6 Drugs Affecting the Blood

Question 1

3 drug types to reduce clotting

Answer 1

• anti-coagulants
• anti-platelet drugs
• thrombolytics

Question 2

• 3 drug types to facilitate clotting

Answer 2

• vitamin K
• replacement factors
• plasminogen inhibitors

Question 3

3 drugs used in bleeding disorders

Answer 3

• vitamin K
• plasma fractions
• antifibrinolytic agents

Question 4

• what 2 forms do vitamin K exist in and where are they found?

Answer 4

• vit K1 (phytomenadione) - in food

- vit K2 (menaquinone) - synthesized by intestinal bacteria

Question 5

vit K MOA

Answer 5

confers biologic activity to prothrombin and F 7, 9, 10

Question 6

vit K uses

Answer 6

• vit K deficiency
• warfarin poisoning
• prevent hemorrhagic disease in newborns

Question 7

• why are plasma fractions used?

- 2 factor deficiencies the their hemophilia types

Answer 7

• deficiencies in plasma coagulation factors cause bleeding
• factor 8 deficiency = hemophilia A
• factor 9 = hemophilia B

Question 8

• how is factor 8 available? 1 example and how it’s used (and MOA)

Answer 8

• available as frozen cryoprecipitate and lyophilized concentrates
• eg. desmopressin acetate for mild hemophilia A or von Willebrand’s disease
• forces vW from endothelial cells with secretory problem to bind and degrade F8, increases F8 acitivity, binds to platelets
• -> increases adhesion at wound sites

Question 9

• how is factor 9 available? how’s it used?

Answer 9

• made of freeze-dried concentrates of prothrombin, F9, F10

- treats deficiencies of these factors

Question 10

• what’s recombinant activate human F7 used for?

Answer 10

uncontrollable bleeding

Question 11

what does plasmin do and how does it act?

Answer 11

• it degrades fibrin and fibrinogen

- attaches to fibrin via lysine binding site

Question 12

what are 2 types of fibrinolytic inhibitors?

Answer 12

• aminocaproic acid

- tranexamic acid

Question 13

aminocaproic acid MOA

Answer 13

drug competitively blocks lysine binding site of plasmin so fibrin can’t bind –> no lysis –> inhibits plasminogen activation

Question 14

tranexamic acid description and use

Answer 14

• analogue of aminocaproic acid but 8x more active
• for hemophilia, bleeding from fibrinolytic therapy, prevention of bleeding from intracranial aneurysms, menstrual bleeding etc

Question 15

3 anticoagulant drugs

Answer 15

• heparin
• coumarin
• NOACs (new oral anticoagulants)

Question 16

• what is heparin?

- MOA

Answer 16

• mixture of sulfated mucopolysaccharides
• inbibits several activated clotting factors (and thrombin)
• enhances action of AT-III (antithrombin III)
• speeds formation of inactive protease complexes
• inhibits activated clotting factors (intrinsic system)

Question 17

• how is heparin monitored?
• use
• toxicity
• reversed by?

Answer 17

• PTT (partial thromboplastin time)
• for immediate effect, prevents/tx of venous thrombosis
• used in pregnant women (non-teratogenic)*****
• tox - increased bleeding
• reversed with protamine sulfate

Question 18

• describe coumarins
• MOA
• reversed by?
• use
• toxicity
• interactions

Answer 18

• lipid soluble, antigoagulant, used as rat poison
• blocks vitamin K-dependent glutamate carboxylation of precursor clotting factors
• 8-12 hours delay in action
• reversed with vit K
• for prevention of veous thrombosis and pulmonary embolism
• not for pregnant women, teratogen *****
• tox - bleeding, birth defects
• interacts with other anticoagulants –> increases bleeding
• P450 inducing drugs increase warfarin metabolism and clearance –> decrease anticoagulant effect

Question 19

• new oral anticoagulant (NOAC), 1 example

- MOA

Answer 19

• eg. dabigatran
• binds to active site of thrombin and inhibits enzyme activity
• better than coumarin, less serious side effects
• no reversal agent

Question 20

4 steps in platelet activation?

Answer 20

• endothelial damage
• platelets bind collagen and become activated
• firbinogen binds to platelets –> aggregation
• thrombin binding –> release platelet granules

Question 21

2 goals for platelet inhibitory drugs and their respective antiplatelet drugs

Answer 21

• decrease COX –> decrease TXA2 (aspirin)

- decrease ADP-induced platelet aggregation (clopidogrel)

Question 22

• NSAID protoype
• MOA
• other NSAID differences
• use

Answer 22

• eg. aspirin
• decrease TXA2 by decreasing COX irreversibly, long acting
• others are reversible = shorter duration
• prevents recurrent MI and decreases incidence of first MI

Question 23

• clopidogrel MOA
• description
• AE

Answer 23

• decrease platelet aggregation by decrease ADP pathway of platelets
• irreversible inhibitor of ADP receptors on platelets
• alternative if aspirin intolerant
• prevents MI/stroke
• AE - hemorrhage

Question 24

3 thrombolytic agents

Answer 24

• streptokinase
• • complexes with proactivator plasminogen
• • free plasminogen –> plasmin
• • fibrinolytic state
• alteplase (tissue Plasminogen Activator)
• • plasminogen –> plasmin
• anistreplase
• • acylated stretokinase-plasminogen complex
• • prolongs half life

Question 25

• thombolytics use

- toxicity

Answer 25

• MI, IV injection, deep venous thrombosis, pulmonary embolism, stroke, recanalization of occluded vessels
• tox - bleeding, streptokinase allergy