Replacement Therapy PDF

Replacement Therapy  Replacement Therapy  The basic objective of replacement therapy is to restore the volume and composition of the body fluids to normal one.  Volume contraction is a life threatening condition because it impairs the circulation, blood volume decreases, cardiac output fall...

Replacement Therapy  Replacement Therapy  The basic objective of replacement therapy is to restore the volume and composition of the body fluids to normal one.  Volume contraction is a life threatening condition because it impairs the circulation, blood volume decreases, cardiac output falls and the integrity of microcirculation is compromised.  In volume depletion of sufficient magnitude to threaten life, a prompt infusion of isotonic sodium chloride solution is indicated.  In an extreme case, intravenous therapy at the rate of 100 ml per minute for the first 1000ml has been considered necessary for the successful treatment of cholera.  A general rule is to replace one half of the estimated volume loss in the first 12-24 hours of treatment. Sodium Replacement Sodium Chloride: NaCl (MW 58.44)  It contains no added substances,it occurs as colourless cubic crystals or as white crystalline powder having saline taste.  It is freely soluble in water, and slightly more soluble in boiling water, soluble in glycerine and slightly soluble in alcohol.  Use: Used as fluid and electrolyte replenisher, manufacture of isotonic solution, flavour enhancer.  Isotonic solutions are used in wet dressings, for irrigating body cavities or tissues  Hypotonic solutions are administered for maintenance therapy when patients are unable to take fluids and nutrients orally for one to three days.  Hypertonic solution/injection are used when there is loss of sodium in excess.  Official preparations of Sodium chloride  Sodium Chloride Injection is a sterile isotonic solution of sodium chloride in water for injection. It contains not less than 0.85 % and not more than 0.95 % w/v of sodium chloride. It contains no antimicrobial agents. It is a clear, colourless solution with pH between 4.5-7.0.  Sodium Chloride Hypertonic Injection (Hypertonic saline) It is a sterile solution of sodium chloride in water for injection. It contains not less than 1.52 % and not more than 1.68 % w/v of sodium chloride. It contains no antimicrobial agents. It is a clear, colourless solution with pH between 5- 7.5. It complies with the test for pyrogens.  Compound Sodium Chloride Injection (Ringer injection) It contains: 1. not less than 0.82 % and not more than 0.9 % w/v of sodium chloride. 2. not less than 0.0285 %, not more than 0.0315 % w/v of potassium chloride. 3. not less than 0.03 % and not more than 0.036% w/v of calcium chloride in water for injection. It contains no antimicrobial agents. It is a clear, colorless solution with pH between 5-7.5.  Sodium Chloride and Dextrose Injection It is a sterile solution of sodium chloride and dextrose in water for injection. It is clear colourless or faintly straw colored solution with pH between 3.5-6.5. It contains not less than 95% and not more than 105 % w/v of the stated amount of sodium chloride and dextrose as given below: Combinations of Sodium Chloride and Dextrose %of Sodium %of Dextrose %of Sodium %of Dextrose Chloride Chloride 0.11 5 0.45 5 0.18 5 0.45 10 0.20 5 0.90 2.5 0.225 5 0.90 5 0.3 5 0.90 10 0.33 5 0.90 25 0.45 2.5  Potassium Replacement Potassium Chloride: KCl (MW 74.56).  Potassium chloride contains not less than 99 % calculated with reference to dried substance.  It occurs as white crystalline solid, cubic crystals. It is less soluble in water than sodium chloride, and slightly more soluble in boiling water, soluble in glycerine and insoluble in alcohol.  Use: Electrolyte replenisher in potassium deficiency, familial periodic paralysis, Meniere’s syndrome (disease of inner ear), antidote in digitalis intoxication, myasthenia gravis.  Contraindication: renal impairment with oligouria, acute dehydration.  