Drug affecting blood & its formation

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DRUG AFFECTING BLOOD AND ITS FORMATION

• Presented by-
• Mrs. Payal Pilaji
• (M pharm in Pharmaceutical chemistry)

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BLOOD

• Blood is type of liq connective tissue.
• Fluid of life carries oxygen from lungs to all
  parts of body and carbon-di-oxide from all parts
  of the body to the lungs
• Fluid of growth carries nutritive substances
  from the digestive system and hormones from
  endocrine gland to all the tissues.
• Fluid of health protects the body against
  diseases and get rid of unwanted substances by
  transporting them into excretory organs like
  kidney.

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PHYSICAL CHARACTERISTICS OF BLOOD
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FUNCTIONS OF BLOOD

• Respiratory
• Transport O2 from lungs to tissues
• Transport CO2 from tissues to lungs
• 2. Nutrition
• Transport food from gut to tissues
• 3. Excretory
• Transport waste from tissues to kidney (urea,
  uric acid)
• 4. Protective
• White blood cells , antibodies, antitoxins.

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• 5. Regulatory
• regulate body temperature
• regulate pH through buffers
• coolant properties of water
• vasodilatation of surface vessels dump heat
• regulate water content of cells by interactions
  with dissolved ions and proteins
• 6. Body Temperature
• Water- high heat capacity, thermal conductivity,
  heat of vaporization
• Typical heat generation is 3000 kcal/day

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COMPOSITION OF BLOOD

• Suspension of cells in plasma (carrier fluid)
• 45 Cells
• 55 Plasma
• Cells
• Red cells (erythrocytes)
  99 5x106/mL
• White cells
  (leukocytes)
• 7x103/mL
  lt 1
  Platelets
  (thrombocytes)

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• Drug classes presented in this chapter include
  nutrients and growth factors affecting formation
  of blood cells and platelets (hematopoiesis)
  and drugs used in the control of blood clotting
  (hemostasis).

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HAEMATINICS

• Haematinics such as iron, vit. 12, folic acid,
  etc. are required for the formation of blood and
  are used in the treatment of anaemia.
• In anaemia, there is decreased in oxygen
  carrying capacity of the blood due to reduction
  in the blood haemoglobin level and the number of
  circulating RBCs.

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CAUSES OF ANAEMIA

• 1. Decreased formation of RBCs-
• Deficiency of essential nutrients
  such as iron, vit. 12,
  folic acid etc.
• 2. Increase destruction of RBCs-
• Haemolytic anaemias and sickle-cell
  anaemia.
• 3. Depression of bone marrow-
• Cytotoxic drugs, radiation and
  toxins.
• 4. Excessive blood loss-
• Due to hookworm infestation, bleeding
  from GIT and other site.

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IRON

• Iron is a mineral.
• Most of the iron in the body is found in the
  haemoglobin of red blood cells and in the
  myoglobin of muscle cells.
• Iron is needed for transporting oxygen and carbon
  dioxide. It also has other important roles in the
  body.
• People take iron supplements for preventing and
  treating low levels of iron (iron deficiency) and
  the resulting iron deficiency anemia.
• In people with iron deficiency anemia, the red
  blood cells cant carry enough oxygen to the body
  because they dont have enough iron. People with
  this condition often feel very tired.

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MECHANISM ON ACTION OF IRON

• Iron helps red blood cells deliver oxygen from
  the lungs to cells all over the body.
• Once the oxygen is delivered, iron then helps red
  blood cells carry carbon dioxide waste back to
  the lungs to be exhaled.
• Iron also plays a role in many important
  chemical reactions in the body

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PHARMACOKINETICS 0F IRON
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PREPARATION OF IRON

