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(HGC) ACNP804 Exam 2 > Harrison's Ch 118: Antiplatelets, anticoagulants, fibrinolytics > Flashcards

Harrison's Ch 118: Antiplatelets, anticoagulants, fibrinolytics Flashcards

1
Q

What is the most common cause of MI, ischemic stroke, and limb gangrene?

A

Arterial thrombosis

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2
Q

What is the danger of DVT?

A

Pulmonary embolus

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3
Q

Where do venus thrombi usually originate?

A 
#Valve cusps of the calf
#Muscular sinuses

They’re triggered by stasis so get to walkin’!

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4
Q

What are 3 classifications of anti-thrombotic drugs?

A

1) Antiplatelets
2) Anticoagulants
3) Fibrinolytics

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5
Q

In vascular injury, what activates platelets?

A

Exposure of subendothelial collagen & von Willebrand factor (vWF)

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6
Q

The most widely-used anti-platelet agent in the world is…

A

…ASPIRIN! Yay!

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7
Q

What does aspirin do that makes it all antiplatelet & stuff?

A

Irreversibly acetylating & inhibiting platelet cyclooxygenase (COX-1)!

Platelets need COX-1, but aspirin gets in the way. Does that make it a COX block?

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8
Q

Indications for aspirin as a SECONDARY anti-platelet?

A 
Secondary prevention of cardiovascular events in patients with:
#coronary artery disease
#cerebrovascular disease
#peripheral vascular disease
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9
Q

Indications for aspirin as a patient’s PRIMARY anti-platelet?

A 
Patients whose annual risk of MI is > 1%. This basically means:
#Pts > 40 yrs with 2 or more major risk factors for CAD
#Pts > 50 yrs with 1 or more risk factors
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10
Q

Aspirin is more effective in men or women?

A

Neither! Aspirin is equal opportunity awesome.

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11
Q

Women get another benefit from aspirin, though. What is it?

A

In women, it lowers the risk of stroke!

The COX-block is more helpful to the ladies. :)

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12
Q

Aspiring: the higher dose the better, right?

A 
NOPE!
#Doses are 75-325 PO daily
#Bigger is NOT better: higher doses are not more effective
#Side effects are dose-dependent though
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13
Q

When you want RAPID antiplatelet effect, what dose?

A

Initial dose of AT LEAST 160 mg.

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14
Q

Aspirin side effects

A 
GASTROINTESTINAL! Ew.
#Erosive gastritis
#Peptic ulcers (possibly bleeding!)
#Side effects are dose-related, so keep it low when you can
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15
Q

But we can use enteric-coated aspirin to eliminate that risk?

A

No, buffering aspirin does not completely eliminate the risk

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16
Q

Aspirin’s side effects are particularly worrisome when you combine it with another specific drug. Which one?

A

Warfarin! Patients be bleeding all over the place.

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17
Q

When a patient must be on dual warfarin-aspirin therapy, what do we know about the aspirin dose?

A

KEEP IT LOW, Y’ALL. 75-100mg daily.

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18
Q

Hard question: if someone has aspirin allergy with bronchospasm, should we be giving them aspirin?

A

That is a negative, captain. This is most common in patients with chronic urticaria or asthma, particularly those with nasal polyps or chronic rhinitis.

So: asthma+chronic stuffy nose? BEST KEEP AN EYE ON THAT TROUBLEMAKER.

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19
Q

What is aspirin resistance, anyway? Is it a helpful thing to know about?

A 
#Clinically: failure of aspirin to protect patient from ischemic events
#Biochemically: failure of aspirin to produce expected inhibitory effects
#Pretty much not useful, as we only ever know about it after the fact
#No good standardized tests for it
#Aspirin resistance is a research tool basically
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20
Q

What are the thienopyridines?

A 
#Ticlopidine
#Clopidogrel
#Prasugrel
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21
Q

How do the thienopyridines work?

A

Block P2Y12, a key ADP receptor on platelets

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22
Q

True or false: the thienopyridines are prodrugs.

A

True. All must be metabolized by the CYP450 enzyme system in the liver before they become active.

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23
Q

Prasugrel has one major benefit over the other 2 drugs in its class. What is it?

A

It’s waaaaaaay faster. Even though it also requires metabolism by the CYP450, its quickly & completely absorbed in the gut & it has more efficient activation pathways.

