Hemeostatis Affecting Drugs

Front 1

Antiplatelet agents?

Back 1

Aspirin
Thienopyridine Agents
Dipyridamole
Glycoprotein IIb/IIIa Inhbitors

Front 2

Aspirin MoA?

Back 2

Irreversible inhibition of platelet cyclooxygenase-1 -> Blocking of the formation of TxA2 from arachidonic acid -> decreased platelet aggregation

Hint 2

Astra is a Cock Blocker, Forming from Archaic Autistic Texans

Front 3

Lifespan of platelets?

Back 3

7 days

Front 4

PKs of Aspirin

Back 4

Rapid absorption in stomach and upper intestine; platelet inhibition after 1 hr of ingestion which takes effect for lifespan of platelet

Front 5

Main thienopyridine?

Back 5

clopidogrel

Hint 5

Theo Clops along with the Dog

Front 6

Clopidogrel MoA?

Back 6

irreversible inhibition of ADP pathway receptor antagonist to inhibit platelet aggregation

Hint 6

Chloe Angrily Decides Peter Must Be Stopped

Front 7

Clopidogrel has no sig effect on the synthesis of what two products?

Back 7

TxA2 & prostacyclin

Hint 7

Texas Protons

Front 8

Dipyridamole MoA?

Back 8

Vasodilatior that inhibits platelet function by inhibiting adenosine uptake and cGMP phosphodiesterase activity which is reversible

Hint 8

The Pyramids Were Slow TO Build for Queen Esther

Front 9

Dipyridamole bioavail: low or high?

Back 9

low

Front 10

Dipyridamole clinical use:

Back 10

Used with aspirin to prevent cerebrovascular ischemia (Aggrenox)

Ltd to no effect mono

Front 11

AEs of dipyridamole?

Back 11

Headache and bleeding not a/w dypyridamole alone

Front 12

Primary Glycoprotein IIb/IIIa inhibitor?

Back 12

Abciximab

Hint 12

I Glide My Finger over the Axim

Front 13

Abciximab (Glycoprotein IIb/IIIa inhibitor) MoA?

Back 13

inhibits formation of platelet thrombi by inhibiting activated receptors from binding with fibrinogen and forming bridges between activated platelets

Hint 13

Andy Stops Bitches from Getting over Fiborous Bridges

Front 14

AEs of Abciximab (Glycoprotein IIb/IIIa inhibitors)?

Back 14

thrombocytopenia (low platelet count)

bleeding

hypersensity rxn with 2nd dose

Front 15

Abciximab is what kind of molecule?

Back 15

Antibody which destroys platelets via antibody action

Front 16

Anticoag agts?

Back 16

Unfractioned heparin
Low molecular weight heparin
Direct thrombin inhibitors
Warfarin

Front 17

suffix for all LMWHs?

Back 17

-parin or -parinux

Front 18

Coag cascade purpose?

Back 18

formation of clots to stop bleeding

Front 19

Unfractioned Heparin MoA?

Back 19

Binds to antithrombin III (ATIII) -> enhanced activity

ATIII binds to factors

Front 20

What clotting factors does ATIII bind to and inhibit?

Back 20

IIa (PT), IXa, Xa, XIa, & XIIa

Front 21

Which pathway does ATIII inhibit?

Back 21

Intrinsic

Front 22

What does UH not affect?

Back 22

formed thrombi which were present prior to UH therapy which are cleared by physiologic thrombolytic mechanisms and it has no fibrinolytic activity

Hint 22

Ursula Fibs and Lies

Front 23

What kind of mix is UH and what is the compound?

Back 23

It's heterogenous mix of complex mucopolysaccharides

Hint 23

Ursula is snotty

Front 24

What portion of heparin molecules are pharmacologically active?

Back 24

Approx 1/3rd

Front 25

What does UH bind together, what is the complex called, and what happens after they bind?

Back 25

It binds ATIII with clotting enzyme; forms a ternary complex formation; it then dissociates and starts again

Front 26

What is the change UH induces in the ternary complex called?

Back 26

Conformational change

Front 27

What are direct thrombin inhibitors not?

Back 27

clot busters

Front 28

What are the 2 routes for UH?

Back 28

SQ or IV

Front 29

Half-life of UH?

Back 29

1-2 hrs in healthy adults

Front 30

Metabolism of UH?

Back 30

hepatic heparinases (still slightly renal)

Front 31

What happens to UH 1/2 life in renally impaired pts?

Back 31

It's slightly prolonged; not diazyble

Front 32

How is UH given?

Back 32

First bolus, then maintainence dosing

Front 33

What is UH dosage based on?

Back 33

weight

Front 34

What is monitored after UH admin?

Back 34

activated partial thromboplastin time (aPTT)

Front 35

What is aPTT sensitive to?

Back 35

Inhibitory effects of heparin on thrombin, factor Xa & XIa

Front 36

What do you maintain aPTT after bolus?

Back 36

1.5x-2.5x reference

Front 37

AEs of UH?

