Dr SINDHU KDr SINDHU K

MVSc SCHOLAR,MVSc SCHOLAR,

DEPT OF VPT,POOKODEDEPT OF VPT,POOKODE

ANTIANEMIC DRUGS ANTIANEMIC DRUGS IN VETERINARY IN VETERINARY

PRACTICEPRACTICE

AnemiaAnemia

Inadequate red blood mass usually is a Inadequate red blood mass usually is a secondary condition rather than secondary condition rather than representing a primary disease of the representing a primary disease of the ERYTHRON ERYTHRON

Deficiency of erythrocytes per unit volume Deficiency of erythrocytes per unit volume of blood of blood In simple words anemia = low hemoglobin, In simple words anemia = low hemoglobin, low RBC count and low RBC mass. low RBC count and low RBC mass.

types of Anemiatypes of Anemia

Primary anemia = occurs due to Primary anemia = occurs due to excessive loss of bloodexcessive loss of bloodeg: hemolysis , hemorrhageeg: hemolysis , hemorrhage

Secondary anemia = impaired cell Secondary anemia = impaired cell formationformationeg: hypothyroidism , arsenic eg: hypothyroidism , arsenic toxicity etctoxicity etc

MACROCYTIC NORMOCHROMICMACROCYTIC NORMOCHROMIC

Cobalt or vitamin b12 Cobalt or vitamin b12 deficiencydeficiency

Folic acid deficiencyFolic acid deficiencyFeLV associated FeLV associated myelodysplasiamyelodysplasia

Congenital erythropoietic Congenital erythropoietic porphyriaporphyria

MACROCYTIC MACROCYTIC HYPOCHROMICHYPOCHROMIC

It is a transient condition occurring It is a transient condition occurring during the active phase of erythroid during the active phase of erythroid regeneration following erythrocyte regeneration following erythrocyte destruction or acute blood lossdestruction or acute blood loss

HemolysisHemolysis Blood parasites, rickettsial agentsBlood parasites, rickettsial agents Ba, viral infectionsBa, viral infections Intrinsic erythrocyte defectsIntrinsic erythrocyte defects

NORMOCYTIC NORMOCYTIC NORMOCHROMICNORMOCHROMIC

Acute blood loss prior to onset of Acute blood loss prior to onset of regenerative responseregenerative response

Anemia of chronic inflammatory Anemia of chronic inflammatory diseases , chronic renal failurediseases , chronic renal failure

Hypoadrenocortisism, hypothyroidism, Hypoadrenocortisism, hypothyroidism, lead poisoning,bracken fern poisoninglead poisoning,bracken fern poisoning

Cytotoxic marrow damage-radiations Cytotoxic marrow damage-radiations & chemicals & chemicals

NORMOCYTIC NORMOCYTIC HYPOCHROMICHYPOCHROMIC

Early iron deficiencyEarly iron deficiency

MICROCYTIC NORMOCHROMICMICROCYTIC NORMOCHROMIC Iron deficiency in progression,Normal Iron deficiency in progression,Normal

asymptomatic characteristic of asymptomatic characteristic of Japanese akitasJapanese akitas

MICROCYTIC HYPOCHROMICMICROCYTIC HYPOCHROMIC

Iron deficiency Iron deficiency congenital anemia of neonatescongenital anemia of neonates Chronic gastro intestinal blood lossChronic gastro intestinal blood loss Infestation with hematophagous Infestation with hematophagous

parasitesparasites Copper deficiencyCopper deficiency Molybdenum toxicityMolybdenum toxicity Pyridoxine toxicityPyridoxine toxicity

BLOOD LOSS ANEMIABLOOD LOSS ANEMIA

Loss of blood from vascular space , Loss of blood from vascular space , whether to the exterior of the body or to whether to the exterior of the body or to extravascular regions with in the tissuesextravascular regions with in the tissues

Acute or chronicAcute or chronic Principal pathophysiological effect is Principal pathophysiological effect is

HYPOVOLUMIAHYPOVOLUMIA Patient with acute blood los die of Patient with acute blood los die of

hemorrhagic shock before anemia is hemorrhagic shock before anemia is manifestedmanifested

TreatmentTreatment

Life threatening problem -> Life threatening problem -> hypovolemia -->hemorrhagic shockhypovolemia -->hemorrhagic shock