• 1. Oral preparation
• 2. Parenteral preparation

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1. Oral preparation- a) Ferrous
sulphate- 20
hydrated salt and 32 dried salt. b)
Ferrous gluconate-
12 elemental iron. c) Ferrous
fumarate- 33
elemental iron. ADVERS EFFECT
Nausea, vomiting, metallic taste, diarrhea,
staining of teeth.
PREPARATION OF IRON
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2. Parenteral preparation- a) Iron
sorbitol citric acid complex - IM. but not
IV. b) Iron dextran- IM and
IV c) Sodium ferric gluconate-
ADVERS EFFECT i) The injection are painful,
abscess and discoloration of the skin at the
site of injection. ii) The systemic side effect
are headache, pyrexia, vomiting, arthralgia,
lymphadenopathy, urticarial rash, and
anaphylactic reaction may occur.
PREPARATION OF IRON
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THERAPEUTIC USES OF IRON

• 1. To treat iron deficiency anaemia-
• a) During pregnancy
• b) Due blood loss
• c) Due to nutritional-iron defidiency
• d) Due to poor absorption of iron
• from the gut.
• 2. Prophylaxis -
• Prophylaxis iron therapy is usually
  indicated during pregnancy and infancy.
• IRON INTERACTIONS
• Diphosphonates (e.g. etidronate), antacids and
  tetracycline's form insoluble chelats with iron
  and thus inhibit the absorption.
• IRON CONTRAINDICATIONS
• Anemiae without iron deficiency hemochromatosis
  iron malabsorption infectious intestinal
  diseases.

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VITAMIN B12

• Cobalt containing compound
• Synthesized by Colonic bacteria
• Present in the food of animal origin such
• as meat, liver, egg, fish, etc.
• Essential for normal haemopoiesis and
• for the maintenance of normal myelin.

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PHARMACOKINETICS 0F VITAMIN B12
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PREPARATION OF VITAMIN B12

• Vitamin B12 is available for oral and
• parenteral administration. The choice of a
• route depends on the causes deficiency.
• There are two preparation of vit. B12
• Cyanocobalamine
• hydroxy cobalamine

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ADVERS EFFECT OF VITAMINE B12

• Allergic reactions to preservatives in the
  preparation for the injection
• Mild diarrhea
• Anxiety
• Panic attacks
• Heart palpitations
• Insomnia
• Breathing problems
• Chest pain
• Rash and/or hives
• Itchy skin
• Heartburn
• Vomiting
• Back pain
• Rhinitis (stuffy nose)

External rare cases- Congestive heart
failure Pulmonary edema Anaphylaxis Peripheral
vascular thrombosis Inflammatory acne
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THERAPEUTIC USES OF B12

• Treatment and prevention of vitamin B12
  deficiency, and diseases caused by low vitamin
  B12 levels.
• Treatment of pernicious anaemia.
• Reducing a condition related to heart disease
  called hyperhomocysteinemia when taken
  with folic acid and vitamin B6.

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FOLIC ACID

• Folic acid is combination of glutamic acid,
  para-aminobenzoic acid and pteridine nucleus.
• Minimum daily requirement of an adult is 50-100
  µg.
• The requirement of folic acid increases during
  preganancy and lactation i.e. 500-800 µg per day.
  

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FOLIC ACID

• Mechanism of action- Folic acid, as it is
  biochemically inactive, is converted to
  tetrahydrofolic acid and methyltetrahydrofolate
  by dihydrofolate reductase.
• These folic acid congeners are transported across
  cells by receptor-mediated endocytosis where they
  are needed to maintain normal erythropoiesis,
  synthesize purine and thymidylate nucleic acids,
  interconvert amino acids, methylate tRNA, and
  generate and use formate.
• Using vitamin B12 as a cofactor, folic acid can
  normalize high homocysteine levels by
  remethylation of homocysteine to methionine via
  methionine synthetase.

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FOLIC ACID

• Pharmacodynamics- Folic acid is a water-soluble
  B-complex vitamin.
• found in body such as liver, kidneys, yeast, and
  in food leafy, green vegetables.
• Folic acid is used to diagnose folate deficiency
  and to treat topical sprue and megaloblastic and
  macrocytic anemias, hematologic complications
  resulting from a deficiency in folic acid.
• Oral absorption of Folic Acid is found to be 75.
  
