Coagulation Disorder Drugs

Question 1

ASPIRIN

Answer 1

irreversible COX inhibitor (acetylation); reduces TxA2
preferentially targets platelets: endothelial cells can produce new prostacyclin; platelet has no nucleus to produce more TXA2
AE: GI, allergy (bronchospasm)
Use: secondary prevention of CV events
overdose: hepatic and renal toxicity

Question 2

ibuprofen

Answer 2

COX inhibitor

Question 3

CLOPIDOGREL

Answer 3

oral: prodrug
irreversible ADP receptor (P2Y12) inhibitor
poor 2C19 metabolizers have reduced response
use: post-MI, stroke, PAD (peripheral artery disease), PCI (percutaneous coronary intervention)
*ischemic heart disease

Question 4

TICLOPIDINE

Answer 4

oral: metabolite more potent
irreversible ADP receptor (P2Y12) inhibitor
BB: agranulocytosis, neutropenia, thrombocytopenia, TTP, anemia
use: secondline due to AE

Question 5

prasugrel

Answer 5

oral: prodrug
irreversible ADP receptor (P2Y12) inhibitor
use: acute MI, arterial thromboembolism, prophylaxis, PCI, unstable angina

Question 6

dipyridamole

Answer 6

Oral/IV
phosphodiesterase (PDE) inhibitors
1. prostacyclin released-> increase adenylate cyclase-> cAMP increases: AA acid not released: decrease TXA2
2. adenosine accumulates (vasodilation)
3. decreases cAMP breakdown
use: prophylaxis of thrombosis for prosthetic heart valve (with warfarin)
CI: hypotension, asthma
hepatic glucoronidation; fecal elimination

Question 7

ABCIXIMAB

Answer 7

IV
non-competitive, irreversible GPIIb/IIIa inhibitor
persists for 2 weeks after stopping administration
AE: bleeding, thrombocytopenia, anaphylaxis
Use: unstable angina, percutaneous transcutaneous coronary angioplasty

Question 8

EFTIFIBATIDE

Answer 8

IV
reversible GPIIb/IIIa inhibitor
only persists 4 hrs
AE: bleeding, thrombocytopenia (less), anaphylaxis
Use: unstable angina, percutaneous transcutaneous coronary angioplasty

Question 9

tirofiban

Answer 9

IV
reversible GPIIb/IIIa inhibitor
only persists 4 hrs
AE: bleeding, thrombocytopenia, anaphylaxis
Use: unstable angina, percutaneous transcutaneous coronary angioplasty

Question 10

vorapaxar

Answer 10

PAR-1 inhibitor: blocks thrombin induced platelet aggregation
slower onset than for GPIIb/IIIa inhibitors
T1/2: 8 days
persists: 4 weeks
CYP3A4 metabolism
AE: bleeding

Question 11

HEPARIN

Answer 11

IV/SC: rapid onset
ONLY for inpatient use
indirect thrombin inhibitor: accelerates AT3 binding coagulation factors (2, 10)
monitor: aPTT (want 1.5-2.5x normal)
SE: bleeding, antigenic (from animals and easy to get) anaphylaxis, thrombocytopenia
acts in blood, rapid onset, use is acute
need to monitor
short T1/2
80 u/kg bolus followed by 18 u/kg/hr

Question 12

PROTAMINE SULFATE

Answer 12

IV
heparin antidote (v. basic): binds up heparin
incompletely neutralizes LMWH; does not reverse fondaparinux
SE: allergy to fish/DMT2: protamine rxn, too much is anticoagulative

Question 13

DABIGATRAN

Answer 13

oral
direct thrombin inhibitor
Tx/prophylaxis: DVT, PE; stroke prophylaxis and HIT
Tox: bleeding (no antidote)

Question 14

bivalirudin

Answer 14

IV
direct thrombin inhibitor
Tx/prophylaxis: DVT, PE; stroke prophylaxis and HIT
Tox: bleeding (no antidote)

Question 15

lepirudin

Answer 15

IV
direct thrombin inhibitorTx/prophylaxis: DVT, PE; stroke prophylaxis and HIT
Tox: bleeding (no antidote)

Question 16

ENOXAPARIN

Answer 16

indirect factor Xa inhibitor (thru ATIII): low MW heparin
compared to heparin: lower incidence of drug induced thrombocytopenia; bleeding may not change
injection
SE: bleeding, anaphylaxis
less impact on aPTT than heparin

