Plasma Expanders

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Chapter: Medicinal Chemistry : Plasma Expanders

A haemorrhagic shock may result from the loss of blood during burns, wounds, or surgery. Mild shock results when there is a loss of 15% to 20% in the total blood volume.


DRUGS ACTING ON BLOOD AND BLOOD FORMING ORGANS

Plasma Expanders

INTRODUCTION

A haemorrhagic shock may result from the loss of blood during burns, wounds, or surgery. Mild shock results when there is a loss of 15% to 20% in the total blood volume. Further loss of blood, up to 40% of total blood volume may lead to severe shock during which the cardiovascular functioning is severely affected. To restore this functioning, saline should be administered as an initial emergency measure. Plasma expanders can also be used to overcome the initial losses.

There are of two types of plasma expanders: (i) Natural products and (ii) Synthetic products

Natural products: These include transfusion of whole blood or the preparations of plasma proteins. Blood products containing plasma proteins are human albumin (albumisol) and plasma protein fraction (PPF). Both of these preparations are usually given by intravenous infusion.

Synthetic products: Dextran, hetastarch, perfluorochemicals, polyvinylpyrrolidone, and gelatin are some of the synthetic plasma expanders, out of which dextran has been used extensively.

 

i. Dextran


Dextran could be considered as being almost close to ideal plasma expanders. Dextrans are colloidal glucose polymers that are obtained from sucrose by the action of bacteria, Leuconostoc mesenteroides. The dextran molecule consists mainly of 1:6 glucoside linkages with relatively few 1:4 linkages and has an average molecular weight of 40 millions. This form is not clinically suitable. Hence, it is partially hydrolyzed in vitro to give dextran with average molecular weight of 40,000, 70,000, 11,000, and 15,000 daltons. They are known as dextran-40, dextran-70, dextran-110, and dextran-150, respectively. Of these, dextran-40 and dextran-70 are of clinical importance. Solutions of dextran in isotonic sodium chloride is used to increase the circulating blood volume and to maintain the venous pressure, right arterial pressure, stroke volume, and cardiac output. Only dextran solutions are used in the treatment of hypoproteinaemia, nephrosis, and toxaemia of late pregnancy. Dextran does not posses oxygen-carrying capacity.

The dextran solution is pharmacologically inactive and has been reported as having no significant deleterious effect on renal, hepatic, or any other vital functions. Occasionally, sensitization reaction may occur in some patients. The bleeding time, fibrin polymerization on platelet function may be impaired in vivo. Dextrans are contraindicated in patients with anaemia, severe thrombocytopenia, and low plasma fibrinogen level.

 

ii. Human albumin

It is obtained from pooled human plasma; 100 ml of 20% human albumin solution is the osmotic equivalent of about 400 ml of fresh frozen plasma or 800 ml of whole blood. It can be used without regard to the patient’s blood group and does not interfere with coagulation. Unlike whole blood or plasma, it is free of risk of transmitting serum hepatitis because the preparation is heat-treated. There is also no risk of sensitization with repeated infusions. It has been used in acute hypoproteinaemia, acute liver failure, and dialysis.

 

iii. Degraded gelatin polymer (polygeline)

It is a polypeptide with an average MW 30,000, which exerts osmotic pressure similar to albumin, and is not antigenic and hypersensitivity reactions are rare. It does not interfere with the grouping and cross matching of blood and remains stable for 3 years. It can be used for the priming of heart–lung dialysis machines.

 

iv. Hydroxyethyl starch (HES, hetastarch)

It is a complex mixture of ethoxylated amylopectin of various molecular sizes, average MW 4.5 lakh (range 10,000–1 million). The colloidal properties of 6% HES approximate those of human albumin. Plasma volume expands slightly in excess of the volume infused. It has been used to improve harvesting of granulocytes because it accelerates erythrocyte sedimentation. Adverse effects are vomiting, mild fever, itching, chills, flu-like symptoms, swelling of salivary glands, urticaria, perorbital oedema, and bronchospasm are the anaphylactoid reactions.

 

v. Polyvinylpyrrolidone (PVP)

It is a synthetic polymer (average MW 40,000) used as a 3.5% solution. It interferes with the blood grouping and cross matching. It has been found to bind penicillin and insulin in circulation, so that the same is not available for action. It is not frequently used as a plasma expander.

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