6. Anticoagulants, Thrombolytics, Antiplatelet Agents, and Antifibrinolytics Flashcards
- What are the key points of anticoagulants?
- What is inhibited?
- Immediate or delayed effect?
- High or low risk of drug drug interaction?
- What are the key points of anticoagulants?
Anticoagulants all inhibit the action or formation of one or more of the clotting factors
Create an immediate defect (minutes for IV, hours for orally) in the clotting mechanism and should be treated with caution
High risk of DDI - a large number of unrelated drugs affect the dose of the anticoagulant needed to produce a desired effect
- 4 What are the key points of anticoagulants?
- Narrow or wide range between sufficient therapy and hemorrhagic risk? Consistent patient outcome?
- How important are individual treatment and frequent laboratory tests?
Narrow range between sufficient therapy and risk. Patient outcome can vary considerably.
Individual treatment and frequent laboratory tests are imperative
5.5 What are the four categories of anticoagulants?
(Bonus points - divide the four into old and new!)
Old:
- indirect thrombin inhibitors (like Heparin)
- Coumarin anticoagulants (like Warfarin)
New:
- Direct thrombin inhibitors
- Direct factor x inhibitors
- 6 Heparin
- What is it comprised of?
- What are the two most common preparations?
Heparin is comprised of a mixture of heparins (protein molecules) with a wide range of molecular weights.
The two most common preparations are:
- Unfractionated heparin (UFH) – Heparin Sodium
- Low-mol. weight heparin (LMWH) – Fragmin, Innohep, Lovenox
- 7 Heparin
- Mechanism- What protein is stimulated by heparin?
- What kind of category of anticoagulant is heparin?
- What protein is stimulated by heparin?
Heparin stimulates antithrombin III, which neutralizes factor X and other clotting factors.
Without factor Xa, prothrombin canot be converted to thrombin (prevents fibrinogen into fibrin).
Heparin also stimulates heparin cofactor II, which inhibits thrombin
An “Indirect” thrombin inhibitor
- 9 Unfractionated Heparin (UFH)
- How is it adminstered?
- What is tricky about dosage?
Given IV (bolus or infusion) - cannot be given orally (heparin proteins destroyed by stomach acidity)
UFH binds to plasma proteins in addition to its normal intended affect, reducing its anticoagulation activity and causing a large variability of anticoagulant response among patients. UFH also binds to endothelial cells and macrophages.
Dosage of UFH is adjusted and effect is monitored with APTT (normal is 25-36 and UFH will be 2-2.5 times that value).
5.11 What form of heparin can be administered either in hospital or out of hospital?
Either in-hospital or out of hospital because they can be administered via syringe on a body weight basis without the need for lab monitoring.
5.12 What is the only major coumarin anticoagulant in the USA?
Warfarin (Coumadin)
Side note - rat poison
- 13 What is Warfarin’s mechanism?
- Which clotting factors does it target?
Inhibits blood clotting mechanisms by interfering with the hepatic synthesis of vitamin-K dependent clotting factors (II, VII, IX, and X)
5.14 What are the main indications for treatment with warfarin?
- Long-term treatment of venous thrombosis or pulmonary embolism
- Post-MI and post-op (after cardiac or vascular surgery) patients
- Prevention of systemic thromboembolism in patients with prosthetic heart valves or atrial fibrillation
5.15 How is Warfarin therapy monitored?
It is defined in terms of the international normalized ratio (INR).
For most patients, an INR of 2.0 to 3.0 is desired.
5.16 What are key drug-drug interactions with Warfarin?
- Cimetidine (Tagamet)
- Acetaminophen (Tylenol)
- High dose, acute alcohol
- Many antibiotics
- Azithromycin (Zithromax)
- Ciprofloxacin
- Clarithromycin
- Erythromycin
Synthetic thyroid hormones increase the catabolism of many clotting factors and can potentiate (increase) the effects of warfarin.
5.17 What can stimulate warfarin metabolism, diminishing the desired effects?
Chronic alcohol use
Phenytoin (dilantin)
5.17 How do oral contraceptives interact with warfarin?
Oral contraceptives increase the synthesis of many clotting factors, reducing the effects of warfarin.
- 18 What foods can decrease warfarin effects?
- How?
- What are some examples of these foods?
Foods rich in Vitamin K
They stimulate the synthesis of vitamin K dependent clotting factors (II, VII, IX, X)
Cabbage, cauliflower, spinach, and other green leafy vegetables, as well as cereals
5.18 How are warfarin overdoses typically treated?
Treated with vitamin K and transfusion
5.19 What is the most common side effect of warfarin and where does this occur?
Most common side effect is bleeding
Occurs most often from the mucous membranes of the GI tract and the genitourinary tract
5.19 Why is warfarin contraindicated during pregnancy (category X)?
It cross the placenta and is teratogenic (affects development of the fetus).
Breast feeding should also be avoided.
5.20 What is the first oral Direct Thrombin Inhibitor that came to market?
- How is this anticoagulant administered?
- Does it require frequent INR tests?
Dabigatran (Pradaxa)
Orally administered anticoagulant
Does not require frequent blood tests for INR
5.22 What are the four types of drugs affecting hemostasis?
- Anticoagulants - prevent coagulation/thrombi
- Thrombolytics/Fibrinolytics - dissolve clots/thrombi
- Antiplatelets - reduce adhesion/aggregation of platelets
- Antifibrinolytics - formation of clots/excess bleeding
5.23 What do thrombolytics/fibrinolytics do?
Thrombolytics rapidly lyse thrombi when adminstered intravenously by catalyzing the formation of plasmin from plasminogen
5.23 What are examples of thrombolytics/fibrinolytics?
Streptokinase
Urokinase
Synthetic tPA
Others
5.23 What are indications for use of thrombolytics/fibrinolytics?
When are thrombolytics/fibrinolytics best used?
Indications include acute MI, acute ischemic stroke, and pulmonary embolism
Best used as soon as possible from the onset of the event
5.24 What are the three main classes of antiplatelets?
- Thienopyridines (ADP inhibitors)
- Cyclooxygenase inhibitors (mainly aspirin)
- GP IIb/IIIa inhibitors)
5.25 How does aspirin (cyclooxygenase inhibitor) act on platelets?
It inhibits the synthesis of TXA2 - a substance that helps make the platelets sticky and more likely to aggregate. (TXA2 normally acts on other platelets)
- 26 How do thienopyridines (ADP inhibitors) work?
- What is an example of this drug?
These drugs act by preventing the binding of ADP to its receptors on platelets, inhibiting the pathway towards platelet aggregation.
Clopidogrel (Plavix)
- 27 GP IIb / IIIa Inhibitors
- Mechanism?
- An example?
- How are they administered?
Inhibit activation of glycoprotein IIb/IIIa receptors on platelets, inhibiting the “final common pathway” for platelet aggregation.
Example is abciximab (ReoPro)
Administered IV with an initial bolus followed by constant infusion
- 28 Antifibrinolytics
- What is an example?
- Mechanism?
- Use in dentistry?
Tranexamic acid
Inhibits activation of plasminogen to plasmin
Used in dentistry as a 5% mouth rinse after extractions or surgery in patients with prolonged bleeding time (from acquired or inherited disorders).