Therapeutic goal = Blood volume Therapeutic goal = Blood volume repletion repletion

A balance crystalloid solutionA balance crystalloid solution ~7.2% sodium chloride to promote fluid ~7.2% sodium chloride to promote fluid

redistribution from extravascular redistribution from extravascular tissues to vascular compartment & tissues to vascular compartment & positive ionotropic effects on heartpositive ionotropic effects on heart

TreatmentTreatment

Synthetic colloids{ hypoproteinemia}Synthetic colloids{ hypoproteinemia} ~0.9%saline solutions with 6-10% ~0.9%saline solutions with 6-10%

dextran-40, dextran-70, pentastarch dextran-40, dextran-70, pentastarch or hetastarchor hetastarch

Plasma transfusionPlasma transfusion ACUTE BLEEDING – whole blood ACUTE BLEEDING – whole blood

transfusion , packed red blood cell transfusion , packed red blood cell transfusion.transfusion.

IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA

If blood loss continues, sufficient IRON If blood loss continues, sufficient IRON eventually will be lost producing iron eventually will be lost producing iron depleted state even with continued depleted state even with continued ingestion of dietary ironingestion of dietary iron

Rate of hemoglobin lost exceeds that Rate of hemoglobin lost exceeds that of iron absorption=animal of iron absorption=animal experiences NEGATIVE IRON BALANCE experiences NEGATIVE IRON BALANCE resulting in typical MICROCYTIC resulting in typical MICROCYTIC HYPOCHROMIC ANEMIA HYPOCHROMIC ANEMIA

treatmenttreatment

Transfusion of whole blood or blood Transfusion of whole blood or blood productsproducts

Dogs <15% PCVDogs <15% PCV Cats < 12% PCVCats < 12% PCV Blood volume expansion - whole Blood volume expansion - whole

blood or cell-free, polymerized blood or cell-free, polymerized hemoglobin, crystalloids or colloid hemoglobin, crystalloids or colloid solution solution

Blood transfusionBlood transfusion

HEMOLYTIC ANEMIAHEMOLYTIC ANEMIA

Destruction of erythrocytes{oxidative Destruction of erythrocytes{oxidative or immunological damage}or immunological damage}

Blood parasites – anaplasma , babesia Blood parasites – anaplasma , babesia , hemobartonella , eperythrozoon., hemobartonella , eperythrozoon.

Rickettsial - erlichia Rickettsial - erlichia Bacterial – leptospirosis , clostridium.Bacterial – leptospirosis , clostridium. Virus – feline leukemia virus, equine Virus – feline leukemia virus, equine

infectious anemia.infectious anemia.

TreatmentTreatment

Supportive therapy – transfusion of Supportive therapy – transfusion of whole bloodwhole blood

Specific treatmentSpecific treatment

glutathione precursor in subduing the glutathione precursor in subduing the action of oxidative drugsaction of oxidative drugs

Eg: N acetyl cysteineEg: N acetyl cysteine

Antioxidants {vitamin A ,E, C }Antioxidants {vitamin A ,E, C }

ANTIMICROBIALSANTIMICROBIALS

NON NON REGENERATIVE/HYPOPLASTIREGENERATIVE/HYPOPLASTI

CC ANEMIA associated with bone ANEMIA associated with bone marrow dysfunctionmarrow dysfunction

Suppressive chemicals- pesticides , Suppressive chemicals- pesticides , insecticides , antineoplastic agents.insecticides , antineoplastic agents.

Endocrine failure affecting cell Endocrine failure affecting cell division & erythropoiesis(EPO, division & erythropoiesis(EPO, insulin, thyroid hormone)insulin, thyroid hormone)

Chronic inflammations Chronic inflammations

TreatmentTreatment

Characterized by erythroid precursor Characterized by erythroid precursor phagocytosis – responds to phagocytosis – responds to immunosuppressive drugs or Human immunosuppressive drugs or Human gamma globulingamma globulin

Dogs – estrogen induced bone Dogs – estrogen induced bone marrow suppressionmarrow suppression

Lithium carbonate 11mg/kg os BIDLithium carbonate 11mg/kg os BID

Primary dietary iron Primary dietary iron deficiency anemiadeficiency anemia

Iron responsiveness, microcytic, Iron responsiveness, microcytic, hypochromic anemia relatively common hypochromic anemia relatively common in neonates especially pigletsin neonates especially piglets

