Iron compounds (Pharmacology)

Iron occurs as tin in the liver and spleen from where it is released and utilized in the heme portion of hemoglobin, which constitutes about 65 % of the total iron in the body.

Daily requirement:
Daily iron requirement is about 0.5-1mg in normal adults.

Mechanism of action:
In the first step, Heme portion of hemoglobin is formed.

In the second step, Hemoglobin is formed.Hemoglobin is the compound for the transportation of oxygen from the lungs to the tissues.

Administration:
It can be given orally or parenterally.

Pharmacokinetics:
Absorption:
It is readily absorbed from duodenum and proximal jejunum. It is more easily absorbed in the form of ferrous ions (Fe2+) than ferric ions (Fe3+).

Distribution:
Ferrous ion is converted into ferric ion and is actively transported in the mucosal cells of the intestine. It is actively transported into the plasma through transferrin. In the liver and spleen, it is converted to ferritin and hemosiderin with the help of certain proteins and get stored.

Elimination:
Approximately 1 mg of the iron is wasted, by the shedding of the tissue surface of the intestinal mucosal cells, through feces and little amount is excreted via urine, sweat and bile.

Iron deficiency:
Iron deficiency occurs in:
1. Chronic or acute loss of blood
2. Inadequate taking in of iron by the children during the period of rapid growth
3. In severely menstruating or pregnant woman.

Therapeutic uses:
The above mentioned deficiencies can be removed by taking sufficient amount of iron in the form of its compounds from outside.

Oral iron preparations can be used for infants and the children in the period of rapid growth as well as for pregnant and lactating women. Whereas parenteral preparations can be taken by the patients who are unable to take orally or who have chronic or acute blood loss.

Dosage:
Oral preparations of iron such as ferrous fumarate, ferrous gluconate and ferrous sulfate can be taken as 3-4 tabs per day in divided doses. Whereas, parenteral preparation is available in the form of iron-sorbitol-citric acid complex and can be taken as 1.5 mg/kg IM upto a maximum of 100 mg per injection in single daily dose.

Adverse effects:
Oral iron preparations can cause nausea, constipation, abdominal cramps and epigastric discomfort. Whereas, parenteral preparations can cause headache, nausea, vomiting, fever, flushing, local pain and tissue staining.

Anti-Anemic Drugs

Anti-anemic drugs are those agents, which are used for the treatment of anemic conditions.

Classification of Anti-anemic drugs:

Iron compounds:
Ferrous fumarate, Ferrous gluconate, Ferrous sulfate, Iron dextran Injection, Polyferose

Agents for Macrocytic anemia:
Vitamin B12, Folic Acid, Folinic Acid

Hematopoeitic growth factors:
Erythropoietin:
Epoetin alpha, Darbepoetin alpha

Granulocyte colony stimulating factor:
Filgrastim

Granulocyte-Macrophage colony stimulating factor:
Sargramostim

Interleukin:
Interleukin 3, Oprelvekin

Agent for Sickle cell anemia:
Hydroxyurea

Anemia

A disease of blood deficiency in which the red blood cell count is decreased resulting in poor health. In this condition, the number of red blood cells per millimeter cube or the amount of hemoglobin in 100 ml of blood is less than normal. It may also be caused by a decrease in the size of red blood cells. The mean corpuscular volume in a normal person is 82-92 µm3.

Anemia shows the following symptoms:
1. Paleness of the skin as well as mucous membranes
2. Short breath
3. Irregular or fast rate of heart beat
4. Soft systolic fluttering sound in the chest
5. Tending to become extremely tired

Main types of anemia:
There are almost 100 various types of anemia. According to the structure, anemia is of the following types:

Macrocytic anemia:
It is the type of anemia in which the size of red blood cells is larger than the normal such as in pernicious anemia. Pernicious anemia is the result of deficient intrinsic factor.

Normocytic anemia:
It is the type of anemia caused by the decrease in the number of red blood cells but the size is normal. Anemia caused by sudden blood loss is a normocytic anemia.

Microcytic anemia:
It is the type of anemia in which the average size of the red blood cell is reduced.

Simple microcytic anemia:
It is marked by smaller than normal red cells. It is found in chronic inflammatory conditions as well as in renal disease.

Microcytic hypochromic anemia:
It is marked not only by decreased red cell size but also by the decrease in hemoglobin concentration. It is seen in iron deficiency anemia and in thalassemia.

Anti-Anemic drugs

Science Research Ideas: Biology

It is still to find out that how the actual replication initiation machinery is taken up by the replication origin. Here the actual replication initiation machinery can be replication protein-A or DNA polymerase a-primase.

The mechanism by which the components of the initiation complex such as Cdc45p or Mcm proteins become part of the elongating replication fork is still not clear.

It is still unclear that whether the protein-DNA interactions, found at the lamin B2 origin, are due to pre-RC (i.e. at the time of G1 phase) and post-RC (i.e. at the time of S phase) formation. But recent studies (RIP mapping analyses) show that the replication start points are close to the site of protein-DNA interaction.

It is still to be found whether Cdc6p and other proteins change origin recognition complex (ORC) binding in higher eukaryotes and whether this change affect the origin choice at the "Origin decision point" in mammalian cells.

It is still not clear whether ORCs of highly developed organisms recognize structural features or specific sequences.

The mechanism by which the iron rule of initiating DNA replication i.e. once and only once per cell cycle,  predominates is still not known.

The relationship between replication start sites and the ORC binding sites is still unclear as the initiation pattern of the chorion origin at the nucleotide level is still to be determined. (Chorion is the outermost membrane around the embryo).

It is still to be found whether HoxC10p and HoxC13p (Proteins involved in morphogenesis of multicellular organisms) can bind to the ORC binding site.

Lagging strand (Okazaki fragment) start sites do not share any consensus sequence, even within a given gene position, and the mechanism underlying their regular spacing is still unclear.

References:
Bielinsky, A. K., & Gerbi, S. A. (2001). Where it all starts: eukaryotic origins of DNA replication. Journal of Cell Science , 643-651.
Tag:
Biology, Year 2001

Science Research ideas

In Eukaryotic cells, DNA synthesis starts at different places of chromosomes. Scientists have still to find the relationship between sites of initiation of replication and replication licensing factor i.e. protein or proteins allowing the replication origin to start DNA replication at that site. It was clear that replication licensing are not specific for particular replication origins.

Work on the genetic origin in higher eukaryotes is still in progress. Infact it is to be found that whether genetic origins of DNA replication exist in higher eukaryotes or not. Different opinions are found in the scientific literature on the specific sequences for origins on studying the DNA replication of metazoan.

Functional origins of replication are shown to be present in higher eukaryotes but the properties are still to be found.

It is still unclear that how the replication process takes place in replication systems which are cell free such as SV40 virus in-vitro replication system. Some work has been done.

It has been suggested to work on the nuclear structure participation in the regulation of the DNA replication as this can be a shining topic in the near future.


Reference:
Rui, W. J. (1999). Regulation of eukaryotic DNA replication and nuclear structure. Cell Research , 163-170.

Tag: Biology, Year 1999

Wolff-Parkinson-White syndrome

Wolff-Parkinson-White syndrome: It is sudden outburst of tachycardia characterized by short PR interval.

Torsade de pointes syndrome

Torsade de pointes syndrome: A form of ventricular tachycardia characterized by long QT interval.