Transcript CVS 5

DRUGS AFFECTING THE
BLOOD
1
Drugs Affecting Blood

Treatment of
 Anemia
 Thrombosis
 Bleeding
2
Drugs used to treat thrombotic
disorders

Anticoagulants

Thrombolytics
3
Drugs for treatment of anemia
Vitamin B12
 Erythropoietin
 Folic acid
 Iron

4
Drugs for treatment of bleeding
Aminocaproic acid
 Enoxaparin
 Heparin
 Warfarin
 Lepirudin

5
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.

6
7
8
Platelet aggregation inhibitors

These agents are beneficial in the
prevention and treatment of occlusive
cardiovascular diseases
9
Antiplatelet drugs
Aspirin
 Ticlopidine and clopidogreal
 Abciximab
 Tirofiban and eptifibatide
 Dipyridamole

10
Platelet Inhibitors

Aspirin
 Blocks
cyclooxygenase 1,
inhibiting the
formation of
thromboxane A2
Arachidonic Acid
Cyclooxygenase
Prostaglandins, Thromboxane
11
ASPIRIN
Used as prophylactic in treatment of TIA &
atrial fibrillation.
 Low dose: prevent incidence of MI and
recurrence
 SE; GI disturbance, Bleeding Time
prolonged.

12
 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)

13
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
14
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
15
16
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.

17
18
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)
19
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
20
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

21
ARGATROBAN
Is a direct thrombin inhibitor
 It does not require ATIII
 Does not interact with heparin-induced
antibodies
 Can be used to treat HIT

22
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.

23
 Lepirudin
is approved for use in patients
with heparin-induced
thrombocytopenia/thrombosis syndromes.
24
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

25
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.

26
27
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
28
Warfarin
 Crosses
placenta
 Teratogenic
 Contraindicated in pregnant women

Anticoagulation in pregnancy heparin
29

Adverse effects:
hemorrhage, skin necrosis, “purple toe”
syndrome, teratogenic (bone
dysmorphogenesis).
30
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.,

31
THROMBOLYTIC AGENTS
ALTEPLASE (t PA)
 STREPTOKINASE

32
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
33
34
 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.
35
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.

36
37
CAUSES OF BLEEDING
Genetic diseases such as hemophilia
 Use of thrombolytics
 Use of anticoagulants

38
DRUGS USED TO TREAT BLEEDING




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
39
ANEMIA

Is defined as a ↓ in Hb concentration
resulting from a ↓ in number of circulating
RBCs.
40
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.

41
AGENTS USED TO TREAT
ANEMIA
Iron
 Folic acid
 Vitamin B12
 Erythropoietin: made by recombinant DNA
technology used in those pts with renal
failure

42
AGENT USED TO TREAT
SICKLE CELL DISEASE
Hydroxyurea: an anticancer drug
 MOA: ↑ fetal Hb levels

↑ nitric oxide level in blood → in
vasodilation → ↓ in sickling

43