~300mg of iron required in first 3 weeks ~300mg of iron required in first 3 weeks but sow milk ~21 mg but sow milk ~21 mg

Poor growth rate, rough hair coat, pale Poor growth rate, rough hair coat, pale & wrinkled skin, dyspnea, fatigue,& wrinkled skin, dyspnea, fatigue,

very high mortality ratevery high mortality rate

TreatmentTreatment

Iron dextran 100-150 mg IM on 2Iron dextran 100-150 mg IM on 2ndnd or 3 or 3rdrd day to day to piglets piglets

Absorbed in to lymphatic system with in 3 days Absorbed in to lymphatic system with in 3 days of administration & enters cells of mononuclear of administration & enters cells of mononuclear phagocytes through circulating blood & phagocytes through circulating blood & combines with TRANSFERRINcombines with TRANSFERRIN

Copper deficiency also participates in Copper deficiency also participates in pathogenesis of baby pig anemia – application pathogenesis of baby pig anemia – application of iron copper preparation to the sow’s udder is of iron copper preparation to the sow’s udder is beneficialbeneficial

POLYCYTHEMIAPOLYCYTHEMIA

A relative or absolute increase in A relative or absolute increase in concentration of circulating erythrocytesconcentration of circulating erythrocytes

Increase in erythrocytic no = increase in Increase in erythrocytic no = increase in hemoglobin concentration of the bloodhemoglobin concentration of the blood

RELATIVE POLYCYTHEMIA results from loss RELATIVE POLYCYTHEMIA results from loss of fluid component of blood or of fluid component of blood or hemoconcentrationhemoconcentration

Transient state secondary to dehydrationTransient state secondary to dehydration

Polycythemia contd.,Polycythemia contd.,

ABSOLUTE POLYCYTHEMIA characterized by ABSOLUTE POLYCYTHEMIA characterized by increase in the total erythonincrease in the total erython

Usually associated with hyperplasia of Usually associated with hyperplasia of erythropoietic elements of bone marrowerythropoietic elements of bone marrow

Idiopathic=polycythemia veraIdiopathic=polycythemia vera dogs ~ carcinoma, fibrosarcoma, dogs ~ carcinoma, fibrosarcoma,

lymphosarcoma of kidneyslymphosarcoma of kidneys Right to left circulatory shunts-chronic Right to left circulatory shunts-chronic

hypoxia stimulating EPO release from hypoxia stimulating EPO release from kidneykidney

treatmenttreatment

Directed at the primary disease & Directed at the primary disease & improvement of oxygen delivery to tissuesimprovement of oxygen delivery to tissues

Paraneoplastic syndrome of absolute Paraneoplastic syndrome of absolute polycythemia = surgical removal of tumorpolycythemia = surgical removal of tumor

Phlebotomy Phlebotomy Myelosuppressive agents = chlorambucil , Myelosuppressive agents = chlorambucil ,

hydroxyurea , busulfan , radiophospheroushydroxyurea , busulfan , radiophospherous

ANAEMIA OF CHRONIC ANAEMIA OF CHRONIC RENAL FAILURERENAL FAILURE

Loss of endogenous EPO resulting from Loss of endogenous EPO resulting from chronic renal failure culminates in non-chronic renal failure culminates in non-regenerative anemiaregenerative anemia

UREMIA ~ reduced erythrocyte survivalUREMIA ~ reduced erythrocyte survival

~ platelet dysfunction~ platelet dysfunction

~ gastrointestinal bleeding~ gastrointestinal bleeding

~uremic inhibitors of ~uremic inhibitors of

erythropoiesiserythropoiesis

treatmenttreatment

Therapy directed at slowing the Therapy directed at slowing the progression of chronic renal failure progression of chronic renal failure

Ameliorating the adverse Ameliorating the adverse consequences of uremiaconsequences of uremia

Modifications of dietary intake of Modifications of dietary intake of water, ph , na , trace minerals iron , water, ph , na , trace minerals iron , water soluble vitamins , antioxidants.water soluble vitamins , antioxidants.

Iron deficiencyIron deficiency

Gastrointestinal hemorrhage = Gastrointestinal hemorrhage = frequent complication of anemiafrequent complication of anemia

H2-receptor antagonist ~ cimetidine, H2-receptor antagonist ~ cimetidine, ranitidine ranitidine

Mucosal protectants ~ sucralfate Mucosal protectants ~ sucralfate

.

