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Pharmacology - Exam 2 > Antithrombotics > Flashcards

Antithrombotics Flashcards

1
Q

difference between red clot and white clot, and what kind of drugs to treat with

A

red: venous slow flow (fibrin, platelets, RBCs)
white: arterial faster flow (fibrin and platelets)

Treat both with anticoagulants and
but also treat white with antiplatelets

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2
Q

the therapeutic range for antithrombotics is…

because…

A

narrow.

hemostasis : fine line between anticlotting (bleed out) and clotting (thombi/emboli)

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3
Q

true or false: much of antithrombosis is for treatment

A

false. it’s mostly for prophylaxis since it doesn’t break up a clot, it stops them from forming/growing

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4
Q

antiplatelets

A

stop platelets from sticking and aggrigating in the clot

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5
Q

antitcoagulants

A

stop fibrin mesh from forming

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6
Q

when do you see red clots (name 3 reasons they are made)

A

1) Hypercoagulable states (genetics)
2) When blood pools/moves slowly (immobile post surgery, long flights, A fib)
3) With Foreign objects (vascular access device, catheter, surgical implants, central venous line)

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7
Q

2 clinical examples of a red clot

A

DVT–> pulmonary embolism

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8
Q

why/when we see white clots

A

Plaque ruptures, then white clot forms on rupture site

so. ..
1) atherosclerosis:
2) foreign objects (mechanical heart valve, Percutaneous coronary intervention)

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9
Q

clinical examples of white clot patents

A

MI, unstable angina, STEMI, nonSTEMI, CVD, TIA from plaque on carotid artery, Peripheral vascular disease

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10
Q

a xymogen is a ___________ and is _____ by a ____________

A

coagulation factors (enzymes that are inactive) and is ACTIVATED by a protease

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11
Q

key targets for anticoagulation

A

the common pathway. Goal is to diminish activity in Factors Xa &/or IIa

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12
Q

4 steps in common pathway to a clot

A

1) X–>Xa–> protrhombinase complex (XaVa)
2) this activates II–>IIa (protrombin–> thrombin)
3) which activates Fibrinogen –> fibrin
4) —> fibrin clot 3D matrix (+platelets or RBCs depending if venous or arterial)

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13
Q

true or false

The grandaddy, Heparin gets rid of the clot in your grandaddy.

A

False. it’s an anticoagulant… they only prevent them not dissolve them.

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14
Q

Heparin wouldn’t get approved by FDA today because

A

it’s a bunch of molecules that are stuck together… polysacharide with a bunch of acidic sulfides.

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15
Q

Heparin gets into the BBB to prevent ischemia (true or false)

A

False… highly charged, can’t take orally, can’t cross BBB, safe for pregnancy… stays in blood vessels

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16
Q

heparin’s 1st mode of action

A

1) Heparin’s pentasaccharide bind to Antithrombin (AT)

2) Xa binds to AT 1000x faster with heparin, so it deactivates the clotting cascade.

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17
Q

antithrombin is most potent anticlotter and called the _________

A

suicide bait (it fools Xa to bind covalently and deactivates it at a 1:1 ratio)

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18
Q

heparin’s 2nd mode of action

A

long chain that has IIa at one side and AT at other, and they bridge and bump and bind (lessoning 3 dimensionally space to 1 dimension (a line)

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19
Q

how does unfractionated Heparin work differently from the other -parin’s

A

Heparin has whole mess of polysaccharides, including the pentasacc that binds AT, and also the long chains that bind AT at end so it does both Xa and IIa

LMW Heparin does Xa and IIa

Fondaparinux is only the pentasaccharide so it only does Xa (not IIa)

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20
Q

IIa is also called

A

thrombin… so heparin knocks out thrombin with antithrombin catalization

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21
Q

what is enoxaparin

A

a low molecular weight heparin… has shorter chains than unfractionated, but deactivates Xa»>IIa

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22
Q

how are the 3 heparins eliminated

A

unfractionated hep: liver
LMW hep: kidney
Fondaparinux: kidney

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23
Q

how do you know if they have too much heparin in their system, and what to do if so?

