Anticoags

Question 1

Oral antiplatelet aggregation

Answer 1

Aspirin, Ticlopidine, Clopidogrel, Prasugrel, & Ticagrelor (PT cat)

Question 2

IV antiplatelet aggregation

Answer 2

Abciximab, Eptifibatide, & Tirofiban

ate

Question 3

*Aspirin MOA

Answer 3

Cycloxygenase (COX) inhibitor
Prevents the production of Thromboxane A2
Action is irreversible, lifespan of a platelet 10 day

Question 4

*ASA prevents what, dose diseases

Answer 4

Recurrent Ischemic Events
Stroke
Myocardial infarction
Symptomatic peripheral arterial disease
Dosage: 81–325 mg qday

Question 5

ASA precautions
drug interaction
tx for bleeding

Answer 5

Children (Reye’s)
Pregnancy
Asthmatics
Cardiovascular drugs
Blunts effect of ACE inhibitors, ß-blockers, & diuretics due to prostaglandin inhibition
Increased bleeding with other anticoagulants. Treatment of bleeding is platelet transfusion: have platelets circulation just don’t stick to each other so platelet count doesn’t matter

Question 6

*Ticlopidine (ticlid) MOA

Answer 6

Thienopyridine - Blocks ADP receptor on platelet and inhibits fibrinogen binding

Question 7

Ticlopidine (ticlid) use

restrictions

Answer 7

Used for prevention of recurrent ischemic events especially in cases of ASA intolerance
**Use is extremely restricted due to: Neutropenia, Thrombotic thrombocytopenic purpura, GI Upset, Teratogenesis

Question 8

*Clopidogrel (Plavix) MOA

Answer 8

Thienopyridine – Irreversibly blocks ADP receptor on platelet and inhibits fibrinogen binding

Question 9

*Clopidogrel (Plavix) prevention of

Answer 9

Used for prevention of recurrent
ischemic events:
Stroke prevention
Recent acute coronary syndrome (dual therapy better than ASA mono therapy)
Post-percutaneous coronary intervention (dual therapy better than ASA monotherapy)

Question 10

which mono therapy is better ASA or Clopidogrel, but what the down side and doses of the 2

Answer 10

Clopidogrel monotherapy better than ASA monotherapy but cost may be prohibitive
Dosage
Loading dose of 300mg or 600mg
Daily dose of 75mg

Question 11

Clopidogrel precautions

Answer 11

Metabolized via CYP2C19, genetic predisposition to poor metabolism along this pathway, may require increased dosing
**CYP-450 inhibitor
Dose adjustment for severe renal or
hepatic disease
Use in conjunction with other anticoagulants

Question 12

Clopidogrel toxicities/bleeding

Answer 12

Increased risk of bleeding
Serious bleeding seen most commonly in the elderly, the underweight, and pts with previous stroke or TIA
Treatment of Bleeding
Discontinuation of drug (at least
temporarily)
Platelet transfusion

Question 13

*Prasugrel (effient)

Answer 13

New Thienopyridine
greater than clopidogrel at reducing risk of recurrent MI and in-stent thrombosis
greater risk of bleeding
works of clopidogrel non-responders

Question 14

Prasugrel dose precautions

Answer 14

10mg qday
Precautions:
Active bleeding
Previous stroke/TIA, underweight, elderly (>75 yrs) – Consider decreasing dose to 5mg qday
*Surgery – Risk of bleeding during CV surgery was 4x greater than clopidogrel. Do not use pre-cardiac cath!

Question 15

*Ticagrelor (brilinta) MOA

Answer 15

Blocks ADP receptors from different binding site (allosteric antagonist)

• better than clopidogrel of MI and stroke
• but higher rate of non-procedure bleeding–including intracranial hemorrhage

Question 16

Ticagrelor uses dose

Answer 16

Prevention of recurrent ischemic events after myocardial infarction
Stroke prevention
Recent acute coronary syndrome
Post-percutaneous coronary intervention
Dosage: 180mg x 1, then 90mg bid
Always given as dual therapy with ASA unless ASA is contraindicated

Question 17

Ticagrelor precautions contraindications

Answer 17

Precautions:
Hepatic dysfunction
ASA use greater than 100mg/day
Hold for >5 days before surgery
bid dosing may have compliance considerations
Contraindications:
Active bleeding
History of intracranial hemorrhage

Question 18

*GPIIb/IIIa inhibitors MOA

Answer 18

Block the GPIIb/IIIa receptor preventing fibrinogen binding

Question 19

*GPIIb/IIIa inhibitors uses and drug names

Answer 19

Acute Coronary Syndrome
Percutaneous Coronary Intervention
Drugs:
Abciximab (ReoPro)
Eptifibatide (Integrillin)
Tirofiban (Agrastat)

