Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

HemOnc > Pharmacology: Anti-coagulant/Antiplatelet > Flashcards

Pharmacology: Anti-coagulant/Antiplatelet Flashcards

1
Q

What are the two classes of Anti-thrombotic drugs ?

A

Anti-Platelets

Anti-Coagulants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where do ‘White Thrombi’ form and what are they primarily composed of ?

A

arteries (high flow conditions)

Platelets predominate
Relatively little fibrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What class of medications would you use to control White Thrombi in the arterial system ?

A

Anti-Platelets (white thrombi are predominantly composed of platelets. Inhibiting their activation and aggregation will limit White Thrombus formation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where do Red Thrombi form and what are they primarily made of ?

A

in veins (slow flow conditions)

Rich in fibrin and trapped red blood cells
Relatively few platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which class of drugs would you use to control Red Thrombi in the veinous system ?

A

Anti-Coagulants (They are predominantly fibrin, if you can block fibrin formation, you will have less Red Thrombi formation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the conceptual difference between and Anti-thrombotic drug and a Thrombolytic drug ?

A

Anti-thrombotic drugs stop thrombi from forming

Thrombolytics break up pre-formed thrombi.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the three important processes that occur leading to ‘platelet plug’ formation ?

A

Platelet adhesion

Platelet activation (and secretion)–> due to mediator release (from granules and de novo synthesis and secretion)

Platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

List effector molecules that lead to platelet activation:

A

Strongest: Collagen,Thrombin, PAF(Platelet Activating Factor)
Weaker:ADP, TxA2, Vassopressin
Weakest:Epi, Serotonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What occurs to a platelet once it is activated ?

A

Once the platelet is activated, there is a conformational change in GP IIB/IIIA which allows platelets to bind fibrinogen–> Aggregation

Caveat: GP-IIB /IIIA antagonist inhibit the ability of platelets (activated) to bind firbrinogen. VERY EFFECTIVE anti-platelet drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Anti-coagulant drugs stop which important thrombi molecule from forming ?

A

Fibrin ( Fibrinogen –> Fibrin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

The Prothrombin Time (PT) is used to measure the effectiveness of Anti-coagulant drugs. Which branch of the coagulation cascade is tested by PT : Intrinsic or Extrinsic ? Which drug is this typically used to test the efficacy of ?

A

Extrinsic (and Common)
(Factor VII is the beginning molecule. Usually activated due to trauma.)

Warfarin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

The Activated Partial Thromboplastin time (aPTT) is used to measure the effectiveness of Anti-coagulant drugs. Which branch of the coagulation cascade is tested by aPTT: Intrinsic or Extrinsic ? What drug is this test specifically designed to test the efficacy of ?

A

Intrinsic (and Common)
(Factor XII is the starting point, typically activated by internal events.)

Unfractionated heparin: activates anti-thrombin III –> Decreased coagulation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

The Factor Xa inhibition assay is used to test the efficacy of which drug ? When is this drug often given in place of Warfarin ?

A

Low-molecular- weight heparin (LMWH) …Not used frequently since LMWH really doesn’t need to be monitored.

Pregnancy (patients who need to be decoagulated and are pregnant cannot take Warfarin since it is teratogenic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

The International normalized ratio (INR) is used to normalize the variability in which test for anti-coagulation efficacy ?

A

Prothrombin Time (PT)

The INR corrects for differences in the thromboplastin reagents used by different laboratories

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Tissue-typePlasminogen Activator (tPA) is part which class of drug ?

A

Fibrionlytic (degrade pre-formed platelet plugs/thrombi)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does tPA activate that leads to fibrinolytic activity ?

A

tPA activates fibrin bound PLASMINOGEN which leads to its activation to PLASMIN (tPA binds directly to Fibrin)

Plasmin is an enzyme which cleaves fibrin –> breakdown of clots.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Streptokinase and Urokinase are also fibrinolytic drugs. What is the main difference in these drugs from tPA ?

A

They are not fibrin specific drugs. They bind free fibrinogen as well as clot bound fibrin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Reteplase (r-PA) and Tenecteplase (TNK-t-PA) are found in what class of drugs ?

A

Fibrinolytics ( Just like tPA and Uro/Streptokinase.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

If you wish to keep a patients clots intact, what can you give to stop plasminogen from being activated to plasmin ? What drugs will this affect ?

A

Plasminogen Activator Inhibitor I/II (Stops the formation of Plasmin.)

tPA, Uro/Streptokinase and Reteplase (r-PA)
Tenecteplase (TNK-t-PA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What can you give to inhibit Plasmin from cleaving fibrin ?