A

constantly monitoring for unfractionated heparin. Give Protamine to neutralize excessive bleeding.

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24
Q

what is HIT in regards to anticoagulants

A

1) Heparin-induced thrombocytopenia.
2) Antibody produced after 8+ days on Heparin because …
3) Platelets release + charged granules (like platelet factor 4) which binds to the - heparin creating an antigen, then body sees foreign and attacks.
4) Atg binds to Aby and activates platelet to make white clot–> thrombi in terminal vessels= HIT
(sorry so long)

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25
Q

what is Gla

A

gamma-Carboxyglutamate aka “Gla” attaches coag factors and AntiCoag to platelets and includes extrinsic, intrinsic, and common pathway (Xa, VII, IX, X), and anticoag’s (protein C and S)

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26
Q

what do Gla’s do?

A

chelate Ca++ and enable attachment to platelet membrane,

required to have functional coagulation factor to work

27
Q

what does Warfarin do

A

it blocks Gla formation, can’t bind to Xa

28
Q

how does Warfarin work?

A

It eliminates VKORC (which recycles vit K (with NADH-> NAD) back to its reduced form) so it limits Glutamate –>Gla (which needs active vit K)

29
Q

what’s the problem giving warfarin solo?

A

It takes 8-12 hours to affect INR, and days for full affect. Delayed until existing clotting factors are turned over.
Also can create pro-clotting state because inhibits protein C and S before inhibiting factors

30
Q

contraindications of warfarin

A

1) pregnancy (hemorrhagic, abnormal bone formation),
2) Can lead to procoagulation so Heprin induced thrombocytopenia
3) Vit K from diet, and other drugs

31
Q

Warfarin is closely monitored with INR because

A

CYP2C9 and VKORC genes vary in the elimination of active form (S enantiomer) AND efficacy (VKORC)
Half life is 20-60 (genetic variation)

32
Q

indications for Warfarin

A

prophylaxis for DVT, PE, A Fib, post PCI, MI, prostetic heart valve, antiphospholipid syndrome
(BUT ALWAYS START WITH HEPARIN TOO)

33
Q

What does Rivaroxaban do?

A

It inhibits Xa “Rivaro-Xa-ban”: It’s a DIRECT inhibitor

34
Q

What does dabigatran etexilate do?

A

Inhibits IIa “T in Tran is for 2”: Its also a DIRECT inhibitor (Warfarin and Heparins are Indirect)

35
Q

which drugs are direct inhibitors and which are indirect

A

Warfarin and Heparins are Indirect

RivaroXaban and dabigaTran are direct

36
Q

how is rivaroxaban eliminated and why care?

A

Transported by P-glycoprotein and metabolized by CYP3A4, so drug-drug interactions.

37
Q

black box warning for Direct anticoags

A

spinal procedures contraindicate use because of spinal hematomas–> paralysis

38
Q

interactions for RivaroXaban

A

other anticoags/platelets, P-gp, CYP3A4 inhibitors (ketaconazole) and inducers (rifampin)

39
Q

Other IIa inhibitors (blue drugs)

A

argatroban (parenteral)
hirudo medcinalis (topical)
desirudin (parenteral)
Bivalirudin (parenteral)

40
Q

interactions for dabigatran etexilate

A

inhibiting CYPs: = more absorbtion= less clotting, and inducers= more clotting

41
Q

contraindications for Rivaroxaban

A

bleeding, hypersensitivity

42
Q

contraindications for dabigatran

A 
mechanical heart (stroke, MI), bleeding, hypersensitivity 
(same as Rivaroxaban + mech heart)
43
Q

argatroban is specificly used for _____by_______

A

1) HIT patients

2) blocking catalytic site of soluble and clot-bound thrombin (reversible) so it can’t cleave fibrinogen into fibrin

44
Q

“Hirudens”: desirudin and bivalirudin work by______ and are administered by_____

A

protein based direct thrombin inhibitors, and because protein, they have to be injected

45
Q

only differences between the two “rudins”

A

desirudin: longer protein, longer half life 2-3 hrs, DVT PPx

bivalirudin’s 25min half life, and shorter protein. used in PPx for HIT and used in angioplasty