Question 20

*Abciximab uses

Answer 20

ACS with planned PCI
– If used with heparin keep aPTT 60-85 sec
PCI
Most expensive agent
Most prolonged effects

Question 21

*Eptifibatide

Answer 21

ACS
– IV bolus – Infusion
Serum Creatinine <2.0 mg/dl
2.0 mcg/kg/min for up to 72 hours
Serum Creatinine 2.0 to 4.0 mg/dl 
1.0 mcg/kg/min for up to 72 hours
PCI – Same as above

Question 22

GPIIb/IIIa Inhibitors toxicities

Answer 22

Bleeding
Abciximab – reverse with platelets
Eptifibatide and Tirofiban – discontinue the drug
Interactions
Other antiplatelet and anticoagulant agents potentiate effects

Question 23

Peri-op mgmt of anti platelet therapy

Answer 23

Temporary interruption of anti-platelet therapy should occur 7-10 days pre-op
Therapy should resume 24hrs (or next AM) post-op as long as hemostasis is achieved
Patients at high risk for cardiac events should continue ASA up and through the OR, clopidogrel should be stopped at least 5 days prior to OR

Question 24

*Heparin MOA

Answer 24

Heterogenous mixture of polysaccharide chains
Activates Antithrombin III
Increases inhibition of Thrombin (IIa) and
Factor Xa by 1000 fold

Question 25

*Heparin uses

Answer 25

DVT prophylaxis and treatment Pulmonary Embolus treatment Acute Coronary Syndrome When warfarin started or contraindicated

Question 26

Heparin doses

Answer 26

DVT prophylaxis: 5,000 Units SQ q8hrs q12 hr dosing occasionally used in high-risk bleeding pts (i.e. Neurosurgery and ESRD) Intravenous infusions Weight-based bolus Weight-based infusion Adjusted based on aPTT or anti-Xa values q6hrs until stable, then qday

Question 27

Heparin interactions/drawbacks

Answer 27

Increased risk of bleeding when used with other anticoagulant or antiplatelet agents Drawbacks of use Variable anticoagulant effect Inability to inhibit clot-bound thrombin

Question 28

Heparin toxicities

Answer 28

*Bleeding STOP THE HEPARIN! Look for hidden heparin! Reverse with Protamine 1mg/100 U Heparin (or just give 50mg bolus) *Benign thrombocytopenia *Heparin-induced thrombocytopenia (HIT) 1% @ 7days ■ 3% @ 14days

Question 29

HIT non-immune mediated (type 1) and immune mediated (type 2)

Answer 29

1.Mild drop in platelets, usually within 4 days of start of heparin treatment, NOT progressive or associated with thrombosis 2. Follows heparin exposure (prophylactic or full) Reduction in platelet count to < 150,000 or a decrease of 50% from baseline (pre heparin) Occurs 5 - 14 days after heparin exposure

Question 30

Thrombocytopenia

Answer 30

Occurs in 2-5% (UF>LMWH) Most common: Surgery >medical > obstetric Typical platelet count 38,000-60,000 Typical onset (66%): Exposure 5-14 days Delayed onset (3-5%): Exposure 2-6 weeks Rapid onset (25-30%): hours to days, usually due to residual circulating antibodies from heparin exposure within last 100 days)

Question 31

HITT venous, arterial

Answer 31

Thrombocytopenia with Thromboembolism (10 – 25% cases) Venous: (4 x more common) DVT, PE, Venous limb gangrene, dural sinus thrombosis Arterial: Cerebral infarction, limb ischemia, skin necrosis, myocardial infarctions, mesenteric ischemia, adrenal, renal, spinal artery infarctions 25 – 30% mortality, 25% amputation rate

Question 32

HIT lab

Answer 32

ELISA: (enzyme linked immunosorbent assay) Antigen assay measures titer of IgG antibody to heparin-PF4 complex Easy to do and readily available Sensitivity 90%, Specificity 80% (detects other antibodies) C-serotonin release assay (SRA): Detects platelet activation Labor intensive, Not readily available, Usually a “send-out” test Sensitivity & Specificity 95% Used primarily as a confirmatory test **Do not delay treatment waiting for test results!

