Term
| Effects of Old Age on warfarin dosing |
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Definition
Decrease Dose
Increased sensitivity to warfarin
Decreased vitamin K stores/decreased plasma concentration |
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Term
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Definition
| Teratogenic = d/c during pregnancy |
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Term
|
Definition
| drug not excreted so dose normally in lactating women |
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Term
| Effects of Alcoholism on warfarin dosing |
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Definition
Acute: inhibits metabolism = acute increase in INR
Chronic: induces drug metabolism = increase dose |
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Term
| Effects of Liver Disease on warfarin dosing |
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Definition
decrease dose
decreased clotting factor production and decreased clearance |
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Term
| Effects of Renal Disease on warfarin dosing |
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Definition
decrease dose
decreased activity of CYP2C9 |
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Term
| Effects of heart failure on warfarin dosing |
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Definition
decrease dose
decreased metabolism (hepatic congestion) |
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Term
| Effects of cardiac valve replacement (post-op) |
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Definition
decrease dose
hypoalbuminemia, decreased oral intake/physical activity, decreased clotting factors |
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Term
| Effects of nutritional status on warfarin dosing |
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Definition
changes in dose will affect changes in vitamin K
-increased vitamin K = increase warfarin |
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Term
| Effects of tube feeding on warfarin dosing |
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Definition
increase dose
changes in absorption or nutritional supplements (decreased sensitivity) |
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Term
| Effects of thyroid disease on warfarin dosing |
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Definition
HYPO: increase dosing (decreased catabolism of clotting factors)
HYPER: decrease dosing (increased catabolism of clotting factors |
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Term
| Effects of smoking on warfarin dosing |
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Definition
increase dose
Smoking: can induce CYP1A2
Chewing tobacco: can contain vitamin K |
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Term
| Effects of fever on warfarin dosing |
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Definition
acute increase in INR
increased catabolism of clotting factors |
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Term
| Effects of diarrhea on warfarin dosing |
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Definition
acute increase in INR
reduced secretion of vitamin K by gut flora |
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Term
| Effects of acute infection/inflammation on warfarin dosing |
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Definition
decrease dose
increased sensitivity to warfarin |
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Term
| Effects of malignancy on warfarin dosing |
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Definition
decrease dose
increased sensitivity to warfarin due to multiple factors |
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Term
| If there is a decrease in INR you should _____________ (increase/decrease) the warfarin dose? |
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Definition
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Term
|
Definition
| Vitamin K Antagonist (VKA) |
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Term
|
Definition
interfere with the cyclic interconversion of vitamin K and vitamin K epoxide
Target: Vitamin K Oxide Reductase (VKOR) |
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Term
| What are the vitamin K-dependent clotting factors? |
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Definition
| Factors II, VII, IX, and X |
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Term
| A transient procoagulant effect may occur when baseline _________ and ________ levels are reduced due to the start of VKA therapy |
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Definition
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Term
| The anticoaguant effect of VKAs can be overcome by ________. |
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Definition
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Term
| Which warfarin enantiomer is more active |
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Definition
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Term
| What two genetic changes have the most significant impact on warfarin therapy? |
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Definition
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Term
| What enzyme is most important in warfarin metabolism? |
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Definition
| CYP2C9 (primary enzyme in S-warfarin metabolism) |
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Term
| Which ethnic group has the highest proportion of sensitive genetic halotypes? |
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Definition
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|
Term
| Which ethnic group has the highest proportion of resistant genetic halotypes? |
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Definition
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Term
| When a patient on warfarin is prescribed a drug that is known to interact with warfarin, what should be done? |
