Drugs For Disorders Of Coagulation

Question 1

_____________ digests fibrin

Answer 1

Plasmin; inactive plasminogen must be converted to active plasmin

Question 2

Families of drugs used to reduced clotting

Answer 2

• platelet aggregation inhibitors (anti platelet drugs)
• anticoagulants
• thrombolytics

Question 3

What are the 4 mechanisms of actions that allow for the inhibition of platelet aggregation

Answer 3

• Cyclooxygenase inhibitors
• ADP receptor blockers
• phosphodiesterase inhibitors
• blockers of platelet GP IIb/IIIA receptors

Question 4

Aspirin inhibits the synthesis of ________ by _______________ of the enzyme ________

Answer 4

Thromboxane A2 (causes platelet degranulation and aggregation) ; Irreverisble acetylation ; 
COX

Question 5

What kind of protein receptor is involved in the aggreagation and activation of platelets?

Answer 5

Gq protein → Phosopholipase C → IP3 and DAG → release of calcium from ER activation PKC which then activates Phospholipase A2 → which activates the receptor (G2b/G3b) allowing for fribonrgen to bind and platelets aggregate

Question 6

_______ forms bridges between adjacent pallets because it is ________

Answer 6

Fibrinogen; bivalent

Question 7

What drugs are ADP receptor blockers?

Answer 7

Clopidogrel & Ticlopidine

Question 8

Mechanism of ADP receptor blockers

Answer 8

Irreversible inhibitors of P2Y12 which is a subtype of ADP receptor

Question 9

Of the ADP receptor blocker drugs, ___________ has fewer adverse effects than ____________

Answer 9

Clopidogrel; ticlopidine

Clopidogrel is preferred over ticlopidine

Question 10

Clopidogrel is a prodrug that is converted to the active form by __________

Answer 10

CYP2C19

Question 11

An individual who is a poor CYP2C19 metabolizer will have _________ plasma levels of clopidogrel

Answer 11

Low; CYP2C19 is used to convert the prodrug form to the active form of clopidogrel

Question 12

Concurrent use of clopidogrel and ______________ should be avoided

Answer 12

Omeprazole (CYP2C19 inhibitor) because then cannot get the active form of clopidogrel

Question 13

Drugs that are phosphodiesterase inhibitors

Answer 13

Dipyridamole: used for stroke prevention
Cilostazol: used for intermittent claudication

Question 14

↑ _______ promotes dormant platelets while ↑ _________ leads to activation and aggregation of platelets

Answer 14

CAMP; calcium

Question 15

Phosphodiesterase inhibitors cause an ↑ in _____________

Answer 15

CAMP; causes platelets to remain dormant

Question 16

Drugs that are blockers of platelet GP 2B/3A receptors

Answer 16

• Abciximab
• Eptifibatide
• Tirofiban (most popular)

Question 17

Platelet GP 2B/3A receptor blockers are used for prevention of _____________

Answer 17

Cardiac ischemic complications after a MI

Question 18

Classes of anticoagulant drugs based on mechanism (4)

Answer 18

• indirect thrombin & factor Xa inhibitors
• direct thrombin inhibitors
• direct factor Xa inhibitors
• Vitamin K antagonists

Question 19

Drugs that are indirect thrombin and factor Xa inhibitors:

Answer 19

Heparin: unfractionated and low molecular weight (enoxaparin)
Fondaparinux

Question 20

Administration method of heparin

Answer 20

Injected; rapidly active

Question 21

UFH vs LMWH: Which one has higher, lower, or equal of the following

• efficacy
• bioavailability
• half life
• dosing requirements

Answer 21

Efficacy: equal
Bioavailability, half life: LMWH has higher (longer half life)
Dosing requirements: LMWH has less frequent dosing req.

Question 22

Mechanism of action of heparin

Answer 22

Heparin acts a cofactor for antithrombin III and accelerates its normal function of inhibitor clotting factor pretenses: thrombin, IXa, and Xa

Question 23

What clotting factors does antithrombin III inhibit?