Potassium Chloride injection: Ringer injection  Calcium Replacement  Calcium Lactate: MW 308.30 Potassium chloride contains not less than 97% and not less than 103% of Calcium Chloride dihydrate. It occurs as white odourless powder, it is soluble in water, practically insoluble in alcohol.  Use: An excellent source of calcium in oral treatment of calcium deficiency. Physiological Acid Base Balance  Abnormalities of the pH of body are frequently encounter and are of major clinical importance.  Acedemia and alkalemia refer respectively to an abnormal decrease or increase in the pH of the blood.  Acidosis and alkalosis refer respectively to clinical state that can lead to either acedemia or alkalemia.  However in each condition the extent to which there is an actual change in pH depends in part on the degree of compensation which varies in most clinical disturbances.  It is most convenient to evaluate clinical disturbances of pH by reference to HCO3– – H2CO3 System  Because it is in buffer system of extracellular fluid, this results from a number of factors: 1. There is considerably more bicarbonate present in extracellular fluid than any other buffer component. 2. There is a limitless supply of carbon dioxide 3. Physiological mechanisms operate to maintain the extracellular pH function by controlling fluid 4. The bicarbonate –carbonic acid buffer system operates in conjunction with haemoglobin.  Acids are constantly being produced during metabolism.  Most metabolic reactions occur only within narrow pH range of 7.38-7.42, therefore the body utilizes several buffer systems, two of them are bicarbonate and carbonic acid (HCO3– : H2CO3) present in plasma and kidney and monohydrogen phosphate/dihydrogen phosphate (HPO42- : H2PO4-) found in cells and kidney.  RBC’s have hemoglobin buffer system which is most effective single buffer system for buffering the carbonic acid produced during metabolic process. For each millimole of oxygen that dissociates from hemoglobin (Hb) 0.7 millimole of H+ are removed.  Carbon dioxide, the acid anhydride of carbonic acid is continuously produced in the cells. It diffuses into the plasma and reacts with water to form carbonic acid. The increased carbonic acid is buffered by plasma proteins. Most CO2 enters the erythrocytes where it either rapidly forms H2CO3by the action of carbonic anhydrase or combines with Hb.  The tendency to lower the pH of the erythrocytes due to increased concentration of H2CO3 is compensated by Hb. CO2 + H2O Carbonic anhydrase H 2CO3  The bicarbonate anion then diffuses out of erythrocytes and chloride anion diffuses in. This has been named as chloride shift. Te bicarbonate in plasma, along with the plasma carbonic acid now acts as efficient buffer system H2CO3 + K+ +HbO2- K + + HCO3- + HHb + O2  The normal HCO3-/ H2CO3 ratio is 27/1.35 meq/lt (20:1) corresponding to pH 7.4. In lungs there is reversal of the above process due to the large amount of O2 present. Oxygen combines with the protonated deoxyhemoglobin releasing proton. These combine with HCO3- forming H2CO3 which then dissociates to CO2 and water. The carbon dioxide is exhaled by the lungs. Thus by regulating breathing it is possible for the body to exert a partial control on the HCO3-/H2CO3 ratio.  The phosphate buffer system is also effective in maintaining physiological pH. At pH 7.4 the HPO4- 2/H2PO4- ratio is approximately 4:1.  In kidney, the pH of urine can drop to 4.5-4.8 corresponding to HPO4-2/H2PO4- ratio of 1:99- 1:100.  The acid is excreted from kidney as follows: 1. sodium salt of mineral or organic acids are removed from the plasma by glomerular filtration 2. Sodium is preferentially removed from the renal filtrate or tubular fluid in the tubular cells. The process known as sodium hydrogen exchange. 3. The sodium bicarbonate returns to plasma (eventually being removed in the lungs as CO2) and protons enter tubular fluid, forming acids of the anions that originally were sodium salts. Factors altering the pH of Extra Cellular Fluid 1.Acidosis: Acidosis is defined as increase in either potential and/or non-volatile hydrogen ion (H+) content of body. Increase in the H+ concentration of plasma is known as acedemia and is manifested by fall in the pH of blood. In case there is no rise in H+ concentration of plasma, such state of acidosis (without acedemia) is known as compensated acidosis.  