Drugs Used to Prevent or Treat Thromboembolic Disorders

Question 1

Antiplatelet and coag vs. thrombolytics

Answer 1

Antiplatelet and coag - inhibit formation of clots

Thombolytics - lyse clots

Question 2

Antidepressants and platelets

Answer 2

Increased serotonin release so can lead to risk of bleeding

Question 3

Aspirin MOA

Answer 3

Irreversible inhibitor (of mostly COX1)
COX1 constitutive in platelets 
INhibits TXA2 formation
No TXA2 can stimulate TP receptor 
Inhibits platelet aggregation for the life of the platelet

Question 4

Other NSAIDs

Answer 4

Are reversible…may compete with aspirin and decrease its effectiveness

Question 5

Uses of aspirin and route of delivery

Answer 5

Oral
Acutely in patients (MI or PCI)
Prophylaxis to prevent primary or secondary CV events

Question 6

Other aspirin uses

Answer 6

Antipyretic
Analgesic
Anti-inflammatory

All at higher doses

Question 7

Aspirin adverse effects and contraindications

Answer 7

Profound bleeding and bruising
Increased risk of heartburn and PUD due to inhibited gastric PG synthesis (less at lower dose)

Hypersensitivity of ASA or asthma

Question 8

Aspirin PK

Answer 8

Half life short

Therapeutic effect 7-10 days

Question 9

Clopidogrel MOA and use

Answer 9

Prodrug
Irreversible antagonist of ADP receptor P2Y12
Prevents ADP induced decrease in cAMP and thus prevents aggregation

similar to aspirin use

Question 10

Clopidogrel metabolism and PK

Answer 10

CYP2C19 metabolized...2 steps 
Don't use with CYP2C19 inhibitors (omeprazole)
Therapeutic is 7-10 days 
Oral 
Genetic variation of CYP2C19

Question 11

Adverse effects of clopidogrel

Answer 11

Bruising and bleeding

Question 12

Vorapaxar MOA and therapeutic use

Answer 12

Antagonist of protease activated receptor 1 (PAR1) thus prevents platelet activation by thrombin via this receptor

Only in patients with history of peripheral artery dz or previous MI…use with aspirin and/or clopidogrel

Question 13

Vorapaxar adverse effects, contraindicated, and drug interactions

Answer 13

Increased bleeding

Patients with history of hemorrhage or TIA (transient ischemic attacks)

NSAIDs, SSRIs, SSNIs, and strong CYP3A4 modifeiers

Question 14

Abciximab MOA and route

Answer 14

IV
GP2B/3A antagonist block platelet aggregation by preventing fibrinogen from binding platelets and consolidating platelet plug
Prevents platelet adhesion and aggregation by ANY stimulus
Prevents prothrombin from binding to platelets —– decreases thrombin formed—-anticoagulant
Monoclonal AB

Question 15

Uses of abciximab

Answer 15

Emergency tx of acute coronary syndromes
During PCI
Crisis situations

Question 16

Adverse effects and PK of abciximab

Answer 16

Bleeding

Half life of about 30 minutes
Gp2b/3a bound for 18-24 hours
PLatlet function back in 48 hours

Question 17

Heparin route and MOA

Answer 17

IV, SC

Complex with AT and increases activity
Inactivates factors 2, 9, and 10 as suicide substrate

Question 18

How to monitor heparin

Answer 18

Anti-10a assay (or aPTT) and platleet count…alters intrinsic pathway

Question 19

Heparin advewrse affects

Answer 19

Bleeding
HIT
Heparin sensitivyt
Osteoporosis

Question 20

Antidote for heparin

Answer 20

Protamine sulfate

Question 21

Enoxaparin MOA and route

Answer 21

Complexes with AT3 and increases activity…only inactivates 10a
IV, SC

Question 22

Fondaparinux MOA and route (with PK)

Answer 22

Only SC
Accelerates activity of AT3 against F10
More predicatble with 17 hour halflife

Question 23

Adverse effects of heparin and derivitives

Answer 23

Bleeding problems…patient education…less with fondaparinux

Question 24

Monitoring of heparin and derivatives

Answer 24

Heparin - must be monitored by Anti 10a (.3-.7 is goal)

Others - Anti 10a if needed

Question 25

PK of heparin and deriviates

Answer 25

Hep and LMWH - SC or IV Fonda - only SC Hep and LMWH - given IV at hospital for acute conditions due to rapid onset All good for SC for long term outpatient use Heparin is dose dependent (1/2 = 30-150 min) Enox - 3-6 hr Fonda - 17hr DO NOT CROSS PLACENTA SO SAFE FOR PREG

Question 26

Use of heprain and deriv

Answer 26

Usually initial short term rx and transition to oral meds | Can also use with antiplatelet therapy in more urgent situations

Question 27

Bivalirudin MOA and route

Answer 27

Direct irreversible inhibitor of thrombin IV infusion T1/2 = 25 minutes

Question 28

Bivalirudin uses

Answer 28

Patients who need heparin but have HIT | Microvascular surgery to reattach digits

Question 29

Warfarin route and MOA

Answer 29

Oral Antagonist of VKOR...inhibits synthesis of factors 2,7,9,10 and protein C and S Onset of action is 8-12 days with full effect in 3 days Alters both intrinsic and extrinsic pathways

Question 30

Warfarin uses

Answer 30

Tx of thrombosis/embolisms | Metal prosthetic valves

Question 31

Warfarin PK

Answer 31

Oral 99% plasma protein bound CYP metabolized therapeutic half life long

Question 32

Warfarin adverse effects

Answer 32

Bleeding NOT GOOD WITH PREG Warfarin induced skin necrosis - use heparin brdige to prevent Purple toe syndrome

Question 33

Warfarin antidotes

Answer 33

Vit K1 FFP Prothrombin complex F7a

Question 34

Dabigatran etexilate advantages

Answer 34

Direct action on thrombin (rapid effect) Prodrug activated by plasma esterases, NOT CYP More effective with less drug interactions and little impact on anything but clotting

Question 35

MOA of dabigatran and route

Answer 35

Prodrug Competitive inhibitor of thrombin activity on both fibrinogen and platelets decrasing both platelet and coag activity Oral

Question 36

Dabigatran uses

Answer 36

Prevent strokes | DVT and PE

Question 37

Dabigatran adverse effect, antidote, and PK

Answer 37

Bleeding Idarucizumab Prodrug cleaved by esterases Dose adjustment needed in renal dz and in combination with drugs that compete for the P glycoprotein efflux transporter which transports active drug into renal tubular fluid

Question 38

Rivaroxaban route, MOA, uses, PK

Answer 38

Oral Directly inhibits factor 10a (not through AT3 like LMWH) Same uses as dabigatran Oral, once a day

Question 39

Rivaroxaban warnings and antidotie

Answer 39

Bleeding, monitor renal function Andexanet alpha

Question 40

Alteplase MOA and PK

Answer 40

Binds to clot bound fibrin and converts plasminogen to plasmin which degrades fibrin Recombinant tPA IV only with short half life

Question 41

When to use alteplase

Answer 41

Acute stroke MI PE DVT

Question 42

Adverse effects of alteplase

Answer 42

Lyse all physiologic thrombi as well

Question 43

Contraindications of alteplase

Answer 43

Surgery, trauma within 10 days Serious GI bleeding in last 3 months Hypertension Activebleeding or threat

Question 44

Antidoes for fibrinolytic therapy

Answer 44

Epsilon aminocaproic acid - PO, IV...inhibits fibrinolysis | Tranxenamic acid - topical, PO...inhibits plasminogen activity...can also be used as rinse to reduce bleeding