Heamatinics Flashcards
Drug Management Of Anemia
What are haematinics?
Haematinics are compounds required in the formation of blood
Haematinics include iron, vitamin B12 and folic acid
Haematinics are used in the treatment of anaemia
What is iron therapy used for?
Iron therapy is used in the treatment of iron deficiency anaemia
Iron therapy is given by the oral or parenteral routes
List the preparations of oral iron therapy
Commonly used preparations include: (1) ferrous sulphate (2) ferrous gluconate (3) ferrous fumarate (4) polysaccharide iron complex
SIDE NOTE: Inorganic acid in the ferrous state is much more readily absorbed than that in the ferric state. Gastric acid and ascorbic acid promote the absorption of ferrous iron.
What is the rationale of oral iron therapy?
In patients with iron deficiency, about 25% of oral iron given as ferrous salt can be absorbed
Oral iron treatment may require 3-6 months to replenish body stores
What are the adverse reactions of oral iron therapy?
Adverse effects of oral iron therapy: nausea, epigastric discomfort, abdominal cramps, constipation and diarrhoea. The effects are dose-related and can be reduced by lowering the daily dose or by taking the tablets immediately after or with meals
What are the clinical indications of parenteral iron therapy?
Indications
- Patients unable to tolerate iron
- Patients with iron absorption disorders (e.g. inflammatory bowel disease, small bowel resection, gastrectomy and hereditary absorption defects)
- Severe anaemia in which rapid correction of iron deficiency is required
- Treatment of iron deficiency that develops when a patient is on treatment with erythropoietin in patients with renal disease (oral iron is poorly absorbed in these patients and the amount of iron required cannot be adequately supplied with oral preparations)
- Patients with hypersensitivity reactions to oral iron salts
What are the contraindications of parenteral iron therapy?
Contraindications: Serum ferritin > 800 ng/mL, transferrin saturation > 50%, early pregnancy, liver disease and acute renal failure
What are the necessary precautions when considering parenteral iron therapy?
Use with caution to minimize acute adverse reactions
Measure of iron status (serum ferritin, total iron binding capacity, and transferrin saturation) and red blood cell indices periodically to re-evaluate the patient’s need for additional iron supplementation
List examples of parenteral iron therapy
- Iron dextran – A stable complex of ferric hydroxide and low molecular weight dextran containing 50mg of elemental iron per ml. Given by deep IM or IV infusion
- Iron-sucrose complex and iron-sodium gluconate complex. Given only intravenously. Less likely than iron dextran to cause hypersensitivity reactions
What are the advantages of iron dextran IV infusion?
no pain, no tissue staining and allows for single dose delivery of the entire dose of iron required to correct the iron deficiency
What are the adverse effects of iron dextran?
Adverse effects: Headache, light-headedness, fever, arthralgia, nausea, vomiting, back pain, flushing, urticaria, bronchospasm, anaphylactoid reactions and death. Some of these effects are due to pseudo-allergy to dextran. Always give a test dose before giving the full dose.
How do you monitor patients on parenteral iron therapy?
Periodic measurement of:
Serum ferritin (protein that stores iron)
Transferrin saturation (ratio of total serum iron concentration to total iron-binding capacity)
How does acute iron toxicity manifest?
Characterised by necrotising gastro-enteritis characterised by vomiting, abdominal pain and bloody diarrhoea followed by shock, lethargy and dyspnea
Severe metabolic acidosis, coma and death may occur
How does chronic iron toxicity (iron overload) manifest?
Also known as haemochromatosis
Results when excess iron is deposited in the heart, liver, pancreas and other organs. Can lead to organ failure and death
Which patients are susceptible to chronic iron toxicity?
Most commonly occurs in (1) patients with inherited haemochromatosis, a disorder characterised by excessive iron absorption (2) patients who receive many red cell transfusions over a long period of time (e.g. patients with thalassemia major)
How do you treat iron toxicity?
The treatment of acute and chronic iron toxicity involves the use of iron chelators which include:
Desferrioxamine
Deferiprone
Defasirox
Chelators bind iron and promote its renal excretion (the chelator-iron complex is excreted in urine)
Patients with chronic iron toxicity who do not have anaemia can also be treated by intermittent phlebotomy
How is desferrioxamine administered and why?
Desferrioxamine is not absorbed from the gut. In acute iron overdose, it is given intragastrically to bind iron in the bowel lumen and prevent its absorption, as well as IM or slow IV infusion in severe poisoning
What are the clinical indications for deferiprone and defasirox?
Deferiprone and defasirox are orally absorbed iron chelators. They are used for treatment of iron overload in patients with thalassaemia major who are unable to take desferrioxamine.
List the vitamin B12 preparations
- Cyanocobalamin (oral, SC, IM, nasal spray and sublingual tablets)
- Hydroxocobalamin (IV, IM)
What are the therapeutic uses of vitamin b12?
- Treatment of pernicious anaemia (inadequate secretion of intrinsic factor with subsequent reduction in vitamin B12 absorption)
- Used after partial or total gastrectomy to mitigate the loss or reduction of intrinsic factor synthesis
- Treatment of vitamin B12 deficiency caused by malabsorption of vitamin B12 in the ileum
- Treatment of deficiency in patients with insufficient dietary intake of vitamin B12
What are the adverse effects of vitamin B12?
Adverse effects of vitamin B12 are uncommon, even at large doses
Hypokalaemia and thrombocytosis can occur upon conversion of severe megaloblastic anaemia to normal erythropoiesis with vitamin B12 therapy
What are the therapeutic uses of folic acid?
