Drugs Used in Disoders of

Cougulation
Prepared by: Ahmad Abdullah Al-boudrees
 Antiplatelet (Antiaggregant) Drugs
Class Irreversible Cyclooxygenase Inhibitors
Name Aspirin
Mechanism ♦ Aspirin irreversibly blocks production of
of Action TxA2 by acetylating a serine residue near the increasing the cellular concentration of
active site of platelet COX.
♦ Aspirin also reversibly inhibits the COX
enzyme in endothelial cells.
Uses ● Prevent arterial thrombosis leading to
transient ischemic attack, stroke, and
myocardial infarction.
● Anti-inflammatory.
● Analgesic & antipyretic.
● Chemoprotective agent in colorectal
cancer.
● May be valuable in treating preeclampsia-
eclampsia.
Toxicity ■ Long-term aspirin therapy can lead to
rashes, gastrointestinal ulceration and
hemorrhage, vomiting nephrotoxicity, and
hepatic injury.
■ Contraindicated in patients with
hemophilia.
■ Causes net retention of uric acid.
■ Contraindicated in patients with gout.
■ Aspirin-induced airway hyperreactivity in
asthmatics and Reye’s syndrome in children.
Drug -Ibuprofen -Warfarin
Interaction
Phosphodiesterase Inhibitors and
Adenosine Reuptake Inhibitors
Dipyridamole
♦ Interferes with platelet function by
cAMP. This effect is mediated by inhibition
of cyclic nucleotide phosphodiesterase
and/or by blockade of uptake of adenosine,
which act at adenosine A2 receptors to
stimulate platelet adenylyl cyclase and
thence cellular Camp.
● It is used to prevent stroke.
● It is used in addition to aspirin in some
patients with stroke or transient ischaemic
attack.
● It is used in patients who are intolerant of
aspirin.
■ Dizziness, headache and gastrointestinal
disturbances.
■ May provoke or worsen angina.
-Vorapaxar -Rivaroxaban
Phosphodiesterase Inhibitors
Cilostazol
♦ A phosphodiesterase type 3 (PDE3)
inhibitor that promotes accumulation of
intracellular cAMP in many cells, including
blood platelets, is poorly understood but
may have selective antiplatelet and
vasodilating effects.
● Used primarily to treat intermittent
claudication.
■ Contraindicated in patients with heart
failure.
■ Headache.
-Aspirin -Amoxicillin -Omeprazole
 Antiplatelet (Antiaggregant) Drugs
Class ADP Receptor Pathway Inhibitors ADP Receptor Pathway Inhibitors ADP Receptor Pathway Inhibitors
Name Clopidogrel Prasugrel Ticagrelor
Mechanism ♦ Inhibit ADP-induced platelet aggregation ♦ Inhibit ADP-induced platelet aggregation ♦ Inhibit ADP-induced platelet aggregation
of Action by irreversible inhibition of P2Y12 receptors by irreversible inhibition of P2Y12 receptors by reversible, but non-competitive
to which they link via a disulfide bond. to which they link via a disulfide bond. inhibition of P2Y12 receptors.
Uses ● It is approved for patients with unstable ● Prasugrel is more effective than ● Treatment of acute coronary syndrome
angina or non-ST-elevation acute clopidogrel in acute coronary syndromes, with ticagrelor as compared with
myocardial infarction (NSTEMI) in but more often causes serious bleeding. clopidogrel significantly reduces the rate of
combination with aspirin. death for unknown reasons.
● It is approved for patients with ST-
elevation myocardial infarction (STEMI); or
recent myocardial infarction, stroke, or
established peripheral arterial disease.
Toxicity ■ Clopidogrel can cause dyspepsia, rash or ■ Prasugrel can cause rash or, rarely ■ Ticagrelor can cause dyspnea and
diarrhea. hypersensitivity reactions and angioedema. bradycardia or, less commonly,
■ The drug is contraindicated in patients gastrointestinal symptoms.
with a history of cerecrovascular disease.
Drug -Omeprazole -Prasugrel -Warfarin -Dipyridamole -Ibuprofen -Warfarin -Phenobarbital
Interaction -Vorapaxar
 Antiplatelet (Antiaggregant) Drugs
Class Glycoprotein IIB/IIIA inhibitors Glycoprotein IIB/IIIA inhibitors Thrombin Receptor (PAR-1) Antagonists
Name Eptifibatide Tirofiban Vorapaxar
Mechanism ♦ Inhibit the binding site of fibrongen on ♦ Inhibit the binding site of fibrongen on ♦ Vorapaxar is a reversible antagonist o
of Action αIIbβ3. αIIbβ3. protease-activated receptor 1 (PAR-1), one
of two major thrombin receptors expressed
on platelets.