Answer 23

Thrombin, IXa, and Xa

Question 24

Difference in the mechanism of action between UFH and LWMH

Answer 24

UFH efficiently inactivates BOTH thrombin and Xa

LMWH has less effect on thrombin but efficiently inactivates Xa

Question 25

__________ is not necessary to accelerate the inactivation of clotting factor ______ by antithrombin III

Answer 25

Ternary complex; Xa | LMWH cannot form a ternary complex but this is why both UFH and LMWH efficiently inhibit factor Xa

Question 26

_____________ is used to monitor heparin levels

Answer 26

APTT assay (activated partial thromboplastin time) which tests for integrity of the intrinsic and common pathways

Question 27

Potency of LMWH can be assessed with __________ usually in ________ patients

Answer 27

Anti-factor Xa assays; obese

Question 28

Uses of heparin

Answer 28

DVT, pulmonary embolism, MI and drug of choice for pregnant women

Question 29

In heparin induced thrombocytpenia type II, ________ binds to the heparin causing it to be immunogenic and then ______ binds to the immune complex and activates platelets causing degranulation and activation and release of more platelet factor 4

Answer 29

Platelet factor 4; IgG

Question 30

Heparin induced thomrbocytopenia type 2 can result in thrombocytopenia and ________

Answer 30

Thrombosis

Question 31

Therapy for heparin induced thrombocytopenia type II

Answer 31

Discontinue heparin and administers a DTI or fondaparinux

Question 32

Antidote for excessive heparin administration

Answer 32

Protamine sulfate

Question 33

Warfarin inhibits ___________

Answer 33

Vitamin K epoxide reductase

Question 34

How long does it take to see the effect of warfarin?

Answer 34

6-60 hours because that is the half life of the circulating clotting factors

Question 35

Fondaparinux is a specific inhibitor of ___________ and is approved for prevention and treatment of _______

Answer 35

``` Factor Xa (negligible antithrombin activity) DVT ```

Question 36

Peak warfarin effect is seen ________

Answer 36

72-96 hrs

Question 37

Antidote to excessive warfarin administration

Answer 37

Vitamin K

Question 38

Monitoring of warfarin levels is done by _____________ which tests the integrity of the ____________ pathways of coagulation

Answer 38

Prothrombin time; extrinsic and common pathways

Question 39

Adverse effects of warfarin

Answer 39

- hemorrhage - cutaneous necrosisdue to ↓ activity of protein C which is an anticoagulant factor that requires vitamin K - teratogenic if taken during pregnancy

Question 40

Cutaneous necrosis is an adverse effect of taking what drug?

Answer 40

Warfarin

Question 41

Which one should be used for pregnant patients: heparin or warfarin

Answer 41

Heparin

Question 42

Drugs that are parenteral DTI’s (direct thrombin inhibitors) and how are they monitored?

Answer 42

- desirudin - bivalirudin - argatroban APTT

Question 43

Oral DTI drugs

Answer 43

Dabigatran etexilate (prodrug)

Question 44

Benefits of oral DTI

Answer 44

Produces a predictable response and does not need to be routinely monitored like you would need to with Heparin

Question 45

Drugs that are director factor Xa inhibitors

Answer 45

Apixaban & rivaroxaban | - do not req. monitoring and given orally

Question 46

Direct oral anticoagulants (DOAC’s) _________________ (3) are replacing warfarin for treating stroke and preventing embolism is atrial fibrillation because:

Answer 46

Dabigatran, apixaban, rivaroxaban DOAC’s have equal efficacy and ↓ bleeding rates, dont need to be monitored, rapid onset of action, predictable pharmacokinetics, wider TW, and fewer drug interactions

Question 47

Thrombolytic drugs and mechanism

Answer 47

``` Streptokinase Urokinase Alteplase Reteplase Tenecteplase ``` Promote conversation of plasminogen to plasmin

Question 48

Urokinase is formed by ___________

Answer 48

Kidney; found in the urine

Question 49

_____________ causes the conversion of plasminogen to plasmin and is “fibrin selective” unlike streptokinase and urokinase; Explain fibrin selective

Answer 49

T-Pa (tissue plasminogen activator) which is a serine protease produced by endothelial cells T-Pa only converts plasminogen to plasmin when the plasminogen is bound to fibrin

Question 50

___________ and _________ are recombinant variants of t-Pa with a longer half life

Answer 50

Reteplase and tenecteplase

Question 51

Classes of drugs used to treat bleeding

Answer 51

- Plasminogen activator inhibitors - protamine sulfate - vitamin K - plasma fractions

Question 52

Drugs that are plasminogen activation inhibitors

Answer 52

Aminocaproic acid and tranexamic acid

Question 53

Protamine sulfate can be used as an antidote for excessive administration of _________ because ______

Answer 53

Heparin; | Charge-charge antagonism: protamine sulfate is very positively charged while heparin is negatively charged

Question 54

Plasma fractions are given to __________

Answer 54

People with genetic defects such as factor XIII or Factor IX deficiencies (hemophilia)