Drugs Used in the disorders of Coagulation Flashcards
3 Types of drugs used to reduce clotting?
Platelet Aggregation Inhibitors
Anticoagulants
Thrombolytics
4 types of platelet aggregation inhibitors?
CYCLOOXYGENASE INHIBITORS
ADP RECEPTOR BLOCKERS
PHOSPHODIESTERASE INHIBITORS
BLOCKERS OF PLATELET GP IIb/IIIA RECEPTORS
Describe Cyclooxgenase inhibitor
ASPIRIN
• Thromboxane A2 causes platelets to
degranulate and aggregate.
• Aspirin inhibits TXA2 synthesis by irreversible
acetylation of the enzyme COX.
• The anuclear platelet can’t synthesize new
proteins.
• Therefore it can’t synthesise new enzyme
during its 10-day lifetime.
Uses of Aspirin
Prophylactic treatment of transient cerebral
ischemia
• To reduce the incidence of recurrent MI
• To decrease mortality in post MI patients.
2 ADP receptor blockers?
CLOPIDOGREL & TICLOPIDINE
Describe ADP receptor blockers?
• Irreversible inhibitors of P2Y12, one of the two
subtypes of ADP receptor on the platelet surface.
• Clopidogrel has fewer adverse effects than
ticlopidine.
• Clopidogrel is preferred over ticlopidine.
Describe Clopidogrel metabolism?
Clopidogrel is a prodrug converted to an active
metabolite, mainly by CYP2C19.
• Patients who are CYP2C19 poor metabolizers
have lower plasma levels of the active
metabolite.
• Alternative treatments should be considered
for CYP2C19 poor metabolizers
concomitant use of clopidogrel with what type of drugs should be avoided, give example?
The concomitant use of clopidogrel and
CYP2C19 inhibitors should be avoided.
• Omeprazole, a CYP2C19 inhibitor, reduces
plasma levels of the active metabolite of
clopidogrel.
• Concurrent use of clopidogrel and
omeprazole should be avoided.
Uses for Clopidogrel?
Indicated to reduce the rate of stroke, MI, and
death in patients with recent MI or stroke or
acute coronary syndrome.
What are the two PHOSPHODIESTERASE INHIBITORS? What is each used for?
DIPYRIDAMOLE - Used for stroke prevention
CILOSTAZOL - Used for intermittent claudication
BLOCKERS OF PLATELET GP IIb/IIIa RECEPTORS and their use?
ABCIXIMAB EPTIFIBATIDE TIROFIBAN Adjuncts to PCI for prevention of cardiac ischemic complications.
What are the 4 types of anticoagulants?
Indirect Thrombin and Factor Xa inhibitors
• Vitamin K Antagonists
• Direct Thrombin Inhibitors
• Direct Factor Xa Inhibitors
3 types of INDIRECT THROMBIN AND FACTOR XA INHIBITORS?
- Unfractionated heparin (UFH)
- Low-molecular-weight heparins (LMWH)
- Fondaparinux
What is Heparin?
UNFRACTIONATED &
LOW-MOLECULAR-WEIGHT HEPARINS weight ranges?
• Heparin is an injectable, rapidly acting
anticoagulant, used to interfere with formation of
thrombi.
Unfractionated heparin (UFH) has a molecular
weight range of 5,000 - 30,000.
• Low-Molecular-Weight Heparins (Enoxaparin)
are produced by depolymerization of UFH. Their
molecular weights range from 1,000 – 5,000.
LMWH vs UFH difference in bioavailability, half-life, and dosing requirements?
LMWH have equal efficacy to UFH, higher
bioavailability, longer half-life, and less frequent
dosing requirements.
• LMWH are replacing UFH in many clinical
situations.
Herparin MOA?
• Antithrombin III inhibits clotting factor
proteases: thrombin, IXa and Xa.
• In the absence of heparin, antithrombin III
inhibits them very slowly.
• Binding of heparin to antithrombin III accelerates
the inhibition.
• Heparin functions as a cofactor for the
antithrombin-protease reaction.
Difference in anticoagulant activity of UFH and LMWH?
UFH efficiently inactivates both thrombin and
factor Xa
LMWH efficently inhibit Xa but have less
effect on thrombin.
Why do LMWH have little efficacy on thrombin?
LMWH molecules are of insufficient length to form the ternary complex and thus catalyze inhibition of
thrombin. In contrast, UFH efficiently inactivates both thrombin and factor Xa
How are Heparin levels monitored?
Monitoring is performed with the activated partial
thromboplastin time (aPTT) assay.
• The aPTT is a test of the integrity of the intrinsic
and common pathways of coagulation.
