Types of anemia

Normochromic normocytic

• Anemia of chronic disease• Hemolytic anemia• Aplastic anemia

Normochromic macrocytic

• Vitamin B12 deficiency• Folate deficiency

Hypochromic microcytic

• Iron deficiency• Thalassemia• Anemia of chronic disease

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IRON DEFICIENCY ANEMIA Definition: too low body iron stores to support RBC production Hemoglobin – Women <12– Men <13.5

Hematocrit – Women <36– Men <41

Pharmacology of anemia

1 Hematopoietic machinery resides in bone marrow in adult humans ..

2 iron , vitb12 , folic acid and hematopoietic growth factors are constantly needed for

hematopoisis .

Anemia

• Anemia is a deficiency in O2 carrying erythrocytes ,due to deficiency iron , vitb12 , and folic acid .

• Sickle cell anemia- genetic alteration in hb molecule

Iron• Basic pharmacology

1- most common cause of ch anemia .2- iron deficiency leads to pallor , fatigue ,

dizziness , exertion dyspnoea , and other journalized symptoms of tissue hypoxia .

3- cardiovascular adaptations of ch anemia leads to tachycardia , inc cardiac output , vasodilatation , and can worsen anemia .

• Nucleus of iron porphyrin heme ring is made by iron which combines with globins and forms hemoglobin .

• Hemoglobin reversibly binds O2 and it supplies O2 to lungs and other tissues.

• Microcytic hypo chromic anemia in the absence of adequate iron , small erythrocytes with inadequate hb are formed , giving rise to microcytic hypo chromic anemia .

• Iron containing heme is also imp for myoglobin , cytochromes and other proteins .

Pharmacokinetics

• Normal people fulfill the iron req by iron taken by food .

• In ppl with more iron requirement (growing children . Preg woman )

• and ppl with increased iron loss ( menstruating woman ) iron req can exceed normal dietary supplies and iron deficiency can develop .

Absorption • Average diet contains 10-15mg of iron daily .• Normal man absorbs 5-10% of this iron .5 -1mg of

iron daily .• It is absorbed in duodenum and proximal jejunum. • The more distal small intestine can absorb iron if

needed .• Iron absorption increases in low iron stores and

increased iron requirements .• It increases up to 1-2 mg per day in menstruating

women and 3-4 mg per day in pregnancy.

Absorption • Iron in meet proteins is well absorbed because

heme iron in meet hb and myoglobin can be absorbed intact without dissociation into elemental iron .

• Iron in other foods like vg and grains are tightly bound to organic compounds and is less available for absorption.

• Non heme iron changes into ferireductase to ferrous iron before it is absorbed by intestinal mucosal cell.

transport

• It is transported in the plasma bound to transferrin which binds 2 molecules of ferric iron.

• Transfrin iron complex enters maturing erythroid cell .

• Transferrin receptors , glycoprotein's are preset on erythroid cells .

• They bind with transferrin iron complex by endocytosis hence ferric iron is reduced to ferrous iron and is transported into cytoplasm where it is used in hb synthesis or stored as ferritin.

Storage • Mainly stored in intestinal mucosal cells .

• In the form of ferratin also stored in macrophages in the liver , spleen , bone and n parenchyma liver cells.

• The iron mobilization of iron from macrophages and hepatocytes is controlled by hepcidin.

• Low hepcidin = more iron release.

• High hepcidin= less iron release.

• Ferritin is detected in serum and is used to estimated total body iron stores in body .

elimination• No specific mech of excretion of iron • Small amounts are lost in feces by exfoliation of

mucosal cells • Traces excreted in bile , urine and sweat . • Upto 1mg per day .

Clinical pharmacology

• Indication Treatment or prevention of iron deficiency anemia . With low (mcv) and

low( mchc). Ppl with more iron requirements Premature infants Growing childrenPregnant and lactating womanPts with ch kidney diseasePts of gastrotomy

Iron therapy

Iron therapy

Vitamin b12• Co factor for several essential biochemical reactions

in human

• Deficiency leads to megaloblastic anemia , gi symptoms ,and neurological abnormalities .

• Its deficiency is due to inadequate absorption of dietary vit b12.

Chemistry

• It contains porphyrin like ring with a central cobalt atom. • Deoxyadenosylcobalamin and methylcobalamin are active

forms of vitamins in humans .• Cynocobalamin and hydroxycobalamin , and other cobalamins

found in food are converted to active form.

• DIRTARY SOURCES = LIVER , eggs , dairy products . • It is also called extrinsic factor .

Pharmacokinetics • 1-5 mcg of iron absorbed daily, and stored in liver .• 3000-5000mcg is the total vit b12 storage pool.• Traces lose daily in urine and stool.• Normal daily req of vit b12 is only 2mcg .• Vit b12 +intrinsic factor than this complex is absorbed

in distal ileum. • Its malabsorption leads to its deficiency due to lack of

intrinsic factor or defective absorption.• Once absorbed , it is transported to various cells of

body , bound with transcobalamin 1-11-111.• Excess is stored in liver .

Clinical pharmacology

• Vit b12 deficiency leads to megaloblastic , macrocytic anemia with mild or moderate leucopenia or thrombocytopenia or both.

• And hyper cellular bone marrow with megaloblastic erythroid or other precursor cells

Neurological syndrome associated with vitb12 deficiency leads to

Par aesthesia in peripheral nerves . WeaknessSpasticity , ataxia , other cns dysfunctions .

Cause of vitb12 deficiency • Pernicious anemia • Partial or total gasterectomy • Malabsorption syndromes• Inflammatory bowel disease • Small bowel resection.

FOLIC ACID

• Reduced form req for bioch reac = precursers in purines and dna formation .

• Folate deficiency = conj malformations in newborns , vascular diseases.

pharmacokinetics

• Av diet = 500-700 mcg of folate daily .• 50-200 mcg is absorbed daily.`