46
Q

Three antiplatelet drugs, and their action

A

all block platelet aggrigation/ recruitement
Aspirin (IRREVERSIBLE: blocks COX-1)
Clopidogrel: irreversible blocks ADP purine receptor P2Y12
Prasugrel: same as clopidogrel

47
Q

aspirin’s mechanism of action

A

prevents platelet aggrigation by inhibiting COX-1 which causes activation signals to bind them together

48
Q

adverse reactions from aspirin

A

bleeding, dyspepsia, gastritis, ulcers, tinnitis, bronchospasm, REYES syndrome

49
Q

interactions with aspirin

A

influenza live vaccine (reyes)

50
Q

contraindications and special considerations for aspirin

A

NSAID hyper sensitivity, asthma, rhinitis, nasal polyps syndrome:–> angioderma, urticarial, bronchospasm, kids under 19 with fever

special considerations: renal /liver function, oxidative phosphorylation from overdose–>metabolic acidosis, seizure, coma

51
Q

indications for aspirin

A

acute MI chew 162-325 immediately, PCI, mech heart valve, MI/CVA PPx, A fib, carotid stenosis, arterial occlusion (PVD), TIA

52
Q

clopidogrel’s mechanism of action, and what does it do?

A

It blocks ADP receptor from binding so can’t attach to other platelets, or activate other platelets to release their granulocytes

53
Q

describe the platelet activation process in regards to IIa/IIIb (2a3b)

A

Platelets activated via IIb IIIa, (dimeric molecule which binds to fibrin)
When platelet is activated, it degranulates
In its granules, are ThromboxinA2 which combines to receptor on platelet and causes activation signals, and there are granules with ADP, which binds to different receptor, which causes IIbIIIa on other platelets, which attaches to the other fibrinogen which is attached to another platelet, so when all activated, they stick together through fibrinogen bridge.

54
Q

how long does taking aspirin affect platelets

A

it binds irreversibly, so as long as they last… 7 days for new platelets to be regenerated.

55
Q

how does CYPs affect Clopidogrel?

A

either extensive metabolizers, or don’t metabolize it fast enough… it’s a prodrug so needs metabolism to become active. monitor this.

56
Q

when might you use clopidogrel?

A

after placing a heart stent to prevent MI, or clot in the coronary artery., keep the stent open

57
Q

What do clopidogrel and prasugrel have in common?

A

both irreversible blocking of P2Y for platelet activation (GPIIbIIIa activation),
both prodrugs activated by CYPs, both have low frequency of TTP, and premature discontinuation may be risky, don’t want to give if history of stroke

58
Q

what is different between clopidogrel and prasugrel?

A

Clopidogrel: CYP2C19, slower activation, poor metabolizers with CYP2C19 have risk of MI/death

Prasugrel: CYP3A/ CYP2B6 (more predictable clinical effects, faster activation, more bleeding than clopidogrel, contraindicated in history of TIA

59
Q

mechanism of activity of thrombolytics, and the risk

A

overcome the inhibitors of plasmin (stems from plasminogen, which is activated by tPA).

The native inhibitors are in solution, and we must give enough tPA to get rid of clot disolution inhibition. the risk is getting rid of all fibrinogen in the plasma, not just in the clot, so can get bleeding.

60
Q

other problem with tPA

A

short half life, and $6,400 per dose

61
Q

indication for alteplase

A

can’t open coronary artery within 14 hrs. with surgery, under 4 hours with ischemic stroke. (cross linking happens so treat earlier)

62
Q

contraindications for thrombolytic drugs

A

have t be pretty desparate to use these… risk is hemorrhagic stroke, lysis of protective thrombi, and bleeding, and stroke.

63
Q

which drugs are used most in arterials

A

antiplatelets because they are only white clots as a general rule: aspirin, clopidogrel, prasugrel

64
Q

which drugs are used most in veins

A

Red/white clots anticoagulants: heparin, enoxaparin, fondaparinux, warfarin, rivaroxaban, apixaban, dabigatran

Pharmacology - Exam 2 (14 decks)

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