Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
Dr.K. R. Prabhakar,
Asst.Proffessor
Pathophysiology
 This is due to vitamin B₁₂ and folic acid deficiency
 Impairment of DNA synthesis and cell proliferatio...
 Mammals can not synthesise vit B₁₂ .
 Sources of vit B₁₂ are- fish, meat, liver, eggs, yeast &
milk.
 Commercial sourc...
 Pernicious anemia:
• Important cause of vit B₁₂ deficiency
• Hereditary autoimmune disease in which antibodies
develop a...
Chemistry:
 Vit B₁₂ is a generic term for cyanocobalamin &
hydroxocobalamin.
 Only cobalt containing amino compounds kno...
Pharmacokinetics
 Absorption from GIT depends on various transfer
mechanisms.
 After liberation from food interacts with...
 In enterocytes IF liberates cobalamin which is
converted to methylcobalamin
 Transcobalamin II transports it to portal ...
Metabolic functions
 Cobalamins- cofactors for 2 main enzymatic process
 1. Cofactor for methionine synthase –converts
h...
In vitB₁₂ deficiency
 5-methyl-tertrahydrofollic acid gets trapped.
 Defective DNA synthesis & ultimately megaloblastic
...
In vitB₁₂ deficiency
 methylmalonyl coA accumulate results in faulty fatty
acid synthesis.
 Incorporates in to cell memb...
Therapeutic uses
 Most commonly used preparations are
 cyanocobalamin
 hydroxycobalamin
 methylcobalamin
 Given orall...
 Methylcobalamin is used to treat neurological
deficits in vit B₁₂ deficiency.
 Dose: cyanocobalamin or hydroxycobalamin...
 Also called polyglutamate as each folic acid molecule
may have 2-8 molecules of glutamic acid.
 Humans can not synthesi...
Pharmacokinetics
 Absorption occurs primarily in proximal jejunum.
 Carboxypeptidases in jejunum hydrolyse dietary
polyg...
 Undergoes enterohepatic circulation similar to vitB₁₂.
 Trace amounts are excreted in urine & faeces.
 Stores last for...
Deficiecy causes
 Dietary lack.
 Malabsorption syndrome (coeliac disease or crohns
disease).
 Excessive demand as in pr...
Therapeutic use
 RDA of folic acid is 50 µg,
 During pregnancy & lactation up to 200-300 µg/day.
 Therapeutic doses are...
 Folic acid is always given with vit B₁₂ to treat
megaloblastic anemia.
 In the presence of vitB₁₂ deficiency if only fo...
 Cytokine produced in juxtatubular cell in kidney &
also macrophages.
 Essential for normal erythropoiesis.
 Anaemia an...
 Recombinant human erythropoietin are Epoetin α, β.
 Administered by i.v. or s.c. injection.
 Plasma t½ of 6–10 hr, but...
Uses
 Primary use- anaemia of chronic renal failure.
 Anaemia in AIDS patients treated with zidovudine.
 Cancer chemoth...
 Preferable for smptomatic patients with Hb ≤ 8 g/dl.
 Epoetin 25–100 U/kg s.c. or i.v. 3 times a week (max.
600 U/kg/we...
Thank you
Treatment  of other anemias
Upcoming SlideShare
Loading in …5
×

