Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
40 Cards in this Set
- Front
- Back
Can anticoaggulant drugs dissolve and already-formed clot? |
No |
|
HMW Heparin mechanism of action? |
causes conformational change in antithrombin III exposing its reactive site =
Catalyzes inhibition of clotting factors IXa, Xa and thrombin by greatly enhancing ATIII activity |
|
1. HMW heparin mode of administration? 2. Reason for the mode? 3. Pregnancy class of HMW Heparin |
1. IV or SC because it is not absorbed into the GI tract 2. large molecular weight (polysaccharide sequence) 3. Does not cross the placenta: therefore it is the drug of choice for anticoagulation during pregnancy. |
|
Clinical indications for HMW Heparin (7)? |
1. Venous thrombosis 2. pulmonary embolism, 3. angina, 4. acute MI 5. atrial fibrillation 6. vascular surgery 7. catheter implantation (A&V) |
|
Adverse effects of Heparin? |
Hemorrhage, osteoporosis and spontaneous fractures, 1–4% patients get heparin-induced thrombocytopenia (HIT) (systemic hypercoagulable state) |
|
HIT:
when does it occur what is the mechanism |
1. Occurs 5-14 days after initiation therapy 2. 50% decrease in platelets 3. bound to platelet factor 4 (PF4), causes heparin-PF4-IgG complex that binds platelet IIa receptor causing platelet activation = Systemic hypercoagulation |
|
What route of administration requires monitoring via heparin? |
IV; monitored every 6 hours |
|
1. Why is HMW Hep monitored? 2. How is HMW heparin monitored? |
1.HMW Heparin has unpredictable bioavailability
2. Activated Partial Thromboplastin Time: -normally 25-39s -with HMWH it should be 2-2.5x normal (1-1:30ish)
SubQ is normally not monitored |
|
What are the LMW Heparins? |
Enoxaprin and Fondaparinux |
|
What is the mechanism of action of LMW Heparin? |
Also interact with AntiThrombin but preferentially inhibits factor Xa > thrombin b/c of small length |
|
What is the result of preferential Xa > Thrombin binding? |
Results in a multiplier effect by blocking earlier in the cascade
(upstream block) |
|
How does LMW compare to HMW in terms of:
1. half life and absorbtion 2. risk of side effects 3. administration 4. monitoring |
1. Longer half-life + faster absorption time |
|
In rare cases in which monitoring the anticoagulant effect is necessary (e.g., in patients with ____________), a ___________ is used. |
In pts with renal dysfunction--because LMWHs are cleared via the kidneys--a factor Xa inhibition assay is used |
|
Clinical indications for LMWH? (3) |
1. prophylaxis against deep venous thrombosis following hip, knee, or abdominal surgery 2.treatment of deep venous thrombosis (with or without pulmonary embolism) 3. management of acute coronary syndromes.
|
|
toxcities of LMWH |
From what I can tell, the same as HMW just not as high of a risk for developing any of them:
Hemorrhage, osteoporosis and spontaneous fractures, 1–4% patients get heparin-induced thrombocytopenia (HIT) (systemic hypercoagulable state) |
|
Administration of fondaparinux
|
administered SC once a day because of long half life |
|
Does fondaparinux interfere with platelet actions? Does it cause HIT? |
no to both |
|
Warfarin mechanism of action? |
Blocks gamma-carboxylation of glutamate in prothrombin and factors VII, IX, and X |
|
_____________, the enzyme that catalyzes the carboxylation reaction, is inhibited by therapeutic doses of warfarin |
vitamin K epoxide reductase |
|
How does warfarin differ from heparin in terms of their effects on clotting factors |
Heparin direclty inactivates coagulation factors that exist already
warfarin inhibits synthesis of NEW coag factors |
|
1. Onset of action for warfarin? 2. when does warfarin reach maximal effect? |
1. onset = 8-12 hours because existing clotting factors must be depleted 2. max effect in 3-5 days |
|
Indications for warfarin? (6) |
1. Acute DVT 2. pulmonary embolism 3. venous thromboembolism 4. following acute MI 5. prosthetic heart valve placement 6. chronic atrial fibrillation |
|
Adverse effects of warfarin (4) |
1. Hemorrhage; risk increases with intensity and duration of therapy 4. drug interactions |
|
Drug interactions associated with warfarin |
Certain substances can increase the effect of warfarin while others can decrease it |
|
How is warfarin metabolized |
Metabolized by CYP2C9 – induction e.g. barbiturate = reduces effects
Isomers of warfarin are metabolized differently |
|
How do you monitor warfarin? |
Monitor with prothrombin time (PT) (time for plasma sample to clot) to calculate International Normalized Ratio (INR)
INR = PTpatient/PTnormal |
|
Normal INR and PTT?
Therapeutic goal for INR and PTT with warfaring |
1. Normal: INR = 1 PTT= 11-13.5s
2. Therapeutic INR = 2-3 times normal 2.5-3.5 for tilting disk heart valves (cool) |
|
1. What is the direct thrombin inhibitor? 2. What state is the drug in when it is administered? |
1. Dabigatran 2. Low molec weight prodrug |
|
Mechanism of action of Dabigatran? |
rapidly (approx. 1 hr) converted to active form from prodrug which binds to exosite 1 on thrombin preventing fibrinogen cleavage to insoluble fibrin |
|
Dabigatran is rapidly (approx. 1 hr) converted to active form from prodrug which binds to ______ on thrombin preventing ? |
binds to exosite 1 on thrombin preventing fibrinogen cleavage to insoluble fibrin |
|
Indications for dabigatran? |
Stroke prevention in patients with nonvalvular atrial fibrillation – equal efficacy to warfarin |
|
Adverse effects of dabigatran? |
Hemorrhage, heartburn, stomach upset, increase in risk of MI |
|
Advantages of dabigitran over warfarin |
1. No patient monitoring or titration 2. rapid onset of action 3. no adverse drug interactions |
|
What is the Oral Direct Xa Inhibitor? |
Rivaroxaban |
|
Rivaroxaban: 1. mechanism 2. administration and monitoring 3. onset |
1. Inhibits factor Xa 2. given as fixed dose (10mg/day), no monitoring 3. rapid onset of action. |
|
1. Indications for rivaroxaban 2. adverse effects? 3. contraindications? |
1. prevention of venous thromboembolism following hip or knee surgery 2. hemorrhage 3. Metabolized by kidney – issue in patients with reduced renal function
|
|
Fibrinolytic agent? mechanism of action? |
Alteplase (an r-tPA) - Directly convert plasminogen to plasmin which then breaks down existing clots |
|
1. How is ateplase metabolized? 2. Half life? 3. administration |
1. metabolized by the Liver 2. 3-8 minutes 3. IV |
|
Indication for ateplase |
Effective only if used rapidly after onset of thrombosis:
|
|
Side effects of ateplase |
hemorrhage, of which intracranial hemorrhage is the most serious |