Heme/lymph - Dr. Panavelil: Coagulation

Front 1

Types of drugs discussed

Back 1

1. anticoagulants
2. platelet inhibitors
3. thrombolytic agents

Front 2

important anticoagulants

Back 2

Heparin
Warfarin
LMWH
Antithrombin III
HIT tx drugs

Front 3

important platelet inhibitors

Back 3

ASA
Dipyridamole
Ticlopidine, Abciximab
Eptifibatide
Tirofiban
Clopidogrel
Prasugrel
Cilostazol
Dabigatran

Front 4

Thrombolytic agents

Back 4

Streptokinase
Tenecteplase
tPA

Front 5

what is the general mechanism of anticoagulants?

platelet inhibitors?

thrombolytic agents?

Back 5

affect coagulation cascade

direct effect platelets

break up clots

Front 6

Thrombin -->

Plasmin -->

Back 6

MAKES/Forms clots (Fribinogen -> Fibrin -- Fibrin Forms)

BREAKS clots

Front 7

PT

Back 7

Extrinsic (anagram: PET -> PTE -> PT = extrinsic)
+ common pathway

PT monitors Warfarin

Front 8

PTT

Back 8

PTTI (ptti -> "pity" -> PTTI -> PTT = intrinsic)
+ common pathway

PTT monitors Heparin

Front 9

What is antithrombin III so important in anticoagulation?***

Back 9

necessary to neutralize coagulation factors to inactive form***

Front 10

what is the function of thrombin?

Back 10

serine protease

catalyses converion of fibrinogen --> fibrin (MAKES/FORMS clots)

Front 11

what is the function of plasmin?

Back 11

BREAKS clots by interfering w/ clot propagation & dissolves fibrin network

Front 12

prostacyclin, thrombin & TXA effects of platelet activation/inactivation

Back 12

↑ prostacyclin, ↓ thrombin & TXA = INactivation of platelets

↓ prostacyclin, ↑ thrombin & TXA = activation of platelets

Front 13

PT identifies:

Back 13

VII, I, II, V, X

Front 14

PTT identities:

Back 14

XII, XI, IX, VIII, I, II, V, X

Front 15

TT identifies:

Back 15

fibrinogen, inhibitors of thrombin-fibrinogen interaction

Front 16

Heparin

Back 16

- GAG

- large MW, (-) charge -> poorly crosses membrane

- administered IV

-**doesn't cross placenta - safe in pregnancy

Front 17

what does antithrombin III do?

Back 17

complexes w/ thrombin and inactivates it

also inactivates: IXa, Xa, XIa, XIIa

Front 18

MOA of heparin?

Back 18

acts indirectly through effect on antithrombin III

- activates neutralizing activity of antithrombin III by x1000

Front 19

sufficient heparin in terms of PTT?

excessive heparin?

Back 19

- prolong PTT to x2 (50->80)

- PTT > x2.5 = risk of spont bleeding

Front 20

reversal of heparin

Back 20

- slow infusion of IV protamine sulfate
- from fish sperm
- complexes w/ heparin & reverses anticoagulant effect

Front 21

heparin toxicity

Back 21

bleeding
thrombocytopenia
frequent abnL in LFTs

Front 22

Lepirudin

Back 22

- recombinant form of natural Hirudin
- found in european medical leeches
- 1st drug approved in US for anticoagulation in pts w/ HIT

Front 23

Lepirudin MOA

Back 23

- thrombin antagonist
- blocks thrombogenic activity of thrombin

Front 24

Argatroban

Back 24

- IV thrombin inhibitor
- indicated for HIT
- eliminated by liver

Front 25

Lepirudin vs. Argatroban

Back 25

Argatroban is eliminated by liver and can be used in pts with ESRD

Front 26

Bivalirudin

Back 26

- analog of hirudin
- tx of unstable angina, acute MI
- used in pts undergoing angioplasty w/ hx of HIT

Front 27

Ancrod

Back 27

- derived from venom of Malayan pit vipers

- alternate to herparin in pts w/ HIT

Front 28

Danaparoid

Back 28

mixture of low-MW wulfated GAGs

Front 29

LMWH

Back 29

- low MW heparin fractions
- prevention of DVT

Front 30

MOA of LMWH

Back 30

- inhibit activated factor X
- much LESS EFFECT on antithrombin III

**- produce a more predictable anitcoagulant response than unfractionated heparin

Front 31

Antithrombin III

Back 31

- heparin cofactor I
- necessary for heparin to exert anticoagulant activity
- inhibits thrombin & factors: IXa, Xa, XIa, XIIa & plasmin

