Plasma substitutes

Plasma substitutesNeed Properties of ideal plasma substituteVarious plasma substitutesGum salinePolyvinylpyrolidoneAbsorbable gelatin spongeOxidised celluloseCalcium alginateDextranHetastarchGelatin Dextran Dextran was first discovered byLouis Pasteuras a microbial product in wineDextran is synthesized from sucrose by certain lactic-acid bacteria eg.Leuconostoc mesenteroidesand Streptococcus mutans

Dextran-sucrase

Sucrose containing mediumLeuconostoc mesenteroidsDextran

Production DRAWBACKS OF LARGER MOLECULESNatural dextran consists of chains of 200,000 glucose units and molecular weights up to about 50 million. Very large molecules with molecular weights above 250,000 have serious drawbacksTherefore it is necessary to produce the molecules of reduced size suitable for medical useReduction of sizeVarious methodsAcid hydrolysis Dextran is adjusted at pH 2 and heated at 90C. As hydrolysis proceeds it becomes less viscous and the reaction is stopped at the required viscosity. Frequently used method. Size range ->10,000 to 1 million

Thermal degradation Heated under pressure at 160C in presence of sodium sulphite to prevent oxidative deterioration and calcium carbonate to neutralize acidity.The method is slower - better yield fewer reducing groups are produced

Ultrasonic disintegration Bombardment with ultrasonic waves splits the molecules into fragments of the same sizeThe product is clinically acceptable while in the previous methods require considerable fractionation. This technique is more expensive

Seeding the fermentorNormally, low mol. weight dextran is included in the culture medium before fermentation where the dextran is used as a template by the organism to build more glucose molecules on it. If no dextran is added, avg.mol. weight is much lower

Drawbacks of small moleculesMolecular wt below 60,000Rapidly excreted in the urineThey pass into the tissue fluids causing an adverse osmotic pressure.

Therefore to summarizeProcess continuedPurification Dextran preparationsAmerican type dextranBritish type dextranDextran 110 injectionDextran 40 injectionDextran 70 injectionDextran 110 Injection, BPBP testsDetermination of intrinsic viscosity of the material precipitated by the addition of 4 volumes of 95% ethanol. A value within the range 0.27 to 0.32 is required.Determination of intrinsic viscosity of top 10 %, i.e. the material in the first 10 percent of the total dextran present to be precipitated when the ethanol conc. Is progressively increased. The intrinsic viscosity for this fraction or cut should not exceed 0.40.A urinary excretion test in rabbit. A high excretion rate indicates an excessive content of material of too small a molecular size

Apart from these test BP specifies the following tests:The permitted pH range.Maximum permitted contents for heavy metals, acetone, ethanol, nitrogen and reducing sugars.Maximum sulphated ash.Tests for foreign protein and pyrogensStorage Dextran 110 Injection 5g/l dextrose stored below 25C will retain its properties for atleast 5 years.

In Sodium Chloride Injection, Dextran 110 stored at tempeartures upto 40C will retain its properties for atleast 5 yrs.

Labeling Additional to general requirements:Concentration of dextranThe name of the solvent.The strain of Leuconostoc mesenteroidesDextran 40 injectionDextran 70 injection It is used as a short term plasma expander.

Used as Infusion (Solution for infusion) glucose intravenous infusion 5% or sodium chloride intravenous infusion 0.9%

Contra-indications: CHF, renal failure; bleeding disordersDosage Short-term blood volume expansion, by rapid intravenous infusionAdult 5001000 ml initially, followed by 500 ml if necessary; total dosage should not exceed 20 ml/kg during the initial 24 hours; if required 10 ml/kg daily may be given for a further 2 days (treatment should not continue for longer than 3 days); Child total dosage should not exceed 20 ml/kgHetastarch Hetastarch is an artificial colloid derived from a waxy starch composed almost entirely of amylopectin. Hydroxyethyl ether groups are introduced into the glucose units of the starch, and the resultant material is hydrolyzed to yield a product with a suitable molecular weight Hetastarch is characterized by its molar substitution and also by its molecular weight.

The molar substitution is approximately 0.75 which means Hetastarch has an average of approximately 75 hydroxyethyl groups for every 100 glucose units. The weight average molecular weight is approximately 6,00,000 with a range of 4,50,000 to 8,00,000 and with at least 80% of the polymers falling within the range of 20,000 to 25,00,000

6% Hetastarch in 0.9% Sodium Chloride Injection (Hetastarch Injection) is a sterile, nonpyrogenic solution for intravenous administration.The composition of each 100 mL is as follows:Hetastarch................................................................6 gSodium Chloride, USP.............................................0.9 gWater for Injection, USP..........................................qspH adjusted with Sodium Hydroxide NF if necessaryConcentration of Electrolytes (mEq/L): Sodium 154, Chloride 154 pH: approximately 5.5 with negligible buffering capacityCalculated Osmolarity: approximately 309 m0sM

Hetastarch injection is a clear, pale yellow to amber solution. Exposure to prolonged adverse storage conditions may result in a change to a turbid deep brown or the formation of a crystalline precipitate. Do not use the solution if these conditions are evident.Elimination of hetastarchIntravenous infusion of Hetastarch injection results in expansion of plasma volume that decreases over the succeeding 24 to 36 hoursHetastarch molecules below 50,000 molecular weight are rapidly eliminated by renal excretion. A single dose of approximately 500 mL of Hetastarch injection (approximately 30 g) results in elimination in the urine of approximately 33% of the dose within 24 hours.Larger molecules are slowly metabolised by enzymes (amylase) until they are small enough to undergo renal excretionIt has low antigenicityDoes not impair renal functionLarge dose of hetastarch may reduce hematocrit and cause hypocoagulability Gelatin Gelatin from bones or hides is subjected to controlled hydrolysis to produce a material with a suitable molecular weightThe mol wt of gelatin as plasma substitutes is 35,000Renal excretion accounts for >60% and plasma half life is 8-18 hrGelatin plasma substitutes produces potentially life-threatening effects which includeanaphylactic reactionswhich are responsible for the discontinuation of gelatin plasma substitutes therapyLimited useBlueprint SuspensionEmulsionSemisolidSuppositoryBlood and plasma productsSutures and ligaturesTotal MarksQ.13 (Q.1a)3 (Q.1b)2 (Q.1c)2 (Q.1d)3 (Q.1e)2 (Q.1f)15Q.2-6(Q.2a)-5 (Q.2b)--11Q.36 (Q.3a)---5(Q.3b)-11Q.4--4(Q.4a)3(Q.4b)-4(Q. 4 c)11Q.53(Q.5a)-3(Q.5b)-3(Q.5c)2(Q. 5d)11Q.6-4(Q.6a)3(Q.6b)-4(Q.6c)-11Total Weightage12 Marks13 Marks12 Marks10 Marks15 Marks8 Marks70Question No. 1 and 6 are compulsory.Question No. 2 Choice in sub question 2aQuestion No. 3 Choice in sub question 3aQuestion No 4. Choice in sub question 4aQuestion No 5. Choice in sub question 5c