Alcohol Biomarkers Flashcards
Alcohol Abuse
Recent study of the American workforce reported that 15% of employees were hung over, drank shortly before work, or were drinking or impaired while at work at least once in the prior year
Among chemically dependent healthcare professionals in Alabama, alcohol was claimed to be the drug of choice 44% of the time
Measurement of ethyl alcohol will provide only a brief detection window
Chronic alcohol abuse can be monitored through various biological markers
How are biomarkers used
Screening, motivating change in behavior, Identifying relapse to drinking, Documenting abstinence
Screening for alcohol problems
Role of alcohol in either causing or exacerbating medical problems is often missed
Used frequently in the insurance industry
Awareness of co-occurring alcohol problems can improve differential diagnosis and treatment
Motivating change in drinking behavior
Important goal of alcohol treatment is motivating the patient to reduce or cease drinking
Objective evidence for feedback to patient
two types of biomarkers
Traditional- Indirect: detect toxic effects on organ system(s) or body chemistry
Non-traditional biomarkers–Direct: analytes of alcohol metabolism
Alcohol metabolized via oxidative processes
Small amount is “broken down” non-oxidative rxn
Traditional Biomarkers
GCT, AST, ALT, MCV, CDT
GCT
gamma-glutamyltransferase
Elevation caused by liver enzyme induction
Alcohol
Many other Rx drugs and OTC
AST
aspartate aminotransferase
ALT
alanine aminotransferase
What can elevated AST and ALT indicate
hepatocyte injury/death
MCV
mean corpuscular volume
Average size of red blood cell
Heavy alcohol consumption can cause an elevation
Serum transferrin function is t transported deliver iron
CDT
carbohydrate-deficient transferrin
Moderate to heavy EtOH consumption
Hepatocytes begin to produce molecules of transferrin that are deficient in carbohydrates
Values less elevated after EtOH intake in women
Main disadvantage is relatively low sensitivity
Long-standing and high doses of alcohol consumption
Greater than two weeks
Greater than 1000 g EtOH ]>5 drinks per day]
Can be influenced by age and/or gender
Variety of Rx and OTC medications can cause an elevation
Non-alcohol-associated diseases may cause increases
Non-Trinational Biomarkers
5-HTOL: 5-hydroxytryptophol
FAEE: fatty acid ethyl esters
Peth: phosphatidyl ethanol
EtG: ethyl Glucuronide
EtS: ethyl sulfate
Serotonin 5- hydroxy tryptamine
Less than 1% of serotonin
Via aldehyde reductase
Elevated urinary concentrations for ~5-15 hours post-ingestion
EtOH competitive interaction with ADHase
Shift in metabolism
Increase in HTOL
FAEE
fatty acid ethyl esters
Non-oxidative metabolite
Enzymatic formation of FAEE was first discovered in 1981
FAEE synthase
Rxn with free fatty acids, triglycerides, lipoproteins
FAEE are cytotoxic
Implicated as a mediator of alcohol-induced organ damage
Alcohol consumption within the last 24 hours
Peth:
phosphatidyl ethanol
First described in 1994
Enzymatic transformation phosphatidylcholine
Phospholipase D in presence of ethanol
Ethyl Glucornide
Non-volatile, water-soluble, stable, direct metabolite
0.02 – 0.06% alcohol metabolized via this route
Concentration is dose-dependent
Serum: EtG t1/2 2-3 hours; detected 6-18 hours post-ingestion
Urine: detected shortly after ingestion [few hours] and up to 80 hours after complete ethyl alcohol elimination
EtG is not detected unless alcohol has been “consumed”
Analytical Cut-Offs
Varying levels for administrative cut-offs: urine
“Zero-tolerance”: 100 ng/mL
Commonly used to monitor recovering healthcare professionals
High sensitivity: 250 ng/mL
Clinical or forensic applications
Moderately high: 500 ng/mL
Moderate: 1000 ng/mL
EtG Stability
EtG stable in urine
Resistant to heat, with degradation observed in less than 1% of the specimens
EtG positive specimens stored under conditions where the sample slowly decomposed at room temperature
Slow decrease was observed over 4 weeks
Samples with bacterial contamination or blood have demonstrated a decrease in EtG concentrations measured over time:
Due to the introduction of glucuronidase activity
cAN eTg HAVE DE NOVO SYNTHESIS
no
Ethyl Sulfate
Another non-oxidative metabolite of EtOH
Positive correlation with EtG
Similar detection window
1.5 days after moderate EtOH in urine
Unaffected by bacterial glucuronidase
Serves as a marker to confirm low EtG due to degradation
Eliminates false negative results due to degradation
Cut-off 100 ng/mL
what can EtG and EtS
Detected in both blood and urine
As alcohol use/abuse urine preferred sample
Concentrated in urine ~200x as compared to blood
Urine detection window up to 90 hours
Other things can give elevated levels that are different from than ingestion of alcohol
Nyquil, Listerine, hand sanitizer, vanilla extract, kraut, mouthwash, non-alcoholic beer
Incidental Exposure
EtG extremely sensitive test for the detection of alcohol consumption
Incidental or unintentional consumption of alcohol significant concern for the interpretation of laboratory result
Small amounts [sometimes large amounts] of ethanol can be found as an ingredient in many foods [flavor extracts and non-alcoholic beers], hygiene products [hair spray, mouthwash,