Back 37

Bleeding (increases w/ dose and duration)

Low platelet count

Front 38

Cx of UH?

Back 38

Aspirin

Front 39

How does Low Molecular Weight Heparin (LMWH) differ from UH?

Back 39

It's homogenous, has superior PK profile, doesn't need lab monitoring, and has decreased anti IIa activity relative to anti-Xa activity (more selective for Xa)

Front 40

What is the mean mol weight of LMWH?

Back 40

4000-5000 daltons

Front 41

How does the ATIII binding action differ in UH versus LMWH?

Back 41

LMWH ATIII binds much less to thrombin relative to factor Xa

Front 42

Why are LMWH agts not interchangable?

Back 42

Due to different PK and different ratios of Anti-Xa:IIa action.

Front 43

What is the preferred LMWH agt? what is its Anti-Xa:IIa activity?

Back 43

enoxaparin; 3.8:1

Front 44

General PKs of LMWH?

Back 44

SQ admin almost 100 percent bioavail

Peak effects occur 3-5 hours after admin

Renal dose adjustment required

Front 45

AEs of LMWH?

Back 45

Bleeding
Low platelet count

Injection site rxn(thrombocytophlebitis)

Front 46

What reverses heparin action?

Back 46

Protamine

Front 47

How does Protamine reverse heparin action?

Back 47

Forms a stable, inactive complex by ionically binding w/ heparin

Front 48

What 2 factors are involved in the efficacy of protamine reversal of heparin?

Back 48

Dosage (should be 1 mg protamine:~100 units of heparin)

Less effective with LMWH

Front 49

PKs of protamine?

Back 49

Onset within 5 minutes; duration is 2 hours

Front 50

AEs of protamine?

Back 50

anaphylaxis

Heparin rebound (antithrombin activity of heparin returns even with effective dose)

Front 51

Direct thrombin inhibitor agts and MoA?

Back 51

Lepirudin, bivalirudin, & agratroban; block either the active site or both active site and exocite I

Front 52

How do DTIs bind to thrombin?

Back 52

inhibit free and clot-bound thrombin w/o requiring endogenous cofactors

Front 53

Half life of DTIs?

Back 53

25-60 mins (short)

Front 54

-rudins PKs?

Back 54

majority excreted renally

Front 55

-rudins dosage considerations?

Back 55

insufficient renal function

Front 56

Agratroban PKs and doseage considerations?

Back 56

Hepat metab; hepatic insuffiency

Front 57

Unique AE of lepirudin?

Back 57

antibody formation

Front 58

Drawback of DTIs?

Back 58

no reversal agt

Front 59

Warfarin MoA?

Back 59

inhibits vitamin K dependent clotting factor synthesis

Front 60

What are the vitamin K dependent clotting factors and regulatory proteins?

Back 60

Factors II, VII, IX, & X

protein C & S

Front 61

What doesn't warfarin do?

Back 61

dissolve the current clot

Front 62

Which pathways does warfarin operate on?

Back 62

Extrinsic (factors VII& X) and common (prothrombin (II))

Front 63

Warfarin PKs?

Back 63

100 % absorption

Hepatic metabolism through 3A4 & 2C9

Long 1/2 life
99 % protein binding

Front 64

Warfarin monitoring?

Back 64

Internation Normalized Ratio (INR) which is pts PTT over normal PTT raised to the power of the ISI value (1-1.4)

Front 65

When initiating warfarin, what should it over lap with and for how long?

Back 65

It should overlap w/ heparin for about 4 days until INR is therapeutic for 2 days

Front 66

Warfarin dosing?

Back 66

Highly individualized (PKs [particularly 2C9 & 3A4 inx] and PDs)

Front 67

What population should never be given warfarin and why?

Back 67

Pregnant women. It's preg cat X.

Front 68

D-D interactions of warfarin that decrease coag?

Back 68

Additive anticoag effect w/ APAP

EtOH acute ingestion -> increased INR -> inhibition (increased bleed)

Antimicrobials (fluoroquinolones) -> greater anticoag

Front 69

D-D interactions of warfarin that increase coag?

Back 69

EtOH chronic ingestion -> increased INR -> induction (decreased bleed)

Carbamazapine is 3A4 inducer -> need much higher warfarin

Front 70

Pharmacodynamic interactions with warfarin?

Back 70

anti-thyriod meds -> reduced thryoid function -> reduced warfarin effect

Front 71

Reversal of warfarin is through what?

Back 71

Vitamin K

Front 72

MoA of Vit K reversal of warfarin?

Back 72

factor II, VII, IX, & X dependent upon Vitamin K

Front 73

Vitamin K route?

Back 73

All 4.

Front 74

Best routes of Vitamin K?

Back 74

PO (absorbed in duodenum)
SQ (readily absorbed)
IV (fastest onset)

Front 75

Vitamin K onset of action?

Back 75

PO: 6-12 h
Parenteral: 1-2 h

Front 76

Vitamin K AE?

Back 76

Hypersensitivity w/ IV & IM route (rash, sometimes lethal), especially if admin is rapid