Updated: 12/2/2019

Anticoagulants

0%
Topic
Review Topic
0
0
N/A
N/A
Questions
11 11
0
0
0%
0%
Evidence
11 11
0
0
Overview

  • Anticoagulants decrease the formation of fibrin clots
    • heparin
    • warfarin (coumadin)
    • bivalirudin
Heparin
  • Mechanism
    • catalyzes the binding of antithrombin III to multiple clotting factors  
    • inactivates several factors
      • IIa (thrombin)
      • Xa
      • IXa
      • XIa
      • XIIa
  • Clinical use
    • immediate anticoagulation
      • pulmonary embolism
      • acute coronary syndrome
      • stroke
      • MI
      • DVT
      • DIC
    • during pregnancy
      • does not cross placenta
  • Toxicity
    • bleeding
    • osteoporosis
    • heparin-induced thrombocytopenia (HIT)
      • heparin binds to platelet factor IV
      • antibodies bind to and activate platelets
      • leads to hypercoagulable state and thrombocytopenia
    • hypersensitivity
  • Pharmacology
    • IV delivery only for therapeutic anticoagulation
    • short half-life (2h)
    • large, water-soluble polysaccharide
    • low-molecular-weight heparins (e.g. enoxaparin) have advantages of
      • longer half-lives (2-4x)
      • less thrombocytopenia
      • enhanced activity against factor Xa
      • administered subcutaneously without laboratory (PTT) monitoring
      • not easily reversible
  • Monitoring
    • partial thromboplastin time (PTT)
  • Antagonist
    • protamine sulfate 
      • positively charged to bind negatively charged heparin
Warfarin (Coumadin)
  • Mechanism
    • ↓ hepatic synthesis of vitamin K-dependent clotting factors
      • prevents the reduction of vitamin K, a necessary step in the synthesis of clotting factors
        • vitamin K epoxide reductase is inhibited
        • γ-carboxylation of clotting factors cannot occur  
      • affected clotting factors include
        • II
        • VII
        • IX
        • X
        • protein C
        • protein S
    • no effect on clotting factors already present
    • affects the extrinsic pathway
  • Clinical use
    • chronic anticoagulation
      • DVT prophylaxis
      • post-STEMI
      • heart valve damage
      • atrial arrhythmias
  • Toxicity
    • transient hypercoagulability 
      • transient protein C deficiency when beginning warfarin treatment
        • due to short half life of protein C
      • coagulation factors have relatively long half lives 
      • can lead to skin necrosis and dermal vascular thrombosis
      • give heparin as you begin warfarin treatment
    • bleeding
    • teratogenic
      • bone dysmorphogenesis
      • not used in pregnancy
    • drug interactions
      • P450 metabolism 
        • inhibitors → ↑ PT
          • decrease in P450 degrades less warfarin and levels rise
          • mnemonics
            • SICKFACES.COM
              • Sodium valproate
              • Isoniazid
              • Cimetidine
              • Ketoconazole
              • Fluconazole
              • Alcohol (binge drinking)
              • Chloramphenicol
              • Erythromycin
              • Sulfonamides
              • Ciprofloxacin
              • Omeprazole
              • Metronidazole
        • inducers → ↓ PT
          • increase in P450 degrades more warfarin and levels fall
          • mnemonics
            • AAA RACKS In GQ Magazine
              • Acute Alcohol Abuse
              • Ritonavir
              • Amiodarone
              • Cimetidine/Ciprofloxacin
              • Ketoconazole
              • Sulfonamides
              • Isoniazid
              • Grapefruit juice
              • Quinidine
              • Macrolides
      • ASA, sulfonamides, and phenytoin
        • displace warfarin from plasma proteins, leading to increased free fraction → ↑ PT
      • cholestyramine
        • ↓ oral absorption
          • due to low pKa
  • Pharmacology
    • oral
    • long half life (>30 hr)
    • small, lipid-soluble
  • Monitoring
    • prothrombin time (PT)
    • INR
      • (tested PT / reference PT)^(calibration value)
  • Antagonist 
    • vitamin K (slow onset)
    • fresh frozen plasma (fast onset) 
Lepirudin and Bivalirudin
  • Mechanism
    • direct inhibtors of thrombin (IIa)
  • Clinical use
    • alternative to heparin during heparin-induced thrombocytopenia 
    • unstable angina during percutaneous transluminal coronary angioplasty
Factor Xa Inhibitors (Apixaban and Rivaroxaban)
  • Mechanism
    • competitive inhibitor of factor Xa
  • Clinical use
    • treatment and prophylaxis for deep venous thrombosis and pulmonary embolism
    • stroke prophylaxis for patients with atrial fibrillation
 

Please rate topic.

Average 4.9 of 8 Ratings

Questions (11)
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK

(M1.HE.13.18) A 58-year-old Caucasian male with a history of peripheral vascular disease is admitted to the hospital with a painful, pulseless foot. He is prescribed antiplatelet and anticoagulant drugs. Which of the following matches a drug with its correct characteristic?
Tested Concept

QID: 100534
1

Warfarin: directly inhibits thrombin

6%

(15/246)

2

Heparin: activates antithrombin 3

56%

(137/246)

3

Aspirin: reversibly inhibits COX-1

8%

(20/246)

4

Clopidogrel: antagonizes ADP receptors on endothelial cells

26%

(64/246)

5

Prasugrel: reduced risk of bleeding compared to other drugs in its class

3%

(8/246)

M 1 D

Select Answer to see Preferred Response

Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK

(M1.HE.12.28) A 66-year-old male with a history of deep venous thrombosis is admitted to the hospital with shortness of breath and pleuritic chest pain. He is treated with an anticoagulant, but he develops significant hematochezia. His BP is now 105/60 and HR is 117; both were within normal limits on admission. The effects of the anticoagulant are virtually completely reversed with the administration of protamine. Which of the following was the anticoagulant most likely administered to this patient? Tested Concept

QID: 101338
1

Warfarin

8%

(6/76)

2

Enoxaparin

3%

(2/76)

3

Heparin

88%

(67/76)

4

Bivalirudin

0%

(0/76)

5

Dabigatran

1%

(1/76)

M 3 E

Select Answer to see Preferred Response

(M1.HE.12.60) A 48-year-old woman is admitted to the hospital and requires anticoagulation. She is administered a drug that binds tightly to antithrombin III. Which of the following drugs was administered? Tested Concept

QID: 101370
1

Aspirin

2%

(3/156)

2

Warfarin

10%

(15/156)

3

Dabigatran

17%

(27/156)

4

Rivaroxaban

4%

(7/156)

5

Enoxaparin

67%

(104/156)

M 1 E

Select Answer to see Preferred Response

Evidence (12)
Topic COMMENTS (36)
Private Note