Anticoagulants, Direct and Indirect Thrombin Inhibitors
-
Upload
rinta-moon -
Category
Documents
-
view
228 -
download
0
Transcript of Anticoagulants, Direct and Indirect Thrombin Inhibitors
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
1/12
ANTICOAGULANTAn anticoagulantis a substance that prevents or
reduces coagulation (clotting) of blood. This group ofpharmaceuticals can be used in vivo as a medication for
thrombotic disorders.
Thrombosisis the
formation of a blood clot(thrombus) inside a blood
vessel, obstructing the flow
of blood through the
circulatory system.
If the clot becomes mobile and is carried away by the
blood circulation, it is called an embolus.
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
2/12
Anticoagulants is required if one has been diagnosed with
or treated for one or more of the following:
Atrial fibrillation (AF)-
lack of an organized atrial contraction can result in some
stagnant blood in the left atrium (LA)
thrombus formation
heparin, warfarin, dabigatran, rivaroxabanArterial embolism-
sudden interruption of blood flow to an organ or body
part due to an embolus adhering to the wall of an artery
blocking the flow of bloodwarfarin, heparin
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
3/12
Deep vein thrombosis (DVT)-
formation of a blood clot (thrombus) in a deep vein,
predominantly in the legs
venous stasis, hypercoagulability, and changes in endothelialblood vessel lining (such as physical damage)
LMWH, fondaparinux, unfractionated heparin, warfarin
Pulmonary embolism (PE)-
blockage of the main artery of the lung or one of its branchesdue to an embolus
most commonly results from deep vein thrombosis
LMWH, fondaparinux, unfractionated heparin, warfarin
Stroke-rapid loss of brain function due to disturbance in the blood
supply to the brain
thrombosis, arterial embolism
Warfarin
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
4/12
Genetic clotting disorders like prothrombin
thrombophilia, Factor V Leiden thrombophilia
congenital thrombophilia -an inborn abnormality of
blood coagulation that increases risk of thrombosis as a
result of overactivity of coagulation factors
prothrombin thrombophilia- a mutation in prothrombin
factor V Leiden thrombophilia- a mutation in the F5 genewarfarin and during pregnancy LMWH
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
5/12
ANTICOAGULANT DRUGS
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
6/12
DIRECT THROMBIN INHIBITORS
Drug name Bivalent/
Univalent
Route of
administration
Binding to
active siteand/or
exosite
Indications
Argatroban Univalent Parenteral (iv) Reversible Prevention and
treatment of
thrombosis
Dabigatran
etexilate
Univalent Oral Reversible Prevention of
stroke and
embolism in
patients with AF
Lepirudin Bivalent Parenteral (iv/sc) Irreversible Prevention of
further
thrombosis
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
7/12
Mechanism:Thrombin has three domains: one active site and two
exosites. Exosite 1 acts as a dock for substrates such as fibrin in order
to promote orientation for active site binding. Exosite 2 is the
heparin-binding domain. Thus, DTIs are able to inactivate both fibrin-
bound and unbound thrombin, unlike UFH and LMWH.
Side-effects:Heart failure; bleeding in injection site, wounds and
allergic skin reactions; nosebleed; gastrointestinal and rectal bleeding;abnormal kidney function, blood in urine
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
8/12
INDIRECT THROMBIN INHIBITORS
A, To inactivate thrombin,
unfractionated heparin
forms a ternary complex
with antithrombin and
thrombin.
B, Because of their lower
molecular weight, LMWH
species are unable to form
the ternary complexes
with antithrombin and
thrombin. Thus, LMWHs
produce their
anticoagulant effect
mainly by inhibiting factor
Xa.
Mechanism of action of UFH and LMWH
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
9/12
Fondaparinux: Mechanism of action
Drug name Route of
administration
Excretion Indications
Fondaparinux SC Renal (Eliminated
unchanged in urine)
Prophylaxis & treatment of
acute deep vein thrombosis
Overview:
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
10/12
Side-effects of fondaparinux:Anemia; Hematoma; Hypokalemia;
Hypotension; Thrombocytopenia; Urinary tract infection; edema; fever;;local irritation (injection site bleeding; rash); nausea
Side effects of heparin:1.Haemorrhagethe risk is greatest in the elderly, and may be
exacerbated by alcohol intake. This is by far the most common side
effect.2.Osteoporosiscan occur if the drug is used for more than a few
weeks. This does not occur with LMWHs.
3.Thrombocytopaeniacan occur after 7-10 days of therapy. It is a
result of heparin induced antiplatelet antibodies.
4.Hyperkalaemiadue to inhibition of aldosterone secretion
5.Hypersensitivity
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
11/12
VITAMIN K ANTAGONISTS
Side-effects:Haemorrhagethis is especially common to the bowel
and brain; hematuria; epistaxis; teratogenicity; necrosis of soft tissues;
leukopenia, agranulocytosis
-
8/13/2019 Anticoagulants, Direct and Indirect Thrombin Inhibitors
12/12
DIRECT Xa INHIBITORSRivaroxaban and Apixaban
oral, reversible, specific inhibitors
of both free and fibrin-boundfactor Xa
do not involve antithrombin III
(ATIII) to exert their
anticoagulant effects
decrease thrombin generationand thrombus development
side-effects: upper GI, lower GI,
and rectal bleeding (0.1% to 1%);
skin rash (less than 1%);
anaphylactic reactions (such asallergic edema) (less than 1%);
intracranial bleeding (0.33%);
syncope (less than 1%);
intraocular bleed (0.21%)