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DRUGS AFFECTING THE
BLOOD
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Drugs Affecting Blood

Treatment of
 Anemia
 Thrombosis
 Bleeding
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Drugs used to treat thrombotic
disorders

Anticoagulants

Thrombolytics
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Drugs for treatment of anemia
Vitamin B12
 Erythropoietin
 Folic acid
 Iron

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Drugs for treatment of bleeding
Aminocaproic acid
 Enoxaparin
 Heparin
 Warfarin
 Lepirudin

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Platelet Response To Vascular
Injury
Platelet adhesion to site of vascular injury
 Activation of platelets by factors that include
TxA2, ADP, serotonin, collagen & thrombin
 Increase expression of glycoprotein IIb/IIIa
receptors
 Aggregation of platelets by a cross-linking
reaction due to fibrinogen binding to
glycoprotein IIb/IIIa receptors
 Formation of the thrombus by fibrin monomer
cross link.

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Platelet aggregation inhibitors

These agents are beneficial in the
prevention and treatment of occlusive
cardiovascular diseases
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Antiplatelet drugs
Aspirin
 Ticlopidine and clopidogreal
 Abciximab
 Tirofiban and eptifibatide
 Dipyridamole
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Platelet Inhibitors

Aspirin
 Blocks
cyclooxygenase 1,
inhibiting the
formation of
thromboxane A2
Arachidonic Acid
Cyclooxygenase
Prostaglandins, Thromboxane
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ASPIRIN
Used as prophylactic in treatment of TIA &
atrial fibrillation.
 Low dose: prevent incidence of MI and
recurrence
 SE; GI disturbance, Bleeding Time
prolonged.
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 Ticlopidine
Inhibits the binding of ADP to its
receptor on platelet resulting in a ↓ in
platelet aggregation and thrombus
formation
 Very effective (adverse effect:
neutropenia)
 Clopidogrel – NEWER DRUG (same
mechanism- no neutropenia)
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Abciximab, Eptifibatide &
Tirofiban
 Tirofiban
& Eptifibatide: antagonists
of glycoprotein IIb/IIIa receptors –
decrease aggregation by preventing
cross- linking reaction.
Abxicimab: is a monoclonal antibody that
binds to GPIIb/IIIa preventing platelet
aggregation
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Anticoagulants

Are drugs used to treat and prevent clotting
via inhibition of various steps in the
coagulation pathway which involves two
interrelated pathways called the intrinsic
and extrinsic pathway
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Heparin

Binds to antithrombin III
in blood causing rapid
inactivation of factors IIa
& Xa (mainly).

Heparin is a large
polysaccharides given
IV/SC.
No placental access.

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Heparin

Effective in acute treatment of
 Venous thrombosis prevention - post
surgical
 Deep venous thromboembolism
 Acute myocardial infarction
 Prevention of clotting in medical devices
(catheters, hemodialysis, heart lung
machines)
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HEPARIN
SE:
 HEMORRHAGE
 HYPERSENSITIVITY
 THROMBOSIS
 THROMBOCYTOPENIA
 Monitor the activated partial thromboplastin time
 CI – hypersensitive pts, OR BLEEDING
DISORDERS, ALCHOLICS..
 Excessive Bleeding caused by heparin use can be
reversed with protamine sulfate
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Low molecular weight Heparin
LMWH e.g., enoxaparin
 Binds to antithrombin III also causing rapid
inactivation of factor Xa
 Longer half-life
 Can be used in hospital as well as out-patient
setting.
 Given subcutaneously
 Uses: same as heparin
 Adverse effect: same as heparin but less likely
to cause HIT
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ARGATROBAN
Is a direct thrombin inhibitor
 It does not require ATIII
 Does not interact with heparin-induced
antibodies
 Can be used to treat HIT
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Lepirudin (hirudin)

Closely related to hirudin –a thrombin
inhibitor from leech

Lepirudin is produced in yeast cells by recombinant DNA
tech
Thrombin inhibition
 Property of preventing
coagulation of the blood.