Iron PreparationsIron Preparations Oral IronOral Iron

– Ferrous SulfateFerrous Sulfate (Feosol) – 300 mg tid (Feosol) – 300 mg tid– Side Effects are extremely mild:Side Effects are extremely mild:

Nausea, upper abdominal pain, constipation or diarrhea. Nausea, upper abdominal pain, constipation or diarrhea.

– CheapestCheapest form of Iron and one of the most form of Iron and one of the most widely widely usedused

Parenteral Parenteral – Iron DextranIron Dextran (Imferon) – IM or IV (Imferon) – IM or IV– Indicated Indicated for patients who cannot tolerate or for patients who cannot tolerate or

absorbabsorb oral ironoral iron or where oral iron is insufficient or where oral iron is insufficient to treat the condition ie. Malabsorption to treat the condition ie. Malabsorption syndrome, prolonged salicylate therapy, dialysis syndrome, prolonged salicylate therapy, dialysis patientspatients

..

Dosing regimenDosing regimen

CLASSIFICATION OF CLASSIFICATION OF ANTI-ANAEMIC DRUGSANTI-ANAEMIC DRUGS

1. HEMATOPOIETIC GROWTH 1. HEMATOPOIETIC GROWTH FACTORSFACTORS

2.NUTRITIONAL AGENTS2.NUTRITIONAL AGENTS

Haematopoietic growth Haematopoietic growth factorsfactors

1. erythroid growth factors1. erythroid growth factors

Eg: erythropoietin Eg: erythropoietin

( epoetin alpha , epoetin beta )( epoetin alpha , epoetin beta )

Darbepoetin alfaDarbepoetin alfa

Sites of action for EPOSites of action for EPO

Therapeutic Uses of EPOTherapeutic Uses of EPO Anemia of end stage renal diseaseAnemia of end stage renal disease

To treat AIDS anemia caused by AZT’s To treat AIDS anemia caused by AZT’s suppression of bone marrowsuppression of bone marrow

Anemia related to cancer chemotherapyAnemia related to cancer chemotherapy

OthersOthers– To increase RBC levels for autologous blood To increase RBC levels for autologous blood

donationdonation– Anemia associated with rheumatoid arthritisAnemia associated with rheumatoid arthritis

ERYTHROPOIETINERYTHROPOIETIN

Replacement therapy of endogenous Replacement therapy of endogenous erythropoietin with a recombinant erythropoietin with a recombinant human erythropoietin rhEPO human erythropoietin rhEPO

Recommended in anemia~ dogs PCV Recommended in anemia~ dogs PCV <30% & CATS PCV < 25% <30% & CATS PCV < 25%

DOSE- 100 units/kg BW s/c 3 times per DOSE- 100 units/kg BW s/c 3 times per weekweek

Regenerative response = appearance of Regenerative response = appearance of reticulocytes in peripheral bloodreticulocytes in peripheral blood

Hematopoietic Growth FactorsHematopoietic Growth Factors

1. Granulocyte/Macrophage Colony Stimulating 1. Granulocyte/Macrophage Colony Stimulating Factor (Factor (GM-CSFGM-CSF)- )- Sargramostim , molgramostim.Sargramostim , molgramostim.

Acts synergistically with IL-3 to stimulate the Acts synergistically with IL-3 to stimulate the formation and proliferation of formation and proliferation of colony forming cellscolony forming cells: : CFU-GEMM, BFU-E, CFU-Meg, CFU-GM, CFU-M, CFU-ECFU-GEMM, BFU-E, CFU-Meg, CFU-GM, CFU-M, CFU-E

Increases cytotoxic Increases cytotoxic phagocytic activityphagocytic activity of mature of mature granulocytesgranulocytes

2. Interleukin 3 2. Interleukin 3 (IL-3) – oprelvekin(IL-3) – oprelvekin Acts Acts synergistically with GM-CSFsynergistically with GM-CSF to stimulate the to stimulate the

formation of granulocytes, macrophages, eosinophils formation of granulocytes, macrophages, eosinophils and megakaryocytes. and megakaryocytes.

