AXAZOLID INTRAVENOUS INJECTION

Indications

• Hypoglycemia
• Caloric supplementation in patients unable to eat
• Fluid replacement therapy
• Parenteral nutrition

Dosage

Children: Paediatric doses must be determined based on clinical condition and specific needs. Refer to the BNF for Children for appropriate dosing information.

Adults: The dosage of dextrose in adults varies based on clinical condition and route of administration. For hypoglycemia, intravenous dextrose 50% (D50W) is commonly administered. Refer to the BNF for specific dosing guidelines.

Mechanism of action

Dextrose supplies energy to tissues by generating ATP and NADH through glycolysis, where glucose is phosphorylated by hexokinase to form glucose 6-phosphate. This activates glucose for breakdown, ultimately converting glucose into energy molecules. Dextrose also plays a role in gene transcription, enzyme activity, and hormone secretion, regulating glucose homeostasis and cellular metabolic integrity.

Pharmacodynamics

Blood glucose acts as a crucial energy source for cellular activities and functions as a signaling molecule. It is oxidized into carbon dioxide and water, producing energy through glycolysis, the citric cycle, and oxidative phosphorylation. Dextrose can be converted into fat for energy storage and is stored as glycogen in the liver and muscles. Its administration, particularly orally, enhances insulin secretion due to stimulation of incretin hormones.

Pharmacokinetics

Dextrose is rapidly absorbed in the gastrointestinal tract, leading to a quick elevation of blood glucose levels. It is distributed throughout the body and can be utilized by various tissues for energy. The metabolism of dextrose primarily occurs in the liver, where it can be stored as glycogen or converted into fat. Renal excretion may occur when blood glucose levels are excessively high.

Adverse effects

• Hyperglycemia
• Fluid overload
• Hypokalemia
• Thrombophlebitis at injection site

Interactions

• Corticosteroids may increase blood glucose levels
• Beta-blockers may mask symptoms of hypoglycemia
• Diuretics may cause electrolyte imbalances

Precautions

• Use with caution in patients with diabetes mellitus
• Monitor blood glucose levels regularly
• Use cautiously in patients with renal impairment or heart failure

Pregnancy

Dextrose is generally considered safe for use during pregnancy when clinically indicated, but should be used with caution.

Breast-feeding

Dextrose can be used during breastfeeding as it is a natural sugar found in breast milk.

Storage

Store at room temperature, away from direct sunlight, and protect from freezing.

Formulations

• Dextrose 5% solution for infusion
• Dextrose 10% solution for infusion
• Dextrose 50% solution for injection
• Oral dextrose tablets

Indications

• Bacterial pneumonia
• Complicated skin and soft-tissue infections
• Diabetic foot infections
• Cellulitis (specialist use only)
• Erysipelas (specialist use only)
• Leg ulcer infection (specialist use only)

Dosage

Children: Refer to BNF for Children; close monitoring is recommended in patients receiving treatment for more than 10

Adults: 600 mg every 12 hours, usually for 10–14 days (maximum duration of treatment is 28 days).

Mechanism of action

Linezolid exerts its antibacterial effects by binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit, preventing the formation of the functional 70S initiation complex necessary for bacterial reproduction. This interference with the translation process inhibits protein synthesis, effectively stopping bacterial growth.

Pharmacodynamics

Linezolid demonstrates bacteriostatic activity against staphylococci and enterococci while being bactericidal against most streptococci. It shows some activity against Gram-negative and anaerobic bacteria but is generally not effective against them. Additionally, Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAO), which can pose a risk for serotonin syndrome when taken with serotonergic medications.

Pharmacokinetics

Linezolid is well absorbed orally, with a bioavailability of approximately 100%. It is extensively distributed in body tissues and fluids, achieving therapeutic concentrations in the lungs, skin, and soft tissues. The drug is primarily metabolized by oxidation, with negligible renal clearance, making it suitable for patients with renal impairment but necessitating caution in those with severe hepatic impairment. Linezolid's half-life is about 4 to 5 hours, allowing for twice-daily dosing.

Contra-indications

• uncontrolled hypertension
• phaeochromocytoma
• carcinoid tumour
• thyrotoxicosis
• bipolar depression
• schizophrenia
• acute confusional states

Adverse effects

• anaemia
• constipation
• diarrhoea
• dizziness
• gastrointestinal discomfort
• headache
• hypertension
• increased risk of infection
• insomnia
• localised pain
• nausea
• skin reactions
• taste alteration
• vomiting
• arrhythmia
• chills
• dry mouth
• eosinophilia
• fatigue
• gastritis
• hyperhidrosis
• hyponatraemia
• leucopenia
• neutropenia
• oral disorders
• pancreatitis
• polyuria
• renal failure
• seizures
• sensation abnormal
• thirst
• thrombocytopenia
• thrombophlebitis
• tinnitus
• tooth discolouration
• antibiotic-associated colitis
• bone marrow disorders
• visual disorders
• vulvovaginal disorder
• alopecia
• angioedema
• lactic acidosis
• nerve disorders
• serotonin syndrome
• severe cutaneous adverse reactions