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24
Q

How long might it take for ticlopidine & clopidogrel to start working at their usual doses?

A

Several days. Ain’t nobody got time for that!

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25
Q

Why don’t we use ticlopidine much anymore?

A

Clopidogrel is more potent & has a better safety profile

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26
Q

What are some considerations when choosing between aspirin & clopidogrel?

A 
#Clopidogrel reduced the risk of CV death, MI, & CVA by 8.7% compared with aspirin
#Aspirin is a LOT cheaper
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27
Q

Should we ever combine aspirin & clopidogrel?

A 
Yes! This combo is recommended:
#For 4 weeks after implantation of a bare metal coronary stent
#Longer than that in a drug-eluting stent
#Patients with unstable angina: 9.3% risk on the combo, but 11.4% risk with aspirin alone
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28
Q

Okay, so what is the catch when you combine aspirin & clopidogrel?

A

It’s BLEEEEEEEEDING! Of course it’s bleeding.Increases the risk of major bleeding to about 2% yearly. Even when you drop the aspiring dose to 100 mg.

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29
Q

So when is it NOT worth it to combine aspirin & clopidogrel?

A 
#Not proven superior to clopidogrel alone in acute ischemic CVA
#Not proven superior to aspirin alone for PRIMARY prevention for those at risk for CV events.
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30
Q

Okay then, prasugrel or clopidogrel? Which one is better?

A

Composite of CV death, MI & CVA significantly lower with prasugrel than with clopidogrel.

31
Q

If prasugrel decreases risk more significantly, why aren’t we using it in everyone?

A

Again with the BLEEDING! Prasugrel has significantly higher rates of fatal & life-threatening bleeding.

32
Q

Who should be careful to avoid prasugrel?

A 
#Generally avoid it in older patients
#Contraindicated in those with history of cerebrovascular disease
33
Q

When would we give a very large dose of clopidogrel?

A

When rapid ADP receptor blockade is required. Loading doses of 300, 600, even 900 may be given before coronary stenting (normal daily doses are 75 mg).

34
Q

Can you give a loading dose of prasugrel?

A

Yes, it’s about 60 mg (daily type doses are 10mg)

35
Q

Side effects of ticlodipine:

A 
#Gastrointestinal
#Hematologic: neutropenia, thrombocytopenia, thrombotic thombocytopenic purpura
#Need some serious blood count monitoring here
36
Q

Side effects of clopidogrel & prasugrel:

A

GI & hematologic side effects are rare.

37
Q

True or false: thienopyridines are totally effective for everyone.

A

False! Genetic polymorphisms can make a huge difference.

38
Q

What specific CYP450 enzyme may cause issues with prasugrel & clopidogrel?

A

Patients with the loss-of-function CYP2C192 allele show much less platelet inhibition & a much higher rate of CV events when treated with clopidogrel, compared to those with the wild-type CYP2C191 allele.

39
Q

How many people are at risk for this genetic resistance to clopidogrel?

A 
#25% of whites
#30% of African-Americans
#50% of Asians
40
Q

Can PPI & clopidogrel be administered at the same time?

A 
#PPIs inhibit CYP2C19, producing a small reduction in clopidogrel effectiveness
#The extent to which this increases CV events is controversial
41
Q

Since genetic polymorphisms may influence clinical outcomes with clopidogrel…

A

…pharmacogenetic profiling might be useful to identify our clopidogrel-resistant patients!

42
Q

In what form is dipyridamole used for antiplatelet purposes?

A

Extended-release dipyridamole in combination with low dose aspirin, called Aggrenox

43
Q

Who gets Aggrenox?

A

Patients with TIA, for prevention of CVA

44
Q

How does dipyridamole work?

A 
#Blocks the breakdown of cyclic AMP, which reduces intracellular calcium & inhibits platelet aggregation
#Blocks update of adenosine by platelets & other cells
45
Q

Are Aggrenox or dipyridamole used to prevent CV events in coronary artery disease?

A

No! It has vasodilatory effects, and it should not be used for stroke prevent in patients with CAD.Use clopidogrel instead!

46
Q

Heparin! How does it work?

A

Activating antithrombin & accelerating the rate at which antithrombin inhibits clotting enzymes.

47
Q

How is heparin administered?

A

Either subcutaneous or IV infusion.

DO NOT EAT THE HEPARIN.

48
Q

What alters clearance of heparin?

