Lesson 5.7. Blood Agents

Vasoconstriction

BLOOD AGENTS PROCESSES:

• done to prevent blood loss and pathogen spread

Thromboxane

BLOOD AGENTS PROCESS:

• participant molecule of vasoconstriction

Platelet Plug Formation

BLOOD AGENTS PROCESSES:

• Platelets migrate to the site of the open wound and undergoes adhesion, activation, and aggregation

Platelet Plug Formation — Adhesion

BLOOD AGENT PROCESSES:

• open wound exposes factors that will attract platelets

TXA, ADP, Glycoprotein IIb/IIIa

BLOOD AGENTS PROCESS:

• participant molecule of activators

Platelet Plug Formation — activation

BLOOD AGENT PROCESSES:

• clump through linking glycoprotein IIb/IIIa receptors at their periphery

cAMP

BLOOD AGENTS PROCESS:

• participant molecule of inhibitors

Coagulation cascade

Fibrin clot/ thrombus formation (Coagulation)

a. _________________________ leads to conversion of prothrombin into thrombin.

b. ___________________ converts soluble fibrinogen into insoluble fibrin.

c. The strands of fibrin wrap around the platelet plug, resulting in a _____________.

a = ?

Thrombin

Fibrin clot/ thrombus formation (Coagulation)

a. _________________________ leads to conversion of prothrombin into thrombin.

b. ___________________ converts soluble fibrinogen into insoluble fibrin.

c. The strands of fibrin wrap around the platelet plug, resulting in a _____________.

b = ?

strong fibrin clot

Fibrin clot/ thrombus formation (Coagulation)

a. _________________________ leads to conversion of prothrombin into thrombin.

b. ___________________ converts soluble fibrinogen into insoluble fibrin.

c. The strands of fibrin wrap around the platelet plug, resulting in a _____________.

c = ?

Clotting Factors

BLOOD AGENT PROCESSES:

• coagulation activator

antithrombin

BLOOD AGENT PROCESSES:

• coagulation inhibitors

Fibrinolysis

BLOOD AGENT PROCESSES:

• The fibrin clot must be dissolved by an active protease called plasmin

Plasmin

must be activated from plasminogen by virtue of tissue plasminogen activator (t-PA).

t-PA, Plasminogen

Fibrinolysis Participating Molecule

Clopidogrel, Ticlopidine, Prasugrel

Antiplatelet drugs (target components responsible for platelet aggregation)

MOA:

• Inhibition of ADP binding on P2Y12 receptor

Aspirin

Antiplatelet drugs (target components responsible for platelet aggregation)

MOA:

• Inhibition of thromboxane A2 (TXA2)

Abciximab, Eptifibatide, Tirofiban

Antiplatelet drugs (target components responsible for platelet aggregation)

MOA:

• Binds to Glycoprotein IIb/IIIa (GP IIb/GP IIIa)

Aspirin

Antiplatelet Drugs

• has anti-inflammatory activity and affects prostaglandin synthesis

COX-1

ASPIRIN MOA:

a. irreversibly inhibits _________ near active site

b. inhibits _________ synthesis

c. reduced __________________

a = ?

TXA2

ASPIRIN MOA:

a. irreversibly inhibits _________ near active site

b. inhibits _________ synthesis

c. reduced lately activation

b = ?

lately activation

ASPIRIN MOA:

a. irreversibly inhibits _________ near active site

b. inhibits _________ synthesis

c. reduced lately activation

c = ?

PDE

PDE Inhibitors MOA:

a. inhibits _________

b. leads to an ___________________

c. reduces ______________

a = ?

increased cAMP

PDE Inhibitors MOA:

a. inhibits _________

b. leads to an ___________________

c. reduces ______________

b = ?

platelet activity

PDE Inhibitors MOA:

a. inhibits _________

b. leads to an ___________________

c. reduces ______________

c = ?

Dipyridamole, Cilostazol

PDE Inhibitor Drugs

P2Y purinergic receptors

P2Y / ADP Inhibitors (thienopyridines) MOA:

a. binds to ________________________

b. leading to decreased _____________

c. decreased _______________________

a = ?

ADP binding

P2Y / ADP Inhibitors (thienopyridines) MOA:

a. binds to ________________________

b. leading to decreased _____________

c. decreased _______________________

b = ?

platelet aggregation

P2Y / ADP Inhibitors (thienopyridines) MOA:

a. binds to ________________________

b. leading to decreased _____________

c. decreased _______________________

c = ?