Acts Acts synergistically with EPOsynergistically with EPO to stimulate formation to stimulate formation of of BFU-EBFU-E colonies colonies

Induces CFU-S and leukemic blast cells into cell cycleInduces CFU-S and leukemic blast cells into cell cycle

More More Hematopoietic Growth Hematopoietic Growth FactorsFactors

3. Colony stimulating Factor-1 (3. Colony stimulating Factor-1 (CSF-1 or M-CSF-1 or M-CSFCSF))

Acts synergistically with GM-CSF and IL-3 to stimulate Acts synergistically with GM-CSF and IL-3 to stimulate monocyte/macrophage colony formation and functionmonocyte/macrophage colony formation and function

4. Granulocyte Colony Stimulating Factor 4. Granulocyte Colony Stimulating Factor ((G-CSFG-CSF) – ) – filgrastimfilgrastim , , pegfilgrastim , pegfilgrastim , lenograstimlenograstim

Acts Acts synergisticallysynergistically with with IL-3, GM-CSF and CSF-1IL-3, GM-CSF and CSF-1 to to stimulate formation of megakaryocytes, granulocyte-stimulate formation of megakaryocytes, granulocyte-macrophage and high proliferative potential (HPP) coloniesmacrophage and high proliferative potential (HPP) colonies

Induces release of granulocytes from marrowInduces release of granulocytes from marrow

More More Hematopoietic Growth Hematopoietic Growth FactorsFactors

5. Thrombopoietin 5. Thrombopoietin (TSF)(TSF) Increases the size and number of megakaryocytes.Increases the size and number of megakaryocytes.

(IL-11 also useful in stimulating production)(IL-11 also useful in stimulating production)

Increases the concentration of early Increases the concentration of early megakaryocytes megakaryocytes cellscells (SACHE+cells) in bone marrow. (SACHE+cells) in bone marrow.

Produces an increase in megakaryocytes Produces an increase in megakaryocytes endomitosis. endomitosis.

Increases platelet size and number in plasma.Increases platelet size and number in plasma.

NUTRITIONAL AGENTSNUTRITIONAL AGENTS

1. MINERALS1. MINERALS

Iron, cobolt, copper.Iron, cobolt, copper.

2. VITAMINS2. VITAMINS

Vitamin B12, folic acid, pyridoxine, Vitamin B12, folic acid, pyridoxine, riboflavin, ascorbic acid`riboflavin, ascorbic acid`

Iron CycleIron Cycle 5 - 10%5 - 10% of ingested of ingested

iron is iron is absorbedabsorbed

Once ingested the Once ingested the acidacid in the in the stomachstomach::

– 1. Aids in 1. Aids in ionization ionization of ironof iron

– 2. 2. Splits chelatedSplits chelated food food ironiron from from chelatorchelator

– 3. Maintains 3. Maintains ironiron in in soluble soluble formform

– 4. Allows iron to 4. Allows iron to remain in the remain in the absorbable form absorbable form FeFe3+3+

Mechanism of Iron AbsorptionMechanism of Iron Absorption

Therapeutic uses of IronTherapeutic uses of Iron

Iron Deficient Iron Deficient AnemiaAnemia

PregnancyPregnancy

Premature BabiesPremature Babies

Blood lossBlood loss

Hookworn Hookworn infestationinfestation

Malabsorption Malabsorption SyndromeSyndrome

GI Bleeding due to:GI Bleeding due to: UlcersUlcers AspirinAspirin Excess consumption Excess consumption

of coffeeof coffee

Iron PreparationsIron Preparations Oral IronOral Iron

– Ferrous SulfateFerrous Sulfate (Feosol) – 300 mg tid (Feosol) – 300 mg tid– Side Effects are extremely mild:Side Effects are extremely mild:

Nausea, upper abdominal pain, constipation or diarrhea. Nausea, upper abdominal pain, constipation or diarrhea.

– CheapestCheapest form of Iron and one of the most form of Iron and one of the most widely widely usedused

Parenteral Parenteral – Iron DextranIron Dextran (Imferon) – IM or IV (Imferon) – IM or IV– Indicated Indicated for patients who cannot tolerate or for patients who cannot tolerate or

absorbabsorb oral ironoral iron or where oral iron is insufficient or where oral iron is insufficient to treat the condition ie. Malabsorption to treat the condition ie. Malabsorption syndrome, prolonged salicylate therapy, dialysis syndrome, prolonged salicylate therapy, dialysis patientspatients

Ferrous sulphate Ferrous sulphate

Dogs: 100-300 mg total dose PO once Dogs: 100-300 mg total dose PO once daily for 14 daysdaily for 14 days