Question 17

APIXABAN

Answer 17

oral
direct factor Xa inhibitor: leads to thrombin inhibition
Use: prophylaxis: DVT, PE, stroke
Tox: bleed without antidote
CYP3A4 metabolism

Question 18

RIVAROXABAN

Answer 18

oral
direct factor Xa inhibitor leads to thrombin inhibition
Use: prophylaxis: DVT, PE, stroke
Tox: bleed without antidote
CYP3A4 metabolism

Question 19

fondaparinux

Answer 19

IV/SC
LMWH: indirect factor Xa inhibitor: binds ATIII-> inhibits factor Xa
Use: prophylaxis: DVT, PE
Tox: bleeding without antidote

Question 20

WARFARIN

Answer 20

oral
clotting factor synthesis inhibitors: blocks vitamin K epoxide reductase (VKORC1): 2, 7, 9, 10, C, S
CYP2C9 important for metabolism (other CYPs too)
SE: hypercoaguability initially due to inhibition of certain factors quicker than others (skin necrosis: protein C and S have shorter T1/2); cholesterol embolism
monitor: PT, INR
teratogen
slow onset, acts on liver, for chronic use
issues: Vit. K consumption is constant, acetaminophen can increase INR, liver disease, skin necrosis: protein C and S have shorter T1/2 than heparin
desired INR: Tx and prophylaxis DVT 2.5; protection of mechanical heart valve 3

Question 21

PROTHROMBIN COMPLEX concentrate

Answer 21

warfarin antidote
factors 2, 7, 9, 10 and protein C and S
contraindication: angina, MI, PVD, stroke, thromboembolism

Question 22

phytonadione

Answer 22

vitamin K1

warfarin antidote

Question 23

ALTEPLASE

Answer 23

IV
(t-PA): thrombolytic
fibrin specific plasminogen activator
SE: anaphylaxis

Question 24

reteplase

Answer 24

IV
(rPA): thrombolytic
fibrin specific plasminogen activator
longer T1/2 than alteplase
SE: anaphylaxis

Question 25

tenectoplase

Answer 25

``` IV (TNK-tPA): thrombolytic fibrin specific plasminogen activator longer T1/2 than alteplase SE: anaphylaxis ```

Question 26

streptokinase

Answer 26

IV thrombolytic non-specific plasminogen activator (no affinity for fibrin bound plasminogen) SE: anaphylaxis

Question 27

aminocaproic acid

Answer 27

fibrinolysis inhibitor: blocks plasminogen to plasmin Use: hemorrhage, hyperfibronlysis CI: DIC, clotting without heparin monitor: hypotension, bradycardia

Question 28

cimetidine

Answer 28

CYP inhibitor: can inhibit hepatic metabolism metabolism

Question 29

PDE

Answer 29

catalyzes hydrolysis of cAMP and cGMP

Question 30

ginkgo biloba

Answer 30

antiplatelet properties

Question 31

garlic

Answer 31

antiplatelet properties

Question 32

ginger

Answer 32

inhibits thromboxane synthetase

Question 33

protamine reaction

Answer 33

shaking, flushing, chills, back/chest/flank pain, vasomotor collapse Tx: morphine, meperidine, diphenhydramine, saline, support low BP

Question 34

vitamin K rich foods

Answer 34

asparagus, basil, beef or pork liver, black eyed peas, broccoli, brussel sprouts, cabbage, chick peas, cucumber peel, green onions, green tea, okra, parsley, green leafy veggies

Question 35

Factors that increase PT time warfarin patients

Answer 35

Kinetic: amiodarone, cimetidine, disulfarim, fluconazole, metronidazole, phenylbutazone, sulfinpyrazone, trimethoprim-sulfamethoxazole dynamic: aspirin (high dose), cephalosporins (gen. 3), heparin, argatroban, dabigatran, revaroxaban, apixaban body: liver disease, hyperthyroidism

Question 36

factors that decrease PT time

Answer 36

kinetic: barbiturates, cholestyramine, rifampin dynamic: vit. K body: hereditary resistance, hypothyroidism

Question 37

What drug is often given with thromoblytic drugs and why?

Answer 37

aspirin or heparin to prevent local thrombi as clot dissolves

Question 38

Use of thrombolytics

Answer 38

``` early MI, early ischemic stroke. PE AE: bleeding CI: bleeding, HTN, a-fib, arrhythmia DI: platelet inhibitors, anticoags, NSAIDs, antineoplastics, antithymocyte glogulin, aminocaproic acid, cephalosporins Heparin ok ```

Question 39

FFP

Answer 39

can reverse the effect of warfarin