A

Alpha2-Anti-plasmin. Inhibits formed plasmin from degrading fibrin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

LIST (5) the main Anti-Platelet drugs (Stop platelet adhesion, activation and aggregation) ?

A 
Aspirin (COX inhibitor)
P2Y12 (ADP)receptor blockers
   Thienopyridines
   Non-thienopyridine (Plasogril)
GP IIb/IIIa inhibitors
Dipyridamole
Cilostazol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Aspirin irreversibly inhibits COX. What platelet activator will be inhibited by this action ?

A

Thromboxane A2 (TxA2)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which 3 group of patients should you think twice about giving Aspirin to ?

A

Patients with ASA allergy

Patients with Asthma and Nasal Polyps

Patients who may have to have surgery in the near future (5 days. May inhibit ability to clot post procedure)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

List the adverse effects seen with ASA ?

A

GI upset (Most common)
ASA allergy
GI mucosal inflammation or erosion (Ulcer)
GI bleeding
Hemorrhagic strokes (decreased clotting ability)
Asthma exacerbation (esp. w/ nasal polyps) **
Tinnitus (ASA toxicity) **
Ringing in the ears

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What platelet activator receptor do Thienopyridines block ?

A

P2Y12 ADP receptor (IRREVERSIBLY)

ADP is an activator of platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Which (3) drugs are Thienopyridine P2Y12 (ADP) receptor blockers ?

A

Ticlopidine (Ticlid)
Clopidogrel (Plavix)** (very common)
Prasugrel (Effient)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

List the Adverse effects seen with Thienopyridine P2Y12 ADP receptor blockers …

A 
Dyspepsia 
Diarrhea*
Bleeding
Severe neutropenia *
Thrombotic thrombocytopenic purpura *

(* =More common with Ticlopidine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Ticlopidine has a worse side effect profile than Clopidogrel or Prasugrel. How often is Ticlopidine dosed daily ?

A

Twice

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Which is more effective for secondary prevention following MI : ASA or Clopidogrel ?

A

Clopidogrel (slightly)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What do you give in concert with Clopidogrel following coronary stenting, and in treating acute coronary syndromes ?

A

ASA !

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How many times a day is Clopidogrel dosed ?

A

Once (Ticlopidine is dosed twice…winning)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Clopidogrel is a pro-drug that must be metabolized by which enzyme before it can be active ?

A

CYP-2C19 (A hepatic Enzyme)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What percentage of Americans are ‘poor responders’ to Clopidogrel due to a genetic defect in CYP-2C19 ?

A

Around 30% !!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Does Prasugrel need to be activated by liver enzymes ?

A

YES ! However, there is less ‘poor responders’ to Prasugrel than to Clopidogrel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Compared to Clopidogrel + ASA therapy for patients with acute coronary syndromes (ACS) who underwent percutaneous coronary intervention (PCI) ; Prasugrel + ASA showed what kind of difference in mortality ?

A

NONE

However, there were less thrombotic events but more serious bleeding events.

It’s kind of a wash then.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is the indication for Prasugrel ?

A

Acute coronary syndrome (ACS) for which percutaneous coronary intervention (PCI) is planned (Unlike Clopidogrel which is given with ASA post PCI)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What are the Three ABSOLUTE contraindications to Prasugrel ?

A

Age > 75 years
History of TIA or CVA
Body weight < 60 kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Ticagrelor is a Non-thienopyridine ADP antagonist. How does its MOA differ from the thienopyridine ADP Agonists ?

A

Binds P2Y12 (ADP) receptor on RBC’s REVERSIBLY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

How is Ticagrelor dosed ?

A

Twice Daily orally.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Is Ticagrelor converted to active drug by hepatic enzymes ?

A

NO . It is NOT a pro-drug.

41
Q

Is Ticagrelor + ASA is better for patients with Acute Cornoary than either Prasugrel or Clopidogrel + ASA ?

A

Yes. Significant reduction in composite endpoint: MI, CVA, & cardiovascular death

42
Q

Ticagrelor + ASA was shown to have significant advantages for patients with ACS who require which procedure ?

A

CABG

43
Q

s Ticagrelor + ASA is better at reducing bleeding rates than either Prasugrel or Clopidogrel + ASA ?

A

Nope. there is no real difference.

44
Q

GP IIb/IIIa inhibitors stop platelets from binding which molecule, thus stopping thrombi formation ?

A

fibrin(ogen) (Not sure, different pictures show both molecules, the lecture says Fibrinogen, though).

45
Q

When are GP IIb/IIIa inhibitors often used ?

A

primarily in interventional cardiology (in anticipation of PCI)

(Use is decreasing, as bivalirudin (Direct thrombin Inhibitor) use is increasing )

46
Q

Abciximab is an GP IIb/IIIa inhibitor and a ….