Question 33

HIT clinical mgmt

Answer 33

Stop all drugs known to cause thrombocytopenia STOP Heparin and START non-heparin anticoagulant (usually Argatroban) Look for any history of heparin exposure Look for unrecognized heparin sources Heparinized flush bags Heparin-coated catheters Prophylactic sq heparin

Question 34

*Low Molecular Weight Heparin (enoxaparin) MOA/uses

Answer 34

``` Saccharide chains ~ 5,000 daltons Binds with Antithrombin III and inhibits Factor Xa Uses: DVT prophylaxis Acute Coronary Syndrome VTE treatment ```

Question 35

Low Molecular Weight Heparin dose

Answer 35

Dosage (subcutaneous injection) Depends on indication DVT Prophylaxis Standard: 40mg q24hrs Hip or knee replacement: 30 mg q12hrs DVT Treatment: 1 mg/kg q12h or 1.5 mg/kg qd Acute Coronary Syndrome: 1mg/kg q12h *Dosage effects not routinely monitored, can check anti-Xa levels

Question 36

Low Molecular Weight Heparin precautions, tx

Answer 36

Precautions Pregnant women – monitor anti-Xa levels Obese patients – use weight-based dosing *Not recommended in severe renal insufficiency (Cr Cl <30 ml/min). If no other alternative, reduce dose by 50% Not for use with spine surgery patients or patients with epidural catheters *Treatment of bleeding – Protamine provides ~60% reversal

Question 37

*Fondaparinux (Arixtra) MOA, uses

Answer 37

``` Synthetic Factor Xa inhibitor Binds with Anti-thrombin III to potentiate Xa inhibition (by 300 times) No direct effect on IIa (thrombin) Uses: Acute Coronary Syndrome PE/DVT tx DVT prophylaxis ```

Question 38

Fondapariunx dosage, contraindications, *tx

Answer 38

``` Dosage 7.5mg subcutaneous qd for prophylaxis, 10mg for VTE or wt > 100kg, duration depends on reason for use Contraindications: CrCl < 30 ml/min Spinal anesthesia or lumbar puncture Treatment of bleeding No known reversal agent FFP is ineffective in reversal Discontinue the drug and provide supportive care ```

Question 39

*IV direct Thrombin (IIa) inhibitors MOA, uses

Answer 39

Do not require Antithrombin III IV Agents include Hirudin, Lepirudin, Desirudin, Hirulog, Argatroban (reversible), Bivalirudin Uses: HIT (Argatroban, Lepirudin) Percutaneous coronary intervention (Bivalirudin)

Question 40

IV direct Thrombin (IIa) inhibitors toxicities, Interactions, *Tx of bleeding

Answer 40

*Toxicities: Bleeding Lepirudin and Desirudin can only be used once d/t problems w/ anaphylaxis *Interactions: Increased bleeding with additional anticoagulants, thrombolytics, or anti platelet agents *Treatment of bleeding: Stop the infusion May respond to a combination of Factor VII, FFP, and cryoprecipitate

Question 41

*Warfarin MOA

Answer 41

Interferes with the production of Vitamin K-dependent clotting factors (II, VII, IX, & X) Interferes with the carboxylation of natural anticoagulants Protein C and Protein S

Question 42

*Warfarin uses

Answer 42

``` Prevention of thrombosis/embolism DVT Atrial fibrillation Mechanical heart valves Long-term treatment of VTE ```

Question 43

Warfarin dosage

Answer 43

Start with 5-10mg/day x 2-5 days, then **Dose based on Prothrombin time/INR Most indications, therapeutic INR goal is 2.0–3.0 High risk patients (i.e. mechanical heart valves, previous thrombus, anti- phospholipid syndrome) goal of 2.5-3.0 **Overlap with heparin or LMWH for 1-2 days Duration of therapy for uncomplicated DVT and PE = 3 months

