.

 Overview
 Hematinic Agents
▪ Iron
▪ Folic Acid and Vitamine B12 – collectively known

as Maturation factors
 Haemopoetic Growth Factors

http://www.theironfiles.co.uk/Sickle-cell/General/SCDBlood.html

 4 globin + 1 haem.
 Haem
▪ consists of a tetrapyrrole

porphyrin ring containing
ferrous (Fe2+) iron.

▪ Each haem group can carry 1
oxygen molecule
▪ bound reversibly to Fe2+ and to a

histidine residue in the globin
chain→ basis of oxygen
transport.

http://www.theironfiles.co.uk/Sickle-cell/General/SCDBlood.html

1

.

IMBALANCE

 Definition: ↓ [Hb] in blood &/ RBC per age, sex and geographical
location. <<<< INPUT: >>>OUTPUT:

Nutritional  Bleeding
 Normal Hb:

deficiency  Haemolysis
▪ 14 – 16 g/dl in Male
▪ 13 – 15 g/dl in Female

 Acute: fatigue → chronic: asymptomatic.

 Classification based on indices of red cell are: BROKEN MACHINE
▪ hypochromic, microcytic anaemia – – Synthesis <<
▪ macrocytic anaemia

– – Chronic disease
▪ normochromic normocytic anaemia
▪ mixed pictures.

IMBALANCE

↓↓↓↓ FORMATION ↑↑ ↑↑DESTRUCTION
<<<< INPUT: >>>OUTPUT:

FIX 1. Nutritional
N uTtrHitiEon aUl NDERLYING 1. Post Haemorrhage

 Bleeding ▪ Iron Deficiency ▪ Acute & chronic blood Loss
deficieCnAcyUSES!!  Haemolysis ▪ Folic Acid/ Vit B12 Deficiency 2. Excessive Haemolysis

▪ Protein Deficiency
▪ Intracellular Defect

2. Decreased Synthesis (Defective RBC)
▪ Aplastic Anaemia ▪ Thalassemia
▪ Replacement of BM (e.g. ▪ Haemoglobinopathies

Leukaemia) ▪ Sickle cell anaemia
BROKEN MACHINE ▪ Thalassemia

▪ Extracellular Defect
3. Chronic Disorder

– – Synthesis << ▪ Rh Incompatibility
▪ Kidney Disease ▪ Auto Immune Haemolytic

– – Chronic disease ▪ Advanced Malignancy Anaemia
▪ Chronic Liver Disease ▪ Certain Snake Venom

 Hematinics are drugs used to stimulate the
formation of red blood cells.

 Used primarily in the treatment of anemia

 Example:
▪ Iron
▪ Folic Acid
▪ Vitamin B12

2

.

 Basic Pharmacology
 Pharmacokinetics
▪ Absorption

 Pharmacodynamics
 Indications
 Drug Interactions
 Side Effects

 Important properties :
 Liver

▪ Absorbed in ferrous form in duodenum
 Egg yolk

▪ Stored in ferric form
 Beans

▪ Ferritin & haemosiderin
 Dry fruits

▪ Transferrin

 Poor sources – milk & its products
 Fe + protoporphyrin →Heme
 Heme + globin →Hemoglobin  Ascorbic acid & HCl ↑ absorption
 Hemoglobin binds O2 & provides O2 delivery  Alkalies, phosphates, phytates & tetracyclines ↓
 Fe deficiency →microcytic hypochromic anemia absorption
 Body content of iron:
▪ Essential: myoglobin, Hb, enzyme, transferrin → not available for

hemoglobin synthesis

Do You Have Anemia?

3

.