Uses ● It is used to treat acute coronary ● It is effective in non-Q-wave myocardial ● Vorapaxar is approved or secondary
syndrome and for angioplastic coronary infarction and unstable angina. prevention of myocardial infarction, death,
interventions. and stroke in patients with a prior
myocardial infarction or with peripheral
artery disease.
Toxicity ■ Bleeding ■ Bleeding ■ Vorapaxar should not be administered to
■ Thrombocytopenia ■ Thrombocytopenia patients with a prior history of stroke,
transient ischemic attack, or intracranial
hemorrhage.
Drug -Dipyridamole -Clopdigrel -Heparin -Dipyridamole -Clopdigrel -Heparin -Abciximab -Eptifibatide -Heparin
Interaction -Prasugrel -Warfarin -Vorapaxar -Prasugrel -Warfarin -Vorapaxar -Prasugrel -Phenobarbital -Warfarin
 Anticoagulants Drugs
Class Vitamin K Antagonist
Name Warfarin
Mechanism ♦ They interfere with the post-translational
of Action γ-carboxylation of glutamic acid residues in
clotting factors II, VII, IX and X as well as the
endogenous anticoagulant proteins C and S.
They do this by inhibiting vitamin K epoxide
reductase component 1 (VKORC1), thus
inhibiting the reduction of vitamin K
epoxide to its active hydroquinone form.
Uses ● Prevent the progression or recurrence of
acute DVT or pulmonary embolism
following an initial course of heparin.
● Prevent venous thromboembolism in
patient undergoing orthopedic or
gynecological surgery, recurrent coronary
ischemia in patient with acute myocardial
infarction, and systemic embolization in
patients with prothestic heart valves or
chronic atrial fibrillation.
Toxicity ■ Bleeding.
■ Birth defect and abortion during
pregnancy.
■ Skin necrosis.
■ Purple toe syndrome.
■ Intramuscular injection is not
recommended because the risk of
hematoma formation.
■ Alopecia, urticaria, dermatitis, fever,
nausea, diarrhea, abdominal cramps, and
anorexia.
Drug -Aspirin -Heparin -Vorapaxar
Interaction -Clopidogrel -Ibuprofen -Urokinase
Antithrombin III Activator (Accelerator)
Heparin (UFH)
♦ Heparin modifies the interaction of
antithrombin III with thrombin (IIa) and
other serine proteases including factors IXa,
Xa, XIa, and XIIa by binding, via a unique
pentasaccharide sequence, to antithrombin
III, changing its conformation and increasing
its affinity for serine proteases.
● Heparins are used or both prophylaxis
and treatment of thromboembolic diseases.
● Used to prevent propagation of
established thromboembolic disease such
as deep vein thrombosis and
pulmonary embolism.
■ Haemorrhage.
■ Thrombosis.
■ Osteoporosis.
■ Hypoaldosteronism.
■ Hypersensitivity reactions.
-Urokinase -Warfarin -Dabigatran
Vorapaxar
Antithrombin III Activator (Accelerator)
Enoxaparin (LMWH)
♦ Efficiently catalyze the inactivation of
factor Xa by antithrombin III but less
efficiently catalyze the inactivation of
thrombin by antithrombin III.
● Unfractionated heparin is often used in
combination with antiplatelet agents in the
treatment of acute coronary syndromes.
● Used to prevent propagation of
established thromboembolic disease such
as deep vein thrombosis and
pulmonary embolism.
■ Haemorrhage.
■ Thrombosis.
■ Osteoporosis.
■ Hypoaldosteronism.
■ Hypersensitivity reactions.
- -Urokinase -Warfarin -Dabigatran -
Vorapaxar
 Anticoagulants Drugs
Class Antithrombin III Activator (Accelerator)
(Selective Factor Xa Inhibitors)
Name Fondaparinux (LMWH)
Mechanism ♦ Fondaparinux avidly binds antithrombin
of Action with high specific activity, resulting in
efficient inactivation of factor Xa.
Uses ● Effective in the prevention and treatment
of venous thromboembolism.
● Approved for prevention and treatment
of deep vein thrombosis.
● Can be used in the initial management of
patient with unstable angina or acute
myocardial infarction.
Toxicity ■ Contraindicated in patient with a
creatinine clearance <30 mL/min.
