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Cardio Exam 2 > Lect 7- CAD & Thromboembolic Stroke Pt 2 > Flashcards

Lect 7- CAD & Thromboembolic Stroke Pt 2 Flashcards

1
Q

what are some factors that stimulate plt activation and aggregation?

A

thrombin, ADP, collagen, thromboxane A2

these can all therefore serve as drug targets to inhibit plt activation and aggregation

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2
Q

ADP in plt aggregation

A

ADP= potent initiator of plt aggregation
effects mediated via purinergic receptors P2Y12 and P2Y1
BOTH P2Y12 and P2Y1 receptors must be stimulated to result in plt activation (so inhibiting either is sufficient to block plt activation)

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3
Q

ADP receptor blockers

A

AKA “thienopyridines”
prasugrel (Effient); clopidogrel (Plavix)
PRODRUGS= activated by P450’s

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4
Q

MOA of ADP receptor blockers

A

metabolites bind COVALENTLY to P2Y12 resulting in permanent blockade (IRREVERSIBLE INHIBITION)
Relatively short t1/2 but have long-lasting effect

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5
Q

therapeutic use of ADP receptor blockers

A

initiated during ACS, particularly w/ angioplasty and stenting
continued for secondary prevention of both MI and atheroembolic stroke

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6
Q

main adverse effects of ADP receptor blockers

A

**increased risk of bleeding

thrombotic thrombocytopenic purpura (TTP) (rare)

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7
Q

which CYP activates clopidogrel?

A

CYP2C19

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8
Q

which CYP activates prasugrel?

A

CYP3A4

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9
Q

Ticagrelor (Brilinta) MOA

A

REVERSIBLE ADP receptor antagonist (non-thienopyridiine) so a little less potent than clopidogrel and prasugrel
reversible blockade of P2Y12 receptor → recovery of plt function after stopping the drug is more rapid → less risk of major bleeding!
**NOT A PRODRUG

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10
Q

which CYP metabolizes Ticagrelor?

A

Metablized by CYP3A4 to inactivate it

inhibits CYP3A4 and P-GP to some extent- drug interactions!

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11
Q

what is a disadvantage of Ticagrelor?

A

taken BID

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12
Q

adverse effects of Ticagrelor

A

bleeding (but less risk of bleeding than clopidogrel or prasugrel

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13
Q

Thrombin effects on plt activation and aggregation

A

Causes plt activation and aggregation through PAR1 and PAR4 receptors
MOST POTENT endogenous activator of plts (thrombin is a protease)
PAR1= high affinity receptor (responds more sensitively/ rapidly to thrombin)

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14
Q

vorapaxar (Zontivity) MOA

A

thrombin receptor (PAR1) antagonist
Binds to the receptor and blocks actions of thrombin
PAR1= protease-activated receptor 1
• Held the ligand as part of their sequence on the extracellular domain
○ Thrombin cleaves part of the receptor so that part left over can fold down and activate the receptor
§ Why they are called protease activated receptors
○ With vorapaxar, the receptor can still be cleaved by proteases but it cannot be activated since drug is blocking the fold-down part

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15
Q

which CYP metabolizes vorapaxar?

A

CYP3A4

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16
Q

special facts about vorapaxar

A

Long half life (3-4 days) so takes 21 days of QD dosing to reach Css

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17
Q

main indications for vorapaxar

A

MI and PAD

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18
Q

C/I for vorapaxar

A

history of stroke, TIA, intracranial hemorrhage, active bleeding

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19
Q

how glycoprotein works in plt aggregation

A

GP iib/iiia is a plt surface protein
receptor for fibrinogen and von Willebrand factor
upon activation, GP iib/iiia ANCHORS PLTS to each other via fibrinogen and to the surface of the injured vasculature via vW factor (vW factor important in forming mesh so plts can adhere)

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20
Q

what activates the GP IIb/IIIa?

A

thrombin, TX-A2, ADP, collagen, norepinephrine, etc
All have their own receptors but all have the ultimate result of activation of GP IIb/IIIa then after that you have aggregation of plts
This blockade of GP is a very powerful mechanism b/c then it doesn’t matter which factor you have around it will still inhibit the last step

21
Q

Glycoprotein IIb/IIIa inhibitors

A

abciximab (Reopro)= monoclonal antibody

eptifibatide (Integrelin; tirofiban (Aggrastat)= require ACTIVATED plts/ GP IIb/IIIa to bind and inhibit

22
Q

Glycoprotein IIb/IIIa inhibitors MOA

A

inhibit interaction of GP IIb/IIIa with fibrinogen and vW factor to impair plt aggregation!