 Iron deficiency anemia can occur under the
following four conditions:
1. Less Intake of Fe, Vitamins and Protein
2. Diminished absorption
3. Increased Loss
4. Excessive Demand

 Oral:
1. Iron deficiency due to dietary lack or to chronic  ferrous sulfate, ferrous succinate, ferrous gluconate and ferrous

blood loss. fumarate.
 S/E: GIT upset, blackened stool, teeth stain, metallic taste

2. Pregnancy
 Form: tablet, liquid, sustained-release

3. GIT abnormality: malabsorption
4. Premature baby  Parenteral iron
5. Early treatment of pernicious anemia  Indication: when oral iron is not absorbed, not tolerated or with

Erythropoietin (EPO)
 Deep IM: iron-dextran or iron-sorbitol citrate
 precaution: local reaction, anaphylaxis

 Slow IV: iron dextran , sodium ferric gluconate complex, iron
sucrose
 Precaution: risk of anaphylaxis!!!

Iron – dextran Iron-sorbitol-citrate

Can be given IV or IM Only IM

Not excreted About 30% excreted in urine

Absorbed through lymphatics Absorbed directly in circulation

Not bound to transferrin Not bound to transferrin

4

.

 Therapeutic dose:
1. Iron chelates in the gut with tetracyclines, penicillamine,

▪ 1000 mg ferrous sulphate tds provides around 60 mg elemental
iron per dose methyldopa, levodopa, carbidopa, ciprofloxacin,

norfloxacin and ofloxacin;
 Adequate response: 2. It also forms stable complexes with thyroxine, captopril
▪ ↑ Hb of 0.5 – 1 g/dl per week and bisphosphonates. Ingestion should be separated by 3

hours.
 Failure of response 3. ↑absorption: vit C
▪ after 2 weeks of oral iron requires re-evaluation for ongoing blood 4. ↓absorption: desferrioxamine, tea (tannins) , Ca, Zn, and

losses, infection, poor compliance or other causes of microcytic bran
anaemia.

 Priority: oral preparation

 Dose related include nausea, abdominal cramps and diarrhea.
▪ overcome : ↓dose or by taking the tablets after or with meals

 Acute iron toxicity
▪ Ingestion of large quantities of iron salts.
▪ Result: severe necrotising gastritis with vomiting, haemorrhage

and diarrhoea→ collapse
▪ Treatment : gastric lavage with NaHCO3, iron chelating agent,

and treatment of causes.
 Chronic iron toxicity

▪ Caused by conditions other than ingestion of iron salts
▪ Cause pancreatic damage leading to diabetes.

▪ Desferrioxamine(Desferal) (t1/2 6 h).
▪ not absorbed from the gut but is nonetheless given

intragastrically following acute overdose (to bind iron in the
bowel lumen and prevent its absorption) as well as IM and IV

▪ forms a complex with ferric iron, excreted in the urine.
Indicated in Acute iron poisoning

▪ Deferiprone
▪ Indicated in Chronic Iron overload
▪ orally absorbed
▪ to treat iron overload in patients with thalassaemia major, in

whom desferrioxamine is contraindicated.
▪ careful monitoring : Agranulocytosis and other blood

dsyscrasias

5

.

Cyanocobalamin Hydroxocobalamin

 Vitamin containing cobalt Synthesis of DNA

 Cyanocobalamin & Hydrocobalamin are 2 forms present in  Methyl-FH4 donates the
diet methyl group to B12, the

 Present in animal foods & legume is the only vegetable cofactor.
source

 The methyl group is then
 Ultimate source: microbial synthesis transferred to
 Also called as Extrinsic factor homocysteine to form
 Active forms are deoxyadenosyl-cobalamin & methyl- methionine

cobalamin
 Deficiency: “methylfolate

 Role: conversion of homocysteine to methionine (folic acid
is also req.), methylmalonyl CoA to succinyl CoA & trap”

methionine to s-adenosyl methionine

 Vit B12 binds to IF & the IF-vit b12 complex is absorbed in distal
 Vit B12 deficiency : accumulation of methyl ileum

malonate-CoA → basis of neuropathy in vit  Released into plasma bound to transcobalamines TC I, II, or III
B12 deficiency

 In circulation, cobalamin binds to transcobalamin II

 Vit B12 deficiency mostly results from malabsorption,
chemotherapy or fish tapeworm infestation

 Nutritional deficiency is rare

6

.

