1c.Iron Preparations_Erythropoeitin.ppts

Hematinics

1. HAEMATINICS
&
ERYTHROPOIETIN

2. ANEMIAANEMIA
1.1.DefinitionDefinition
2.2.CausesCauses
3.3.TypesTypes
4.4.Treatment: Treatment:
Haematinics & Adjuvant haematinicsHaematinics & Adjuvant haematinics

3. HAEMATINICSHAEMATINICS
These are substances required in the These are substances required in the
formation of blood and are used in the formation of blood and are used in the
treatment of anemia.treatment of anemia.
1.1.Iron Iron
2.2.Vitamin B 12Vitamin B 12
3.3.Folic acidFolic acid
Adjuvant Haematinics:Adjuvant Haematinics:
1. Copper1. Copper
2. Cobalt2. Cobalt
3. Manganese3. Manganese

4. Iron
•Rich:Rich:
liver, egg yolk, oyster, dry beans, liver, egg yolk, oyster, dry beans, dry dry
fruits, wheat germ, yeast.fruits, wheat germ, yeast.
•Medium:Medium:
meat, chicken, fish, spinach, banana, applemeat, chicken, fish, spinach, banana, apple
•Poor:Poor:
milk & its products , root vegetablemilk & its products , root vegetabless

5. Factors facilitating absorption
Facilitating Fe Abs.Facilitating Fe Abs.
1.1.AcidAcid
2.2.Reducing Reducing
substancessubstances
3.3.MeatMeat
Decreasing Fe Abs.Decreasing Fe Abs.
1.1.AlkaliesAlkalies
2.2.PhosphatesPhosphates
3.3.PhytatesPhytates
4.4.TetracyclinesTetracyclines
5.5.Presence of foodPresence of food

6. Absorption of iron
•0.5 to 1 mg iron 0.5 to 1 mg iron is absorbed dailyis absorbed daily
•SITE of Abs. SITE of Abs. – duodenum & jejunum– duodenum & jejunum
•Iron absorption increases in response to :Iron absorption increases in response to :
low iron stores / increased iron needlow iron stores / increased iron need
•Iron in inorganic iron salts and complexes must be Iron in inorganic iron salts and complexes must be
reduced to ferrous ironreduced to ferrous iron before in can be absorbed before in can be absorbed
by intestinal mucosal cellsby intestinal mucosal cells--

8. TransportTransport
•Iron is transported in the plasma bound to Iron is transported in the plasma bound to
transferrin,transferrin, a beta globulin that specifically binds a beta globulin that specifically binds
two molecules of two molecules of ferric iron.ferric iron.
•The transferrin-iron complex enters:The transferrin-iron complex enters:
1. maturing erythroid cells in bone marrow by a 1. maturing erythroid cells in bone marrow by a
specific receptor mechanism andspecific receptor mechanism and utilized for utilized for
HB HB synthesis synthesis
2. muscle to form myoglobin2. muscle to form myoglobin
3. Other tissues & cytochromes.3. Other tissues & cytochromes.

9. Storage
1.1.Iron is Iron is stored only in stored only in ferric form ferric form in combination with a in combination with a
large protein large protein apoferritin apoferritin
2.2.ApoferritinApoferritin + + Fe Fe
3+3+
 - - - - FerritinFerritin stored in stored in GIT GIT
mucosal cells, liver& spleenmucosal cells, liver& spleen
- - Haemosiderin Haemosiderin stored in stored in liver & spleenliver & spleen
Daily requirement:Daily requirement:
Adult maleAdult male -1mg / -1mg / Adult femaleAdult female - 2mg - 2mg
Pregnancy- Pregnancy- 3-5mg & 3-5mg & growing childrengrowing children – up to 25 mg / day – up to 25 mg / day

10. Iron Containing Haematinic
Preparations
1.1.B complex & zinc B complex & zinc should not be includedshould not be included
2.2.Variety of drugs marketed Variety of drugs marketed
Fefol, Fesovit, Livogen, HaemupFefol, Fesovit, Livogen, Haemup
3.3.ExpensiveExpensive
4.4.Liquid preparations - Liquid preparations - stain teethstain teeth
5.5.SR preparations- SR preparations- irrationalirrational
6.6.Elemental iron content –Elemental iron content –importantimportant
7.7.Oral preparations –Oral preparations –not suitable for Parenteral use?not suitable for Parenteral use?

