Haematopoietic agents, Vitamins & Antioxidants

Dr. Rishi Pal

Assistant Professor

Department of Pharmacology

Haematopoietic system

Erythrocytes Leukocytes Thrombocytes

Exogenous nutrients Endogenous nutrients

Types of anaemia

Microcytic hypochromic anaemia Megaloblastic anaemia Pernicious anaemia Haemolytic anaemia Aplastic anaemia Sickle cell anaemia Sideroblastic anaemia

Iron deficiency anaemia

Pallor Fatigue Dizziness Exertional dyspnoea Iron deficiency Dietary deficiency Faulty absorption, transport and storage Excessive blood loss Worm infestation

Max iron absorption: duodenum & jejunum Haem iron & non haem iron (Fe+++) Ascorbic acid, SH, Succinic acid facilitate

conversion of Fe+++ to Fe++ form

Body requirement of iron Hb has 33% of iron (50 mg in 100 ml of

blood) Daily requirement

Male: 0.5-1 mg

Female: 1-2 mg

Children: 25 mg

Pharmacokinetics of iron

Iron absorbs by active transport across intestinal mucosa.

Converted Fe2+ to Fe3+

Apoprotein-iron complex (ferritin) Release on demand Absorption depends on apoprotein to ferritin ratio. Transferrin binds with free Fe2+ or Fe3+ from ferritin

and carries to bone marrow

Haemosiderin granules seen with iron overload & gives rise to haemosiderosis or bronze diabetes.

Treatment of iron defeciency anaemia

Oral iron therapy: ferrous salts of sulfate,fumerate,gluconate, lactate, succinate and

glycine sulfate etc.

Ferric salts: ferric ammonium citrate, iron polysaccharide and ferric hydroxide polymaltose complex.

Ferrous salts better absorbed than ferric salts.

Ferrous salts: 100mg provides 20% of elemental iron Ferrous fumerate: 33% Ferrous sulfate:19% Ferrous succinate: 12% Adult: 200mg of elemental iron administered in 2-3

divided doses after meal Children:3-5mg/kg in 3 divided doses 325mg tablets of ferrous sulfate, thrice a day

Ferrous sulfate: FERSOLATE 200mg tab Ferrous fumerate: NORI-A 200mg tab Ferrous gluconate:FERRONICUM 300mg tab Collodial ferric hydroxide: NEOFERRUM 200

mg tab. 400mg/5ml syrup

Parenteral iron therapy

For those who are not able to absorb oral iron preparations.

Not able to maintained iron content because of acute/chronic blood loss or GITdisorders like sprue or inflammatory bowel disease.

Iron-dextran: iv or im (50mg/ml) Iron sucrose complex: iv or im Iron-sodium gluconate: iv or im Iron-sorbitol-citrate: only im

Vitamin B12

Cyanocobalamine Hydroxycobalamine Methylcobalamine 5’ deoxyadenosyl cobalamine

Pharmacokinetics of cobalamine Intrinsic factor (IF) Transcobalamine-II Metabolic functions Therapeutic uses Daily requirement: 2-3 ug/day Therapeutic dose: 100-1000ug/day i.m

Cyanocobalamine REDISOL, MACRABIN 100µg, 500µg/day Hydroxocobalamine REDISOL-H, MACRABIN-H 500µg, 1000µg

per vial inj. Methylcobalamine METHYLCOBAL 500µg tab, NEUROKIND-

OD 1500µg tab., 500µg/ml inj.

Folic acid

Pteroylglutamic acid Pharmacokinetics Metabolic functions Deficiency Therapeutic uses Daily requirement: 50µg Therapeutic doses: 1-5mg/day

Folic acid

FOLVITE, FOLITAB 5mg tab Folinic acid

RECOVORIN 15 mg tab., 75mg/ml, 10mg/ml inj.

Haematopoietic growth factors

Erythropoietin: epoietin 100 IU/kg s.c or i.v 3 times a week, darbepoetin.

Preparations available EPOX, ZYROP,EPREX 2000IU, 4000IU/ml

inj. Colony stimulating factor (CSF) G-CSF & GM-CSF Filgrastim & pegfilgrastim 300µg/inj.

