Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: solutions for parenteral nutrition, carbohydrates ATC code: B05B A03

Mechanism of action

Glucose, as a natural substrate of the cells in the body, is ubiquitously metabolised. Under physiological conditions, glucose is the most important energy-supplying carbohydrate with a calorific value of approx. 17 kJ/g or 4 kcal/g. Nerve tissue, erythrocytes and renal medulla are among those dependent on glucose supply. The normal range for blood glucose concentration is reported to be 60-100 mg/100 mL or 3.3-5.6 mmol/L (fasting).

On the one hand, glucose is used to produce glycogen as the storage form of carbohydrates, while on the other hand it is broken down by glycolysis to pyruvate or lactate in order to generate energy in the cells. Furthermore, glucose serves to maintain blood glucose levels and the biosynthesis of important body constituents. Primarily insulin, glucagon, glucocorticoids and catecholamines are involved in the hormonal regulation of blood glucose levels.

Clinical efficacy and safety

A normal electrolyte and acid-base balance is the prerequisite for optimum utilisation of supplied glucose. In particular, acidosis may indicate impaired oxidative utilisation.

There are close interrelationships between electrolytes and carbohydrate metabolism which affect potassium in particular. Increased glucose utilisation is associated with increased potassium requirements. If this relationship is not taken into account, this may cause considerable potassium metabolism abnormalities, which may result in significant cardiac arrhythmias, among other conditions.

Abnormal glucose utilisation (glucose intolerance) can occur under conditions of pathological metabolism. These mainly include diabetes mellitus and the hormone-mediated reduction of glucose tolerance that occurs in so-called states of metabolic stress (e.g., intra- and postoperative, serious illness, injury), which can lead to hyperglycaemia even without exogenous supply of the substrate.
Hyperglycaemia can - depending on its severity - lead to osmotically mediated renal fluid losses with consequential hypertonic dehydration and hyperosmotic disorders culminating in hyperosmotic coma.

Excessive administration of glucose, particularly in the context of a post-traumatic metabolism, may result in a pronounced exacerbation of the glucose utilisation disorder and, due to impaired oxidative glucose utilisation, contribute to increased conversion of glucose to fat. This may in turn be accompanied by, for instance, increased carbon dioxide levels in the body (issues whilst weaning from the respirator), as well as increased fatty infiltration of tissues, in particular in the liver. Recent literature reports furthermore also suggest a negative impact of the administration of carbohydrates in high doses in an intensive-care setting on the peripheral nervous system (paralysis). Patients with traumatic brain injury and cerebral oedema are at a particular risk of glucose homoeostasis abnormalities. Even minor blood glucose level abnormalities and the associated increase in plasma (serum) osmolarity may result in a significant worsening of cerebral damage.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Distribution
On injection, glucose is first distributed in the intravascular space and then is taken up into the intracellular space.

Biotransformation

In glycolysis, glucose is metabolised to pyruvate or lactate. Under aerobic conditions, pyruvate is completely oxidised to carbon dioxide and water. The end products of the complete oxidation of glucose are eliminated via the lungs (carbon dioxide) and the kidneys (water).

Elimination

Practically no glucose is eliminated renally by healthy persons. In pathological metabolic conditions (e.g., diabetes mellitus, post-traumatic metabolism) associated with hyperglycaemia (blood glucose concentration of more than 120 mg/100 mL or 6.7 mmol/L), glucose is also excreted via the kidneys (glycosuria) if the maximum tubular transport capacity (180 mg/100 mL or 10 mmol/L) is exceeded.