11 Haemopoietic system and treatment of anaemia

Question 1

11.01 HAEMATINIC AGENTS

Folic acid - actions and MOA

Answer 1

folic acid is essential for DNA synthesis and cell proliferation
in the tetrahydrofolate (FH4) form, it is a cofactor in the synthesis of purines and pyrimidines, being particularly important in thymidylate synthesis

Question 2

11.01 HAEMATINIC AGENTS

Folic acid - abs/distrib/elim

Answer 2

given orally, it is absorbed by active transport into intestinal mucosal cells where it is reduced to FH4, then methylated to methyl-FH4, which passes into the plasma and from thence into cells
the functionally inactive methyl-FH4 is demethylated in a vitamin B12-dependent reaction

Question 3

11.01 HAEMATINIC AGENTS

Folic acid - clinical use

Answer 3

folate deficiency anaemias
to prevent folate deficiency in susceptible individuals (e.g. premature infants, patients with severe chronic haemolytic anaemias)
supplementation in pregnancy to reduce risk of neural tube defects in infants
to treat toxicity caused by methotrexate (a folate antagonist)

Question 4

11.01 HAEMATINIC AGENTS

Folic acid - adverse effects

Answer 4

rare
occasionally GIT disturbances

Question 5

11.01 HAEMATINIC AGENTS

Folic acid - special points

Answer 5

should not be used in undiagnosed megaloblastic anaemias because if the anaemia is due to vitamin B12 deficiency, the anaemia may improve but the neurological lesions will persist and could get worse

Question 6

11.02 HAEMATINIC AGENTS

Hydroxocobalamin (a vitamin B12 haematinic preparation) - actions

Answer 6

restores the blood picture in megaloblastic anaemias (e.g. pernicious anaemia) and results in partial to full recovery of the neurological syndrome (subacute combined degeneration of the spinal cord)

Question 7

11.02 HAEMATINIC AGENTS

Hydroxocobalamin (a vitamin B12 haematinic preparation) - MOA

Answer 7

it is necessary for the conversion of methyl-tetrahydrofolate (methyl-FH4) to tetrahydrofolate (FH4), which is essential for thymidylate synthesis and thus for DNA synthesis

Question 8

11.02 HAEMATINIC AGENTS

Hydroxocobalamin (a vitamin B12 haematinic preparation) - abs/distrib/elim

Answer 8

given by IM injection

Question 9

11.02 HAEMATINIC AGENTS

Hydroxocobalamin (a vitamin B12 haematinic preparation) - clinical use

Answer 9

to treat pernicious anaemia and other causes of vitamin B12 deficiency

Question 10

11.02 HAEMATINIC AGENTS

Hydroxocobalamin (a vitamin B12 haematinic preparation) - adverse effects

Answer 10

nausea, dizziness, headache, hypersensitivity reactions
hypokalaemia at start of treatment

Question 11

11.02 HAEMATINIC AGENTS

Hydroxocobalamin (a vitamin B12 haematinic preparation) - drugs with similar action

Answer 11

cyanocobalamin

Question 12

11.03 HAEMATINIC AGENTS

Ferrous sulfate, ferrous fumarate, ferrous gluconate - actions

Answer 12

necessary for haemoglobin formation and for the oxidative processes of living tissues

Question 13

11.03 HAEMATINIC AGENTS

Ferrous sulfate, ferrous fumarate, ferrous gluconate - MOA

Answer 13

they are used in haemoglobin production in red blood cell precursors in the bone marrow

Question 14

11.03 HAEMATINIC AGENTS

Ferrous sulfate, ferrous fumarate, ferrous gluconate - abs/distrib/elim

Answer 14

given orally
can also be given IV (iron sucrose or carboxymaltose)

Question 15

11.03 HAEMATINIC AGENTS

Ferrous sulfate, ferrous fumarate, ferrous gluconate - clinical use

Answer 15

iron-deficiency anaemia caused by chronic blood loss
increased demand (pregnancy and early infancy)
inadequate dietary intake
inadequate absorption (post-gastrectomy, coeliac disease)

Question 16

11.03 HAEMATINIC AGENTS

Ferrous sulfate, ferrous fumarate, ferrous gluconate - adverse effects

Answer 16

dose-related GIT disturbances - nausea, epigastric pain, abdominal cramps, diarrhoea

Question 17

11.03 HAEMATINIC AGENTS

Ferrous sulfate, ferrous fumarate, ferrous gluconate - special points

Answer 17

iron toxicity both acute (due to excessive ingestion of iron salts) or chronic (e.g. from repeated blood transfusions) is treated with the iron chelator desferrioxamine

Question 18

11.04 HAEMOPOIETIC GROWTH FACTORS

Epoetin, darbepoetin - actions

Answer 18

recombinant growth factors controlling erythropoiesis

Question 19

11.04 HAEMOPOIETIC GROWTH FACTORS

Epoetin, darbepoetin - MOA

Answer 19

they bind to receptors on committed erythrocyte progenitor cells stimulating proliferation and differentiation

Question 20

11.04 HAEMOPOIETIC GROWTH FACTORS

Epoetin, darbepoetin - abs/distrib/elim

Answer 20

given by SC or IV injection

Question 21

11.04 HAEMOPOIETIC GROWTH FACTORS

Epoetin, darbepoetin - clinical use

Answer 21

to treat anaemia due to chronic renal failure or myelodsyplasia
to alleviate anaemia caused by cytotoxic anticancer drugs

Question 22

11.04 HAEMOPOIETIC GROWTH FACTORS

Epoetin, darbepoetin - adverse effects

Answer 22

GIT disturbances
hypertension
thrombotic vascular events

Question 23

11.05 HAEMOPOIETIC GROWTH FACTORS

Filgrastim, lenograstim, pegfilgrastim - actions

Answer 23

recombinant human granulocyte colony-stimulating factors

Question 24

11.05 HAEMOPOIETIC GROWTH FACTORS

Filgrastim, lenograstim, pegfilgrastim - MOA

Answer 24

interact with specific receptors on myeloid progenitor cells stimulating proliferation and differentiation
they can mobilise haemopoietic stem cells from bone marrow to blood

Question 25

11.05 HAEMOPOIETIC GROWTH FACTORS

Filgrastim, lenograstim, pegfilgrastim - abs/distrib/elim

Answer 25

given by SC injection, SC infusion or IV injection

Question 26

11.05 HAEMOPOIETIC GROWTH FACTORS

Filgrastim, lenograstim, pegfilgrastim - clinical use

Answer 26

neutropenia associated with cytotoxic cancer chemotherapy, bone marrow transplantation or HIV infection

Question 27

11.05 HAEMOPOIETIC GROWTH FACTORS

Filgrastim, lenograstim, pegfilgrastim - adverse effects

Answer 27

GIT disturbances, bone pain, muscle pain, fever, rash, alopecia