1. Pernicious anemia

2. Dietary deficiency: vegetarian

3. Malabsorption syndrome : stagnant loop syndrome ,Crohn’s
disease, Fish tape worm infestation, gastrectomy

4. ↑ requirements: pregnancy, hemolytic anemia, hepatic disease

5. Neurological abnormalities (diabetes, alcohol or drug intake) –
Methylcobalamin

6. Tobacco amblyopia – Hydroxocobalamin

Prime – Phenytoin
Primidone

B – B12 & Folic acid deficiency
A – Alcohol
T – Trimethoprim
S – Sulfasalazine
M – Metformin
A – Antifolates (Methotrexate, Pyrimethamine, Proguanil)
N – N2O

 Contraindication
▪ Inconclusively diagnosed anemia
▪ Allergic to cobalt

 Interaction
▪ Alcohol, aminosalicylic acid, neomycin and colchicine may

decrease the absorption of oral vit B12

 Hydroxocobalamin is preferred to cyanocobalamin:First choice :
injection

7

.

Folate: Pharmacodynamics

 Etiology :
▪ Causes : inadequate diet, alcoholism, pregnancy, drug therapy,

malabsorption syndrome
▪ Other causes : increased requirement, enhanced metabolism,

interference in the metabolism
 Gastrointestinal manifestations
▪ More widespread and more severe, diarrhea is often present
▪ Cheilosis
▪ Glossitis

 Neurologic abnormalities do not occur !!!
 THFA involved in conversion of homocysteine to

methionine (B12 is also req) & generation of thymidylate

Management : 1. Megaloblastic Anemia
 Folic acid should not be given until B12 def. and pernicious

anemia have been excluded 2. Anemia associated with dihydrofolate reductase
inhibitors.

 Oral dose: 1 mg/day
▪ Administration of citrovorum factor (methylated folic acid)

 Absorption is normal : 50-100 mcg/d alleviates the anemia.
 Malabsorption : 250-500 mcg/d 3. Ingestion of drugs that interfere with intestinal
 To replenish depleted folate stores, a daily dose of 1-2 absorption and storage of folic acid.

mg/d for 2-3 weeks
 Duration of therapy depend on underlying causes : 3-4

4. Malabsorption – Sprue, Celiac disease, partial
months to clear folate-deficient erythrocytes from the gastrectomy.
blood

5. Rheumatoid arthritis – increased folic acid demand or
utilization.

 It is a sialo-glycoprotein hormone (MW 34000) produced
by kidney.

 Anaemia & hypoxia act as stimulus.
❖ Proliferation of colony forming cells of erythroid series.
❖ Hb formation & erythroblast maturation
❖ Releases reticulocytes in circulation

 EPO receptor is JAK-STAT binding receptor

 It has no effect on RBC life span.

 Preparations- Epoetin α,β IV/SC

8

.

Blood Growth factor Drug Indication
cell

RBC Erythropoietin Epoietin Anemia in CRF,
Darbopoietin myelosuppressive

1. Anemia of chronic renal failure Peginesatide drug use (Zidovudine
2. Anemia in AIDS patients on Zidovudine & cancer
3. Cancer chemotherapy induced anemia chemotherapy)
4. Pre-operative increased blood production for autologous WBC G-CSF Filgrastim Neutropenia due to

transfusion during surgery Peg-filgrastim anticancer drugs,
Lenograstim severe chronic

Darbopoietin alpha is long acting derivative given weekly neutropenia, stem
GM-CSF Sargramograstim cell transplantation

Peginesatide (erythropoiesis stimulating agent) – given in anemia Molgramograstim
due to CRF in dialysis patients Platelets IL-11 Oprelvekin Thrombocytopenia

Thrombopoietin Romiplastim due to anticancer
ADRs – polycythemia & hypertension Eltrombopag drugs, ITP

9