PARENTERAL anticoagulants

1. PARENTERAL
ANTICOAGULANTS
Dr.M.Karthiga
M.D., DNB., Pharmacology

2. • Hemostasis - finely regulated dynamic process
of maintaining fluidity of the blood, repairing
vascular injury, and limiting blood loss while
avoiding vessel occlusion (thrombosis) and
inadequate perfusion of vital organs.
Injured vessel
wall
Platelets
Coagulation
factors

4. ANTITHROMBOSIS
Some factors also oppose clot formation, rather
lyse it
To check the balance, these anticoagulants are
present
They operate to maintain blood in fluid state in
circulation & allows rapid haemostatis following
injury
E.g. antithrombin, protein C, protein S,
antithromboplastin & fibrinolysin system
NOTE – PT is raised in common & extrinsic
pathway disturbance & a PTT is raised in common
& intrinsic pathway damage
Normally, PT=12-14 S, a PTT= 26-32 S units

6. Drugs to reduce coagulability of blood
Inhibition of formation of fibrin clots
1) USED IN-VIVO-
PARENTERAL (Heparin LMW);
ORAL- Coumarins & Indandiones (Warfarin, dicoumarol)
2) USED IN-VITRO-
Heparin
CALCIUM COMPLEXES- sodium citrate/ oxalate/
edetate
6

7. Antithrombin

8. HEPARIN

9. HEPARIN
UFH
Large sulfated polysaccharide
polymer obtained from animal
sources.
Anionic glycosaminoglycans
Average molecular weight- 15,000–
20,000.
Highly acidic and can be neutralized by
basic molecules (eg, protamine).
IV/SC- avoid the risk of hematoma
associated with intramuscular injection.

10. Low-molecular-weight (LMW)
heparin
Breakdown by alkalisation of heparin
benzyl ester
Molecular weights of 2000–6000
Greater bioavailability and longer
durations of action than
unfractionated heparin
SC
Fondaparinux is a small
pentasaccharide fragment of heparin

11. MOA

12. MOA

13. • Binds to clotting factors
Xa, IIa, IXa, XIa, XIIa,
XIIIa  inactivates
intrinsic pathway only
• Heparin provides
anticoagulation
immediately after
administration because
it acts on preformed
blood components
• aPTT
• LMW heparins and
fondaparinux, like
unfractionated heparin,
bind ATIII.
• These complexes have
the same inhibitory
effect on factor Xa as
the unfractionated
heparin–ATIII complex
• Provide a more
selective action
because they fail to
affect thrombin

16. systemic hypercoagulable
immunological reaction
degradation of platelets
T/t - argatroban
.

22. FONDAPARINUX
Synthetically derived pentasaccharide
anticoagulant that selectively inhibits factor
Xa.
DVT and PE and for the prophylaxis of
venous thromboembolism in the setting of
orthopedic and abdominal surgery.
Predictable pharmacokinetic profile
Eliminated in the urine mainly as
unchanged drug with an elimination half-life
of 17 to 21 hours.
Bleeding is the major side effect of
fondaparinux.

24. Direct Thrombin Inhibitors
• Hirudin ,
• Lepirudin ,
• Bivalirudin
• Argatroban
Parenteral
• Ximelagatran Melagatran
• Dabigatran
Oral
Based on proteins made by Hirudo
medicinalis, the medicinal leech.

25. • Lepirudin - recombinant form
of the leech protein hirudin,
while desirudin and
bivalirudin are modified forms
of hirudin.
Predictable pharmacokinetics,
which allows for fixed dosing,
as well as a predictable
immediate anticoagulant
response
• Lepirudin bind simultaneously
to the active site of thrombin
and to thrombin substrates.
• Argatroban binds solely to the
thrombin-active site.
• Inhibit both soluble
thrombin and the thrombin
enmeshed within
developing clots.
• Bivalirudin also inhibits
platelet activation.
• Bleeding.
• No reversal agents
• Prolonged infusion of
lepirudin can induce
antibodies that form a
complex with lepirudin and
prolong its action, and it can
induce anaphylactic
reactions.
Dabigatran
Prevention of stroke and
systemic embolism in
nonvalvular atrial fibrillation.

28. Drugs that activates the conversion of
plasminogen to plasmin, a serine
protease that hydrolyzes fibrin and, thus,
dissolves clots
Streptokinase
Urokinase
Alteplase
Tenecteplase
Reteplase

29. STREPTOKINASE
Extracellular protein purified from culture
broths of group C b-hemolytic streptococci.
It forms an active one-to-one complex with
plasminogen.
This enzymatically active complex converts
uncomplexed plasminogen to the active
enzyme
Catalyzes the degradation of clotting
factors V and VII
Acute myocardial infarction, acute
pulmonary embolism (PE), deep vein
thrombosis (DVT), reperfusion of occluded
peripheral arteries, and venous catheters

30. Urokinase
Naturally in the body by the kidneys.
Therapeutic urokinase is isolated from
cultures of human kidney cells and
has low antigenicity.
Directly cleaves the arginine—
valine bond of plasminogen to
yield active plasmin.
Lysis of pulmonary emboli..

31. Alteplase
tissue
plasminogen
activator
Half-life-5-30
mins
Angioedema
Reteplase
Smaller
derivative of
recombinant
tPA.
Tenecteplase
Greater binding
affinity for fibrin
longer half-life

32. MOA
Start early as clots become more resistant to lysis
as they age.
Administration of antiplatelet drugs, such as
aspirin, or antithrombotics, such as heparin

33. THERAPEUTIC USES
For MI, intracoronary delivery of the drugs
is the most reliable in terms of achieving
recanalization.
Restoring catheter and shunt function, by
lysing clots causing occlusions.
To dissolve clots that result in strokes.
Alteplase is approved for the treatment of
MI, massive PE, and acute ischemic
stroke.
Tenecteplase is approved only for use in
acute MI.

34. Adverse effects
Hemorrhage is a major adverse effect. For
example, a previously unsuspected lesion,
such as a gastric ulcer, may hemorrhage
following injection of a thrombolytic agent
Contraindicated in pregnancy, and in
patients with healing wounds, a history of
cerebrovascular accident, brain tumor,
head trauma, intracranial bleeding, and
metastatic cancer