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 Lepirudin
is approved for use in patients
with heparin-induced
thrombocytopenia/thrombosis syndromes.
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DANAPAROID
Anti-factor IIa and Xa but more an anti-Xa
 Given SC
 USES: prophylaxis of DVT in hip
replacement surgery
 Used for HIT
 Adverse effect: bleeding
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Warfarin (Coumarin)
Is an antagonist of vitamin K that prevents
gamma carboxylation reactions in hepatic
synthesis of coagulation factors II, VII, IX , X,
protein C & S by inhibing the enzyme vit Kepoxide reductase
 No effect on factors already made by the liver
 – slow onset – 24 – 48 hrs.
 Reversal (antagonist): vitamin K – Increase
cofactor synthesis, but slow onset; fresh frozen
plasma – rapid.
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Warfarin – Vitamin K-Antagonist
 ORAL
 Met:
by liver via P450
 Effective in:
 longer-term anticoagulation for
thromboses, emboli, post MI, heart
valve damage & artificial heart valves
caused thromboembolism
 Monitor prothrombin time
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Warfarin
 Crosses
placenta
 Teratogenic
 Contraindicated in pregnant women

Anticoagulation in pregnancy heparin
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
Adverse effects:
hemorrhage, skin necrosis, “purple toe”
syndrome, teratogenic (bone
dysmorphogenesis).
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Drug interaction
↑es warfarin level and activity:
 Aspirin, sulfonamides, cimetidine, acute
alcohol, metronidazole e.t.c.,
 ↓es warfarin level and activity:
 Chronic alcohol ingestion, barbiturates,
rifampin, griseofulvin etc.,
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THROMBOLYTIC AGENTS
ALTEPLASE (t PA)
 STREPTOKINASE
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Thrombolytics


tPA (Tissue Plasminogen
Activator
 Activates plasminogen
bound to fibrin
Streptokinase
 Activates free plasminogen
into active plasmin
Plasminogen
tPA, Streptokinase
Plasmin
Fibrin
Fibrin
Degradation
Products
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 Alteplase
(tPA): natural activator, so
no allergy problems; clot(fibrin)specific, acting on fibrin-bound
plasminogen.
 Streptokinase:
acts on bound & free
plasminogen
 Decrease fibrinogen and factors V &
VIII;
 Bacterial protein - hypersensitivity.
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Rx uses: short term emergency treatment before
infarction of tissues ensues:
 coronary thromboses in MI,
 deep venous thromboses,
 pulmonary embolism &
 ischemic stroke (tPA).

Adverse effects: bleeding, intracerebral
hemorrhage.
 Reversal: aminocaproic & tranexamic acids.
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CAUSES OF BLEEDING
Genetic diseases such as hemophilia
 Use of thrombolytics
 Use of anticoagulants
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DRUGS USED TO TREAT BLEEDING

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
Infusion of factors VIII and IX made by recombinant
DNA technology or from human blood serum to treat
hemophilia
Aminocaproic acid and tranexamic acid: to reverse
bleeding caused by use of thrombolytics. Act by inhibiting
plasminogen activation
Protamine sulfate: reverse bleeding caused by heparin.
Acts by binding ionically to heparin forming an ion
complex
Vitamin K: reverse bleeding caused by warfarin use.
Though fresh-frozen plasma is used if immediate
hemostasis is required.
 Blood
transfusion
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ANEMIA

Is defined as a ↓ in Hb concentration
resulting from a ↓ in number of circulating
RBCs.
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CAUSES OF ANEMIA
Chronic blood loss
 Bone marrow abnormalities
 Increased hemolysis
 Malignancies
 Renal disease
 Drugs: anticancer agents
 Nutritional deficiency: in iron, folic acid
and vitamin B12.
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AGENTS USED TO TREAT
ANEMIA
Iron
 Folic acid
 Vitamin B12
 Erythropoietin: made by recombinant DNA
technology used in those pts with renal
failure
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AGENT USED TO TREAT
SICKLE CELL DISEASE
Hydroxyurea: an anticancer drug
 MOA: ↑ fetal Hb levels

↑ nitric oxide level in blood → in
vasodilation → ↓ in sickling
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