A

Monoclonal Antibody (MAB = Monoclonal Antibody)

47
Q

Abciximab is dosed how ?

A

IV only

Has extended duration of anti-platelet activity (surgeons hate it)

48
Q

Eptifibatide is an IIb/IIIa inhibitor and a…

A

peptide inhibitor

49
Q

How is Eptifibatide dosed ?

A

IV only

Eptifibatide is the most commonly used IIb/IIIa inhibitor.

50
Q

Tirofiban is a non-peptide antagonist of GP IIb/IIIa and is dosed by …

A

IV only

51
Q

The major adverse effect of GP IIb/IIIa inhibitors is Thrombocytopenia. Which drug is the biggest culprit of this ?

A

Abciximab

52
Q

Explain Dipyridamole’s MOA ..

A

Increases RBC cAMP levels. This will lead to a lowered cytosolic Ca++ level –> Decreased platelet AGGREGATION.

53
Q

How effective is Dipyridamole as an Anti-Thrombotic ?

A

Not very at all

54
Q

Cilostazol is an Phosphodiesterase inhibitor. How does this cause its anti-platelet effect ?

A

Leads to increased NO levels –> Vasodilation.

Vasodilation will cause platelet AGGREGATION to decrease.

55
Q

What is Cilostazol (Phosphodiesterase inhibitor) typically used to treat ?

A

ambulatory claudication

56
Q

What does Warfarin inhibit to achieve its Anti-COAGULANT effect ?

A

Vitamin K Epoxide Reductase

57
Q

Vitamin K is needed for the action of which coagulation cascade factors ?

A

II, VII, IX and X ( II + VII =IX and if you are stupid, it = X)

58
Q

Why does Warfarin have an extended anti-coagulant effect ?

A

It has an incredibly long half-life of 37 hours. ( 5 half-lives to get to steady state)

Warfarin show an DELAYED Anti-Coagulation effect since it takes 2-7 days to reach therapeutic ranges.

59
Q

What 2 factors can lead to a variability in Warfarins Anti-Coagulation effect ?

A 
Amount of dietary Vit K intake (watch out for spinach)
DRUG INTERACTIONS (Many)
60
Q

What anti-coagulation test(s) must be implemented when you put a patient on Warfarin ?

A

PT (Extrinsic) and INR (To normalize inconsistency of PT)

Daily until stable state is reached and then once a month post.

61
Q

Which anti-coagulation proteins are reliant on Vit K and thus are inhibited by Warfarin, leading to a paradoxical hyper-coaguable state when first giving Warfarin ?

A

Protein C and S (Vit K dependent Anti-Coagulation proteins)

62
Q

What must be given with Warfarin at the beginning of treatment in patients with Thrombotic disease (to curve the paradoxical hyper-coaguable state) ?

A

Heparin (should be given prior to giving Warfarin and needs to be continued for several days)

Avoid large ‘Loading Dose’

63
Q

Can you give Warfarin to patients who are pregnant ?

A

NOPE…teratogenic.

64
Q

Besides being teratogenic, what are the side effects seen with Warfarin

A

Bleeding
Embryopathy
Skin Necrosis (RARE, More likely to occur in patients with inherited protein C or protein S deficiency )

65
Q

In non-emergent bleeding conditions seen as a side effect to Warfarin therapy, what can you do reverse the bleeding ?

A

STOP WARFARIN

GIve Vit K (should turn around the effects quickly)

66
Q

In emergent bleeding conditions seen as a side effect to Warfarin therapy, what can you do to treat this ?

A

Transfuse fresh frozen plasma (FFP)/ cryoprecipitate

replenishes functional clotting factors II, VII, IX, X

67
Q

What is the MOA for Unfractionated (UFH)

A

Combine and Activate Anti-Thrombin III (As the name implies, Anti-Thrombin III inhibits thrombin which normally would cause Firbrin formation from fibrinogen)

68
Q

What is the MOA for Low-molecular-weight heparin (LMWH) ?

A

It is stated that LMWH is better (more selective for) at inhibiting Factor Xa (which activated thrombin from pro-thrombin) than binding AT-III. This give LMWH a more predictable effect than UFH.

LMWH has variable composition. only a small amount reaches 18 residues which is needed to bind AT-III leading to its activation

69
Q

Besides having a more predictable effect (Inhibiting factor Xa) LMWH has the advantage of UFH in that it does not need…

A

Routine blood Monitoring.

Also, LMWH has:
Simpler dosing
Lower incidence of heparin-induced thrombocytopenia (HIT)

70
Q

In which patients will you need to REDUCE the does of LMWH ?

A

Those with renal insufficiency

71
Q

List the three forms of LMWH reviewed in lecture

A

Enoxaparin (Used the most)
Dalteparin
Tinzaparin

72
Q

What are the adverse effects seen with Heparin ?