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Definition
1. Look to see if there is a feasable alternative drug that can be given.
2. If not, increase therapeutic monitoring/adjusting doses based on INR
NOTE: prospective dosing is inappropriate because of the unpredictable nature of patient response |
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Term
| Drug Interaction: Wafarin and Cholestyramine |
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Definition
| Cholestyramine can decrease warfarin absorption |
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Term
| Drug interaction: warfarin and metronidazole or SMX-TMP |
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Definition
| inhibits clearance of S-warfarin (potentiates warfarin's effect on PT) |
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Term
| Drug Interaction: warfarin and cimetidine or omeprazole |
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Definition
| inhibits clearance of R-warfarin (potentiates PT modestly) |
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Term
| Drug interaction: warfarin and amiodorone |
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Definition
| Amiodarone is a potent inhibitor of clearance of S and R-warfarin --> potentiates anticoagulation |
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Term
| Drug interaction: warfarin and barbiturates, rifampin, azathioprine, or carbamazepine |
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Definition
| all increase hepatic clearance of warfarin |
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Term
| Drug interaction: warfarin and long-term alcohol consumption |
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Definition
| potential to increase clearance of warfarin, but little seen in real-life application |
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Term
| Drug interaction: warfarin and 2nd/3rd gen cephalosporins |
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Definition
| Cephalosporins inhibit cyclic interconversion of vitamin K by thyroxine--> increases metabolism of coagulation factors --> increases activity of warfarin |
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Term
| Drug interaction: warfarin and aspirin |
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Definition
increase anticoagulant effect
increase risk of warfarin-associated bleeding by inhibiting platelet function
can also produce gastric erosions = GI bleeds |
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Term
| Drug interaction: warfarin and Ginseng |
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Definition
| ginseng reduces the effect of warfarin |
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Term
| Drug interaction: warfarin and green tea |
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Definition
| Green tea has a high vitamin K content so it reduces warfarin's anticoagulant effect |
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Term
| Why is overlapping therapy necessary when starting warfarin? |
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Definition
the suggestion that the antithrombotic effect of VKAs is reflected in lower levels of prothrombin (factor II) forms the basis for overlapping the administration of a parenteral anticoagulant with warfarin until the PT (aka INR) is prolonged into the therapeutic range
Since the half-life of prothrombin is 60-72 hours, at least 5 days of overlap is necessary |
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Term
| Because of the half-life of warfarin, doses taken within the last 7 days must be considered when making dosing decision, BUT doses taken _______ days ago will have the most prominent effect on current INR |
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Definition
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Term
| When is the goal INR NOT 2-3? |
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Definition
| For mechanical valve replacements that are either mitral (all) or non-bileaflet aortic |
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Term
| T or F: warfarin can dissolve previously formed clots? |
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Definition
| F: warfarin has not direct effect on previously circulating clotting factors or previously formed thrombus |
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Term
| T or F: warfarin is highly protein bound in the plasma? |
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Definition
| T: 99% PPB (albumin mainly) |
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Term
| T or F: warfarin is easily absorbed |
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Definition
| T: rapid and extensive absorption |
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Term
| What is warfarin's pregnancy category? |
|
Definition
Category X
crosses placenta and is associated with embryopathies (CNS abnormalities)
fetal hemorrhage and teratogenic complications seen
Use UFH or LMWH instead (too big to cross placenta) |
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Term
| Which type of drug interaction results in a change in the INR? |
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Definition
PharmacoKINETIC
PD may not affect INR but rather can cause synergistic or additive effects through different mechanisms |
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Term
| Which strength of warfarin should be given to patients allergic to dyes |
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Definition
| Warfarin 10 mg because it has no dyes-may need to split |
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Term
| T or F: warfarin is available in IV form |
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Definition
| T: can be given IV push over 1-2 minutes |
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Term
| Warfarin initiation via the 'average daily dosing method' starts warfarin dosing at what? |
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Definition
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Term
| Acutely ill patients should start at what dose of warfarin? |
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Definition
| 2.5 to 3 mg daily because increased risk for bleeding |
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|
Term
| For the first month of warfarin therapy how often should INR be measured? |
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Definition
at least weekly
**If starting on the average daily dosing method (5 mg QD) take INR Q3-5 days |
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Term