Cats: 50-100 mg total dose PO once Cats: 50-100 mg total dose PO once daily for 14 daysdaily for 14 days

Cattle: 8-15 g total PO once daily for 14 Cattle: 8-15 g total PO once daily for 14 daysdays

Horses: 2-8 g total dose PO daily for 14 Horses: 2-8 g total dose PO daily for 14 daysdays

Sheep & goat: 0.5-2 g PO daily 14 daysSheep & goat: 0.5-2 g PO daily 14 days

IRON DEXTRAN IRON DEXTRAN

FOR TREATMENT OF IRON DEFICIENCY FOR TREATMENT OF IRON DEFICIENCY ANEMIAANEMIA

Dogs: 10-20 mg/kg IM once daily Dogs: 10-20 mg/kg IM once daily followed by oral therapy with ferrous followed by oral therapy with ferrous sulphatesulphate

Piglets: 100-200 mg of elemental iron Piglets: 100-200 mg of elemental iron total dose IM on 2total dose IM on 2ndnd or 3 or 3rdrd day day

repeated on 10repeated on 10thth to 40 to 40thth day day depending on the requirement of piglet depending on the requirement of piglet

Toxicity of Iron OverdoseToxicity of Iron Overdose

5000 deaths/year5000 deaths/year in the US, usually in in the US, usually in childrenchildren

20% of children presenting with iron toxicity 20% of children presenting with iron toxicity will diewill die

1 to 2 grams are sufficient to cause death1 to 2 grams are sufficient to cause death

At high doses, Iron is absorbed through At high doses, Iron is absorbed through passive diffusion with no regulationpassive diffusion with no regulation

Iron – Clinical EffectsIron – Clinical Effects Early changesEarly changes

– Vomiting, diarrhea Blood Volume HR TPR Vomiting, diarrhea Blood Volume HR TPR (reflex)(reflex)

– Acidosis from Iron oxidation, Krebs cycle and Acidosis from Iron oxidation, Krebs cycle and anaerobic metabolism citric acid and lactic anaerobic metabolism citric acid and lactic

acidacid

Intermediate changesIntermediate changes Improvement (short lived) profound shock Improvement (short lived) profound shock

and CV Collapse Hepatic Failure, jaundice, and CV Collapse Hepatic Failure, jaundice, pulmonary edema and deathpulmonary edema and death

Late StageLate Stage Intestinal scarring, fatty acid degeneration of Intestinal scarring, fatty acid degeneration of

liver, cirrhosis and death.liver, cirrhosis and death.

Treatment of Iron OverdoseTreatment of Iron Overdose

Toxic levelsToxic levels ALD – 200-300mgkg, plasma iron > 300ug/dlALD – 200-300mgkg, plasma iron > 300ug/dl

ABC’s supportive careABC’s supportive care

Bicarbonate for acidosisBicarbonate for acidosis

FluidsFluids for blood loss for blood loss

Ipecac or lavageIpecac or lavage

Chelation with Chelation with DeferoxamineDeferoxamine

COBOLT COBOLT

ESSENTIAL TRACE ELEMENT & key ESSENTIAL TRACE ELEMENT & key component of COBOLAMIN / vitamin B-component of COBOLAMIN / vitamin B-1212

Synthesized by rumen microflora & CO Synthesized by rumen microflora & CO supplementations are necessary for supplementations are necessary for erythropoiesis in ruminantserythropoiesis in ruminants

MOA: enhances synthesis of vitamin B MOA: enhances synthesis of vitamin B 12 by rumen microflora & increases 12 by rumen microflora & increases production of erythropoietin in kidney production of erythropoietin in kidney

Cobolt cont..,Cobolt cont..,

Deficiency of cobolt- marked anemia , Deficiency of cobolt- marked anemia , decrease in blood volume , loss of decrease in blood volume , loss of body weight emaciation , failure to body weight emaciation , failure to thrivethrive

Predominant in young growing Predominant in young growing ruminants & sheep reared on pasture ruminants & sheep reared on pasture where soil is CO deficientwhere soil is CO deficient

Topical dressing of soil 100-150 g Topical dressing of soil 100-150 g cobalt sulphate per acre cobalt sulphate per acre

COPPERCOPPER

Essential component required for Essential component required for formation of hemoglobin, bone, formation of hemoglobin, bone, melanin & keratin.melanin & keratin.