11. Elemental iron content in 100 mg oral iron preparationsElemental iron content in 100 mg oral iron preparations
•Ferrous SO4 (hydrated) : 20% Ferrous SO4 (hydrated) : 20%
•Ferrous SO4 (dry salt) : 32% Ferrous SO4 (dry salt) : 32%
•Ferrous gluconateFerrous gluconate : 12% : 12% better absorbedbetter absorbed
•Ferrous fumerate Ferrous fumerate : 33% : 33%
•Ferrous succinateFerrous succinate : 35% : 35%
--------------------------------------------------------------------------------------
•Ferric hydroxide polymaltose Ferric hydroxide polymaltose 1. 100% iron content1. 100% iron content
•Iron polysaccharideIron polysaccharide 2. better GI tolerance2. better GI tolerance
•Ferric ammonium Ferric ammonium citrate citrate 3. < overdose toxicity 3. < overdose toxicity
•Carbonyl iron complexCarbonyl iron complex

12. DoseDose
•Therapeutic : 200 mg of elemental iron , tds
•Prophylactic: 30 mg of elemental iron / day
•FeSO4, 325 mg / TDS / empty stomach 
50% deficit correction within 3 weeks 100%
correction by 2 months  when continued
for 3 months replenishes the stores

13. ADR of oral ironADR of oral iron
1.1.Epigastric pain, heart burn, Epigastric pain, heart burn,
2.2.nausea, vomiting, nausea, vomiting,
3.3.staining of teeth with liqiuid staining of teeth with liqiuid
preparationspreparations
4.4.metallic taste,metallic taste,
5.5.Constipation Constipation or or diarrhea diarrhea

14. Parenteral iron : indicationsParenteral iron : indications
1.1.Oral iron - not tolerated Oral iron - not tolerated
2.2.Non compliance Non compliance
3.3.Failure to absorb: Failure to absorb:
Malabsorption, sprue, IBS,Malabsorption, sprue, IBS,
4.4.Severe deficiencySevere deficiency
5.5.Along with erythropoietin therapyAlong with erythropoietin therapy
increased need of ironincreased need of iron

15. Calculation of Iron RequirementCalculation of Iron Requirement
For Parenteral iron therapyFor Parenteral iron therapy
Elemental Iron requirement in mg =
4.4 4.4 xx body weight body weight in Kg xx Hb deficit Hb deficit G%
For iron therapyFor iron therapy
25 mg of elemental iron is needed to correct 1% 25 mg of elemental iron is needed to correct 1%
deficit of Hb by Sahli’s method.deficit of Hb by Sahli’s method.
To this dose is added To this dose is added ½ of the calculated amount ½ of the calculated amount for for
replenishing body iron stores.replenishing body iron stores.

16. Parenteral Iron PreparationsParenteral Iron Preparations
•Iron-dextranIron-dextran- - im, iv infusion for hoursim, iv infusion for hours
•Iron-sorbitol-citrate - Iron-sorbitol-citrate - only imonly im
•IM-IM- gluteus regiongluteus region- - Z track techniqueZ track technique
•IV- IV- after test dose of after test dose of 0.5ml 0.5ml iv over 5 miniv over 5 min
Newer agents: Newer agents:
•Iron Sucrose complexIron Sucrose complex
•Iron sodium gluconate complexIron sodium gluconate complex
Safe. Safe. Admn. < 5 minutes: Admn. < 5 minutes: no need for test dose.no need for test dose.

