Usage
- 2-Deoxy-D-glucose (2-DG) is primarily used as an imaging agent in its radiolabeled form ([18F]fluoro-2-deoxy-D-glucose or FDG) for positron emission tomography (PET) scans. FDG-PET is used to measure glucose metabolism, which is altered in various conditions, including cancer and some infections. It has also been investigated as an adjunct therapy in COVID-19.
- Pharmacological Classification: Antimetabolite, glucose analog.
- Mechanism of Action: 2-DG acts as a glucose analog and competes with glucose for uptake into cells. However, unlike glucose, 2-DG cannot be fully metabolized. This leads to disruption of glycolysis, inhibiting energy production and other cellular processes dependent on glucose metabolism.
Alternate Names
- 2-DG
- [18F]fluoro-2-deoxy-D-glucose (FDG) (radiolabeled form)
How It Works
- Pharmacodynamics: 2-DG inhibits glycolysis, leading to reduced cellular energy production and impacting other glucose-dependent processes. In cancer cells, this can lead to decreased proliferation and potentially cell death.
- Pharmacokinetics: 2-DG is administered orally and is absorbed from the gastrointestinal tract. It distributes to various tissues, mimicking glucose uptake. It is partially metabolized, but unlike glucose, it cannot undergo complete glycolysis. Elimination pathways are not fully characterized, but some excretion occurs via the kidneys.
- Mode of Action: 2-DG competitively inhibits glucose uptake and phosphorylation by hexokinase, the first enzyme in glycolysis. This blocks further glucose metabolism and disrupts cellular energy production.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Primarily involves competitive inhibition of hexokinase.
Dosage
Standard Dosage
2-DG is not FDA-approved for therapeutic use in the United States. Dosage information below is based on clinical trials and emergency use authorization in certain contexts.
Adults: Dosages have varied in clinical trials. Dosages of 45 mg/kg, 63 mg/kg, and up to 126 mg/kg/day have been studied.
Children: No established pediatric dosing guidelines are currently available.
Clinical Use Cases
Currently, clinical use cases are primarily limited to research settings. Clinical trials have investigated 2-DG as an adjunct therapy in cancer and COVID-19. Emergency use authorization has been granted in some countries for COVID-19.
Dosage Adjustments
Dose adjustments may be necessary based on individual patient tolerance and any emerging adverse effects.
Side Effects
Common Side Effects
Fatigue, dizziness, nausea, sweating, and hyperglycemia.
Rare but Serious Side Effects
QTc prolongation, gastrointestinal bleeding, cardiac conduction abnormalities (e.g., AV block, bradycardia).
Long-Term Effects
Long-term effects are not well-established due to limited long-term clinical use of 2-DG.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include QTc prolongation, cardiac conduction abnormalities, and gastrointestinal bleeding. These require close monitoring and potential intervention.
Contraindications
Currently, specific contraindications are not well-defined due to the drug’s limited clinical use. However, patients with pre-existing cardiac conduction abnormalities should be carefully monitored.
Drug Interactions
Drug interactions are not fully characterized. Clinical trials have indicated no significant interaction between 2-DG and docetaxel.
Pregnancy and Breastfeeding
The safety of 2-DG during pregnancy and breastfeeding has not been established. It should be avoided unless the potential benefit outweighs the unknown risk to the fetus or neonate.
Drug Profile Summary
- Mechanism of Action: Glucose analog, inhibits glycolysis.
- Side Effects: Fatigue, dizziness, nausea, hyperglycemia; QTc prolongation, gastrointestinal bleeding.
- Contraindications: Limited data available. Caution in patients with cardiac conduction abnormalities.
- Drug Interactions: Not fully characterized.
- Pregnancy & Breastfeeding: Avoid unless potential benefit outweighs risk.
- Dosage: Varies based on clinical trial; 45-126 mg/kg/day has been studied.
- Monitoring Parameters: ECG (for QTc prolongation), blood glucose, cardiac function.
Popular Combinations
Combinations of 2-DG with other cancer therapies are under investigation.
Precautions
General precautions include monitoring for cardiac and metabolic effects. Precautions for specific populations are not well-defined due to limited data.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for 2-Deoxy-D-Glucose?
A: 2-DG does not have a standardized recommended dosage for therapeutic use. Dosages used in research settings vary depending on the condition being studied.
Q2: What are the primary uses of 2-DG in medicine?
A: The primary use is as a radiolabeled imaging agent (FDG) in PET scans. Therapeutic uses are largely experimental.
Q3: How does 2-DG work at the cellular level?
A: It competitively inhibits hexokinase, the enzyme responsible for the first step of glycolysis, disrupting glucose metabolism.
Q4: What are the most common side effects?
A: Fatigue, dizziness, nausea, sweating, and hyperglycemia.
Q5: Are there any serious side effects to be aware of?
A: Yes, QTc prolongation, cardiac arrhythmias, and gastrointestinal bleeding have been reported.
Q6: Can 2-DG be used during pregnancy?
A: Its safety during pregnancy and breastfeeding has not been established and should generally be avoided.
Q7: Does 2-DG interact with other medications?
A: Drug interactions are not well-characterized.
Q8: What is the long-term prognosis for patients treated with 2-DG?
A: Long-term effects are not well-established due to the limited duration of most 2-DG clinical trials.
Q9: What should be monitored in patients receiving 2-DG?
A: ECG for QTc prolongation, blood glucose levels, and cardiac function.