23
Q

abciximab (Reopro)

A

monoclonal antibody

blocks the receptor from activation

24
Q

therapeutic use of abciximab (Reopro)

A
  1. in conjugation w/ percutaneous angioplasty for coronary thromboses
  2. in combo w/ aspirin & heparin to prevent restenosis and recurrent MI
25
Q

main adverse effects of GP IIb/IIIa inhibitors

A

MAJOR= bleeding (can be very severe so you have to be very careful with these)
thrombocytopenia

26
Q

therapeutic use of eptifibatide and tirofiban

A
  1. unstable angina, ACS, MI

2. angioplastic coronary interventions

27
Q

C/I’s for GP IIb/IIIa inhibitors

A

LOOK AT SLIDE

28
Q

fibrinolytic (thrombolytic) agents

A

Deals with a thrombus that are already in place
alteplase (Activase)= tPA prod by recombinant DNA technology
reteplase (Retavase) and tenecteplase (TNKase)

29
Q

therapeutic use of fibrinolytic agents

A

acute MI & thromboembolic stroke

30
Q

main adverse effect of fibrinolytic agents

A

HEMORRHAGE
lysis of fibrin at “physiological thrombi” at sites of vascular injury results in systemic lytic state
If we cut ourselves, we can bleed to death

31
Q

C/I for fibrinolytic agents

A

same as the ones for GP IIb/IIIa inhibitors

32
Q

fibrinolytic agents MOA

A

tPA= tissue plasminogen activator; converts plasminogen to plasmin which then enhances degradation of fibrin
Drugs are recombinant tPA

33
Q

pure antianginal agents

A

ranolazine (Ranexa)
used for treatment of chronic angina
usually in combo with amlodipine, beta-blockers, or nitrates

34
Q

MOA of Ranexa

A

not well understood
effects are NOT b/c of reduction of HR or myocardial workload
speculated mechanisms: inhibition of FA oxidation or inhibition of late Na+ currents

35
Q

which CYP metabolizes ranolazine?

A

CYP3A4

is also a substrate for P-GP inhibitors

36
Q

main adverse effects of ranolazine

A

constipation, headache, dizziness, nausea

prolongation of QT interval if overdosed or combined with drugs affecting its metabolism or elimination

37
Q

stroke definition

A

disease affecting blood vessels that supply blood to the brain

38
Q

2 main types of stroke

A
  1. hemorrhagic= damage of a vessel & bleeding (higher death rates)
  2. ischemic (87% of all cases)= blockage of a blood vessel by clot of some mass
39
Q

“wandering clot” or embolus causing a stroke

A

formed away from the brain and blocks blood flow to the brain
usually comes from the heart in the result of atrial fibrillation

40
Q

therapeutic goals of ischemic and thromboembolic stroke

A
  • reduce ongoing neurologic injury
  • decrease mortality and long-term disability
  • prevent complications secondary to immobility & dysfunction
  • prevent stroke recurrence
41
Q

pharmacological agents used in acute stroke

A
  1. fibrinolytic agents (tPA analogs)= help to restore perfusion in affected areas (CAUTION: some pts may be ineligible; see C/Is)
  2. antiplatelet agents (aspirin)= reduces aggregative activity of platelets (CAUTION: increase bleeding risk w/ fibrinolytic agents
42
Q

pharmacological agents used in secondary prevention of ischemic stroke

A
  1. antiplatelet agents= primarily used for atheroembolic stroke where plts are a major component of the thrombus
  2. anticoagulants= primarily used for cardio/thromboembolic stroke where clotting factors are major component of thrombus
43
Q

when are antiplatlet agents used as secondary prevention of ischemic stroke?

A

arterial plaque rupture

44
Q

when are anticoagulants used as secondary prevention of ischemic stroke?

A

stasis of blood as a result of arrhythmia or valvular disease

45
Q

blood pressure lowering agents used in ischemic stroke

A

Have neuroprotective effects on their own too

  • ACE-I & diuretics (thiazides)
  • ARBs
46
Q

ACE-I and thiazides in ischemic stroke

A

beneficial INDEPENDENT of accompanying HTN
reduce risk of stroke
NOT used in the 1st 7 days of the acute stroke period (to avoid less cerebral blood flow from decrease in BP)

47
Q

ARBs in ischemic stroke

A

alternative to ACE-I if intolerant to ACE-I

ARBs that cross BBB may have more beneficial effects

48
Q

statins in ischemic stroke

A

reduce risk of stroke by 30% in pts w/ CAD and high plasma lipids
use should be considered in ALL ischemic stroke pts
effects are due to both lipid lowering effects and pleiotropic effects

Cardio Exam 2 (7 decks)

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