A 
Bleeding
Thrombocytopenia (HIT)
Heparin induced thrombocytopenia (less with LMWH)
Osteoporosis (cumulative dose-dependent)
Skin necrosis
Alopecia
Hypoaldosteronism
73
Q

If a patient undergoes serious bleeding complications while on heparin therapy, how would you handle this ?

A

TAKE THEM OFF HEPARIN

Give Protamine Sulfate (Antedote) for serious bleeds. Immediately reverses heparins effect.

74
Q

Which is more common : Non-immune-mediated HIT or Immune Mediated HIT

A

Non-Immune Mediated :
More common (up to 15% of patients on heparin)
Dose-dependent
Benign, self-limited

75
Q

Which is more serious : Non-immune-mediated HIT or Immune Mediated HIT

A

Immune Mediated HIT:

Often, the drop in platelet count doesn’t occur until 4 - 14 days after starting heparin
Not dose-dependent
Can cause life-threatening bleeding, or…
**Life- and limb-threatening thrombosis **

IgG + Heparin + Platelet Factor IV = Thrombus

76
Q

What is the treatment regimen for a patient with Immune Mediated HIT ?

A

STOP HEPARIN IMMEDIATELY

Anticoagulate with a Direct Thrombin Inhibitor ( ie. Bivalrudin)

77
Q

Direct Thrombin Inhibitors (DTI) are effective against: circulating, clot bound or both kinds of thrombin ?

A

BOTH !

78
Q

What is a major advantage of Direct Thrombin Inhibitors (DTI) over Heparin ?

A

Does not cause HIT (duh, no heparin)

79
Q

What are the Direct Thrombin Inhibitors (3) ?

A

Lepirudin (Refludan)
Bivalirudin (Angiomax)
Argatroban (Novastan)
Dabigatran (Pradaxa):

80
Q

What is a major use of the Direct Thrombin Inhibitors, especially bivalrudin ?

A

During PCI in interventional cardiology

81
Q

What is are the major advantages of Dabigatran (Pradaxa) as compared to Warfarin ?

A

No monitoring of coagulation studies needed

No dietary restrictions

Minimal drug interactions

82
Q

In which patients will you need to decrease the dose of Dabigatran ?

A

Those with renal insufficiency.

83
Q

If you decide to discontinue Dabigatran what must you do ?

A

Adequately decoagulate the patient with another therapy. If not it increases the risk of thrombotic events ( Stroke)

84
Q

What is the major adverse effect of DTI’s ?

A

BLEEDING

85
Q

Factor Xa inhibitors are active against the formation of which thrombotic molecule ?

A

Thrombin (stops Xa from turning prothrombin to thrombin).

86
Q

Is there an anti-dote for Factor Xa inhibitors ?

A

Nope !

87
Q

What are the three examples of Factor Xa Inhibitors covered in lecture ?

A

Fondaparinux

Rivaroxaban

Apixaban

88
Q

Fondaparinux (a Factor Xa inhibitor) binds to what factor to stop thrombosis ?

A

Anti-Thrombin III

Interesting note: Anti-Thrombin III binds Factor X. So, really, Fondaparinux and Heparin have a very similar activity. Both lead to Factor Xa inhibition by activation Anti-Thrombin III.

89
Q

How is fondaparinux dosed ?

A

IV only.

90
Q

What are the two indications for Fondaparinux ?

A

Deep venous thrombosis (DVT) prophylaxis for hip and knee orthopedic surgery

Treatment of DVT and pulmonary embolism

91
Q

Rivaroxiban is different from Fondaparinux in that it binds ..

A

Factor Xa NOT Anti-Thrombin III.

92
Q

How is Rivaroxaban dosed ?

A

Orally

93
Q

In what patient population will you need to change the dose of Rivaroxaban ?

A

Renal insufficiency.

94
Q

What are the two indications for Rivaroxaban ?

A

Deep venous thrombosis (DVT) prophylaxis for hip and knee replacement surgery (Like Fondaparinux)

Reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation

95
Q

If you plan to take a patient off of Rivaroxaban (and Apixiban), what must you do ?

A

Adequately anti-coagulate with other drugs failing to do so will increases the risk of thrombotic events (e.g. stroke).

96
Q

Does Apixiaban bind anti-thrombin III ?

A

Nope (Like Rivaroxiban)

97
Q

How is Apixiban dosed ?

A

Orally , Twice Daily

98
Q

In which patients will you need to reduce the dose of apixiban ?

A

Patients with renal insufficiency

99
Q

What is the ONLY indication for Apixiban ?

A

Reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation

HemOnc (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions