Term
| What are 3 drugs/drug classes that prevent clot formation and extension? |
|
Definition
Anticoagulant drugs: Warfarin,
Heparins,
Direct thrombin inhibitors |
|
|
Term
| What are 4 drugs that interfere with platelet activity? |
|
Definition
Antiplatelet drugs: Aspirin,
Clopidogrel (Plavix),
Dipyridamole,
Glycoprotein IIb/IIIa antagonists |
|
|
Term
| What are 3 drugs that dissolve existing thrombi? |
|
Definition
Fibrinolytic (thrombolytic) drugs: Alteplase,
Streptokinase,
Urokinase |
|
|
Term
| 3 Abnormalities of blood flow |
|
Definition
Atrial fibrillation,
Immobilization/ bed rest,
Venous obstruction from tumor/pregnancy |
|
|
Term
| 5 Abnormalities of clotting components |
|
Definition
Protein C or S deficiencies,
Malignancy,
Pregnancy,
Thrombocytosis,
Estrogen therapy |
|
|
Term
| 5 Abnormalities of surfaces in contact with blood |
|
Definition
Vascular injury/trauma,
Heart valve replacement,
Indwelling catheters,
Atherosclerosis,
Fractures |
|
|
Term
| 4 steps in Formation of a Fibrin Clot |
|
Definition
1. Vasospasm and platelet adherence
2. Release of mediators and platelet aggregation 3.
Release of tissue factors and fibrin clot formation 4.
Removal of clot after vessel repaired |
|
|
Term
| Which pathway involves Factor XII activated by vessel injury or exposure to foreign body (ie. artificial valve)? |
|
Definition
|
|
Term
| Which pathway involves Factor VII activated by exposure to tissue factor expressed by endothelial cells and leukocytes at site of injury? |
|
Definition
|
|
Term
| What is the timeframe for unfractionated heparin to take effect? |
|
Definition
| Immediate anticoagulant effect |
|
|
Term
| What Binds to and activates antithrombin (a natural anticoagulant), which then inactivates Factor Xa and thrombin? |
|
Definition
| Unfractionated Heparin (UFH) |
|
|
Term
| How is UFH administered and eliminated? |
|
Definition
Not absorbed orally.
Administered by IV infusion and, sometimes, SC for prophylaxis.
Half-life varies with dose (average = 90 minutes).
Removed by reticuloendothelial system and eliminated by kidneys |
|
|
Term
| Are the effects of UFH dose dependent or linear? |
|
Definition
Dose dependent kinetics.
Dose/effect not linear |
|
|
Term
| On what does the body's response to ufh depend? |
|
Definition
Chain length determines activity;
Clearance influenced by size of chain |
|
|
Term
| What is teh antidote to hemorrhage d/t ufh? |
|
Definition
| *protamine sulfate* 1 mg for every 100 units heparin given by slow IV infusion |
|
|
Term
|
Definition
Hemorrhage
(At increased risk with high dose, recent surgery, trauma, peptic ulcer disease, platelet dysfunction). Osteoporosis
(With long term use).
Heparin-Induced Thrombocytopenia (HIT) |
|
|
Term
| LMWH has lower incidence of what? |
|
Definition
| HIT: Lower incidence with LMWH, but contraindicated once HIT develops from UFH |
|
|
Term
| How do you proceed if HIT develops w/heparin tx? |
|
Definition
| D/C heparin and continue warfarin |
|
|
Term
| what is an Idiosyncratic late allergic drug reaction occurring 5-14 days after start of heparin (Type 2)? |
|
Definition
|
|
Term
what Occurs in 1-3% of patients on heparin tx, causing a
Decrease in platelet count by 50% as well as a hypercoagulable state and 50% chance of thrombosis? |
|
Definition
|
|
Term
| Why must you Monitor platelets every other day while getting heparin IV? |
|
Definition
|
|
Term
|
Definition
Weight-based dosing more effective, less bleeding
(Use special order form in hospital).
Average loading dose: 80 units/kg.
Average maintenance dose: 18 units/kg/hr |
|
|
Term
|
Definition
Activated partial thromboplastin time (*aPTT*).
Normal range: 24-36 seconds.
Heparinization: 1.5-2.5 times normal.
Obtain aPTT 6 hours after 1st dose and subsequent dosage changes. |
|
|
Term
| What is teh *Drug of choice for anticoagulation during pregnancy*? |
|
Definition
uhf: does not cross the placenta;
not associated with fetal malformations |
|
|
Term
What is used for the following purposes: To initially treat venous thrombosis and pulmonary embolism because of its rapid onset of action,
During and after coronary angioplasty or stent placement,
Cardiopulmonary bypass surgery,
Selected patients with disseminated intravascular coagulation,
In IV dialysis to prevent thrombosis in the pumps? |
|
Definition
|
|
Term
| how do uhf and lmwh compare in activity against factor xa and factor iia (thromin)? |
|
Definition
| Equally active against Factor Xa but less active than UFH against thrombin (Factor IIa) due to short chain length |
|
|
Term
| how do ufh and lmwh differ in chemical structure? |
|
Definition
lmwh: Fragments of unfractionated heparin;
LMWH is around 5,000 D vs 3,000 - 30,000 D for UFH |
|
|
Term
| What are 3 lmwh available agents? how are they administered? How can they be interchanged? |
|
Definition
Administered SC.
*Enoxaparin (Lovenox)* - Aventis
(30, 40, 60, 80, 90, 100, 120, and 150mg).
Dalteparin (Fragmin) - Pharmacia
(2500, 5000 IU/0.2ml).
Tinzaparin (Innohep) – Dupont
(20,000 IU/ml)
Approved only for treatment of DVT.
Agents not interchangeable |
|
|
Term
| How do indications vary between lmwh and ufh? |
|
Definition
| *Almost all the same indications as UFH including use during pregnancy* |
|
|
Term
|
Definition
Decreased binding to plasma proteins, endothelial cell surfaces, and macrophages
(less heparin resistance;
predictable and reproducible response).
No laboratory monitoring necessary.
Higher bioavailabilty SC (90%)
(Given QD or BID SC as outpatient).
Longer half-life because not cleared by liver with macrophages
(renal elimination with half-life = 4-6 hrs).
Less heparin-induced thrombocytopenia. |
|
|
Term
| 4 Disadvantages of LMWH? cost? |
|
Definition
Onset of action is slower than UFH for life threatening thromboembolism
Requires self injection by SC
May not be covered by some insurance
High personal cost (*$60 per dose*) |
|
|
Term
| Enoxaparin (Lovenox) - 4 Current FDA Indications |
|
Definition
Prevention of DVT:
Hip and Knee Replacement Surgery
(30mg SC q12 hrs
40mg SC QD (hip only));
Abdominal Surgery
(40mg SC QD).
Treatment of DVT when given with warfarin
(1 mg/kg q12 hrs,
1.5 mg/kg QD (inpatient only)).
Prevention of ischemic complications of unstable angina and non-Q-wave MI (with ASA)
(1 mg/kg q12 hrs) |
|
|
Term
Synthetic analog of heparin sequence- Inhibits Factor Xa
Approved for prevention of DVT after hip fracture surgery or knee or hip replacement |
|
Definition
|
|
Term
Which has longer t1/2: Fondaparinux (Arixtra)
or lmwh? |
|
Definition
| Fondaparinux (Arixtra): Similar to LMWH in efficacy with longer T ½ |
|
|
Term
| when is Fondaparinux (Arixtra) contraindicated? how is it dosed? |
|
Definition
| Contraindicated if ClCr < 30 ml/min. given 2.5mg SC QD. |
|
|
Term
what is a Direct thrombin inhibitor that is a
Recombinant derivative of hirudin, a
Natural anticoagulant from leeches |
|
Definition
|
|
Term
what is a Replacement for heparin after HIT develops;
Cost for one week: $4,000? |
|
Definition
|
|
Term
| How does delayed antithrombic effect relate to warfarin serum levels? Does it inhibit formation or elimination of clotting factors? |
|
Definition
| Delayed antithrombotic effect unrelated to warfarin serum levels: inhibits formation but not elimination of clotting factors |
|
|
Term
| warfarin structurally related to which vitamin? how does it act? |
|
Definition
k: Active (reduced) Vitamin K necessary for factor activation.