Question 44

Warfarin toxicities,

Answer 44

Toxicities: | Bleeding, Birth defects, Cutaneous necrosis

Question 45

Warfarin interactions increased effect

Answer 45

Amiodarone Cimetidine Acetaminophen Phenylbutazone

Question 46

Warfarin interactions decreased effects

Answer 46

``` Sucralfate Cholestyramine Spironolactone Barbituates Vitamin K containing foods ```

Question 47

Warfarin precautions

Answer 47

Concomitant anti-platelet therapy and/or NSAID use

Question 48

Warfarin INR

Answer 48

Sub-therapeutic INR: Continue same dose, recheck in 1-2 wks: Super-therapeutic INR without bleeding, Hold next dose, recheck within 1 wk Reversal/Treatment of bleeding: Vitamin K – either oral or IV, FFP -(1.4 to 1.5 of INR) can't get INR below 1.5 with FFP

Question 49

Periop mgmt of Warfarin Therapy

Answer 49

* Pts who require temporary interruption of warfarin and normalization of INR, warfarin should be held 5 days prior to OR * Warfarin should be resumed 12-24 hours post-op as long as hemostasis has been achieved * For high-risk patients bridging with heparin up until 4-6hrs of surgery is recommended

Question 50

*Dabigatran (pradaxa) MOA, uses, dosage

Answer 50

Direct Thrombin Inhibitor (IIa) Uses: Prevention of stroke in non-valvular atrial fibrillation (2010) and treatment of DVT/PE (2014) Dosage: 110mg bid vs 150mg bid Lower dosing suggested if high-risk for bleeding, elderly, or mod/severe renal impairment

Question 51

Dabigatran

Answer 51

superior to 150mg bid of warfarin for stroke and systemic embolism, no significant difference in major bleeding *110mg bid just as good as warfarin for preventing with a 20% relative risk reduction for major bleeding

Question 52

Dabigatran advantages

Answer 52

No routine monitoring required, predictable pharmacokinetics Less influence by diet and drug interactions Rapid time to peak action (1 hr) Short half-life (12-14 hrs) in pts with normal renal function

Question 53

Dabigatran disadvantages

Answer 53

High cost and bid dosing which may impact compliance No antidote yet – Idarucizumab, an antibody, is currently under investigation. May be a potentially effective and rapid antidote No assay for monitoring of anticoagulant effect No long term data – Several reports of post- marketing serious or fatal bleeding events that requires investigation

Question 54

*Rivaroxaban (Xarelto) MOA uses dose

Answer 54

Direct Factor Xa inhibitor Uses: Stroke and systemic embolism prevention in non-valvular atrial fibrillation Prevention of DVT after hip or knee replacement surgery Treatment of PE/DVT Dosage: 20mg qday

Question 55

Rivaroxaban *

Answer 55

just as good as warfarin for prevention | overall risk of bleeding same by decreased risk of intracranial and fatal bleeding compared to warfarin

Question 56

RIvaroxaban advantages

Answer 56

No routine monitoring required, predictable pharmacokinetics Less influence by diet and drug interactions Once daily dosing may improve compliance Rapid time to peak action (2.5-4 hrs) Short half-life (7-11 hrs)

Question 57

Rivaroxaban disadvantages

Answer 57

High cost which may impact compliance No antidote: Andexanet, a Factor Xa decoy currently under investigation, may assist in reversal of the effects No assay for monitoring of anticoagulant effect No long term data

Question 58

*Apixaban (Eliquis) MOA uses dose

Answer 58

Direct Factor Xa inhibitor Uses: Stroke and systemic embolism prevention in non-valvular atrial fibrillation, prevention of DVT in hip and knee replacement surgery, and treatment of DVT/PE Dosage: 5mg bid

Question 59

*Apixaban

Answer 59

clear benefit over ASA for pt who are not candidates for warfarin superior to warfarin in prevention and has significant decreased in bleeding risk

Question 60

Apixaban advantages

Answer 60

No routine monitoring required, predictable pharmacokinetics Less influence by diet and drug interactions Rapid time to peak action (3 hrs) Short half-life (12 hrs)

Question 61

Apixaban disadvantages

Answer 61

High cost and bid dosing which may impact compliance Reversed only with prothrombin complex concentrate No assay for monitoring of anticoagulant effect No long term data

Question 62

*Fibrinolytic what they do and drug names

Answer 62

``` Plasminogen activators convert plasminogen to plasmin Plasmin causes fibrinolysis *Agents: Streptokinase Urokinase Tissue-type Plasminogen Activator (t-PA) Recombinant t-PA (Alteplase, Reteplase) Tenecteplase (TNK-ase) ```

Question 63

*Fibrinolytic use

Answer 63

``` Acute ST-elevation myocardial infarction Acute ischemic stroke (within 6 hours of onset of symptoms) - tPA Urokinase Central venous catheter de-clotting Pulmonary embolism ```

Question 64

Fibrinolytics dose, toxicities

Answer 64

Recombinant tPA: 10 Units over 2 min; Repeat in 30 min TNKase: 30 – 50 mg single bolus over 5 seconds (wt- based) Toxicities Bleeding - Evaluate absolute versus relative contraindications for the administration of fibrinolytics

Question 65

Firbinolytics absolute contraindications

Answer 65

Previous hemorrhagic stroke Ischemic stroke within 3 months Known intracranial neoplasm Active internal bleeding (excluding menses) Suspected aortic dissection Significant closed head or facial trauma within 3 months

Question 66

Fibrinolytics relative contraindications

Answer 66

Recent trauma within 2-4 weeks (including traumatic CPR) Major surgery < 3 weeks Recent (2-4 weeks) internal bleeding or active PUD Pregnancy For streptokinase - allergy or prior exposure (5 days to 2 years)