A

Heparin clearance is dose-dependent! It binds to the endothelium. When the endothelium is saturated, suddenly your half-life is gonna get loooooooonger!

49
Q

How ‘bout that heparin half-life?

A

30-60 minutes with bolus IV doses of 25-100 units/kg, respectively.

50
Q

Does heparin bind ONLY to antithrombin?

A

NOPE! It can bind to other proteins as well, which is what makes it so variable from person to person. Everyone’s got different amounts of heparin-binding proteins in there, so everyone’s gonna have a different response.

51
Q

So since everyone responds differently to heparin administration, what do we do? What are the labs used to monitor it?

A 
We keep close tabs on it! 
#aPTT
#anti-factor Xa level
52
Q

Up to 25% of patients need > 35,000 units per day of heparin to achieve therapeutic aPTT! What do we do for these “heparin-resistant” patients?

A

We monitor using anti-factor Xa levels. They’re usually “resistant” because of elevated serum fibrinogen & factor VIII, which shorten aPTT.

53
Q

IV Heparin dosing

A

BOLUS: 5000 units, or 70 units/kg

54
Q

Which requires more heparin: venous thromboembolism or acute coronary syndromes?

A

The DVT. Probably because DVTs are relatively more HUUUUGE than tiny little coronary thrombi.

55
Q

Limitations of Heparin

A 
#Poor availability at low doses
#Dose-dependent clearance
#Variable anti-coag response
#Reduced activity in vicinity of platelet-rich thrombi
#Limited activity against factor Xa incorporated into the prothrombinase complex, and thrombin bound to fibrin
56
Q

Side effects of heparin

A 
#Bleeding. (I know you're shocked.)
#Thrombocytopenia
57
Q

How do we reverse heparin? How much of that drug do we give?

A

Protamine sulfate!Typically, 1mg of protamine sulfate neutralizes 100 units of heparin.

58
Q

What can be a serious problem with protamine sulfate?

A

Oh, just that people can have anaphylactoid reactions to it.

NO BIG DEAL, RIGHT?

59
Q

What is low-molecular weight heparin?

A

A drug consisting of smaller heparin fragments

60
Q

Advantages of LMWH over heparin

A 
#Better bioavailability
#Dose-independent clearance
#Predictable anti-coagulation response
#Lower risk of heparin-induced thrombocytopenia
#Lower risk of osteoporosis
61
Q

Warfarin was first used as…

A

…rat poison!

Your little old farmer patients will look at you all crazy if you tell them they need to start warfarin. That might warrant some patient education.

62
Q

How does warfarin work?

A

Keeps vitamin K from being reduced, which decreases the effectiveness of clotting factors that use reduced vitamin K in their synthesis: II, VII, IX, and X

63
Q

Why is there a delay in warfarin’s onset of action?

A

It’s delayed while the newly synthesized clotting factors (with reduced activity) gradually replace their fully active counterparts

64
Q

What should we know about warfarin, genetics, & the CYP450 system?

A

Warfarin is metabolized in the liver, SO, patients with variants of CYP2C92 AND CYP2C93 or VKORC1 will need LOWER MAINTENANCE DOSES. These genetic polymorphisms decrease the warfarin requirement!

65
Q

What should we tell patients re: warfarin & diet?

A

Warfarin is easily affected by fluctuations in dietary vitamin K intake!If you’re gonna eat spinach, eat the same amount each day!

66
Q

How do we monitor warfarin?

A

INR

67
Q

Target INR for various purposes

A 
#For most: INR 2-3
#Mechanical heart valve: 2.5-3.5
#Atrial fib: > 1.7
#Bleeding risk increases: > 4.5
68
Q

How can we reverse warfarin if needed?

A

Vitamin K administration

69
Q

Newest oral anticoagulants:

A 
#Dabigatran
#Rivaroxaban
70
Q

What are the newest oral anticoagulants licensed for in the US & Canada?

A

CVA prevention in patients with ATRIAL FIB!

71
Q

What are the fibrinolytics?

A 
#Streptokinase
#Anistreplase
#Urokinase
#tPA  or alteplase (tissue-type plasminogen activator)
#Tenecteplase
#Reteplase
72
Q

What are fibrinolytic drugs for?

A

Used to degrade thrombi

73
Q

How are fibrinolytic drugs administered for treatment of acute MI?

A

Systemically!

(HGC) ACNP804 Exam 2 (7 decks)

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