Warfarin depletes active Vitamin K.
Warfarin action can be reversed by exogenous Vitamin K. Inhibits Vitamin K epoxide reductase enzyme responsible for conversion of inactive Vitamin K epoxide to active Vitamin K. Clotting factors VII, IX, X, and prothrombin (II) dependent on Vitamin K for carboxylation and activity. Also inhibits endogenous anticoagulants Protein C and Protein S that promote fibrinolysis |
|
|
Term
| 6 vitamin k-dependent clotting factors |
|
Definition
| vii, ix, x, prothrombin, c, s |
|
|
Term
| vitamin k synthesis decreased in what organ dz? |
|
Definition
|
|
Term
| s-warfarin metabolized by what enzyme? |
|
Definition
|
|
Term
| what isomers are involved w/warfarin? |
|
Definition
Racemic mixture of R and S isomers.
70% of warfarin activity due to S isomer.
Hepatic metabolism:
S-warfarin metabolized by CYP2C9 enzyme;
R-warfarin metabolized by CYP1A2, 2C19, and 3A4 enzymes |
|
|
Term
| What do genetic variations in cyp2c9 enzyme indicate in metabolism of warfarin |
|
Definition
| Genetic variation in CYP2C9 enzyme means 1/4 of population may have reduced metabolism: s isomer. |
|
|
Term
| What is the t1/2 of warfarin? how well is it absorbed? to what is warfarin bound? |
|
Definition
Usual half-life = 40 hrs
(Longer if elderly or reduced metabolizer). Well absorbed.
Highly protein bound. |
|
|
Term
| On what 7 factors is the *risk of bleeding* w/warfin dependent? |
|
Definition
1. Dosing
2. Metabolism
3. Vitamin K levels
[Low levels potentiate bleeding
(Malabsorption;
Decrease of vitamin K in diet;
Elimination of bacteria in gut by antibiotics)
High levels potentiate clotting
(Vitamin K in green, leafy vegetables and
Vitamin K in vitamins)]
4. Genetic polymorphism of genes coding for CYP 2C9 and VKORC1
5. Clotting factor production
(Reduced in liver disease, chronic illness)
6. Inadequate patient education and monitoring
(Need frequent laboratory monitoring)
7. Drug Interactions |
|
|
Term
| What are 4 Drugs with synergistic bleeding potential when combined w/warfarin? |
|
Definition
Antiplatelet drugs: Aspirin, clopidogrel
NSAIDs
Ethanol
Corticosteroids |
|
|
Term
| What are 2 Drugs that decrease protein binding when combined w/warfarin? |
|
Definition
| Phenytoin, high dose aspirin |
|
|
Term
| what is a Drug that decrease absorption when combined w/warfarin? |
|
Definition
|
|
Term
| How do the following drugs interact w/warfarin: Amiodarone, fluconazole, fluoxetine, metronidazole, paroxetine, sulfonamides? |
|
Definition
| Drugs that inhibit CYP 2C9 enzyme (major) |
|
|
Term
| How do the following drugs interact w/warfarin: Carbamazepine, phenobarbital, rifampin? |
|
Definition
|
|
Term
| How do the following drugs interact w/warfarin: Macrolides, azole antifungals, diltiazem, ciprofloxacin, etc? |
|
Definition
| inhibit cyp 1a2, 2c19, 3a4 (minor) |
|
|
Term
| How do the following drugs interact w/warfarin? |
|
Definition
| induce CYP 1A2, 2C19, 3A4 (minor) |
|
|
Term
| How do the following drugs interact w/warfarin? |
|
Definition
| Herbals that potentiate warfarin effect |
|
|
Term
| What is the new way to monitor warfarin? what is the equation for this? what was the old way? |
|
Definition
| inr = (pt's pt in sec / mean nml pt in sec) old: pt |
|
|
Term
| How do you individualize warfarin dosing? What should be considered with initial doses? |
|
Definition
Individualize dose according to patient response (as indicated by INR).
