Drugs used in anemia Flashcards
What is anemia?
It is a decrease in normal plasma hemoglobin concentration due to either:
1) Decreased number of RBC
2) Decreased hemoglobin content per unit of blood volume (MCHC “Mean corpuscular hemoglobin concentration)
What are the different types of anemia?
1) Hypoproliferative
2) Maturation disorder
3) Hemorrhage/hemolysis
What are the types of hyperproliferative anemia?
1) Iron deficiency anemia
2) Renal disease
What are the different types of maturation disorder anemia?
1) Iron deficiency anemia
2) Thalassemia
3) Sideroblastic anemia
4) Sickle cell anemia
5) Folate deficiency
6) Vitamin B 12 deficiency
What are the different types of hemorrhagic/hemolytic anemia?
1) Blood loss anemia
2) Intravascular hemolysis
3) Autoimmune disease
4) Metabolic defects
What causes iron deficiency anemia (microcytic anemia)?
1) Bleeding (acute or chronic)
2) Dietary (iron deficiency)
3) Malabsorption
4) Increased iron demands (pregnancy or lactation)
What is the treatment of iron deficiency anemia?
Oral or parenteral (injections) iron
- For elderly with severe iron-deficiencies anemia and CVS instability they might require RBC transfusion
- Patient with renal disease who are undergoing hemodialysis treatment parenteral administration is preffered
describe the pharmacokinetic (ADME) of oral iron tablets
- Iron is absorbed after oral administration
- The acidic conditions of the stomach keep the iron in its reduced form Fe+2 which is more soluble
- The iron is absorbed in the duodenum (and its absorption depends on its bodily availability)
- FYI, the absorption of iron decreases with increasing doses, and thus it is recommended to divide the daily doses into 2-3 doses
What is the difference between ferric and ferrous iron?
Ferrous “Fe+2” is better for absorption, while ferric “Fe+3” is better for storage and transportation
What is the difference between ferritin and transferrin?
1) Ferritin and hemosiderin (many ferritin particles linked together) are proteins that can store iron in cells
2) While transferrin are proteins that transport iron
DESCRIBE THE ABSORPTION OF IRON
1-Inorganic iron is transported into the mucosal cell by a proton-linked divalent metal ion transporter
2- They are accumulated intracellularly by binding to ferritin
3-Iron leaves the mucosal cell via a transport protein ferroportin, but only if there is free transferrin in plasma to bind to
4-Once transferrin is saturated with iron, any iron that has accumulated in the mucosal cells is lost when the cells are shed.
5-Expression of the ferroportin gene (and possibly also that for the divalent metal ion transporter) is downregulated by hepcidin (peptide secreted by the liver when body iron reserves are adequate) In response to hypoxia, anemia, or hemorrhage, the synthesis of hepcidin is reduced, leading to increased synthesis of ferroportin and increased iron absorption. As a result of this mucosal barrier, only ∼10% of dietary iron is absorbed, and only 1% to 5% from many plant foods.
- mainly given as salts as it enhances its bioavailability, Approx 25% of orally administered iron is absorbed, they might require 3-6months before they reload body stores and they should be taken in an empty stomach as food might inhibit iron absorption
What are the indications for parenteral (IV/IM) iron supplementation?
- It is administered in patients with iron absorption problems like in:
1) Inflammatory bowel disease
2) Small-bowel resection
3) Gastrectomy
4) Heredity absorption defects
What are the different formulations of parenteral iron supplements?
1) Iron dextran (most used)
2) Iron sucrose (most used)
3) Sodium ferric gluconate
4) Ferric carboxymaltose
- We inject the ferric form to be readily carried by transferrin, and we use them in acute cases where we need to elevate iron levels rapidly
Describe the mechanism of action of different iron supplements
- Fe+2-salts:
1) Absorbed by the duodenum, upper jejunum
2) Transported in the plasma by transferrin
3) It is then uptaken into erythroblasts bone marrow
4) Then they are found in the erythrocyte which are recycled by the macrophages and some are lost through bleeding
- Iron form:
1) Macrophages will phagocytize iron dextran and release the iron from the dextran molecule then it will bind it to transferrin, when iron sucrose is used specific exchange mechanism will transfer iron to transferrin
What are the adverse and toxic effects of iron supplements?
1) GI distress (most prominent), abdominal pain, nausea, vomiting, or constipation, to overcome this small doses of iron or iron preparations with delayed release might help
2) Hypersensitivity (most common with parenteral administration)
3) Fatal overdose (1-10mg), we use deferoxamine “iron chelating aging” to treat iron toxicity by binding to it and promoting its excretion
What is erythropoietin?
It is a glycoprotein secreted by the peritubular cells in the kidney as a response to hypoxia, EPO will stimulate stem cells to differentiate into proerythroblasts promotes the release of reticulocytes from the marrow, and helps in the initiation of the formation of hemoglobin
What are the various factors that can lead to hypoxia?
1) Reduced RBC count due to hemorrhage or lysis of RBC
2) Inadequate hemoglobin levels per RBC (observed in iron deficiency cases)
3) Diminished O2 availability like in high altitudes
What are the different forms of EPO?
1- Recombinant human EPO (Epoetin-alfa), it is the first generation
2- Darbepoetin (second generation of EPO, with twice the half-life or epoetin-alpha)
- Due to their delayed onset they are of no use in cases of acute anemia, and coadministration with iron supplements might be required
- They are administered parentally as they can be destroyed by the stomach acidity
What are the therapeutic uses of EPO?
It treats anemia in the following patients;
1) Patients with chronic renal failure
2) HIV-infected patients treated with zidovudine (an antiviral drug that can suppress the bone marrow)
3) Cancer patients treated with chemotherapy
What are the adverse effects and toxic effects of EPO?
1) Hypertension
2) Seizures
3) Headache (probably due to the expansion of blood volume)
4) Thromboembolic events (as it increases the blood viscosity)
What is meant by sideroblastic anemia?
Impaired hemoglobin synthesis, although adequate iron is available accumulates iron in the perinuclear mitochondria of erythroid precursor cells (ringed sideroblasts)
- Its ring structure is very characteristic of it due to the excess formation of iron
- In heme synthesis, ALA synthase requires vitamin B6 as a co-factor, if there is no B6, there will be no porphyrin, and as you know, heme is made of porphyrin and iron.
during heme synthesis, the iron will go into the mitochondria and will wait to be bound to the porphyrin, but because of the lack of porphyrin in this case, the iron will just accumulate in the mitochondria and will form these blue dots that are characteristic of sideroblastic anemia
What are the different causes of sideroblastic anemia?
- Usually it is caused by agents that antagonizes/depletes pyridoxine (Vitamin B6)
1) Acquired:
- Alcoholics
- Patients on antitubercular (TB) therapy (like isoniazid and pyrazinamide, as they cause vitamin B6 deficiency)
- Certain inflammatory and malignant disorder
2) Inherited:
- X-linked
What is the treatment of sideroblastic anemia?
It is treated with pyridoxine, it can be administered orally or parenterally
What is meant by megaloblastic/pernicious anemias?
AKA vitamin B-12/folate deficiency, & macrocytic anemia
They are characterized by RBCs that are larger than normal and there are not enough of them, caused by a deficiency of either vitamin B12 or folic acid which impairs the DNA synthesis in any cell in which the chromosomal replication and division are taking place
