HEMOSTASIS
HEMOSTASIS
It is the arrest of blood loss from
damaged vessels and is essential to
life
HEMOSTASIS
HEMOSTASIS
Physical trauma to the vascular
system causes
vasoconstriction
and
initiates series of interactions
between
platelets
,
endothelial cells
and
the
coagulation cascade
.
Formation of a hemostatic
Formation of a hemostatic
plug
plug
1.
Damage to vessel exposes
collagen of sub-endothelium
2.
Platelet adhesion and release of
granules
3.
Platelet aggregation and activation
factors in plasma
THROMBOSIS
THROMBOSIS
It is a pathological condition resulting
from inappropriate activation of
haemostatic mechanisms.
VENOUS THROMBOSIS
VENOUS THROMBOSIS
Usually associated with stasis of
blood;
Venous thrombus has a small platelet
component and a large component of
fibrin
ARTERIAL THROMBOSIS
ARTERIAL THROMBOSIS
Usually associated with
atherosclerosis;
Arterial thrombus has a large platelet
component
Drugs affect haemostasis
Drugs affect haemostasis
and thrombosis
and thrombosis
By affecting:
•
Blood coagulation (fibrin formation)
•
Platelet function
•
Fibrin removal (fibrynolysis)
DRUG AFFECTING BLOOD
PLATELET INHIBITORS
ANTICOAGULANTS
THROMBOLYTIC AGENTS
DRUG AFFECTING BLOOD
PLATELET INHIBITORS
Aspirin
Clopidogrel
Ticlopidine
Glycoprotein IIb/IIIa
Receptor Antagonists
ANTIPLATELET DRUGS –
ANTIPLATELET DRUGS –
ASPIRIN
ASPIRIN
•
Inactivates constitutive form of
cyclooxygenase
(COX-1), the key enzyme
which takes part in synthesis among other
thromboxane
A
2
(TXA
2
) in platelet from
arachidonic acid
•
TXA
2
promotes aggregation
•
Suppression of platelet aggregation last to
the end of platelet’s life (7-10 days)
ANTIPLATELET DRUGS –
ANTIPLATELET DRUGS –
ASPIRIN
ASPIRIN
•
Daily recommended dose is 75-100mg
•
Clinical uses:
•
prophylactic treatment of transient
ischemic atacks (TIA)
•
Reduction of the incidence of myocardial
infarction
•
decrease mortality in postmyocardial
infarction patients
ANTIPLATELET DRUGS –
ANTIPLATELET DRUGS –
ASPIRIN
ASPIRIN
•
Unwanted effects:
•
Bleeding time is prolonged
•
Increased incidence of hemorrhagic
stroke
•
Increased incidence of gastrointestinal
bleeding (ulcer)
ANTIPLATELET DRUGS –
ANTIPLATELET DRUGS –
TICLOPIDINE
TICLOPIDINE
•
It inhibits ADP-dependent aggregation of the
platelet
•
Decreases the incidence of thrombotic stroke
•
Clinical uses:
•
For patients who cannot tolerate Aspirin
•
Unwanted effects:
•
Prolonged bleedings
•
Neutropenia
ANTIPLATELET DRUGS –
ANTIPLATELET DRUGS –
CLOPIDOGREL
CLOPIDOGREL
•
It is analog of ticlopidine
•
Also inhibits ADP-induced aggregation
•
It is more effective than Aspirin
•
It is recommended for patients before PTCA
•
The main unwanted effect is bleeding
•
It can inhibit cytochrom P-450 so it may interfere
with metabolism of other drugs (warfarin or
fluvastatin)
ANTIPLATELET DRUGS –
ANTIPLATELET DRUGS –
antagonists of GP IIb/IIIa
antagonists of GP IIb/IIIa
receptors
receptors
•
ABCIXIMAB a monoconal antibody
•
TIROFIBAN oligopeptid
ANTIPLATELET DRUGS –
ANTIPLATELET DRUGS –
antagonists of GP IIb/IIIa
antagonists of GP IIb/IIIa
receptors
receptors
•
They inhibit all pathways of platelet
activation
•
By binding to GP IIb/IIIa receptor they
block the binding of fibrynogen and other
factor and aggregation does not occur
ANTIPLATELET DRUGS –
ANTIPLATELET DRUGS –
antagonists of GP IIb/IIIa
antagonists of GP IIb/IIIa
receptors
receptors
•
They are used intravenously for single
administration
•
CLINICAL USES:
•
in high-risk patients undergoing coronary angioplasty
to reduce the risk of restenosis
•
UNWANTED EFFECTS:
•
potencial of bleeding
•
immunogenicity
DRUG AFFECTING BLOOD
ANTICOAGULANTS
