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PHARM/MHD - Exam #4 > Pharm #1 - Antithrombolytics I and II > Flashcards

Pharm #1 - Antithrombolytics I and II Flashcards

1
Q

What is the mechanism of action of heparin?

How is it monitored?

Route of administration?

A

Complex with AT(antithrombin) and inhibits factors Xa and IIa. (thrombin)

Monitored by APTT
(2-2.5 baseline therapeutic)

IV & Subcutaneous

(oral only for warfarin)

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2
Q

What is the indication for heparin?

A

SURGICAL ANTI-COAGULATION! (only one indicated for this)

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3
Q

What are the adverse effects of heparin (4)

2 major

A
  1. bleeding
  2. HIT (heparin induced thrombocytopenia)
  3. osteoporosis
  4. alopecia
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4
Q

LMW Heparins
(branded and generic)

  1. MOA
  2. How is it monitored
  3. Route
A

1.Complex with AT
inhibits factors Xa and IIa

  1. monitored by anti-Xa
  2. Subcutaneous
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5
Q

LMW Heparins
(Enoxaparin or Lovenox)

Indications?

Adverse effect?

Differences with heparin? (2 main, 2 others)

A

prophylaxis and tx. of DVT and ACS

BLEEDING

  1. better bioavailability!!
  2. Longer duration of action (6 hours)
  3. Less bleeding
  4. Less thrombocytopenia
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6
Q

What are the names of the heparin anticoagulants? (5)

Heparin antagonist?

A

Heparin & LMW Heparin

  1. Argatroban
  2. Bivalirudin
  3. Hirudin
  4. Fondaparinux (pentasaccharide)
  5. Antithrombin Concentrate

Protamine Sulfate - heparin antagonist

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7
Q

MOA for Fondaparinux (Pentasaccharide)

Route of administration?

Indication?

A

Complex with AT and inhibits factor Xa

  • Subcutaneous
  • Management of DVT
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8
Q

Adverse effect of Fondaparinux

A

BLEEDING

  • same for argatroban, bivalirudin, hirudin
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9
Q

What is the MOA of argatroban, bivalirudin, hirudin, and Antithrombin concentrate?

How are they all administered?

A

Directly inhibits IIa (thrombin - they all inhibit thrombin!)

IV!!! (same with LMW Heparins)

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10
Q

State the MOA of Argatroban

Route?

Indications?

Adverse effect?

A
  1. inhibits IIa (thrombin)
  2. IV
  3. Anticoagulant
    - management of HIT
  4. BLEEDING
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11
Q

State the following for argatroban, bivalirudin, hirudin:

  1. Route of admin
  2. MOA
  3. Indication
  4. Adverse effect
A
  1. Route = IV
  2. MOA = inhibits IIa (thrombin)
  3. Anticoagulant
    - management of HIT
  4. Adverse - BLEEDING
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12
Q

State the following for Antithrombin Concentrate:

  1. Route of admin
  2. MOA
  3. Indications (4)
  4. Adverse effect
A
  1. IV
  2. Inhibits IIA (thrombin)
3. 
DIC
Sepsis
Thrombophilia
hypercoaguable state
  1. NO ADVERSE EFFECTS
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13
Q

What drug has the following indications

DIC
Sepsis
Thrombophilia
hypercoaguable state

A

ANTI - THROMBIN CONCENTRATE!!!

  • big gun!!
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14
Q

What is the MOA of protamine sulfate?

How is it administered?

Indication?

A

HEPARIN ANTAGONIST

  • IV
  • Reversal for heparin
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15
Q

What are the 2 major adverse effects of protamine sulfate?

A
  1. Bradycardia

2. Hypotension

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16
Q

MOA of Warfarin (2)

A
  • competitive antagonist of vitamin K

- suppresses the synthesis of factors 2,7,9,10

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17
Q

How is warfarin monitored?

What are the 2 indications?

A
  1. PT/ INR
  2. Prolonged treatment of DVT
  3. Atrial Fibrillation
18
Q

What are the side effects of warfarin? (3)

A
  • bleeding
  • coumadin induced necrosis
  • INTERACTION WITH SEVERAL MEDICATIONS (since it is highly protein bound) which results in bleeding due to the potentiating effect of warfarin
19
Q

MOA of vitamin K

monitoring?

A
  • Cofactor in the synthesis of functional forms of factors:

2, 7, 9 , 10

(inhibited by warfarin)

  1. monitoring NOT REQUIRED
20
Q

What are the indications of vitamin K?

A
  1. Hypoprothrombinemia
  2. Intestinal disorders
  3. Gastrectomy
  4. reverses the effects of WARFARIN
    - which is why patients are advised NOT to eat green leafy vegetables
21
Q

What is the main side effect of Vitamin K

A

Hemolysis

22
Q

Oral Anti-Xa

What are the 3 drugs in this category?

