C H A P T E R 4 9
Drugs used to treat anaemias
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B
lood is essential for cell survival because it carries
oxygen and nutrients and removes waste products that
could be toxic to the tissues. It also contains clotting
factors that help to maintain the vascular system and
keep it sealed. In addition, blood contains the important
components of the immune and inflammatory systems
that protect the body from infection.
Blood is composed of liquid and formed elements.
The liquid part of blood is called
plasma
. Plasma is
mostly water, but it also contains proteins that are essen-
tial for the immune response and for blood clotting. The
formed elements of the blood include leucocytes (white
blood cells), which are an important part of the immune
system (see Chapter 15);
erythrocytes
(red blood cells
[RBCs]), which carry oxygen to the tissues and remove
carbon dioxide for delivery to the lungs; and plate-
lets, which play an important role in coagulation (see
Chapter 48). This chapter discusses drugs that are used
to treat
anaemias
, which are disorders that involve too
few RBCs or ineffective RBCs that can alter the blood’s
ability to carry oxygen.
ANAEMIA
Anaemia results from some alteration in
erythropoie-
sis
, the process of RBC production, which occurs in the
myeloid tissue of the bone marrow. The rate of RBC
production is controlled by the glycoprotein
erythro-
poietin
, which is released from the kidneys in response
to decreased blood flow or decreased oxygen tension
in the kidneys. Under the influence of erythropoietin,
an undifferentiated cell in the bone marrow becomes
a haemocytoblast. This cell uses certain amino acids,
lipids, carbohydrates, vitamin B
12
, folic acid and iron
to become an immature RBC. In the last phase of RBC
production, the cell loses its nucleus and enters circula-
tion. This cell, called a
reticulocyte
, finishes its maturing
process in circulation (see Figure 49.1).
Although the mature RBC has no nucleus, it does
have a vast surface area to improve its ability to trans-
port oxygen and carbon dioxide. Because it lacks a
nucleus, the RBC cannot reproduce or maintain itself,
and so it will eventually wear out. The average lifespan
of an RBC is about 120 days. At that time, the elderly
RBC is lysed in the liver, spleen or bone marrow. The
building blocks of the RBC (e.g. iron, vitamin B
12
)
are then recycled and returned to the bone marrow
for the production of new RBCs. The only part of the
RBC that cannot be recycled is the toxic pigment bili-
rubin, which is conjugated in the liver, passed into the
bile and excreted from the body in the faeces or the
urine. Bilirubin is what gives colour to both of these
excretions. Erythropoiesis is a constant process by
which about 1% of the body’s RBCs are destroyed and
replaced each day.
Aetiology of anaemia
Anaemia can occur if erythropoietin levels are low.
This is seen in renal failure, when the kidneys are no
longer able to produce erythropoietin. It can also occur
ERYTHROPOIESIS-
STIMULATING AGENTS
darbepoetin alfa
epoetin alfa
epoetin beta
epoetin lambda
methoxy polyethylene
glycol-epoetin beta
AGENTS USED FOR IRON-
DEFICIENCY ANAEMIA
ferric pyrophosphate
ferrous fumarate
ferrous sulfate
iron polymaltose
iron sucrose
AGENTS USED FOR OTHER
ANAEMIAS
Agents for megaloblastic
anaemias
Folic acid derivatives
calcium folinate
folic acid
Vitamin B
12
co-methylcobalamin
cyanocobalamin
hydroxocobalamin
Agent for sickle cell anaemia
hydroxyurea
Myeloid tissue of bone marrow
Haemocytoblasts
Mature erythrocytes
Circulation
Haemolysis: Liver, spleen, bone marrow
Bilirubin
Bile
Erythropoietin
Amino acids, lipids,
carbohydrates
Vitamin B
12
Folic acid
Iron
Macrocytic anaemia
Megaloblastic anaemia
Iron deficiency anaemia
120 days
Iron
Vitamin B
12
Reticulocytes
FIGURE 49.1
Erythropoiesis. Red blood cells are produced in the
myeloid tissue of the bone marrow in response to the hormone
erythropoietin. The haemocytoblasts require various essential
factors to produce mature erythrocytes. A lack of any one of these
can result in an anaemia of the type indicated opposite each factor.
Mature erythrocytes survive for about 120 days and are then lysed
in the liver, spleen or bone marrow.