| For patients who are medically stable in an outpatient setting, how often should their INR be measured? |
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Definition
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Term
| If the INR is greater than _____ 2.5 - 5 mg of oral vit K is recommended |
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Definition
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Term
| T or F: warfarin causes bleeding |
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Definition
F: warfarin is not thought to CAUSE bleeding but rather unmasks bleeding from existing lesions and enabling bleeding from an ordinarily minor source
GI and nose are most common |
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Term
| What two tests should be conducted prior to initiating warfarin therapy? |
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Definition
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|
Term
| How often should INR be measured in patients with an acute thromboembolic event? |
|
Definition
| every 3 days during the first week of therapy |
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Term
| What is the difference between PT and INR? |
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Definition
| INR is PT standardized for the differences in thromboplastin reagents |
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|
Term
| What does a PT test measure? |
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Definition
| the time required for clot formation after adding calcium and thromboplastin to citrated plasma |
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Term
| In general, maintenance dose changes should not be made more frequently than _____. |
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Definition
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Term
| T or F: For patients with acute venous thrombosis, UFH, LMWH, or fondaparinux should be overlapped with warfarin therapy for at least 5 days, regardless of whether the target INR has been achieved. |
|
Definition
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|
Term
| Patient variables associated with requiring a lower dose of warfarin |
|
Definition
advanced age
elevated baseline INR
poor nutritional status
liver disease
hyperthyroidism
genetic polymorphisms (CYP2C9 and VKOR)
concurrent use of medications known to enhance effect of warfarin |
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Term
| What are the two anti-Xa inhibitors? |
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Definition
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|
Term
| What is the MOA of rivaroxaban? |
|
Definition
| Direct inhibitor of factor Xa (does tno require antithrombin = benefit) |
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|
Term
| Metabolism of rivaroxaban and apixaban? |
|
Definition
CYP3A4 and CYP-independent enzymes
inhibitors of CYP3A4 and PGP may increase plasma concentrations |
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Term
| T or F: routine coagulation monitoring is still required for the anti-Xa inhibitors? |
|
Definition
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|
Term
| Benefits of newer anticoagulants over the more traditional anticoagulants (heparin, warfarin) |
|
Definition
wider therapeutic window and more predictable dose-response
(less monitoring and dose changes) |
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|
Term
| T or F: new oral anticoagulants (dabigatran, rivaroxaban, and apixaban) have different degrees of renal excretion and this will have specific dosing adjustments based on renal function |
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Definition
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Term
| What is the only indication for Dabigatran |
|
Definition
| prevention of stroke in patients with nonvalvular atrial fibrillation |
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|
Term
| Does dabigatran inactivate fibrin-bound or unbound thrombin? |
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Definition
| Both, unlike some of the parenteral DTI, it is univalent (binds to just the active site and doesnt require a second binding site) and therefore can bind to both unbound and bound thrombin |
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|
Term
| What should be done with a dabigatran overdose? |
|
Definition
discontinue med and supportive measures
potentially used hemodialysis
NO antidote |
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|
Term
| Why must dabigatran be administered as a prodrug? |
|
Definition
| because it is a zwitterion, so it must be administered as uncharged and lipophilic |
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|
Term
| Does dabigatran require a high or low pH for absorption? |
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Definition
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|
Term
| T or F: dabigatran should be stored in the original container and should only be used for 30 days after opening |
|
Definition
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|
Term
| T or F: dabigatran is highly protein bound? |
|
Definition
| F-this allows a significant amount to be cleared by hemodialysis (in cases of toxicity) |
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Term
|
Definition
ecarin clotting time (test)
not available in most institutions
most promising test for dabigatran monitoring |
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Term
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Definition
measures conversion of fibrinogen to fibrin
might be too sensitive to blood levels to monitor dabigatran |
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Term
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Definition
| can help to show if the drug is being used or not, but levels dont necessarily correlate to the amount given or effectiveness (nonlinear relationship) |
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Term
|
Definition
| test is to insensitive at therapeutic levels |
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Term
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Definition
| must be dispensed in its original container (desiccant cap) and once opened must be used within 30 days |
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|
Term
| What dose of aspirin is beset for anticoagulation? |
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Definition
| Low dose is better than high dose |
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