17. ADR of Parenteral ironADR of Parenteral iron
1.1.Local - Local - pain at site of injection, sterile abscess, pain at site of injection, sterile abscess,
pigmentation of skin pigmentation of skin
2.2.SystemicSystemic – – Fever, headache, joint pain, Fever, headache, joint pain,
flushing, palpitation,chest flushing, palpitation,chest
pain,pain,dyspnoeadyspnoea
3.3.Anaphylactoid reactions Anaphylactoid reactions – –
more common with iron sorbitolmore common with iron sorbitol
4.4.Free inorganic iron is extremely toxicFree inorganic iron is extremely toxic

18. Indications for IronIndications for Iron
1. Iron deficiency anemia – 1. Iron deficiency anemia – correction takes 1-3 months correction takes 1-3 months
A rise in Hb level by 0.5 to 1 G % / week is an A rise in Hb level by 0.5 to 1 G % / week is an
optimum response to iron therapy.optimum response to iron therapy.
2. Prophylaxis – pregnancy & infancy2. Prophylaxis – pregnancy & infancy
3. Megaloblastic anemia3. Megaloblastic anemia
4. Anemia due to acute / chronic blood loss4. Anemia due to acute / chronic blood loss
5. Along with erythropoitein 5. Along with erythropoitein

19. Acute iron poisoningAcute iron poisoning
Common in childrenCommon in children
1.1.Vomiting and diarrhea Vomiting and diarrhea
2.2.Abdominal pain Abdominal pain
3.3.Hematemesis Hematemesis
4.4.Cyanosis Cyanosis
5.5.SeizuresSeizures
6.6.CVS collapse and deathCVS collapse and death

20. TreatmentTreatment
1.1.General measuresGeneral measures
2. Gastric lavage with Na bicarbonate – 2. Gastric lavage with Na bicarbonate – precipitates ironprecipitates iron
3. Egg yolk and milk orally- 3. Egg yolk and milk orally- complexes ironcomplexes iron
Specific antidote :Specific antidote :
- - Desferrioxamine:Desferrioxamine: Specific iron chelatorSpecific iron chelator
- 50 mg / kg / iv- - 50 mg / kg / iv- to remove absorbed ironto remove absorbed iron
- 5-10 G in 100ml saline - left in stomach - 5-10 G in 100ml saline - left in stomach
- - to remove unabsorbed iron to remove unabsorbed iron
Chronic Iron Toxicity:Chronic Iron Toxicity:
Deferiprone & Deferasirox-Deferiprone & Deferasirox- oral oral

21. Maturation factors- BMaturation factors- B
1212, folic acid, folic acid
Cyanocobalamin, Hydroxocoblamin, Methylcobalamin (SL) Cyanocobalamin, Hydroxocoblamin, Methylcobalamin (SL)
•Liver, kidney, sea fish, egg yolk, meat, cheeseLiver, kidney, sea fish, egg yolk, meat, cheese
Deficiency : Deficiency :
•Megaloblastic anemiaMegaloblastic anemia
•Glossitis,Glossitis,
•Sub acute combined degeneration of spinal cordSub acute combined degeneration of spinal cord
•Peripheral neuritisPeripheral neuritis
•Mental changesMental changes

22. Functions:Functions:
•1. Homocysteine 1. Homocysteine  methionine methionine needed for needed for one carbon one carbon
transfer reactions & for protein synthesistransfer reactions & for protein synthesis
BB
12 12 Deficiency Deficiency  (-) (-) of DNA productionof DNA production
•2. Melonic acid 2. Melonic acid  Succinic acid Succinic acid  FA synthesis in nervous T FA synthesis in nervous T
BB
12 12 Deficiency Deficiency  demyelinationdemyelination
•3. Methionine 3. Methionine  S-adenosyl methionine S-adenosyl methionine myelin synthsismyelin synthsis
BB
12 12 Deficiency Deficiency  neurological deficitneurological deficit
•4. Cell growth & multiplication4. Cell growth & multiplication

24. BB
1212
USES USES
1.1.Prophylaxis & treatment of BProphylaxis & treatment of B
12 12 deficiencydeficiency
2.2.NeuropathiesNeuropathies
3.3.Tobacco Tobacco amblyopiaamblyopia
ADRADR
Rare & includes Anaphylactic reactionsRare & includes Anaphylactic reactions
Dosing in pernicious anemiaDosing in pernicious anemia
- Daily 100 mcg , im / sc for 1 week - Daily 100 mcg , im / sc for 1 week 
weekly for 1 month weekly for 1 month  monthly once for life time monthly once for life time
Oral / sublingual admn . – equally good Oral / sublingual admn . – equally good