Types and Causes of Acidosis:  Metabolic acidosis: it occurs due to excess production of proton in the body which may be because of: i) Acceleration of normal metabolic process i.e. excessive catabolism e.g. in fever. ii) Administration of drugs which are proton donors e.g. salicylates, chlorides. iii) Excessive loss of alkaline fluid from the intestine, as in diarrhea. iv) Administration of large quantity of saline.  Metabolic acidosis treatment  Metabolic acidosis is treated with sodium salts of bicarbonate, lactate, acetate and occasionally citrate.  When there is bicarbonate deficit, administration of bicarbonate increases the HCO3-/H2CO3 ratio.  Lactate, acetate and citrate ions are normal components of metabolism and are degraded to carbon dioxide and water by TCA cycle (Citric acid cycle or Krebs cycle).  Renal Acidosis: where increase in H+ is due to defective renal excretion of H+. Seen in Tubular disorders, Addisons disease, drugs which interfere with tubular secretion of H+ e.g. carbonic anhydrase inhibitors  Respiratory Acidosis: is due to increase in retention of carbon dioxide leading to rise in plasma carbonic acid content. It occurs due to chronic lung disease, respiratory muscle paralysis, by drugs that depress respiratory center. 2. Alkalosis: Alkalosis is reduction in the total hydrogen ion content of the body. Alkalemia is reduction of hydrogen ion content in plasma and is manifested by increase in the pH of blood. In case there is no decrease in H+ concentration of plasma, such state of alkalosis (without alkalemia) is known as compensated alkalosis.  Metabolic alkalosis: Due to renal damage that cannot excrete an appreciable amount of alkali. Occurs due to alkali ingestion in presence of renal damage, excessive vomiting which causes loss of H+ and Cl- ions.  Metabolic alkalosis has been treated with ammonium salts. Its action is in kidney where it retards the Na+- H+ exchange.  Contraction alkalosis: seen following administration of mercurial diuretics which cause excessive loss of Cl– and sodium.  Respiratory alkalosis: Respiratory alkalosis is caused by hyperventilation which washes away large amount of carbon dioxide formed in metabolism causes lowering of arterial pCO2 and reduction in ratio of bicarbonate ion and carbonic acid with fall in hydrogen ion concentration.  It Occurs due to high altitude, fever, encephalitis, hypothalamic tumor, drugs like salicylate, hot bath.  Electrolytes used in acid base balance  Sodium bicarbonate  Sodium bicarbonate contains not less than 99.0 % and not more than 101 % of sodium bicarbonate.  Sodium bicarbonate occurs as a white odourless crystalline powder or granules. It is soluble in water (1 in 12); partially soluble in alcohol.  Alkalinity increases on standing, agitation or heating. It is stored in well closed containers.  Sodium bicarbonate when mixed with calcium or magnesium salts, cisplatin, dobutamine hydrochloride or oxytetracyclin forms insoluble precipitates.  The following drugs are susceptible to inactivation on mixing with sodium bicarbonate; adrenaline hydrochloride, benzyl penicillin potassium, carmustine, glycopyrronium bromide; isoprenaline hydrochloride and suxamethonium chloride.  Uses :1. used in the treatment of metabolic acidosis 2.diarrohoea, 3.acute poisoning from acidic drugs (phenobarbitone and salicylates) , 4.an antacid to relieve dyspepsia. 5.Solutions of sodium bicarbonate are used as eye lotions, to aid the removal of crusts in blepharitis, as eardrops, to soften and remove ear wax, and as lubricating fluid for contact lenses.  Sodium acetate  Sodium acetate contains not less than 99.0 % of CH3COONa 3H2O.  it occurs as colourless, transparent crystals or a white granular powder or white flakes: odourless or with a slight odour of acetic acid; m.p. 58°; decomposes at higher temperature, soluble in water (1 in 0.8), and alcohol (1 in 19). A 5 % solution in water has a pH of 7.5 to 9.2. It is kept in airtight containers.  