Megakaryocyte growth factors Interleukin-11

Vitamins

Fat soluble vitamins: A, D, E and K Water soluble vitamins B-complex group: B1,B2,B3,B5,B6 and Biotin

Haematopoietic B-complex vitamins

Folic acid and cyanocobalamin

Non B-complex group: Ascorbic acid (vitamin-C)

Vitamin A (Retinol)

Dietary sources Physiological role a) Proper vision in dim light b) Structural integrity of epithelial cells Deficiency a) Night blindness b) Keratomalacia c) Xerophthalmia

Vitamin A analogs

Beta-Carotene: 30-300µg/day

Tritinoin

Isotritinoin:500µg/kg in 2 divided doses for 3-4 months

Etretinate: For refractory Psoriasis

Tazarotene and Bexarotene

Daily requirements

Adult doses: 4000IU/day Therapeutic doses

50,000IU-1 lac IU orally for 3 days Hypervitaminosis Preparations available AROVIT 50,000IU tab., 1 lacIU/2 ml inj AQUQSOL-A 50,000IU cap

Vitamin E(Tocoferol)

Dietary sources Phyiological role Deficiency symptoms: Peripheral

neuropathy,Sterility in males and Recurrent abortion in females

Therapeutic doses:400mg/day Nocturnal muscle cramps:400mg/day for 6-12

weeks

Vitamin E contd.

Fibrocystic breast disease:600mg/day for 3-6 months

Intermittent claudication:400mg/day for 12-15 weeks

Acanthocytosis:100mg/week i.m inj

Thiamine (Vitamin B1)

Dietary sources Physiological role Deficiency symptoms Dry Beri-Beri,Wet Beri-Beri Therapeutic doses:100mg/day i.m or iv then

5-10mg/day orally as maintenance dose Preparations available:BERIN 50mg-100mg

tab,100mg/ml inj,BENALGIS 75mg tab

Riboflavin (Vitamin B2)

Dietary sources Physiological role Deficiency symptoms:

Glossitis,Cheilosis,Cataract formation Therapeutic doses:5-20mg/day Preparations available:RIBOFLAVIN10mg

tab,10mg/ml inj.

Niacin (Vitamin B3)

Dietary sources Physiological role Deficiency symptomsPellagra(Dermatitis,Dementia,Insomnia,Diarrhoea,Deat

h) Prophylactic doses:15-20mg/day Therapeutic doses:200-500mg/day oral Preparations available:NEASION-SR,NIALIP

375mg,500mg tab

Pantothenic acid (Vitamin B5)

Dietary sources Physiological role Deficiency symptoms:Intermittent diarrhoea,

Leg cramps,Paraesthesia,Insomnia Therapeutic doses:50-100mg/day

Pyridoxine (Vitamin B6)

Dietary sources Physiological role Deficiency symptoms

Peripheral neuropathy,Stomatitis,Precipitation of epilepsy and growth retardation.

Prophylactic doses:2-5mg/day Therapeutic doses:50-200mg/day Preparations

available:PYRIDOX,BENADON50mg tab

Ascorbic acid (Vitamin C)

Dietary sources Physiological role Deficiency symptoms: Scurvy (defect in collegen

formation) Prophylactic doses:50-500mg/day Therapeutic doses:1-1.5g/day As antioxidant:100mg/day Haematinic formulations 150mg/day Preparations

available:CELIN,CHEWCEE,REDOXON 500mg tab

Antioxidants

Erythropoietin

Cytokine produced in juxtatubular cells in the kidney and also in macrophages.

Produced by recombinant technology. Available as epoeitin α and β. 25-100 IU/kg, s.c. or i.v. 3 times a week.

Uses of Erythropoietin

Anaemia due to: Chronic renal failure. Cancer chemotherapy. AIDS. Premature infants. Blood transfusion Adverse effects: flu-like symptoms, mild

hypertension, encephalopathy, occasionally convulsions, risk of thrombosis due to hematocrit rises.