Vitamin B12

It is used for Macrocytic anemia.
It is also called as cobalamin or cyanocobalamin. It is present in liver, milk, egg and fish. Physiologically active forms of vitamin B12 coenzymes are methylcobalamin and 5-deoxyadenosinecobalamine.


Daily requirement:
Daily B12 requirement is about 2 µg in normal adults.

Mechanism of action:
It acts as a co-factor in the formation of Succinyl-CoA from methylmalonyl-CoA.

Methylmalonyl-CoA is an intermediate product during the degradation process of many metabolites in the body. In the case of pernicious anemia, its amount is increased. Whereas, succinyl-CoA is a precursor in the synthesis of heme.

Accumulation of methylmalonyl-CoA leads to abnormal production of fatty acid as well as its incorporation to cell membranes. This causes demyelination of the nerve cells.

It acts as a co-factor in the formation of H4 folate and methionine leading to the formation of DNA.

Accumulation of 5-CH3-H4 folate leads to the deficiency of folate cofactors resulting in reduced DNA synthesis and megaloblastic anemia.

Administration:
It can be administered orally, IM or deep subcutaneously.

Pharmacokinetics:
Absorption:
Vitamin B12 gets bind to intrinsic factor (IF) and form a complex. This IF-B12 complex is then absorbed in distal ileum. This absorption is done by a very specific receptor mediated transport system.

Distribution:
Vitamin B12 is distributed to different cells of the body upon binding to transcobalamin II. It is stored in the liver in amount of 300-500 µg.

Elimination:
Normally, very little amount is excreted through urine or feces but upon parenteral administration large amount is found in urine.

Vitamin B12 deficiency:
Its deficiency causes pernicious anemia due to spoiled synthesis of red blood cells. Its deficiency can be caused by:

1. Low level of intake of Vitamin B12
2. Decreased absorption of vitamin due to less amount of intrinsic factor (IF) produced by gastric parietal cells
3. Lessened activity of the receptor for uptake of the vitamin from intestine
4. Non-specific malabsorption syndrome.

Therapeutic uses:
It is used in megaloblastic anemia and pernicious anemia as it is important in the formation of blood and growth. It is also important in proper neural functioning.

Dosage:
It is given in the dose of 100-1000 µg daily for 1-2 weeks than as a maintenance therapy the same dose is required once a month for life.

Adverse effects:
It has no adverse effects as extra amount is excreted via urine.

Dispensing

Dispensing refers to the provision of medicine according to the prescription.

Following steps are involved in a Pharmacy setup:

1. Prescription: Medicines recommended by the physician as a remedy
2. Formulation: Darwing and expressing the medicines and ingredients of the prescription
3. Compounding: Preparing and mixing of the ingredients and/or medicines of the prescription
4. Dispensing: Giving the medicines to the patient. Medicines are given in a container with proper labelling. This label helps the patient for subsequent use of the medicine.

Dispensing may also involve the preparation of device for the use of patients.

Extemporaneous dispensing:Extemporaneous dispensing refers to the compounding and dispensing of medicines with little or no preparation in response to the stimulus of one's immediate environment.

Search Methods

Search methods are used in optimization.

In these methods, the response surfaces are examined by different methods in order to determine the combination of independent variables, so that the optimum results can be obtained. Response surface methodology is used to determine the connection between different explanatory variables (independent variables) and one or more of the response variables (dependent variables).

Following steps are followed in the search methods:
1. A system is selected
2. Independent and Dependent variables are selected
3. Experiments are performed and product is tested
4. Data is submitted (to computer) for statistical and regression analysis
5. Specifications are set for feasibility program
6. Constraints are set for grid search
7. Grid search printouts are evaluated
8. Partial derivative plots (single or composite) and contour plots are evaluated.

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