Clopidogrel, Ticlopidine, Prasugrelm, Ticagrelor

P2Y / ADP Inhibitors (thienopyridines) Drugs

protease-activated receptor

PAR blockers MOA:

a. inhibits ___________________________

b. leads to __________________________ for platelet aggregation

a = ?

decreased thrombin capacity

PAR blockers MOA:

a. inhibits ___________________________

b. leads to __________________________ for platelet aggregation

b = ?

Vorapaxar

PAR blockers Drugs

Heparin, Enoxaparin, Fondapirinux

Anticoagulant drugs (inhibit clotting factors before a clot is formed) MOA:

• Inhibition of Factor IIa (thrombin)

Apixaban, Rivaroxaban, Edoxaban

Anticoagulant drugs (inhibit clotting factors before a clot is formed) MOA:

• Inhibition of Factor Xa

Warfarin

Anticoagulant drugs (inhibit clotting factors before a clot is formed) MOA:

• Inhibition of Vit. K-dependent Factors

sulfate glycosaminoglycan

Heparin is a ______________________

indirectly inhibit thrombin

Heparin MOA:

a. ____________________________ by activating antithrombin

b. __________________________ requires monitoring of use.

c. _______________________________________________ are more predictable w/ less monitoring.

a = ?

Unfractionated heparin (UFH)

Heparin MOA:

a. ____________________________ by activating antithrombin

b. __________________________ requires monitoring of use.

c. _______________________________________________ are more predictable w/ less monitoring.

b = ?

Low Molecular Weight heparin (LMWH) and Fondaparinux

Heparin MOA:

a. ____________________________ by activating antithrombin

b. __________________________ requires monitoring of use.

c. _______________________________________________ are more predictable w/ less monitoring.

c = ?

bleeding

ADR of Heparin

Protamine

Heparin ADR antidote

Heparin Structure

Fondaparinux Structure

Factor IIa

Direct Thrombin Inhibitors (from Hirudo medicinalis, medical leech) MOA:

• directly binds and inhibits _____________________

Hirudin, Lepirudin, Desirudin, Bivalirudin

Direct Thrombin Inhibitors (from Hirudo medicinalis, medical leech) Drugs:

a. From leech:

b. Small molecule inhibitors:

a = ?

Argatroban, Dabigatran

Direct Thrombin Inhibitors (from Hirudo medicinalis, medical leech) Drugs:

a. From leech:

b. Small molecule inhibitors:

b = ?

Vit. K epoxide reductase complex (VKORC)

Coumarins (Warfarin) MOA:

a. inhibits ____________________________________

b. leads to reduced synthesis of ________________________________

a = ?

cofactors 10, 9, 7 and 2 (“1972”)

Coumarins (Warfarin) MOA:

a. inhibits ____________________________________

b. leads to reduced synthesis of ________________________________

b = ?

Vitamin K

antidote of Warfarin ADR

Warfarin Structure

Fibrinolytics / Thrombolytics

Dissolve fibrin clots that may be blocking blood flowinthevessels.

All Fibrinolytic agents are derivatives of ________________________.

tissue Plasminogen Activators (tPAs)

tissue Plasminogen Activators (tPAs)

Fibrinolytics MOA:

a. works like _________________________________

b. converts______________________

c. breaks _____________

a = ?

plasminogen to plasmin

Fibrinolytics MOA:

a. works like _________________________________

b. converts______________________

c. breaks _____________

b = ?

blood clots

Fibrinolytics MOA:

a. works like _________________________________

b. converts______________________

c. breaks _____________

c = ?

Streptokinase, Urokinase, Alteplase, Reteplase, Tenecteplase

Fibrinolytic Drugs

plasminogen to plasmin

Antifibrinolytics MOA:

a. inhibit conversion of ____________________

b. prevents __________________

a = ?

bleeding

Antifibrinolytics MOA:

a. inhibit conversion of ____________________

b. prevents __________________

b = ?

Tranexamic acid and Aminocaproic acid

Antifibrinolytic Drugs

Antiplatelets and anticoagulants

Prevention of thrombi that can lead to: myocardial infarction, pulmonaryembolism, and/or deep vein thrombosis.

Fibrinolytics / Thrombolytic

Dissolution of thrombi that has already been formed especiallywhenitcompletely blocks major cardiac blood vessels. Preventsvascularblockade that may lead to stroke.

Antifibrinolytics

Prevention of excessive bleeding from cases where wounds or bleedingare expected (e.g. surgery, hemophilia patients).

Novel Drugs

Improves platelet synthesis for patients with thrombocytopenicepisodesor for patients having very low blood counts.

Eltrombopag and Romiplostim

Example of Novel Drugs (thrombopoeitinagonist)