2

Share

Download to read offline

Treatment of other anemias

Download to read offline

vitamin B12 & folic acid deficiency anemia

Related Books

Free with a 30 day trial from Scribd

See all

Related Audiobooks

Free with a 30 day trial from Scribd

See all

Treatment of other anemias

  1. 1. Dr.K. R. Prabhakar, Asst.Proffessor
  2. 2. Pathophysiology  This is due to vitamin B₁₂ and folic acid deficiency  Impairment of DNA synthesis and cell proliferation in precursor cells of RBCs.  Cytosolic growth is not impaired ,cytosole ↑  Hence primitive RBCs become big(megaloblast)  Mature RBCs diminish(anemia),  Prone to hemolysis-hemolytic anemia.
  3. 3.  Mammals can not synthesise vit B₁₂ .  Sources of vit B₁₂ are- fish, meat, liver, eggs, yeast & milk.  Commercial source- from streptomyces griseus. Deficiency causes:  Insufficient dietary intake (RDA-2µg)  ↓absorption or utilisation  Prolonged chemotherapy (interfers with purine metabolism).  Fish tape worm infestation
  4. 4.  Pernicious anemia: • Important cause of vit B₁₂ deficiency • Hereditary autoimmune disease in which antibodies develop against intrinsic factor(IF) • ABs either bind to IF or IF-B₁₂ complex and prevents binding to IF receptors in ileum.  Availability of IF decreases in • Post gastrectomy patients, diseases of ileum & surgical removal of ileum.
  5. 5. Chemistry:  Vit B₁₂ is a generic term for cyanocobalamin & hydroxocobalamin.  Only cobalt containing amino compounds known to occur in nature.  Methylcobalamin & 5deoxoadenosyl cobalamin act as coenzymes and are active forms of vit B₁₂ though unstable.
  6. 6. Pharmacokinetics  Absorption from GIT depends on various transfer mechanisms.  After liberation from food interacts with R-proteins in stomach protect it from acid degradation.  In the duodenum the pancreatic proteases degrade the complex to free cobalamin.  Vit B₁₂ is now absorbed on to the IF .  IF- cobalamin complex is transported across ileum cell membrane through IF specific receptors
  7. 7.  In enterocytes IF liberates cobalamin which is converted to methylcobalamin  Transcobalamin II transports it to portal circulation.  Vit B₁₂ is taken up by cells by endocytosis.  Excess vit B₁₂ is stored as 5-deoxoadenosylcobalamin in hepatocytes.  Liver can store up to 4-6 mg of vit B₁₂ .  Stores can last for 5 yrs even if intake is stopped.
  8. 8. Metabolic functions  Cobalamins- cofactors for 2 main enzymatic process  1. Cofactor for methionine synthase –converts homocysteine to methionine &  5-methyl tetrahydrofolate to tetrahydrofolic acid.
  9. 9. In vitB₁₂ deficiency  5-methyl-tertrahydrofollic acid gets trapped.  Defective DNA synthesis & ultimately megaloblastic bone marrow.  2. Deoxyadenosyl cobalamin activates methylmalonyl-coA mutase
  10. 10. In vitB₁₂ deficiency  methylmalonyl coA accumulate results in faulty fatty acid synthesis.  Incorporates in to cell membranes of CNS leads to neurological symptoms due to inadequate myelin synthesis-  Peripheral neuropathy,  Dementia,  Loss of motor and sensory reflexes.
  11. 11. Therapeutic uses  Most commonly used preparations are  cyanocobalamin  hydroxycobalamin  methylcobalamin  Given orally or deep intramuscularly never given i.v.  Hydroxycobalamin is longer acting but development of Abs to transcobalamin II –vit B₁₂ complex made its use lesser.
  12. 12.  Methylcobalamin is used to treat neurological deficits in vit B₁₂ deficiency.  Dose: cyanocobalamin or hydroxycobalamin 100- 1000 µg/day i.m on alternative days for 2 weeks followed by once a month.  Methylcobalamin 1000-1500 µg/day orally.  I.M therapy brings changes in bone marrow with in 2-3 mts with improvement in neurological symptoms
  13. 13.  Also called polyglutamate as each folic acid molecule may have 2-8 molecules of glutamic acid.  Humans can not synthesise folic acid Dietary sources:  Green leafy vegetables, fruits, mushrooms, liver, meat, kidney, eggs, milk & yeast.  One of the B group vitamin.
  14. 14. Pharmacokinetics  Absorption occurs primarily in proximal jejunum.  Carboxypeptidases in jejunum hydrolyse dietary polyglutamates to folic acid.  Dihydrofolate reductase converts folic acid to tetrahydrofolic acid(THFA) in mucosa & methylated to (5-MeTHFA)  Converted to THFA by methionine synthase in tissues.  About 5-20 mg is stored in liver.
  15. 15.  Undergoes enterohepatic circulation similar to vitB₁₂.  Trace amounts are excreted in urine & faeces.  Stores last for about only 3 months. Metabolic functions:  THFA is transformed to folate cofactors – folinic acid, 10-formyl THFA, 5,10-methylene-THFA etc. donates one carbon units in oxidation.  THFA through 1-C transfer reactions is involved in synthesis of purines and pyrimidines which are essential for DNA synthesis.
  16. 16. Deficiecy causes  Dietary lack.  Malabsorption syndrome (coeliac disease or crohns disease).  Excessive demand as in pregnancy & anemia.  Liver diseases and renal dialysis.  Drug induced- methotrexate, phenytoin, phenobarbitone.  Deficiecy leads to megaloblast anemia and teratogenic effects.
  17. 17. Therapeutic use  RDA of folic acid is 50 µg,  During pregnancy & lactation up to 200-300 µg/day.  Therapeutic doses are 1-5 mg/day. Uses-  Folinic acid for prophylaxis or treatment of methotrexate toxicity.  Folate deficiency by phenobarbitone & phenytoin.  Prophylactically during pregnancy, lactation.
  18. 18.  Folic acid is always given with vit B₁₂ to treat megaloblastic anemia.  In the presence of vitB₁₂ deficiency if only folic acid is used it will improve only anemia but worsen neurological deficit as it does not convert methylmalonyl CoA to succinyl CoA.  Adverse effects :rare for both vit B₁₂ &folic acid.
  19. 19.  Cytokine produced in juxtatubular cell in kidney & also macrophages.  Essential for normal erythropoiesis.  Anaemia and hypoxia are sensed by kidney cells.  Induce rapid secretion of EPO→ acts on erythroid marrow.  EPO receptor is a JAK-STAT-binding receptor.
  20. 20.  Recombinant human erythropoietin are Epoetin α, β.  Administered by i.v. or s.c. injection.  Plasma t½ of 6–10 hr, but action lasts several days.  Darbepoetin – longer acting glycosylated form of epoetin, injected weekly.
  21. 21. Uses  Primary use- anaemia of chronic renal failure.  Anaemia in AIDS patients treated with zidovudine.  Cancer chemotherapy induced anaemia.  Preoperative increased blood production for autologous transfusion during surgery.  Anemia in premature infants.  Supplemented with iron & folic acid.
  22. 22.  Preferable for smptomatic patients with Hb ≤ 8 g/dl.  Epoetin 25–100 U/kg s.c. or i.v. 3 times a week (max. 600 U/kg/week).  Reduces need for transfusions  It is prudent to start with a low dose and titrate upwards to keep haematocrit between 30–36%, and Hb 10–11 g (max 12 g) per dl.
  23. 23. Thank you
  • RanajoySarkar3

    Aug. 28, 2020
  • drchetan2385

    May. 30, 2018

vitamin B12 & folic acid deficiency anemia

Views

Total views

635

On Slideshare

0

From embeds

0

Number of embeds

1

Actions

Downloads

21

Shares

0

Comments

0

Likes

2

×