Uses: An effective buffer in metabolic acidosis. It is used as pharmaceutical aid (for peritoneal dialysis fluid). Potassium acetate  Potassium acetate contains from 99 to 101.0% of CH3COOK.  It occurs as colourless crystals or a white crystalline powder; odourless with a faint acetic acid like odour.  It is soluble in water and alcohol. A 5 % solution in water has a pH of 7.5 to 9.5.  Potassium acetate should be kept in a well-closed container.  Sodium citrate  Sodium citrate contains about 99% of C6H5Na3O7.  it occurs as white, granular crystals or a white crystalline powder; slightly deliquescent in moist air. It is freely soluble in water; practically insoluble in ethanol. A solution containing such particles must not be used.  Uses: It is used as 1.systemic alkalizing substance, 2. has anticlotting properties and is employed in mixtures as the acid citrate in the anticoagulation and preservation of blood for transfusion purposes. 3. It is also used for dentifrices as desensitizing agent and added to milk for infant feeding to prevent the formation in the stomach of large curds. 4. It also has a diuretic effect due to increased body salt concentration.  Potassium Citrate  Potassium citrate contains about 99% of K3C6H5O7.  Potassium citrate occurs as transparent, odourless, hygroscopic crystals or a white granular powder, taste is saline. It is soluble in water (1 in 1) and glycerol (1 in 25), practically insoluble in alcohol.  Aqueous solutions are slightly alkaline and may be incompatible with acidifying agents.  Uses: it is used as systemic alkalizer and gastric antacid. it is used to relieve painful irritation caused by cystitis (inflammation of gall bladder)  Ammonium Chloride  Ammonium chloride is a sterile solution of ammonium chloride in water for injection  It contains not less than 99.5 % and not more than 105 % with reference to dried substance. HCl may be added to adjust pH.  The NH4+ cation possess certain pharmacological activities 1. acid base equilibrium of the body  2. diuretic effect  3. expectorant effect  Ammonium chloride is contraindicated in patients with impaired renal and hepatic functions.  Uses: It is used in acid base therapy, as a diuretic. It is also used to correct hypochloremic alkalosis due to prolonged use of mercurial diuretics.  Electrolyte Combination Therapy  Combinations of glucose and saline solutions are usually sufficient in short term therapy for restoring electrolyte loss. But in severe deficit of electrolytes due to heavy blood loss or chronic diarrhea, solutions containing additional electrolytes are usually required.  The combination products are of two types : 1. fluid maintenance therapy 2. electrolyte replacement therapy  Maintenance therapy with iv fluids is required to supply normal necessity of water and electrolyte to patient who cannot take them orally.  All maintenance therapies should contain at least 5% dextrose.  Replacement therapy is required when there is excess loss of water and electrolytes caused by fever, severe vomiting and diarrhea  General electrolyte composition of maintenance therapy includes: Electrolyte Concentrations (mEq/l) Sodium 25-30 Potassium 15-20 Chloride 22 Bicarbonate 20-23 Magnesium 3 Phosphorous 3  Two types of solutions are used in replacement therapy: i) solution for rapid initial replacement. ii) a solution for subsequent replacement  The electrolyte concentrations in solutions for rapid initial replacement are almost similar to the electrolyte concentrations found in extracellular fluids. The electrolyte concentrations of these solutions are given as Electrolyte Concentrations (mEq/l) for rapid Concentrations (mEq/l) for initial replacement subsequent replacement Sodium 130 -150 40-121 Potassium 4-12 16-35 Chloride 98-109 30-103 Bicarbonate 28-55 16-53 Calcium 3-5 0-5 Magnesium 3-5 0-13 Phosphorous 0-13