Use of loading dose controversial:
May increase hemorrhagic complications.
May offer more rapid protection.
Low initiation doses are recommended for elderly/ frail/ hepatic failure/ malnourished patients |
|
|
Term
| How should dosing start for warfarin? |
|
Definition
Start low:
Initiate 5-10 mg for 1st two days, then 5 mg/day *.
Educate patient.
*Elderly, frail, liver disease, malnourished: < 5 mg/day |
|
|
Term
| How should warfarin be stabilizes? |
|
Definition
Titrate to appropriate INR.
Monitor INR frequently (daily then weekly) |
|
|
Term
| How should warfarin be adjusted? |
|
Definition
| Adjust as necessary (decrease or increase weekly dose by 10-20%) |
|
|
Term
| How should warfarin be monitored? |
|
Definition
| Monitor INR regularly (every 1–4 weeks) and adjust |
|
|
Term
| How does increasing age affect reponse to warfarin and how does this affect dosing |
|
Definition
Increasing age has been associated with an
increased response to the effects of warfarin: decrease dose w/increasing age |
|
|
Term
| At what inr target range is there no change in dosing w/nexte dose determined by follow-up algorithm? |
|
Definition
|
|
Term
| At what inr dose do you *hold* *1* day *decrease* dose by 2 levels, and recheck inr in 3 days? |
|
Definition
|
|
Term
| At what inr dose do you *hold* *2* days *decrease* dose by 2 levels, and recheck inr in 3 days? |
|
Definition
|
|
Term
| at what inr do you notify md and check next inr per md? |
|
Definition
|
|
Term
| what are Relative Contraindications to Warfarin Therapy? |
|
Definition
*Pregnancy* – fetal hemorrhage.
Situations where the risk of hemorrhage is greater than the potential clinical benefits of therapy
-Uncontrolled alcohol or drug abuse
-Unsupervised dementia or psychosis |
|
|
Term
| Conversion from Heparin to Warfarin |
|
Definition
May begin concomitantly with heparin therapy (in hospital).
Heparin should be continued for a minimum of four days
-Time to peak antithrombotic effect of warfarin is delayed 96 hours (despite INR).
When INR reaches desired therapeutic range, discontinue heparin (after a minimum of four days) |
|
|
Term
| Signs of Warfarin Overdosage |
|
Definition
Any unusual bleeding:
Blood in stools or urine,
Excessive menstrual bleeding,
Bruising,
Excessive nose bleeds/bleeding gums,
Persistent oozing from superficial injuries,
Bleeding from tumor, ulcer, or other lesion |
|
|
Term
| if a pt forgets to take med, what should they do? |
|
Definition
If you forget to take your medication and you remember before midnight of that same day, take it as soon as you remember.
If you do not remember until the next day, wait until your next scheduled dose and do not double-up |
|
|
Term
| of what 4 s/s of bleeding should pts be aware? |
|
Definition
Signs and symptoms of bleeding:
Urine,
Stool,
Excessive bleeding (>30mins) from a cut,
Unusual bruising |
|
|
Term
| what should be avoided w/meds? |
|
Definition
Excessive intake (>2 beers or 2oz.whiskey) should be avoided.
Cigarettes may counteract beneficial effects |
|
|
Term
| How should pts be counseled regarding diet? |
|
Definition
Many green leafy foods contain large amount of vitamin K.
You do not have to avoid foods high in vitamin K, but should not make major changes in your diet |
|
|
Term
| How should pts be counseled regarding drugs? |
|
Definition
| Numerous factors, alone or in combination (including travel, changes in diet, environment, physical state, and medication, including botanicals), may influence response of the patient to anticoagulants. |
|
|
Term
| Does asa act as reversible or irreversible inhibition of platelet function? |
|
Definition
*Irreversible inhibition* of platelet function.