Interactions

• beta 2 agonists
• buspirone
• levodopa
• methylphenidate
• ozanimod
• reboxetine
• sympathomimetics
• vasoconstrictors (e.g., adrenaline, ephedrine, isometheptene, noradrenaline, phenylephrine)
• pseudoephedrine
• bupropion
• MAO inhibitors

Precautions

• Close observation of blood pressure required in certain conditions
• Monitor full blood count weekly during treatment
• Caution in renal impairment

Mechanism of action

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 two main phases where the preparatory phase is initiated by the phosphorylation of glucose by hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for the 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 the 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. These energy-producing reactions of glucose are limited to D-glucose as L-glucose cannot be phosphorylated 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 to preserve cellular and whole body metabolic integrity. Vascular calcification is a hallmark of type 2 diabetes. Glucose stimulates calcification in culture of vascular smooth muscle cells (VSMCs) but the underlying mechanisms remain obscure. We observed that high glucose levels stimulated mouse and human VSMC trans-differentiation into chondrocytes, with increased levels of Sox9, type II collagen, glycosaminoglycan and Runx2 expression, and increased alkaline phosphatase activity and mineralization. These effects were associated with increased expression of IL-1beta, which stimulated alkaline phosphatase and calcification, suggesting that glucose induces chondrocyte differentiation of VSMCs, possibly through IL-1beta activation.

Pharmacodynamics

Blood glucose is an obligatory energy source for humans involved in various cellular activities, and it also acts as a signaling molecule for diverse glucose-sensing molecules and proteins. Glucose undergoes oxidation into carbon dioxide, water, and yields energy molecules in the process of glycolysis and subsequent citric cycle and oxidative phosphorylation. Glucose is readily converted into fat in the body which can be used as a source of energy as required. Under a similar conversion into storage of energy, glucose is stored in the liver and muscles as glycogen. Glucose stores are mobilized in a regulated manner, depending on the tissues' metabolic demands. Oral glucose tablets or injections serve to increase the supply of glucose and oral glucose administration is more effective in stimulating insulin secretion because it stimulates the incretin hormones from the gut, which promotes insulin secretion.

Mechanism of action

Linezolid exerts its antibacterial effects by interfering with bacterial protein translation. It binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is essential for bacterial reproduction, thereby preventing bacteria from dividing. Point mutations in the bacterial 23S rRNA can lead to linezolid resistance, and the development of linezolid-resistant _Enterococcus faecium_ and _Staphylococcus aureus_ have been documented during its clinical use. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use. Linezolid is a synthetic oxazolidinone anti-infective agent that is structurally unrelated to other anti-infectives commercially available in the US. In contrast to other anti-infectives that inhibit bacterial protein synthesis, linezolid acts early in translation by binding to a site on the bacterial 23S ribosomal RNA of the 50S subunit and preventing the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. Linezolid acts via inhibition of protein synthesis. It bind to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex. This step is essential for the bacterial translation process. Linezolid is an oxazolidinone antibiotic that is increasingly used to treat drug-resistant, gram-positive pathogens. The mechanism of action is inhibition of bacterial protein synthesis. Optic and/or peripheral neuropathy and lactic acidosis are reported side effects, but the underlying pathophysiological mechanism has not been unravelled. Mitochondrial ultrastructure, mitochondrial respiratory chain enzyme activity /were studied/, and mitochondrial DNA (mtDNA) in muscle, liver, and kidney samples obtained from a patient who developed optic neuropathy, encephalopathy, skeletal myopathy, lactic acidosis, and renal failure after prolonged use of linezolid. In addition, mtDNA, respiratory chain enzyme activity, and protein amount in muscle and liver samples obtained from experimental animals that received linezolid or placebo /were evaluated/. In the patient, mitochondrial respiratory chain enzyme activity was decreased in affected tissues, without ultrastructural mitochondrial abnormalities and without mutations or depletion of mtDNA. In the experimental animals, linezolid induced a dose- and time-dependent decrease of the activity of respiratory chain complexes containing mtDNA-encoded subunits and a decreased amount of protein of these complexes, whereas the amount of mtDNA was normal. These results provide direct evidence that linezolid inhibits mitochondrial protein synthesis with potentially severe clinical consequences.

Pharmacodynamics

Linezolid is an oxazolidinone antibacterial agent effective against most strains of aerobic Gram-positive bacteria and mycobacteria. It appears to be bacteriostatic against both staphylococci and enterococci and bactericidal against most isolates of streptococci. Linezolid has shown some _in vitro_ activity against Gram-negative and anaerobic bacteria but is not considered efficacious against these organisms. Linezolid is a reversible and non-selective inhibitor of monoamine oxidase (MAO) enzymes and can therefore contribute to the development of serotonin syndrome when administered alongside serotonergic agents such as selective serotonin re-uptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). Linezolid should not be used for the treatment of catheter-related bloodstream infections or catheter-site infections, as the risk of therapy appears to outweigh its benefits under these circumstances.