■ Contraindicated in patient with body
weight <50 kg undergoing hip fracture, hip
replacement, knee replacement surgery or
abdominal surgery.
Drug -Heparin -Ibuprofen -Urokinase
Interaction -Warfarin -Vorapaxar
Direct Thrombin Inhibitor
Dabigatran etexilate
♦ Reversibly blocks the active site of
thrombin.
● Approved for prevention of
thromboembolism in patients with non-
valvular atrial fbrillation.
● It is also indicated for the treatment of
established deep vein thrombosis and
pulmonary embolism.
■ The primary toxicity of dabigatran is
bleeding. In one study, there was an
increase in gastrointestinal adverse
reactions and gastrointestinal bleeding
compared with warfarin.
-Urokinase -Verapamil -Vorapaxar
-Warfarin -Ibuprofen -Heparin
Recombinant Activated Protein C
(r-APC)
Drotrecogin alfa
♦ It inhibits coagulation by proteolytic
inactivation of factors Va and VIIIa.
♦ Also reduces the amount of circulating
plasminogen activator inhibitor 1, thereby
enhancing fibrinolysis.
♦ Also reduces inflammation by inhibiting
the release of tumor necrosis factor (TNF-α)
by monocytes.
● It is approved for the treatment of
patients with severe sepsis who
demonstrate evidence of acute organ
dysfunction, shock, oliguria, acidosis, and
hypoxemia.
● It has anti-inflammatory effects.
■ Bleeding.
■ It is contraindicated in patients who have
recently undergone a surgical procedure and
in those with chronic liver failure, kidney
failure, or thrombocytopenia.
-Aspirin -Clopidogrel -Dabigatran
-Eptifibatide -Heparin -Ibuprofen
-Prasugrel -Urokinase -Vorapaxar
-Warfarin
 Thrombolytic Drugs
Class Indirectly Acting Plasminogen Activator Directly Acting Plasminogen Activator Recombinant Tissue Plasminogen Activator
(t-PA)
Name Streptokinase Urokinase Alteplase
Mechanism ♦ It has no intrinsic enzymatic activity but ♦ It is a human enzyme synthesized by the ♦ It is a poor plasminogen activator in the
of Action forms a stable, noncovalent 1:1 complex kidney that directly converts plasminogen absence of fibrin. It bind to fibrin via its
with plasminogen. This produces a to active plasmin. finger domain and second lyine-binding
conformational change that exposes the kringle domain and activates fibrin-bound
active site on plasminogen that cleaves plasminogen several hundredfold more
Arg560 on free plasminogen to form plasmin. rapidly than it activates plasminogen in the
circulation.
Uses ● Streptokinase is approved for treatment ● It is used to treat blood clots in the lungs. ● It is approved for treating strokes.
of ST elevation myocardial infarction and or ● It is effective at recanalizing occluded
treatment of life-threatening pulmonary coronary arteries, limiting cardiac
embolism. dysfunction, and reducing mortality
following an ST elevation myocardial
infarction.
Toxicity ■ Patients with antistreptococcal antibodies ■ Bleeding. ■ Bleeding.
can develop fever, allergic reactions, and
therapeutic resistance.
■ Streptokinase has been associated with
increased bleeding risk in acute ischemic
stroke when given at a dose of 1.5 million
units, and its use is not recommended in
this setting.
■ Streptokinase causes a burst of plasmin
formation, generating kinins, and can cause
hypotension by this mechanism.
■ Thrombolytic actions of streptokinase are
relatively nonspecific and can result in
systemic fbrinolysis.
Drug -Dabigatran -Eptifibatide -Heparin -Dabigatran -Eptifibatide -Heparin -Dabigatran -Eptifibatide -Heparin
Interaction -Prasugrel -Vorapaxar -Warfarin -Prasugrel -Vorapaxar -Warfarin -Prasugrel -Vorapaxar -Warfarin
References:
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2. Brunton L, Chabner B, Knollman B. Goodman and Gilman's, The Pharmacological Basis of Therapeutics; McGraw-Hill, Twelfth
Edition. 2011.
3. Golan DE, Armstrong EJ, Armstrong AW. Principles of Pharmacology, The Pathophysiologic Basis of Drug Therapy; LWW, Forth
Edition. 2016.
4. Humphrey P. Rang, Maureen M. Dale. Rang & Dale's Pharmacology, Publisher; Churchill Livingstone, Eighth Edition 2016.
5. https://www.drugs.com