Inhibition of COX-1 prevents synthesis of thromboxane A2 by platelets, preventing clot formation.
Single dose effect lasts 8-10 day life of platelet |
|
|
Term
|
Definition
Uses: angina, post-myocardial infarction, secondary prevention of stroke.
Usual prophylactic dose: 81mg |
|
|
Term
| moa of dipyridamole (persantine)? ade? use? |
|
Definition
MOA: inhibits platelet adhesion to vessel wall.
Adverse effects: headache 40% (due to vasodilation).
Use: less effective alone than aspirin |
|
|
Term
| Dipyridamole (Persantine) considered by some better when combined w/what? *what drug is this combination*? |
|
Definition
Combination with ASA considered better than ASA alone by some.
*Aggrenox*: 200mg dipyridamole and 25mg ASA given BID |
|
|
Term
| Does Ticlopidine (Ticlid) act reversibly or irreversibly? |
|
Definition
| *Irreversibly* inhibits adenosine diphosphate (ADP), a promoter of platelet binding |
|
|
Term
| ade and uses of ticlopidine (ticlid)? |
|
Definition
Adverse effect: neutropenia in 2%
-Must get CBC every 2 weeks for 1st 3 months.
Uses: same as aspirin, but now rarely used because of adverse effect profile |
|
|
Term
| When is clopidogrel (plavix) indicated? |
|
Definition
*use if unable to tolerate asprin*. Used with aspirin after acute coronary syndrome or stent replacement for up to 1 year
-Bleeding incidence greater than either drug alone |
|
|
Term
| moa of clopidogrel (plavix) |
|
Definition
| same as ticlid: *Irreversibly* inhibits adenosine diphosphate (ADP), a promoter of platelet binding |
|
|
Term
| When must you d/c Clopidogrel (Plavix)? what's the dose? |
|
Definition
Must discontinue drug at least 5 days before major surgery.
Dose: 75mg per day |
|
|
Term
| 3 Glycoprotein IIb/IIIa antagonists |
|
Definition
Abciximab (ReoPro)
Tirofiban (Aggrastat)
Eptifibatide (Integrelin) |
|
|
Term
Glycoprotein IIb/IIIa antagonists:
Abciximab (ReoPro),
Tirofiban (Aggrastat),
Eptifibatide (Integrelin): indications? significantly decrease risk of what? given how? ade? |
|
Definition
Indicated for acute coronary syndrome and in preparation for percutaneous coronary intervention (PCI)
Significantly decrease the risk of death and acute MI
Given in intravenously during and for 24 hrs after PCI in addition to aspirin and heparin
Adverse effects include bleeding and thrombocytopenia |
|
|
Term
| Fibrinolytic Drug (Thrombolytic) Derived from β-hemolytic Streptococcus |
|
Definition
|
|
Term
| Fibrinolytic Drug (Thrombolytic) Recombinant form of human tissue plasminogen activator (t-PA) |
|
Definition
|
|
Term
| Fibrinolytic Drug (Thrombolytic) Similar to t-PA but longer T ½ |
|
Definition
|
|
Term
Fibrinolytic Drugs (Thrombolytics): Streptokinase,
Alteplase (Activase),
Retaplase (Retavase)- what is the major potential ade? |
|
Definition
|
|
Term
Fibrinolytic Drugs (Thrombolytics): Streptokinase,
Alteplase (Activase),
Retaplase (Retavase)- catalyze what? plasmin then breaks down what? used how? |
|
Definition
Catalyze conversion of plasminogen to plasmin
Plasmin then breaks down fibrin and fibrinogen to degradation products
Used to dissolve thrombus causing acute MI or pulmonary embolism |
|
|
Term
| Antithrombotic Drug Use Guidelines – The Gold Standard |
|
Definition
American College of Chest Physicians (ACCP)
Official journal: Chest |
|
|
Term
| don't use plavix w/this prodrug |
|
Definition
clopidogrel don't use w/ ppi.
also prilosec, esomeprazole |
|
|