Front 32

specific use of AT III

Back 32

in pts w/ congenital AT III deficiency & sometimes acquired AT III deficiency (ex. DIC)

Front 33

Pentosan

Back 33

used in US orally for relief of pain & discomfort w/ interstitial cystitis

Front 34

Dabigatran

Back 34

- oral
- direct thrombin inhibitor (factor IIa)
** - may help reduce frequent monitoring & substituting heparins w/ an oral drug

Front 35

Warfarin

Back 35

- oral anti-coagulant

- inhibits hepatic synthesis of vitK dependent clotting factors (II, VII, IX, X)

- need few days of therapy (**not rapid)

Front 36

MOA of Warfarin

Back 36

- inhibits epoxide reductase --> no activated vitK

- vitK --epoxide reductase--> act vitK --cofactor--> precursors to mature (II, VII, IX, X, C, S)

Front 37

which cofactor is most affected by Warfarin?

Why?

Back 37

VII b/c has the shortest 1/2 life

Front 38

PT levels at what?

Back 38

- PT prolonged x1.5 - 2.5 nL = adequate

- PT prolonged to >2.5x nL = spont bleed

Front 39

Reversal of warfarin

Back 39

1. vitK administration (slow)

2. transfusion of fresh frozen plasma (FFP) - immediate [risk of viral infxn]

Front 40

drug intrxns w/ Warfarin

what are the mechanisms?

Back 40

nSAIDs, barbiturates, anti-TB meds, anabolic steroids

1. alter hepatic metabolic rate
2. displace warfarin from albumin

Front 41

Warfarin toxicity

Back 41

bleeding
birth defects
abortion in pregos
(nasal hypoplasia, fetal hemorrhage, CNS defects)

Front 42

ASA

Back 42

- irreversibly inhibits COX (which is necessary for PG & TXA2)

- rapid effect

- suppression of TXA2 synthesis resulting in platelet suppression

Front 43

ASA adverse effects

Back 43

hemorrhagic shock
Cinchonism (tinnitus, blurred vision, dizziness, low BP)

Front 44

Ticlopidine

Back 44

- blocks platelet aggregation through inhibiting ADP pathway
- this is involved in binding of platelets to firbrinogen & platelets to platelets

Front 45

Ticlopidine
use
sfx

Back 45

use - prevention of TIAs
sfx - neutopenia

Front 46

Dipyridamole

Back 46

-coronary vasodilator

- inhibits cyclic nuclotide phosphodiesterase

- keeps IC cAMP levels high
- high cAMP inhibits TXA2

Front 47

dipyridamole:
combo?
use?

Back 47

w/ Warfarin to inhibit embolization from prosthetic heart valves

Front 48

Abciximab

Back 48

mouse/human chimeric monoclonal against platelet IIb/IIIa receptors

**inhibits fibrin binding to receptors

Front 49

Clopidogrel

Back 49

blocks ADP binding to platelets

- inhibits platelet aggregation

- 2nd MC used anti-coag --> has GI sfx

Front 50

Clopidogrel
use?
sfx?

Back 50

- acute coronary syndrome, storkes, MI

- bleeding

- inhibits CYP phase I rxns & may inc [drug] of other agents

Front 51

Prasugrel

Back 51

- newer platelet aggregation inhibitor
- indicated for reduction of thrombotic CV events

Front 52

Clopidogrel vs. Prasugrel
- effects
- sfx

Back 52

Prasugrel:
- greater red. in CV death, non-fatal MI or non-fatal stroke:
due to --> reduction in MI
BUT
- bleeding more frequently seen

Front 53

Cilostazol

Back 53

platelet aggregation inhibitor

Front 54

Streptokinase

Back 54

- no enzymatic activity
- indirectly activates plasminogen by forming a 1:1 complex
- inc. protease activity that converts plasminogen to plasmin

- used in acute PE, MI, stroke

Front 55

Anistreplase

Back 55

- streptokinase + recominb human plasminogen

- improves kinetics

Front 56

Tenecteplase

Back 56

- thrombolytic agent
- rapid IV bolus for tx of acute MI

Front 57

Tenecteplase MOA

Back 57

- modified form of human tissue plasminogen activator (tPA) which BINDS to fibrin & converts plasminogen to plasmin