Anti-platelets and anti-thrombotics

Question 1

anti-clotting drugs

Answer 1

a. Antiplatelet drugs
b. anticoagulants
c. thrombolytics

Question 2

antiplatelet drugs

Answer 2

a. Non-steroidal, anti-inflammatory drugs (Aspirin)
b. platelet GPIIB/ IIIA receptor blockers (Abciximab, Eptifibatide, Tirofiban)
c. ADP receptor blockers (ticlopidine, clopidogrel)
d. PDE inhibitor (Dipyridamole)

Question 3

thrombolytics

Answer 3

plasminogen activators : streptokinase, alteplase, anistreplase, urokinase

Question 4

anticoagulants

Answer 4

heparin, warfarin

Question 5

Aspirin

Answer 5

MOA: Aspirin is an irreversible cyclooxygenase inhibitor = reduce TXA2, PGI2, PGE2, PGF2alpha
- inhibitory effect is rapid and lasts 7-10 days, approx life of a platelet

clinical uses = transient cerebral ischemia, reduce incidence of recurrent MI, decrease mortality in post-MI infarction patients

adverse effects = bleeding (due to PGI2), Gastric upset and ulcers (due to PGE2), Bronchus and uterine contractions (due to PGF2alpha)

Question 6

GP IIB/IIA receptor blockers

Answer 6

Glycoprotein IIB/IIA is a platelet membrane surface protein that acts as a receptor for fibrinogen and vitronectin

MOA: since activation of receptor triggers platelet aggregation, blocking receptor will block platelet aggregation

E.g. Abciximab - humanised monoclonal Ab against IIb/IIa complex
E.g. Eptifibatide - blocks receptor by acting as a fibrinogen analog

clinical uses = prevent restenosis after coronary angioplasty

Question 7

ADP receptor blockers

Answer 7

Clopidogrel and ticlopidine
MOA: blocks ADP from binding to its receptor = blocks platelet conformation change and aggregation, decrease generation of TbxA2

Question 8

PDE inhibitor

Answer 8

Dipyridamole
MOA: blocks phosphodiesterase to increase cAMP = increase inhibitory signal (prostacyclins) to granules = decrease ADP

Question 9

Thrombolytics - breaking apart the clot even after it has formed

Answer 9

Plasminogen activators - streptokinase, alteplase, anistreplase, urokinase
MOA: activate plasminogen to plasmin for plasmin to breakdown fibrin into fibrin degradation products

clinical uses = emergency txt of coronary artery thrombosis, peripheral arterial thrombosis and emboli, ischaemic stroke (must be given within 4.5hr)

adverse effects = bleeding
contraindicated in pregnancy and healing wounds

Question 10

Anticoagulants - warfarin

Answer 10

MOA: Warfarin is a Vit K reductase inhibitor = Vit K becomes permanently oxidised = No reduced Vit K for the carboxylation of glutamate residues in F2,7,9 and 10

note: Warfarin’s elimination is by hepatic cytochrome P450. P450 inhibitors = reduce dose of warfarin and vice versa

Clinical uses (both warfarin and heparin) = deep vein thrombosis, pulmonary embolism, acute MI, combination with GP IIa/IIb inhibitors during angioplasty and placement of coronary stents, combination with thrombolytics for revascularisation

adverse effects = bleeding when given too much
contraindicated in pregnancy as warfarin can cross placenta to cause hemorrhagic disorder in fetus

Question 11

Anticoagulants - heparin (family of sulfated glycosaminoglycans)

Answer 11

MOA: active heparin molecules bind tightly to ATIII and cause a conformational change = exposes AS for more rapid interaction with thrombin (IIa), IXa and Xa to irreversibly inactivate clotting factor proteases

Adverse effects = haemorrhage when given too much (solution = stop heparin therapy and give protamine sulfate, a cationic peptide that binds to heparin and sequesters it), thrombocytopenia (low platelets)

note: heparin is the only anticoagulant that can be used in pregnancy
note: heparin is given IV or SC, not intramuscularly as it can lead to hematomas

Question 12

low molecular weight heparin VS unfractionated heparin

Answer 12

LMWHs have better bioavailability and longer half-life
BUT only able to allow antithrombin to inhibit Xa

Unfractionated heparin = can bind to FXa and FIIa (thrombin) with AT III