A
  1. Rivaroxaban
  2. Apixaban
  3. Edoxaban
  • all 3 have “exo & all inhibit Xa!!’
23
Q

What is the MOA of

  1. Rivaroxaban
  2. Apixaban
  3. Edoxaban
A

Inhibits factos Xa

24
Q

For what is monitoring not required? (because there is no available monitoring)

A
  1. Vitamin K
  2. Rivaroxaban
  3. Apixaban
  4. Edoxaban
25
Q

What are the Indication for the Oral Anti-Xa agents?

  1. Rivaroxaban
  2. Apixaban
  3. Edoxaban

What is Rivaroxaban approved for?

A

Stroke prevention in patients with AF

Ravaroxaban also approved for prophylaxis and tx. of DVT

26
Q

What is are the 2 major adverse effects of Oral Anti-Xa agents?

  1. Rivaroxaban
  2. Apixaban
  3. Edoxaban
A
  1. Bleeding
  2. Liver toxicity!

(same as Dabigatran - oral anti-thrombin)

27
Q

What is the MOA of Dabigatran?

A

Inhibits thrombin (IIa)

28
Q

How is Dabigatran monitored?

A

It is NOT monitored!

- no tests for Dabigtran

29
Q

What is the major indication for Dabigatran (Oral antithrombin)

A

Stroke prevention in patients with AF

30
Q

What are the major side effects of Dabigatran? (2)

A

Bleeding

Liver toxicity

31
Q

Which drug has a duration of 1-2 hours and a half life that is dose dependent with a RAPID onset?

A

HEPARIN

32
Q

How is heparin metabolized?

What has better bioavailability, heparin or LMW Heparins?

Which is used for surgical anticoagulation (warfarin/hep); which is used for CHRONIC anticoagulation?

A

Metabolized by the LIVER, some by kidney (20-25%)

  • some picked up by mast cells
    2. Low molecular weight heparins! - when given subcutaneously

DOSED IN MG , not units like HEPARIN!

  1. Surgical: heparin (no oral!)
    Chronic anticoagulation = warfarin (at war with your body!)
33
Q

Which drug is contraindicated in pregnant women?

A

WARFARIN

  • can cross placenta and cause bone & bleeding problems
  • All oral anticoagulants pass the placental barrier and may cause fetal bone malformation.
34
Q

What is hirudin used for?

What is the commercial recombinant preparation called?

A

Direct Thrombin Inhibitor (DTI) used in patients that are heparin compromised

hirudin keeps the blood flowing and prevents clots from forming!

  1. REFLUDAN
    - used for anti-coagulant management for HIT patients
35
Q

What are the main factors that effect warfarin dose?

A
  1. DIET - vitamin K can increase clotting - green leafy veggies (warfarin inhibits vitamin K synthesis)
  2. LIVER - disease can result in a lower production of coagulation factors
  3. DRUGS - aspirin is highly protein bound and can displace warfarin resulting in an increased INR and more anti-coagulation
36
Q

What is the principal toxicity of warfarin?

A

hypoprothrombinemia

ecchymosis, purpura, hematuria, hemorrhage.

37
Q

What is coumadin skin necrosis?

A

the impairment of the functionality of protein C

  • This protein also requires gamma-carboxylation of glutamic acid for functionality (vitamin K dep)

Protein C normally acts as an anti-coagulant by interacting with factors 5 and 8
inhibits their activation!

Takes 48 hours before factor 7 begins to decrease after warfarin, but prior to this PROTEIN C decreases!!!!!
- cannot act as an anti-coagulant by inhibiting factor 5 and 8 so acts as an additional phenomenon causing the blood to CLOT
may result in HEMORRHAGIC LESIONS!

38
Q

What is the tx for coumadin skin necrosis/ oral anti-coagulant overdose?

A
  1. Infuse factors 2,7,9,10 by giving fresh blood or frozen plasma
  2. Recombinant factor 7a
  3. Vitamin K
39
Q

Rivaroxaban and Apixaban, Edoxaban are cleared how?

Which has less plasma protein binding than the rest?

A
  1. R - RENALLY (65%)
  2. Apixaban = 25%
  3. Edoxaban - 35% renal (rest of drugs are LIVER)
    - are oral Anti-10a agents
  4. EDOXABAN

do not need to monitor if on these drugs BUT there is no test to monitor them!!!

40
Q

What is an anti-thrombin agent?

How is it eliminated?

A

DABIGATRAN

  • RENAL elimination!!!! 100%
41
Q

What type of drugs are

Enoxaparin or Lovenox

A

LMW Heparins

42
Q

What is the difference between heparin and LMW heparin in terms of elimination kinetics?

A

Heparin is dose dependent

LMW hep is dose independent and has a longer half life

PHARM/MHD - Exam #4 (20 decks)

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