HEPARIN
ENOXAPRIN
VITAMIN K
ANTAGONISTS
WARFARIN
ACENOCOUMAROL
CLINICAL USE OF
CLINICAL USE OF
ANTICOAGULANTS
ANTICOAGULANTS
They are used for prevention of:
•
Deep vein thrombosis
•
Extension of established deep vein
thrombosis or recurrence of
pulmonary embolus
•
Thrombosis and embolisation in
patients with atrial fibrillation
CLINICAL USE OF
CLINICAL USE OF
ANTICOAGULANTS
ANTICOAGULANTS
•
Thrombosis on prosthetic heart valves
•
Cardiac events in patients with
unstable coronary syndromes
•
Cotting in extracorporeal circulations
(haemodialysis or bypass surgery)
HEPARIN
HEPARIN
•
It is not a single substance but a family of
mucopolysaccharides
•
It is present with histamine in the
granules of mast cells
HEPARIN
HEPARIN
•
Inhibits coagulation by activating
antithrombin III, which inhibits thrombin
(IIa) , factor Xa and other serine proteases
by binding to the active site
HEPARIN
HEPARIN
•
Is given intravenously or subcutaneously
•
The activated partial thromboplastin time
(APTT) must be measured
(targed range 1,5-2,5 times control)
HEPARIN
HEPARIN
ADVERSE EFFECTS
•
Hemorrhage
•
Hypersensitivity reactions: chills, fever
and even anaphylactic shock
•
Thrombocytopenia (after 8-10 days of
treatment)
ENOXAPRIN
ENOXAPRIN
It is one of low-molecular-weight heparins
(LMWHs);
It is fractionated heparin
ENOXAPRIN
ENOXAPRIN
•
Increase the action of antithrombin III on
factor Xa
•
Does not act on thrombin
•
Has a longer elimination half-time than
heparin
•
Does not prolong the APTT
ORAL ANTICOAGULANTS -
ORAL ANTICOAGULANTS -
WARFARIN
WARFARIN
•
Warfarin has structual similarity to
vitamin K
•
Inhibits activation of factors II, VII, IX, X,
which are depend on present of vitamin K
ORAL ANTICOAGULANTS -
ORAL ANTICOAGULANTS -
WARFARIN
WARFARIN
•
Pharmacological effect is delayed, it can
occur about 48 hours after first
administration
•
The effect must be monitored by
measuring INR (target range 2-3)
•
Dose are given indyvidualised according
to INR
ORAL ANTICOAGULANTS -
ORAL ANTICOAGULANTS -
WARFARIN
WARFARIN
ADVERSE EFFECTS
•
Hemorrhage and bleeding
•
Cause abortion
•
It is teratogenic agent
WARFARIN - interactions
Increased effect
Amiodarone
Ciprofloxacin
Metronidazole
Some of NSAIDs
Sulfonamides
Decreased effect
Vitamin K
Barbiturates
DRUG AFFECTING BLOOD
THROMBOLYTIC AGENTS
ALTEPLASE
STREPTOKINASE
THROMBOLYTIC DRUGS
THROMBOLYTIC DRUGS
CLINICAL USES:
Acute myocardial infarction within 12
hours of onset
THE EARLIER THE BETTER!
Acute thrombotic stroke within 3
hours of onset (in selected patients)
Acute arterial thromboembolism
Clearing arterial shunts and cannulae
THROMBOLYTIC DRUGS
THROMBOLYTIC DRUGS
STREPTOKINASE
Is a protein extracted from culture of
streptococci
Activates free plasminogen to convert
to plasmin, which in turn cleaves
fibrin, thus lysing thrombi
THROMBOLYTIC DRUGS
THROMBOLYTIC DRUGS
STREPTOKINASE
ADVERSE EFFECTS
Bleeding disorders
Hypersensivity – rashes, fever,
anaphylactic shock
THROMBOLYTIC DRUGS
THROMBOLYTIC DRUGS
STREPTOKINASE
Drug does not act in patients who
have circulating antibodies against
streptokinase (in case streptococcal
infection);
they may neutralize its fibrynolytic
effect
THROMBOLYTIC DRUGS
THROMBOLYTIC DRUGS
Alteplase
Known as tissue-type plasminogen
Known as tissue-type plasminogen
activator (tPA)
activator (tPA)
•
Is a serine protease from cultured
human mellanoma cells
•
Activates only plasminogen bound to
fibrin in a thrombus or a hemostatic
plug („fibrin selective”)
THROMBOLYTIC DRUGS
THROMBOLYTIC DRUGS
Alteplase (tPA)
ADVERSE EFFECTS
ADVERSE EFFECTS
•
BLEEDING complication
(gastrointestinal and cerebral
hemorrhages)