Integral component of certain enzymesIntegral component of certain enzymes

-ascorbic acid oxidases-ascorbic acid oxidases

-polyphenol oxidases-polyphenol oxidases

-cytochrome oxidases-cytochrome oxidases

-monoamine oxidases-monoamine oxidases

Cu cont..,Cu cont..,

As hematinic necessary for normal As hematinic necessary for normal utilization of iron in hemoglobin & utilization of iron in hemoglobin & absorption & increasing outflow of iron absorption & increasing outflow of iron from reticulo-endothelial cellsfrom reticulo-endothelial cells

Copper deficiency= High level of Copper deficiency= High level of dietary molybdenum , iron or sulphur dietary molybdenum , iron or sulphur

Unthriftiness, anemia , loss of coat Unthriftiness, anemia , loss of coat color & temporary sterilitycolor & temporary sterility

DosesDoses

Copper sulphateCopper sulphate

Cattle:1-2g PO once daily 7 days, Cattle:1-2g PO once daily 7 days, break of 5 days & again treatment for break of 5 days & again treatment for 7 days7 days

Sheep:0.25g/45kg PO once daily Sheep:0.25g/45kg PO once daily

Copper glycinate ( depot preparation )Copper glycinate ( depot preparation )

Cattle: 120mg IMCattle: 120mg IM

Sheep: 40mg IMSheep: 40mg IM

Vitamin BVitamin B1212

Source: In food, especially in liver and Source: In food, especially in liver and kidneys. GI Microorganism synthesis, Vitamin kidneys. GI Microorganism synthesis, Vitamin Supplements (Cyanocobalamin)Supplements (Cyanocobalamin)

Necessary for normal DNA synthesisNecessary for normal DNA synthesis

Absorption of BAbsorption of B1212

1. 1. Intrinsic FactorIntrinsic Factor (low dose): a protein made by (low dose): a protein made by stomach parietal cells that binds to Bstomach parietal cells that binds to B12 12 and delivers it and delivers it from the ileum via a calcium mediated event. from the ileum via a calcium mediated event.

2. 2. Mass ActionMass Action (High dose): 1000mg/day, absorbed (High dose): 1000mg/day, absorbed via passive diffusionvia passive diffusion

BB1212 Deficiency Deficiency

A A BB1212 deficiency deficiency will cause peripheral will cause peripheral neuropathy and a neuropathy and a macrocytic anemiamacrocytic anemia, a , a pernicious anemia. pernicious anemia.

Folic AcidFolic Acid administration can correct the administration can correct the macrocytic anemia but will macrocytic anemia but will fail to correctfail to correct the the peripheral neuropathyperipheral neuropathy. .

To treat the To treat the neuropathy, Vit Bneuropathy, Vit B1212 must be must be utilized. utilized.

Mechanism for Peripheral Mechanism for Peripheral NeuropathyNeuropathy

Cobalamin is a cofactor for the enzyme Cobalamin is a cofactor for the enzyme Methylmalonyl-CoA mutase which converts Methylmalonyl-CoA mutase which converts methylmalonyl-CoA to succinyl-CoAmethylmalonyl-CoA to succinyl-CoA. .

Succinyl-CoA enters the Krebs cycles and Succinyl-CoA enters the Krebs cycles and goes into nerves to make myelin. goes into nerves to make myelin.

If no Vitamin BIf no Vitamin B1212, methylmalonyl-CoA goes , methylmalonyl-CoA goes on to form on to form abnormal fatty acidsabnormal fatty acids and and causes subacute degeneration of the causes subacute degeneration of the nerves. Only Bnerves. Only B1212 can correct this problem. can correct this problem.

Therapeutic Uses of BTherapeutic Uses of B1212

Daily Requirements - 0.6-1.0mh/day; TDaily Requirements - 0.6-1.0mh/day; T1/21/2 ~ 1 year ~ 1 year

Pernicious AnemiaPernicious Anemia

Impaired GI absorption of BImpaired GI absorption of B1212

GastrectomyGastrectomy

Corrosive InjuryCorrosive Injury of GI mucosa of GI mucosa

Fish tape wormFish tape worm: worm siphons off B: worm siphons off B1212

Placebo abuse with BPlacebo abuse with B12, 12, especially in elderly especially in elderly patients. patients.