25. Folic acidFolic acid
Causes of Folic acid deficiencyCauses of Folic acid deficiency
1.1.In adequate dietary intake.In adequate dietary intake.
2.2.Malabsorption: Malabsorption: celiac disease, tropical sprue, celiac disease, tropical sprue, regional regional
ileitisileitis
3.3.Biliary fistula Biliary fistula
4.4.Chronic alcoholismChronic alcoholism
5.5.Increase demand due toIncrease demand due to pregnancy & lactation pregnancy & lactation..
6.6.Drug induced – Drug induced – phenytoin, phenobarbitone, primidonephenytoin, phenobarbitone, primidone

26. ManifestationsManifestations
1.1.Megaloblastic anemiaMegaloblastic anemia
2.2.Epithelial damage –Epithelial damage –
glossitis, enteritis, diarrhoeaglossitis, enteritis, diarrhoea
3. Neural tube defects3. Neural tube defects
Source: Source:
Liver, spinach, Egg, meat, milk.Liver, spinach, Egg, meat, milk.

28. Uses of Folic acidUses of Folic acid
1.1.Prophylaxis & Treatment of megaloblastic anemia and Prophylaxis & Treatment of megaloblastic anemia and
pernicious anemia due to: pernicious anemia due to:
dietary deficiency, drug induced dietary deficiency, drug induced (phenytoin, (phenytoin,
methotrexate, etc.), methotrexate, etc.), increased requirement increased requirement
(pregnancy, hyperthyroidism, RA, leukemia)(pregnancy, hyperthyroidism, RA, leukemia) caution: caution:
Should never be given alone to patients Should never be given alone to patients
with pernicious anemiawith pernicious anemia
2. Antinatal: 2. Antinatal: to prevent neural tube defects to prevent neural tube defects
3.3.Methotrexate toxicity: Methotrexate toxicity: folinic acidfolinic acid
Dose: Dose: 5-20 mg / day5-20 mg / day

29. Erythropoietin (EPO)Erythropoietin (EPO)
•Produced by peritubular cells of kidney. Produced by peritubular cells of kidney.
•Essential for normal erythropoiesis.Essential for normal erythropoiesis.
Functions Functions
1.1.Stimulates proliferations of colony forming cellsStimulates proliferations of colony forming cells
2.2.Induces Hb formation & erythroblast maturation.,Induces Hb formation & erythroblast maturation.,
3.3.Releases reticulocytes in circulation.Releases reticulocytes in circulation.
PreparationsPreparations
1.1.Epoetin Epoetin αα,,ββ:: r DNA human erythropoietin r DNA human erythropoietin
2.2.Darbepoietin:Darbepoietin: Hyperglycosylated prep. of Hyperglycosylated prep. of EPOEPO

30. ErythropoietinErythropoietin
USES
1.1.Chronic renal failureChronic renal failure
2.2.25 - 100 unit per kg s.c or 25 - 100 unit per kg s.c or
i.v , 3 times a weeki.v , 3 times a week
3.3.Anemia in AIDS patient Anemia in AIDS patient
treated with zidovudine.treated with zidovudine.
4.4.Cancer chemotherapyCancer chemotherapy
5.5.Autologous transfusion Autologous transfusion
during surgeryduring surgery
ADR
1.1.Clot formation in A – V Clot formation in A – V
shunts.shunts.
2.2.Hypertensive episodes.Hypertensive episodes.
3.3.Seizures occasionally Seizures occasionally
4.4.Flu like symptoms.Flu like symptoms.

31. University questionsUniversity questions
Short notes:Short notes:
1. Oral iron preparations1. Oral iron preparations
2. Parenteral iron preparations2. Parenteral iron preparations
3. Treatment of iron toxicity3. Treatment of iron toxicity
4. Folic Acid4. Folic Acid
5. Vitamin B5. Vitamin B
1212
6. Erythropoietin preparations 6. Erythropoietin preparations