Dextran

Uses

This is used for thromboembolic disorders, hypovolaemic shock, pulmonary embolism, venous thrombosis.

Dextran is also used to associated treatment for these conditions: Blood Circulation Disorder, Capillary disorder, Dry Eyes, Ocular Irritation, Pulmonary Embolism, Pulmonary Embolism caused by procedures associated with a high incidence of thromboembolic complications, Shock, Thrombosis, Venous, Venous Thrombosis caused by procedures associated with a high incidence of thromboembolic complications, Thrombotic events, Plasma Volume Replacement, Priming fluid in pump oxygenators therapyArrhythmia, Caloric Deficit, Edema of the cerebrum, Metabolic Alkalosis, Hypoglycemic reaction, Blood Specimen Collection, Electrolyte replacement, Nutritional supplementation, Parenteral Nutrition, Parenteral rehydration therapy, Plasmapheresis, Positive cardiac inotropic effect, Total parenteral nutrition therapy, Urine alkalinization therapy, Fluid and electrolyte maintenance therapy

How Dextran works

In preclinical studies, the mechanism of action is thought to be related to the blockage of the uptake of tissue plasminogen activator by mannose-binding receptors. This process has a direct effect by enhancing endogenous fibrinolysis.

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into 2 main phases where the preparatory phase is initiated by the phosphorylation of glucose by a hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. This energy-producing reactions of glucose is limited to D-glucose as L-glucose cannot be phosphorlyated by hexokinase. Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation in order to preserve cellular and whole body metabolic integrity .

Dosage

Dextran dosage

Adult: IV Hypovolaemic shock As dextran 40 (10% soln): 10 mL/kg/day for up to 5 days.

Thromboembolic disorders:

• As dextran 40 (10% soln): Initial: 500 ml on day 1, followed by 500 ml on day 2 and subsequently on alternate days up to 10 days. Prophylaxis of post-op thromboembolic disorders. 500 ml during or at the end of surgery. May repeat dose next day and continue treatment on alternate days for up to 10 days in high-risk patients.

Child: As dextran 40: Up to 5 ml/kg in infants and 10 ml/kg in children.

Hypersensitivity. Severe renal disease with oliguria or anuria. Marked cardiac decompensation. Pregnancy.

Side Effects

Congestive heart failure, Mild hypotension, Tightness of chest, Thrombocytopenia, Anaphylaxis, Injection site infection/phlebitis, Acute renal failure, Acidosis (if NaCI soln used), Pulmonary edema, Wheezing

Toxicity

Some reports have shown adverse effects when used in therapeutical doses and some teratogenic effects have been demonstrated when used in large doses. The current LD50 reported in rats is 10700 mg/kg.

Oral LD50 value in rats is 25800mg/kg. The administration of glucose infusions can cause fluid and/or solute overloading resulting in dilution of the serum electrolyte concentrations, over-hydration, congested states, or pulmonary oedema. Hypersensitivity reactions may also occur including anaphylactic/anaphylactoid reactions from oral tablets and intravenous infusions.

Precaution

Caution should be taken during pregnency

Interaction

Dextran:

• Enzyme inducers e.g. phenytoin or carbamazepine
• enzyme inhibitors e.g. cimetidine.

Volume of Distribution

The reported volume of distribution of dextran suggested a distribution throughout the blood volume. This volume of distribution is reported to be of around 120 ml. The organ that presented a higher accumulation of dextran was the liver.

The mean volume of distribution after intravenous infusion is 10.6L.

Elimination Route

Dextran presents a very low oral bioavailability that is reduced as the chain gets longer. Thus, the bioavailability of dextran is inversely proportional to the length of the carbohydrate chain.

Polysaccharides can be broken down into smaller units by pancreatic and intestinal glycosidases or intestinal flora. Sodium-dependent glucose transporter SGLT1 and GLUT2 (SLC2A2) play predominant roles in intestinal transport of glucose into the circulation. SGLT1 is located in the apical membrane of the intestinal wall while GLUT2 is located in the basolateral membrane, but it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion . Oral preparation of glucose reaches the peak concentration within 40 minutes and the intravenous infusions display 100% bioavailability.

Half Life

The elimination half-life will depend on the length of the carbohydrate chain. The higher the molecular weight of the dextran the longer it will be the elimination half-life. The half-life will go from 1.9 hours from dextran 1 to 42 hours in the case of dextran 60.

The approximate half-life is 14.3 minutes following intravenous infusion. Gut glucose half-life was markedly higher in females (79 ± 2 min) than in males (65 ± 3 min, P < 0.0001) and negatively related to body height (r = -0.481; P < 0.0001).

Clearance

The mean metabolic clearance rate of glucose (MCR) for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglyglycemia.

Elimination Route

The elimination of dextran will depend on the length of the carbohydrate chain, the administration route, and the molecular weight. For dextran 1, it is reported to be mainly secreted unchanged in the urine in a ratio of 80% of the administered dose when administered parentally. It is registered that the weight threshold for unrestricted glomerular filtration is about 15 kDa and if the dextran overpasses 50 kDa it will not be renally eliminated in any significant amount.

Glucose can be renally excreted.

Pregnancy & Breastfeeding use

Pregnancy Category - C

Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Contraindication

Concentrated dextrose solution is contraindicated in patients with Glucose-Galactose Malabsorption Syndrome and severe hydration. The infusion of hypertonic dextrose injections is contraindicated in patients having intracranial or intraspinal hemorrhage, in patients who are severely dehydrated, in patients who are anuric, and in patients in hepatic coma. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Acute Overdose

Reevaluate patient's condition and institute appropriate symptomatic treatment.

Storage Condition

Store at 25°C.

Innovators Monograph

You find simplified version here Dextran