• Plasma protien binding is 70.

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ADVERSE EFFECT OF FOLIC ACID

• The severe or irreversible adverse effects of
  Folic Acid Which include
•  Neuropathy, 
• Bronchospasm, 
• Itchy skin eruptions,  
• Status epilepticus.
• The symptomatic adverse reactions produced by
  Folic Acid are-  
• Anorexia, 
• Erythema, 
• Itching, 
• Skin rash

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FOLIC ACID

• PREPARATION OF FOLIC ACID -
• Folic acid is available for oral administration
  as tablet and liquid form.
• Injectable preparation is available only in
• combination formulation.
• THERAPEUTIC USES OF FOLIC ACID
• Megaloblastic anaemias due to-
• Nutritional folate deficiny-
• Increased demand ( pregnancy, lactation)
• Pernicious anaemia
• Prophylactic therapy
• Methotrexate toxicity

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DRUG AFFECTING BLOOD AND ITS FORMATION

• Cause of Anaemia.
• Haematinics.
• Iron, Vit. B12, Folic Acid.
• Coagulation
• factor of coagulation.
• Processes of coagulation.
• Anticoagulant
• Classification of anticoagulant.
• Fibrinolytic Agents.

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COAGULATION

• When blood vessel ruptures, bleeding occurs and
  within a short period blood looses its fluidity
  and set into semisolid mass, known as clot.
• The process of formation of clot is known as
  blood as clotting.
• These process can be divided into 3
• stages. These are-
• Extrinsic pathway (Tissue damage)
• Intrinsic pathway (Vascular injury)
• Common pathway.

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FACTOR OF COAGULATION
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PHYSICAL PROCESS OF COAGULATION
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CHEMICAL PROCESS OF COAGULATION
EXTRINSIC PATHWAY
INTRINSIC PATHWAY
Damage to tissue outside
Damage the blood vessels
Inactive factor x
Tissue thromboplastic
Cascade of clotting factor
Activated factor x
Prothrombin
Thrombin
Factor XIII
Fibrin
Blood clot
Fibrinogen
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ANTICOAGULANT
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VIVO ANTICOAGULANT

• INJECTEBLE ANTICOAGULANT-
• HEPARIN-
• Heparine is a naturally occurring substance in
  mast cell and it is mainly present in lungs and
  liver.
• It is mucopoly saccharide.
• For therapeutic purpose it is obtained from
  animal like pigs and oxen.
• Molecular weight of Heparin range from 3000 to
  30,000 with an average of 15,000.

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MECHANISM ON ACTION OF HEPARIN
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MECHANISM ON ACTION OF HEPARIN

• Some additional action of Heparine-
• It inhibits the plate aggregation and help
• in preventing clot formation.
• It reduce the proliferation of vascular smooth
  muscle.
• Heparine has got some antiinflementary action.

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PHARMACOKINETICS OF HEPARINE

• IM - causes hematoma.
• Heparin is poorly absorbed from GIT and form
  precipitation, hence it is administered by IV and
  SC routes.
• Heparin is metabolized by the liver by
  heparinase.
• Some heparin is excreted unchanged in urine.
• It is predominantly distributed in mast cell
  which act as store of external heparin.
• Not cross BBB or placental barrier.
• It can be safely given during pregnancy.

