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Anticoagulation
Anticoagulation
36
Pharmacology
Graduate
10/16/2010

Additional Pharmacology Flashcards

 


 

Cards

Term
Pathologic clot formation:  Virchow's Triad
Definition

venous stasis

 

vascular injury

 

hypercoagulability

Term
what do anti-coags do to clots
Definition
prevent clots.  DO NOT break them down!
Term

Unfractionated Heparin (UFH)

 

mechanism

Definition

-potentiates anti-thrombin, thereby inactivationg thrombin

 

-Inactivates Factors 9-12a

 

-prevents conversion of fibrinogen to fibrin

 

-prevents coag, pts own thrombolytic system degrades clot

Term
Indications for use of UFH
Definition

1.  venousthromboembolism tx/prophylaxis

2.  unstable angina/acute MI

3.  coronary bypass surgery

4.  hemodialysis

5.  angioplasty

6.  IV line flushes

Term
AE UFH
Definition

must be monitored for:

1.  hemorrhage

2.  heparin-induced throbocytopenia (HIT)

3.  Heparin Associated Thrombocytopenia (HAT)

4.  Osteoporosis (long term use)

5.  Hyperkalemia (long term use)

Term
HIT vs HAT adverse reactions of UFH
Definition

heparin-induced throbocytopenia (HIT):

-platelets <100,000 or < 50% baseline

*if this happens:  d/c and start alt anti-coag w/ Direct Thrombin Inhibitor

 

heparin associated thrombocytopenia (HAT):

-mild thrombocytopenia, platelets rarely drop < 100,000

-no antibody formation

-manage by observation (platelets will recover with cont tx)

Term
pregnancy category of UFH
Definition

category C

 

does not crsoss placenta but caution maternal hemorrhage, osteoporosis

 

OK to breast fee with too as it does not enter the breast milk

Term
contraindications to using UFH
Definition
basically anything that already puts pt at risk for bleeding
Term
dosing UFH in DVT/PE
Definition

loading dose:  IV push

                                                       followed by:

continuous infusion

 

-elderly doses usu lower

-can be administered SubQ for non-acute situations (VTE)

Term
monitoring UFH
Definition

aPTT in 6 hrs

 

reference range: 25-39sec

historical tx range:  1.5-2.5 X control aPTT

(for control of 30sec, 45-75 sec tx range)

 

platelets check qod x 14days or until UFH stopped, whichever first

Term
agent used to reverse excess heparin anticoagulation
Definition

Protamine (heparine antidote):  binds heparin to inhibit it from affecting clotting cascade

 

-1mg protamine neutralizes 90units heparin (impt to know so do not overshoot and increase risk of clotting!)

-max dose:  50mg, infused over 10min

 

caution hypotension and anaphylactoid rxns

Term

c/cx of low molecular weight heparin

(LMWH)

Definition

Enoxaparin (Lovenox):  for DVT prophylaxis and VTE tx

 

-1/3 size of UFH

-subQ bioavailability 92%

-inhibits only clotting factor 10a (vs 9-12a)

-predictable dose response

-longer half life:  q12hr

-reduced need for lab monitoring

Term
AE of LMWH
Definition

-hemorrhage

-thrombocytopenia

*lower incidence of HIT than with heparin; check platelets on day 3 of tx

-injection site hematoma

-osteoporosis (may be less than with heparin)

Term
monitoring of LMWH
Definition

-routine monitoring not neccessary

 

-anti-factor 10a activity:  in pts w/ CrCl <30ml/min, weight <50kg, morbid obesity, prolonged tx >14days, during pregnancy

 

-draw steady state level 4 hrs after subq dose

 

VTE dose much higher than prophylaxis

Term
reversal of excess LMWH
Definition

protamine

 

cannot completely neutralize anti-coag effect

 

1mg protamine/1mg enoxaparin

Term
Factor 10a inhibitors
Definition

Fondaparinux (Arixtra)

 

FDA-approved for VTE prophylaxis in lower extremity ortho procedures

-indicated for VTE tx

 

-unapproved use for pt where heparin forms caused HIT

-no reversal agents!

-cautions:  renal function, weight- dose adjust

Term
direct thrombin inhibitors
Definition

requiring aPTT monitoring:  Lepirudin, Argatroban

 

others:  bivalirudin, desirudin

 

-potential for use in many indications

-relatively high incidence of bleeding and high cost

-no reversal agents!

