VITAMIN B12, FOLIC ACID, AND THE TREATMENT OF MEGALOBLASTIC ANEMIAS
Cyanocobalamin (vitamin B12) Vit B12 -water soluble, Thermostable Red crystals ( It is synthesized in nature only by Microorganisms) The commercial source is Streptomyces griseus Daily requirement : 1–3 μg , pregnancy and lactation 3–5 μ g.
Metabolic functions of B12
Vitamin B12 and FA - water soluble -B-complex group. Essential -DNA synthesis. Their deficiency -impaired DNA synthesis Abnormal maturation of RBCs and other rapidly dividing cells. -- Megaloblastic anaemia Vitamin B12 and folic acid are therefore called maturation factors.
Functions Vitamin B12 and folic acid act as coenzymes For several vital metabolic reactions and are essential for DNA synthesis. Deficiency 1. Addisonian pernicious anaemia 2. Other causes Gastrectomy
Deficiency Vit B12 deficiency occurs due to : 1. Addisonian pernicious anaemia 2. Other causes of gastric mucosal damage, e.g. chronic gastritis , gastric carcinoma, gastrectomy, etc. 3. Malabsorption (damaged intestinal mucosa), bowel resection. 4. Consumption of vit B12 by abnormal flora in intestine (blind loop syndrome) or fish tape worm. 5. Nutritional deficiency: less common cause. 6. Increased demand: pregnancy, infancy.
USES V it B12 deficiency Mega doses - neuropathies, psychiatric disorders Tobacco amblyopia [hydroxocobalamin is of some benefit—it probably traps cyanide derived from tobacco to form cyanocobalamin.] Adverse effects Even large doses of vit B12 are quite safe. Allergic reactions have occurred on injection, probably due to contaminants. Anaphylactoid
FOLIC ACID Folate pteroylglutamic acid (PGA) Dietary source Green vegetables liver yeast egg milk and some fruits. Prolonged cooking with spices destroys folic acid A dult is < 0.1 mg/day During pregnancy, lactation 0.8 mg/ day Absorption D uodenum and J ejunum T ransported in the blood by active and passive transport Widely distributed in the body S tored in the liver.
Metabolic Functions Folic acid is converted to d i h ydro f olic a cid and then to t etra h ydro f olic a cid which serves as a coenzyme for many vital reactions necessary for DNA synthesis. Conversion of homocysteine to methionine: vit B12 acts as an intermediary Generation of thymidylate , an essential constitute of DNA
Metabolic Functions Conversion of serine to glycine : needs THFA and results in the formation of methylene-THFA which is utilized in thymidylate synthesis. Purine synthesis : de novo building of purine ring requires formyl-THFA and methenyl -THFA Histidine metabolism
Deficiency Folate deficiency occurs due to: (a) Inadequate dietary intake (b) Malabsorption (c) Biliary fistula; bile containing folate for recirculation is drained (d) Chronic alcoholism (e) Increased demand: pregnancy, lactation, rapid growth periods, haemolytic anaemia (f) Drug induced: prolonged therapy with anticonvulsants (phenytoin, phenobarbitone, primidone) and oral contraceptives—interfere with absorption and storage of folate.
Uses Megaloblastic anaemia Prophylactically in pregnancy, lactation Methotrexate toxicity Adverse effects Oral folic acid is entirely nontoxic. Injections rarely cause sensitivity reactions.
Erythropoietin R egulate erythropoiesis. P roduced by the kidney in response to hypoxia and anaemia. It binds to erythropoietin receptors on red cell progenitors and stimulates red cell production. ADR Hypertension T hrombosis and Allergic reactions.
Functions and uses of Haematopoietic growth factors DRUGS FUCTION USES Erythropoetin Epoetin alfa Stimulate erythropoiesis Anaemia associated with Renal failure, anticancer. HG-CSF: Filgrastim HGM-CSF:Sargramostin Stimulate proliferation and differentiation of WBC Patients whose WBCs are suspended by anticancer or antiretroviral drugs Thrombopoietic growth factor : Interleukin –II [ Oprelvekin ] Stimulate the production of platelets Cancer chemotherapy indued thrombocytopenia
Plasma Volume Expanders Plasma Substitutes Plasma Extenders Blood Volume Extenders Synthetic Colloids Artificial Colloids HMW Attract and hold Water in vascular space These are synthetic colloids which restore circulating volume by mimicking the action of plasma protein such as albumin Not enhance O2 carryings capacity
Properties of PVE Should not exceed oncoitic –P than palsma Inert-Pharmacologically Not pyrogenic and antigenic Not Adversely affect any vital organs Should be in circulation for desired period Not readily leak out in tissues Not interfere with Cross matching of Blood Long storage period Easley sterile Economical Oncotic pressure is the osmotic pressure generated by large molecules (especially proteins) in solution