- To correct folic acid deficiency
- Supplementation during pregnancy to decrease the risk of neural tubal defects
- Supplementation during lactation
- Supplementation in cases of rapid cell turnover (e.g. in chronic haemolytic anaemias)
- To reverse the effects of folate antagonists (inhibitors of dihydrofolate reductase) such as methotrexate and pyrimethamine (5-formyl-tetrahydrofolate [folinic acid, leucovorin] which does not require metabolism by dihydrofolate reductase is used)
What causes folate deficiency?
Causes: increased demand (pregnancy, lactation, chronic haemolytic anaemias such sickle cell disease), malabsorption, haemodialysis (folate is removed from plasma during dialysis), alcoholism and liver disease (poor diet and poor storage), drugs (e.g. phenytoin, methotrexate, trimethoprim, pyrimethamine)
What is a complication of folic acid deficiency?
Folate deficiency results in megaloblastic anaemia
Unlike vitamin B12 deficiency, does not cause neurological deficits
How do you treat folic acid deficiency? :)
Treatment: folic acid given orally. Folic acid has no known toxicity.
What are haemopoietic growth factors?
HGFs are glycoprotein hormones that regulate the proliferation and differentiation of haemopoietic progenitor cells in the bone marrow
Recombinant DNA technology is used to produce HGFs for clinical use
List the haemopoietic growth factors available for clinical use
HGFs available for clinical use include:
1. Erythropoesis stimulating agents (ESAs)
2. Colony stimulating factors: Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)
3. Interleukin-11 (IL-11)
What is the MoA of erythropoiesis stimulating agents?
Actions: stimulate erythroid proliferation and differentiation, and induce release of reticulocytes from the bone marrow. Action requires adequate stores of iron.
Endogenous erythropoietin is primarily produced in the kidney (thus levels are low in patients with kidney disease)
What are the clinical indications of erythropoiesis stimulating agents?
Indications: (1) Anaemia in chronic renal failure, HIV, cancer chemotherapy and Primary bone marrow disorders (2) Prevention of anaemia of prematurity (3) In surgical patients to reduce the need for blood transfusions
List the preparations for erythropoiesis stimulating agents used
Preparations: Epoetin alfa (recombinant human erythropoietin), methoxy polyethylene glycol-epoetin beta (longer half-life than epoetin alfa) and darbepoetin (a second generation ESA that has half-life twice that of epoetin alfa)
What is the route of administration for erythropoiesis stimulating agents?
Route of administration: Intravenous (in haemodialysis patients – bioavailability is low and absorption is variable in these patients) and subcutaneous (in other patients)
What are the adverse effects of erythropoiesis stimulating agents?
Adverse effects: Hypertension, seizures, headache, thrombosis, allergic reactions, and increased risk of arterial and venous thromboembolic events
What are colony stimulating factors?
The CSFs are cytokines that stimulate the formation of maturing colonies of leukocytes
G-CSF: stimulates proliferation and differentiation of neutrophil progenitors
GM-CSF: stimulates proliferation and differentiation of granulocyte, erythroid and megakaryocyte progenitors
What are the clinical uses of colony stimulating factors?
Clinical uses: (1) cancer chemotherapy induced neutropenia (2) neutropenia associated with congenital neutropenia, myelodysplasia and aplastic anaemia (3) bone marrow graft failure
State the therapeutic preparations and routes of administration for colony stimulating factors
The preparations used in therapy are filgrastim, pegfilgrastim and lenograstim (G-CSF), and sargranostim (GM-CSF). They are recombinant proteins
Routes of administration: IV (G-CSF & GM-CSF) and SC (G-CSF)
G-CSF is used more frequently because it is better tolerated
What are the adverse effects of colony stimulating factors?
Adverse effects of G-CSF: bone pain, allergic reactions
Adverse effects of GM-CSF: granulocytosis, fever, malaise, arthralgia, myalgia, capillary leak syndrome and allergic reactions
What is interleukin-11?
IL-11 is a protein produced by fibroblast and stromal cells in the bone marrow
Stimulates the growth of megakaryocyte progenitors and increases the number of peripheral platelets and neutrophils
What is the clinical use of interleukin-11?
Clinical use: treatment of chemotherapy-induced thrombocytopaenia
What are the adverse effects of interleukin-11?
Adverse effects: fatigue, headache, dizziness, dyspnoea, anaemia
What preparation of interleukin-11 is used therapeutically?
Preparation: oprelvekin (a genetically engineered form of human interleukin-11). Administered SC.
What are the indications of hydroxyurea in sickle cell disease?
Indications in SCD: To reduce complications of sickle cell disease in patients who have a history of severe symptoms, including: frequent painful events (at least three in a year), history of recurrent acute chest syndrome and severe anemia
Given orally
What are the adverse effects of hydroxyurea?
Adverse effects: drowsiness, nausea, vomiting and diarrhea, constipation, mucositis, anorexia, stomatitis, bone marrow toxicity (dose-limiting toxicity)
What is pentoxifylline?
A synthetic dimethylxanthine structurally similar to caffeine
What is the MoA of pentoxifylline?
MOA: Inhibits erythrocyte phosphodiesterase causing an increase in erythrocyte cyclic AMP activity. This results in increased erythrocyte membrane flexibility and decreased viscosity
What is the therapeutic use of pentoxifylline in SCD?
Uses in SCD: Prevention of vaso-occlusive crises
What are sideroblastic anemias?
Sideroblastic anaemias are characterised by decreased haemoglobin synthesis and intracellular accumulation of iron in erythroid precursor cells
What are the causes of sideroblastic anemia?
Causes of sideroblastic anaemia: Hereditary sideroblastic anaemia(X-linked), alcoholism, drugs that antagonise or deplete pyridoxal phosphate (e.g. isoniazid and pyrazinamide), and certain inflammatory and malignant disorders
How do you treat sideroblastic anemia?
Treatment: Pyridoxine (vitamin B6) administered orally or parenterally
