Drugs with Important

Actions on Blood

Agents Used in Anemias and

Hematopoietic Growth Factor
cells essential for oxygenation of
tissues, coagulation, protection against
infectious agents, and tissue repair
The most common cause erytrocyte
deficiency or anemia :
- insufficient supply of iron, vitamin B12, or
folic acid
Blood

Blood cells deficiencies

deficiency microcytic hypochromic
anemia (the most common type)
Deficiency of vitamin B12 or folic acid
megaloblastic anemia
Pernicious anemia the most common type of
vit B12 deficiency anemia caused by a defect in
the synthesis of intrinsic factor or by surgical
removal of that part of stomach that secretes
intrinsic factor
Deficiency in the concentration of various blood
cells can be manifestation of a disease or side
effect of radiation
Iron

IRON
An

essential metalic component of heme

Deficiency this agent occurs most often in:
- women (menstrual blood)
- vegetarian or malnourished individual
- children and pregnant women (increased
requirements)

IRON
Clinical use :
Iron deficiency anemia (the only indication)
Should not be given in hemolytic anemia because iron store
are elevated
Toxicity :
Acute iron intoxication
sign & symptoms : necrotizing gastroenteritis, shock,
metabolic acidosis, coma.
Tx : deferoxamine parenterally, which chelats circulating iron
Chronic iron intoxication
occurs most often in individuals who receive frequent
transfusions; hemochromatosis.
treatment of hemochromatosis is usually by phlebotomy

VITAMIN B12
Vitamin

B12 is cofactor required for the

normal maturation of red blood cells
It is absorbed from the GI tract in the
presence of intrinsic factor
The 2 available form of vitamin B12;
cyanocobalamin and hydroxocobalamin

VITAMIN B12
Clinical use
Pernicious anemia
Anemia caused by gastric resection
Vitamin B12 def anemia is almost always
caused by inadequate absorption
therapy using parentally of vitamin B12
Toxicity :
Has no significant toxicity

FOLIC ACID
Folic

acid is required for normal DNA

synthesis
Deficiency of this agent usually present as
megaloblastic anemia; increases the risk
of neural tube defect in the fetus (during
pregnancy)
Folic acid is absorbed from GI tract

FOLIC ACID
Clinical use :
Anemia resulting from folic acid deficiency
Folic acid supplement will correct anemia
but not the neurologic deficits of vit B12
deficiency
Toxicity :
Has no recognized toxicity

HEMATOPOIETIC GROWTH
FACTORS
Erythropoietin
Myeloid

Growth Factors (Filgrastim,

sargramostrim

Erythropoietin

Produced by the kidney

Reduction in its synthesis is responsible for the anemia
of renal failure
Erythropoietin stimulates the production of red cells and
increases their release from the bone marrow
Clinical use :
- routinely used for the anemia associated with renal
failure
- patient with other forms of anemia (primary or
secondary bone marrow disorder to cancer
chemotherapy or HIV treatment, bone marrow
transplantation

Myeloid Growth Factor

Filgrastim (granulocyte colony-stimulating factor; G-CSF)

Sagramostin (granulocyte-macrophage colonystimulating factor; GM-CSF)
Clinical use :
Both are used to accelerate the recovery of neutrophils
after cancer chemotherapy & to treat other forms of
secondary or primary neutropenia (eg; aplastic anemia,
congenital neutropenia)
Toxicity :
G-CSF minimal, sometimes causes bone pain
GM-CSF fever, arthralgia, capillary damage with
edema, allergic reaction

DRUGS USED IN
COAGULATION DISORDERS
Include

: drugs used in clotting and bleeding

disorder
Anticlotting drugs :
- anticoagulants
- antiplatelet agents
- thrombolytics
Drugs that facilitate clotting :
- replacement factors
- vitamin K
- antiplasmin drugs

ANTICOAGULANTS
Anticoagulants

reduce the formation of

fibrin clots
Three major types of anticoagulants :
- heparin
- direct thrombin inhibitors
- coumarin (eg;warfarin)

Heparin

Heparin is a large polymers, acidic

Mechanism of action & Pharmacokinetics:
activates antithrombin III, which proteolyses factors
including thrombin and factors Xa
given parenterally, has rapid onset
Clinical use :
- Deep Vein Thrombosis (DVT)
- pulmonary embolism
- acute myocardial infarction(AMI)
- combination with thrombolytics for revascularization
during angiplasty and placement coronary stent
- DOC when an anticoagulant must be used in
pregnancy (because it does not cross the placental
barrier)

Heparin
Toxicity

:
- increased bleeding result in
hemorrhagic stroke
- Thrombocytopenia

Coumarin

Pharmacokinetics :
- the coumarin anticoagulants (eg, warfarin) are small, lipid soluble
- given orally administration
- cross the placenta & potentially dangerous to the fetus
Mechanism of action :
- interfere with the normal posttranlational modification of clotting in the
liver, depends on vitamin K
Clinical use
- used for chronic anticoagulants in all of the clinical situations, except in
pregnant women
Toxicity
- bleeding
- bone defects and hemorrhage in the developing fetus
- because their narrow therapeutics window, the interaction with
barbiturates, carbamazepin, phenytoin (Cytochrome P-450 inducing drug)
increase warfarin clearance and reduce the anticoagulant effects.
Cytochrome P-450 inhibitors (cimetidine, amiodarone, selective serotonin
reuptake inh) reduce warfarin clearance & increase anticoagulant effect

ANTIPLATELET DRUGS

Platelet agregation is important in clots that form in the

arterial circulation
Platelet agregation is facilitated by thromboxane, ADP,
fibrin, serotonin, & other substances
Antiplatelet agregation that inhibit platelet agregation
include :
- aspirine and other NSAIDs
- antagonis of ADP receptor (ticlopidine, clopidogrel)
- inhibitors of phosphodiesterase (dipyridamol, cilostazol)
- glycoprotein II/IIIa receptor inhibitor (abciximab,
tirofiban, eptifibated)

ANTIPLATELET DRUGS
Aspirin and other NSAIDs
MoA : inhibit thromboxane synthesis by blocking the enzyme
cyclooxigenase
Clinical Use :
- prevent further infarcts in individuals who had 1 or more
myocardial infarcts
- prevent transient ischemic attacks (TIA) and ischemic strokes
Ticlopidine and clopidogrel
MoA : irreversible inhibition of the ADP receptor (inhibition of ADPmediated platelet agregation)
Clinical use :
- prevent TIA and ischemic strokes, especially in patient who cannot
tolerate aspirin
- prevent thrombosis in patient who have recently received a
coronary stent

ANTIPLATELET DRUGS
Abciximab
A monoclonal antibody that reversibly
inhibits the binding of fibrin & other ligand

 Inhibitor

trombosit: aspirin, dipiridamol,

tiklopidin.
Antikoagulan: enoksaprin, heparin, warfarin
Obat trombolitik: alteplase, anistreplase,
streptokinase, urokinase
Pengobatan perdarahan: asam
aminnoksproat, protamin sulfat, asam
traneksamat, vitamin K

 Pengobatan

anemia: sianokobalamin,
erotropoetin, asam folat, besi
Pengobatan anemia sel sabit:
hidroksiurea