Transcript Drugs-Affecting-Haemostasis.22.Mar.2011

Drugs affecting haemostasis,
Antianemic drugs
A. Kohút
Drugs used to treat blood disorders
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1. Anticoagulants
2. Antiagregatory drugs (antiplatelets)
3. Thrombolytics
4. Antifibrinolitics
5. Drugs for anemia
Anticoagulants
Hemostasis:
Injury
Tissue
Factor
Neural
Blood Vessel
Platelet
Coagulation
Constriction
Activation
Primary hemostatic plug
Activation
Reduced
Plt-Fusion
Blood flow
Thromibn,
Fibrin
Stable Hemostatic Plug
Coagulation:
Intrinsic 12,11,9,8
(aPTT-)
Extrinsic-7
(PT)
Common Path (TT)
FX  FXa
Prothrombin Thrombin
Fibrinogen  Fibrin
Process- primary haemostasis
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In a normal individual, coagulation is
initiated within 20 seconds after an injury
occurs to the blood vessel damaging the
endothelial cells.
Platelets immediately form a haemostatic
plug at the site of injury. This is called
primary haemostasis.
Secondary haemostasis
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Secondary haemostasis then follows—plasma
components called coagulation factors respond (in
a complex cascade) to form fibrin strands which
strengthen the platelet plug.
Contrary to popular belief, coagulation from a cut
on the skin is not initiated by air or drying out, but
by platelets adhering to and activated by collagen
in the blood vessel endothelium.
The activated platelets then release the contents of
their granules, these contain a variety of
substances that stimulate further platelet activation
and enhance the haemostatic process.
Mechanism of action of warfarin
Comparisson of heparin and
warfarin
Unfractionated heparin UFH)
• (UFH) is able to inactivate fa
IIa through formation of a
tertiary complex, unlike
LMWH.
• UFH binds more to plasma
proteins, endothelium and
macrophages, resulting in
reduced bioavailability and
greater patient variability to
a given dose.
• UFH inactivates factors IIa
and Xa and affects the aPTT,
a measure of anti-factor IIa
activity. (aPTT=activated
partial thromboplastin time)
Low molecular weight size heparin
(LMW)
• LMW heparins are fragments
of parent heparins (1/3 of
parent compound.
• Inhibit fa Xa and augment
tissue-factor-pathway
inhibitor
• minimally affect thrombin, or
factor IIa
• Thus, a measure of
antithrombin (anti-factor IIa)
activity (aPTT=activated
partial thromboplastin time) ,
is not used to measure the
activity of LMW heparins,
• requires instead a specific
anti-Xa assay.
Indication and contraindication of
anticoagulants
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Indications
Atrial fibrilation,
Venouse
thromboembolism,
Acute myocardial
infarction,
Prevention of venous
thromboembolism.
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Contraindications
Severe hypertension,
Recent cerebral
haemorhage,
Gastric ulcer,
Severe liver and renal
disease,
Pregnancy (warfarin),
Preexisting bleeding
disorders.
Heparin induced thrombocytopenia
Heparin-Antibiotic Interactions
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The second-generation cephalosporins- cefamandole, cefotetan,
and cefoperazone, contain an N-methylthiotetrazole (NMTT) side
chain. This NMTT group can:
- Dissociate from the parent antibiotic in solution or in vivo and
competitively inhibit vitamin K action, leading to prolongation of
the prothrombin time and bleeding.
- This side chain is also associated with a disulfiram-like reaction
to alcohol.
- Clinical bleeding has been less frequently reported with
Cefotetan than with cefoperazone or cefamandole.
Drugs and conditions interacting with warfarin
The action of thrombolitics and
antifibrinolytics
The action of thrombolitics and antifibrinolytics
Therapeutic uses
of thrombolitics and antitfibrinolytics
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Thrombolitics : treatment of myocardial
infarction, acute thrombotic stroke
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Antifibrinolytics: excessive bleeding
after dental extraction in haemophiliacs
after overdoses of streptokinase
DRUG USED TO TREAT BLEEDING
Vitamin K
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formation of clotting factors II,
VII, IX and X
given orally, i.m. or i.v.
synthetic preparation (menadiol
sodium diphophate) is water
soluble and thus not require bile
salt for its absorption
Clinical use: - bleeding caused
by the oral anticoagulants, hypoprotrombinemia in
newborn (intestinal flora is not
established)
Aprotinin -
antifibrinolitic
Aminocaproic acid,
tranexamic acid, -
bleeding after fibrinolytic
therapy.- inhibit plasminogen
activation
Protamine sulfate
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- antagonizes the anticoagulant
effect of heparin
- positively charged protein
interacts with negatively
charged heparin to form stable
complex without anticoagulant
activity
Antiagregatory drugs
(Antiplatelet drugs)
Mechanisms of action of antiplatelet drugs
Antianemic drugs
Causes of anaemia
Inadequate production of red blood cells in bone marrow
due to:
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Excessive destruction of red blood cells due to:
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Lack of raw materials e.g. nutritional anaemia.
Depression of bone marrow e.g. chronic infections, drugs,
radiation etc.
Infiltration of bone marrow in conditions like malignancy.
Abnormality of haemoglobin like thalassemia,
Deficiency of red cell enzymes like Glucose 6 phosphate
dehydrogenase deficiency,
Abnormality of red cell membrane like hereditary sperocytosis
Auto immune haemolytic anaemias
Blood loss due to any cause
Megaloblastic anaemia
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Deficiency of vitamin B12 or folate or both.
Deficiency of these nutrients may be due to:
Decreased intake - vitamin B12 deficiency is seen
in strict vegetarians. Over cooking in boiling water
reduce folate content in food.
Impaired absorption - due to disease of
gastrointestinal tract and surgical resection of
intestine.
Defective utilisation - due to drugs like few types
of cancer drugs and epilepsy drug interfere with
metabolism of folic acids.
Increased demand - pregnancy, recovery from
chronic illness etc.
Microcytic anaemia
Due to reduced intake or absorption of iron:
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Iron poor diet
Malabsorption syndromes
Chronic diarrhoea
Gastrointestinal surgery
Due to increased loss:
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Gastrointestinal bleeding due to any cause
Hook worm infestation
Bleeding disorders
Excessive menstruation
Due to increased demands:
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Pregnancy
Lactation
Prematurity and low birth weight
Adolescence
Chronic illness
Types and the treatment of anaemias
Hematopoietic growth factors
• SCF - stem cell factor
• BFU-E - . burst-forming units
erythroblasts
• CFU-E- colony-forming units
erythroid
• GM-CSF, granulocytemacrophage colonystimulating factor interleukin-4,
and interleukin-9.
• EPO - erythropoietin is a
specific distal acting factor,
which stimulates maturation of
CFU-E to mature erythrocytes.
Factors involved in the development of
anaemia and the role of EPO
• TNF may inhibit the actions
of erythropoietin,
• IL-1 affect utilization EPO
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IF-beta and IF-gamma
suppress erythropoiesis.
• administration of
• EPO can actually improve
anemia across a wide range
of disease states.