis control

1) UFH + Antithrombin bind --> change in shape of Antithrombin
2) Shape change = increased ability to bind with Xa or Thrombin --> inactivation

- NOT orally (must be given parentally via SC, IV)
- Variable activity (b/c variable smt Antithrombin) --> must monitor levels via aPTT or Anti-Xa
- Antidote = Protamine
- Dosing = wt-based, in units (IV if tx MI/DVT; SC if preventing DVT)

- For:
Rapid anticoagulation (acute MI, PE, DVT, stroke)
Prevention of VTE

- Hemorrhage = main complication (STOP UFH infusion! Protamine)
- Heparin-Induced Thrombocytopenia (HIT) - immune-rxn (Abs + Heparin + platelets bind --> aggregation)
Develops 1-2wks after starting therapy (immediately if previous heparin exposure...already have Abs)
IVC filter (trap clots) & IV immune globulin (IVIG) - gets rid of clots
D/C Heparin! Use alternative anticoagulation agent

- Same mechanism as UFH --> but preferentially binds to inactivate Xa (not lrg enough for Thrombin binding)
- More predictable than UFH
- No monitoring
- Less risk of HIT (safer), also less risk of bleeding
Avoid in pts with HIT (cross-reactivity)
- SC for both tx & prevention (pre-filled syringes)
Good for outpatient setting

- Protamine not as effective in countering it

- Inhibits Xa activity via Antithrombin (same mech) --> less Thrombin --> less Fibrin
- Prevention or Tx of VTE
- SC injection once daily (convenient)
- No monitoring

- X HIT
- SE: bleeding

- Vitamin K antagonist --> blocks synthesis of 4 factors
Delayed onset (doesn't affect those alrdy created)
Not for emergencies
Need consistent Vit K intake (don't have to avoid)
- For prophylaxis of thrombosis
- Intx!! - assume it will interact with any drug
- Very little free & thus active (basis for many intx)
- Monitor!!
Prothrombin Time (PT): detects change in 4 factors
International Normalized Ratio (INR) = better - how thin pts blood (normal: 2.0-3.0; high risk: 2.5-3.5)
Monitor INR for first 7-10 days, once in range decrease
- Orally (IV fastest but risk of anaphylaxis) - no oral form so give injectable stuff orally
- PT EDUCATION (signs of bleeding, safety measures to decrease bleeding, inform other HCPs, consistent Vit K, drugs must be approved)

- Hemorrhage (screen for high risk, D/C prior to surg)
- Vit K can reverse INR

- Not during pregnancy or breastfeeding (use Heparin during preg)

- Less monitoring req'd, No titration, Less interactions
- Expensive (not covered bc limited clinical experience)

- Rivaroxaban (inhibitor of Xa)
- Dabigatran (inhibitor of Thrombin)
- End result of both: less Thrombin --> less Fibrin
- Prophylaxis of VTE, stroke

- Irreversibly inhibits COX enzyme --> decreases platelet activation (less binding to GP IIb/IIIa Rs)

- Prevention of MI, stroke in those withTIA hx
- AEs: increased risk of bleeding, hemorrhagic stroke, GI effects

- 81mg Oral --> preventative
- 160-325 mg CHEWED --> after acute MI = loading dose

- Irreversibly blocks ADP R --> prevents platelet aggregation --> preventing coagulation
- Prevention of MI, stroke (in those with hx), during coronary stenting

- Well tolerated (GI = minor SE + bleeding)
- No Monitoring

- PPI blocks conversion of Clopidogrel --> active form --> decreased efficacy of Clopidogrel & increased risk of vascular events

- Chews up clots that are already formed
- For acute MI, ischemic stroke, pulmonary embolus
- Can only give w/i certain amt of time
- SE: bleeding (minimize physical manipulation, invasive procedures, concurrent use of antiplatelet/anticoagulant drugs, monitor potential bleeding sites)

- Increases conversion of Plasminogen --> Plasmin --> gets rid of clots via digestion of Fibrin
- Is a Thrombolytic --> for acute MI, PE, ischemic stroke
Low-dose tPA: unblock occluded catheters (Central Venous Catheters)

- Expensive!!
- CONTRAINDICATIONS! (recent bleed, HTN, etc.)