Other vitaminsOther vitamins

Vitamin B 5 – pyridoxineVitamin B 5 – pyridoxine

Promotes RBC production & aids in Promotes RBC production & aids in biosynthesis of monoamino biosynthesis of monoamino neurotransmitters serotonin, neurotransmitters serotonin, dopamine, norepinephrine.dopamine, norepinephrine.

Used in dogs cats for treating Used in dogs cats for treating microcytic hypochromic anemia but microcytic hypochromic anemia but of Less significantof Less significant

Vit cont..,Vit cont..,

Riboflavin { vitamin B 2} - required Riboflavin { vitamin B 2} - required for wide variety of cellular processfor wide variety of cellular process

Ascorbic acid { vitamin C } – water Ascorbic acid { vitamin C } – water soluble vitamin which facilitates iron soluble vitamin which facilitates iron absorptionabsorption

Folic AcidFolic Acid

SourceSource in food – yeast, egg yolk, liver and leafy in food – yeast, egg yolk, liver and leafy vegetablesvegetables

Folic Acid (F.A.) is absorbed in the Folic Acid (F.A.) is absorbed in the small intestines.small intestines.

F.A. is converted to F.A. is converted to tetrahydrofolatetetrahydrofolate by by dihydrofolatedihydrofolate reductase.reductase.

Folic Acid deficiency (F.A. Deficiency) is also called Folic Acid deficiency (F.A. Deficiency) is also called Will’s Disease.Will’s Disease.

Deficiency may produce megaloblastic anemia; Deficiency may produce megaloblastic anemia; neural tube defect in fetus. neural tube defect in fetus.

Therapeutic Uses of Folic AcidTherapeutic Uses of Folic Acid

1. 1. Megaloblastic AnemiaMegaloblastic Anemia due to due to inadequate dietary intake of folic acid inadequate dietary intake of folic acid

Can be due to chronic alcoholism, pregnancy, Can be due to chronic alcoholism, pregnancy, infancy, impaired utilization: uremia, cancer or infancy, impaired utilization: uremia, cancer or hepatic disease. hepatic disease.

2. To alleviate 2. To alleviate anemiaanemia that is that is associatedassociated with with dihydrofolate reductase inhibitorsdihydrofolate reductase inhibitors. .

i.ei.e. Methotrexate. Methotrexate (Cancer chemotherapy), (Cancer chemotherapy), PyrimethaminePyrimethamine (Antimalarial) (Antimalarial)

Administration of Administration of citrovorum factorcitrovorum factor (methylated (methylated folic acid) alleviates the anemia. folic acid) alleviates the anemia.

Therapeutic Uses of Folic Acid Therapeutic Uses of Folic Acid (cont)(cont)

3. Ingestion of 3. Ingestion of drugs that interfere with drugs that interfere with intestinalintestinal absorptionabsorption and storage of folic acid. and storage of folic acid.

Mechanism- inhibition of the conjugases that break Mechanism- inhibition of the conjugases that break off folic acid from its food chelators. off folic acid from its food chelators.

Ex. – Ex. – phenytoinphenytoin, progestin/estrogens (, progestin/estrogens (oral oral contraceptivescontraceptives) )

4. Malabsorption – Sprue, Celiac disease, 4. Malabsorption – Sprue, Celiac disease, partial gastrectomy. partial gastrectomy.

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

MISCELLANEOUS DRUGSMISCELLANEOUS DRUGS

ANDROGENIC steroidsANDROGENIC steroids

Structurally related to testosteroneStructurally related to testosterone

Stimulates erythropoiesisStimulates erythropoiesis

Anabolic steroids increases Anabolic steroids increases intracellular concentration of 2,3-intracellular concentration of 2,3-bisphosphoglycerate in erythrocytes bisphosphoglycerate in erythrocytes thereby enhancing oxygen release thereby enhancing oxygen release into tissuesinto tissues

Clinical useClinical use

To stimulate erythropoiesis in To stimulate erythropoiesis in anemia particularly those associated anemia particularly those associated with renal disease accompanied by with renal disease accompanied by low EPO levels.low EPO levels.

REFERENCESREFERENCES

RICHARD ADAMS RICHARD ADAMS veterinary pharmacology and therapeutics. 8th edition

Sandhu HS Essentials of veterinary pharmacology and therapeutics. 2nd edition

Google images Online links

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