Term

Lepirudin use

 

Argatroban use

Definition

Lepirudin:  HIT pts

 

Argatroban:  HIT pts, HIT w/ PTCA

 

Bivalirudin:  pt undergoing PTCA

 

Desirudin:  VTE prophylaxis in pts undergoing elective hip surgery

Term

Warfarin (Coumadin)

 

mechanism of action

Definition

-does not affect established thrombus

 

-interferes with hepatic synthesis of vitamin K-dependent clotting factors

*specifically 2, 7, 9, 10

 

-onset of anti-coag effect 36-72hrs, peak effect 5-7days (d/t clotting factor half life: 6hr-72hr)

-does not affect already formed clotting factors

Term
indications for use of warfarin
Definition

1.  venous thromboembolism tx/prophylaxis

2.  prosthetic heart valves

3.  a. fib

4.  TIA/stroke

5.  acute MI

6.  hypercoagulable states

7.  peripheral arterial occlusive dz

Term
warfarin and pregnancy
Definition

contraindicated in pregnancy

 

BUT

 

inactive form in breast milk, so OK to breastfeed when taking

Term
AE of warfarin
Definition

-hemorrhage (2-10%)

 

-skin necrosis (rare, appears early (3-8days after initiation))

*pt w/ protein C deficiency at most risk- D/C, administer Vitamin K or fresh frozen plasma and heparin

 

-purple toe syndrome (rare, occurs later (3-10wks))

*D/C drug to prevent progression to necrosis

Term
contraindications of warfarin
Definition

-spinal anesthesia or spinal injections

-pregnancy category X

-pt w/ additional risk for hemorrhage

-noncompliance w/ drug therapy or monitoring

-EtOH

-surgery, dental work

Term
dosing warfarin
Definition

-average dose:  4-5mg, however patient specific and can range from 1-15mg

 

-dosed qday, usu overlap w/ heparin for 4-5days (takes 5-7days for warfarin to peak)

 

-higher the INR ratio, more likely to bleed- less likely to give warfarin

-lower the INR ratio, more likely to clot- more likely to give warfarin

Term
reversal of excess warfarin anticoagulation
Definition

give vitamin K! antagonizes warfarin

-induces metabolism of warfarin:  therefore decreases the serum conc. of warfarin, therefore decreases the INR (low INR- faster clotting time, high INR- slower clotting time)

 

green vegetables MC source of dietary vitamin K

multivitamins

consistent intake to stabilize INR

Term
warfarin drug intrxns
Definition

assume an intrxn until proven otherwise

 

increases bleeding risk (does not effect INR):  ASA, NSAIDS

increases anti-coag effect (inc INR (takes longer to clot)):  sulfamethoxazole

decreases anti-coag effect (dec INR (quicker to clot)):  vitamin K

 

CONTRAINDICATED:  pt taking sulfamethoxazole (septra, bactrim)

Term
warfarin intrxns with EtOH
Definition

acute ingestion:  increases INR

*metabolism is slowed because acute ingestion inhibits CytP450

 

chronic ingestion:  decreases INR

*induces CytP450

 

cirrhosis:  increases INR

Term
prevention of VTE
Definition

-heparin

-LMWH

-compression stockings/intermittent pneumatic compression device

 

measure of prevention varies with degree of risk

Term
heparin + warfarin tx of VTE
Definition

continuous infusion heparin 5-7days

 

warfarin begins on day 1 or 2

 

must have therapeutic INR for 2 days in a row before stopping heparin

Term
LMWH + warfarin tx of VTE
Definition

subcutaneous LMWH 5-7days

 

warfarin tx begins on day 1 or 2

 

must have therapeutic INR for 2 days in a row before stopping heparin

Term
thrombolytic tx of VTE
Definition

systemic lytic tx NOT recommended for most pt

 

intracranial bleed 0.5-1% of pt

 

contraindicated if major surgery w/in 10 days, active internal bleeding, stroke w/in 3 months, intracranial tumor

Term
define:  pharmacogenetics
Definition
study of variability in hereditary factors as it relates to drug response in different populations
Term
discuss CYP2C9 and anti-coagulation
Definition

genetic variations of CYP2C9 lead to significant differences in pt response to warfarin

 

study found that CYP2C9*2 and CYP2C9*3 are associated with:

1.  warfarin maintenance dose

2.  time to stable warfarin dose

3.  rate of above range INRs

4.  bleeding events

Term
warfarin genetic test 
Definition

-identifies pt who need lower doses d/t inc risk for bleeding

-tests for variations in CYP2C9 and VKORC1 genes

*help determine pt sensitivity to warfarin metabolism and anti-coag process

-specifically overanticoagulation

 

-help achieve maintenance dose faster and likely increase safety and efficacy

Term
what is the hepatic microsomal enzyme CYP2C9 impt in
Definition
enzyme that constitutes the primary pathway for metabolism of s-warfarin
Term
when administering reversal tx, what is an impt consideration
Definition
administer it in small doses to be careful not to overshoot anti-coag
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