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HEPARIN

• ADVERSE EFFECT OF HEPARIN
• Bleeding
• Hematuria
• Thrombocytopenia
• Alopecia
• Osteoporosis and
• Hypersensitivity reaction.
• THERAPEUTIC USES OF HEPARINE
• Prevention of thrombosis.
• In vitro anticoagulant

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• CONTRAINDICATIONS
• Bleeding disorder
• Hypertension
• Bacterial endocardities
• Active tuberculosis
• Ulcerative lesions of GIT
• Surgery

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LOWER MOLECULAR WEIGHT HEPARIN

• These molecule are obtained from depolymerisation
  of standard heparin.
• Molecular weight of range from 1000 to 9000.
• There major action is on Xa and comparatively
  less action is on Prothrombin.
• ADVANTAGES OF LMW HEPARIN-
• Higher bioavailability.
• Long half-life, longer duration of action,
  therefore once a day administration.
• More predictable clinical response
• Reduce chances of hemorrhagic complications.
• Eg. Enxoparin, Dalteparin and Finzaparin are the
  agents that are used in almost all the where
  heparin is used.

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ORAL ANTICOAGULANT

• Among the oral anticoagulant, coumarin
• derivatives are commonly used.
• Oral anticoagulant are chemically related
• to vitamin K.
• Therefore, these drugs competitively
• inhibit the action of vitamin k and vitamin k
• can be used to treat overdose of oral
• anticoagulant.
• Oral anticoagulat like warfarine acts only
• in vivo.

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WARFARIN

• Is oral medication.
• It is synthetic derivative of coumarin.
• It widely used to control prevent
  thromboembolic disorder.
• It clinically available as racemic mixture of R
  S warfarin.
• The S- enantiomer has 3-5 times greater than
  R-enantiomer.

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WARFARIN
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WARFARIN

• PHARMACOKINETICS-
• Warfarin are orally absorbed that is great
  advantage over heparin.
• Bioavability of warfarin is 100.
• Over 99 of warfarin is plasma protein-bound
  which lead to-
• Very low volume of disribution.
• No urinary excretion
• Long plasma time.
• It is metabolized in the liver and then excreted
  by the kidneys.

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THERAPEUTIC USES OF WARFARIN

• Deep vein thrombosis
• Reduce the risk of pulmonary embolism.
• Patients with atrial fibrillation
• To reduce the risk of strokes, and after a heart
  attack.
•  knee replacement

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DRUG INTERACTIONS OF WARFARIN

• Cholestrymine
• Barbiturates/carbamazepine/ rimapicine/
  griseofulvin.
• Salicylates / sulfonamides
• Alcohol, Chloramphenicol, isoniazide,
• Imidazole's, diasufiram.
• Aspirine and other NSAIDs.

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SIDE EFFECTS WARFARIN

• Headache and paralysis (brain)
• Joint pain
• Weakness, fainting spells, black tarry
  stools, vomiting (stomach)
• Back pain and blood in urine (kidneys)
• Rash, hair loss, bloating, diarrhea,
  and jaundice.
•  
• PREPARATION OF WARFARIN-
• Warfarin sodium
• Uniwarfarin

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WARFARIN IN PREGNANCY

• Crosses the placenta
• Produces characteristic embryopathy,
• CNS abnormalities, fetal bleeding
• Embryopathy consists of
• nasal hypoplasia
• stippled epiphyses
• agenesis of corpus callosum
• ventral midline dysplasia - optic atrophy

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MANAGEMENT OF WARFARIN OVERDOSE

• Excessive anticoagulant effect of warfarin can be
  reversed by

• stopping the drug
• administering large doses of vitamin K1
• (5 to 10 mg may need to repeat dose)
• administering fresh-frozen plasma (10-20 ml/kg)
  combined with vitamin K1
• administering factor IX concentrate
• Improvement in hemostasis does not occur for
  several hours - may require 24 hours.

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FIBRINOLYTIC AGENTS

• Fibrinolytic agent break the thrombus that is
  already is formed and reestablish the
  circulation.
• They are also called as thrombolytic agent.

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MECHANISM ON ACTION OF FIBRINOLYTIC AGENTS
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CONTRAINDICATIONS OF FIBRINOLYTIC AGENTS

• Recent Trauma,
• Recent surgery,
• Recent Abortion,
• Peptic ulcer,
• Bleeding disorders.

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