toxicology drugs in acute intoxication Flashcards
acute & chronic toxicity
- Acute - a single, short-term exposure to a substance
- Chronic - repeated, frequent exposure for extended periods
- Acute exposure is often a STAT request.
- If a person presents to the ER in a coma, often a serum and/or urine drug screen is ordered if an overdose is suspected
serum drug screen
- Ethanol
- Salicylates
- Acetaminophen
toxicology
- Toxicology is the study of adverse effects of xenobiotics in humans.
- involves the analysis of drugs, heavy metals, and other chemical agents in body fluids and tissues for the purposes of patient care.
- Xenobiotics are chemicals and drugs that are not normally found in or produced by the body.
- The terms xenobiotic, poison, and toxin are often used interchangeably but there are important differences between them.
- Drugs are the most commonly encountered xenobiotic in the clinical chemistry lab
xenobiotics vs poisons vs toxins
Xenobiotics
•Exogenous agents that may have adverse effects on a living organism
•environmental chemicals or drug exposures
•Eg. antibiotics, anti-depressants, brominated compounds
Poisons
•Exogenous agents that can have adverse effects on a living organism
• substances from an animal, plant, mineral or gas
•Eg. Snake/spider venom, poison hemlock, arsenic, lead, carbon monoxide
Toxins
•Endogenous substances that have adverse effects on a living organism
• synthesized in living cells or microorganisms
•Eg. Botulism toxin from Clostridium botulinum, mycotoxins from fungus
exposure to toxins
50% intentional poisonings are suicide attempts
- highest mortality rate
30% accidental exposures
- most frequently seen in children
- adults & adolescent from therapeutic drugs or illicit drugs
the remainder are a result of homicide or occupational exposure
testing clinically significant toxins & drug screening
There is no need to test for all clinically significant toxins that may be encountered( too many to test)
•~24 drugs account for 80% of intoxications treated in the ED
•The value of drug screening is well-established in the following situations:
•In the workplace
•Some athletic competitions
•To identify drug use
•To evaluate drug exposure and/or withdrawal in newborns
•To monitor patients in pain management and drug abuse treatment programs
•To aid in prompt diagnosis of toxicity when a specific antidote or treatment is
required.
routes of exposure
Most common routes:
•Ingestion ( most common)
•Inhalation
•Transdermal absorption
factors affecting absorption
- pH
- Rate of dissolution ( depends on how drug was taken)
- Gastric mobility
- Resistance to degradation in GI tract
dose response relationship ( ED, TD & LD)
- Dosage and response varies amongst individuals
- 2 individuals getting the same dose can have different blood levels of the drug and different effects from the drug
Terminology to explain population variance to dosages of a drug:
•ED50(Effective Dose): dose of drug in which 50% of population will experience benefit
•TD50 (Toxic Dose): dose of drug in which 50% of population will experience toxic adverse effects
•LD50 (Lethal Dose): dose of drug in which 50% of population will result in mortality
Analysis of toxic agents
usually blood or urine specimens
- Random urine specimens are good for screening and qualitative detection of toxic agents
- 24-hour collections are preferred to compensate for variations throughout the day.
Two-Step Process:
- Screening Test ( Qualitative)
- A rapid, simple, qualitative procedure (negative or positive result)
- Intended to detect specific substances or classes of toxicants
- Confirmatory Test ( Quantitative)
- Quantitative measurement
- Used to confirm a positive result from the screening test
Screening Procedures for Detection of Drugs
initial tests used to “screen” specimens to eliminate negative ones from further consideration and to identify presumptive positive specimens that will require confirmatory testing.
• often simple visual color tests (spot tests) or immunoassays.
•Electrocardiograms (ECGs) can be used to detect changes caused by drugs in the poisoned patient.
- This aids appropriate lab testing, diagnosis and management of care.
Lab Procedures for the Detection of Drugs - Anion Gap
metabolic panel is usually performed as an initial screen for all poisoned patients.
•If serum bicarb is found to be low, anion gap is checked to see if there is an elevation.
•Formula:
AG = [Na+] - [Cl- + HCO3-]
RR: 7 - 16 mmol/L
or RR of 10-20 mmol/L if K+ in equation
•An increased anion gap will be seen with: M - Methanol U - Uremia D - Diabetes P - Paraldehyde I - Iron, inhalants L - Lactate E - Ethylene Glycol S - Salicylates
Lab Procedures for the Detection of Drugs - Osmolal Gap
•Osmolality formula:
OSMc (mOsm/kg) = 1.86[Na+] + [glucose] + [urea]
(RR: 275 - 295 mOsm/kg)
•Osmolal gap is the difference between the measured osmolality (using a freezing point depression Osmometer) and the calculated osmolality.
OSMg = OSMm - OSMc
(RR: 5 - 10 mOsm/kg)
•Increased osmolal gap indicates presence of unmeasured osmotically active substances
- Ethanol, methanol, isopropanol, acetone, ethylene glycol
Lab Procedures for the Detection of Drugs - Analytic Techniques
Drug screens commonly use immunoassays.
- Other methods include:
- Thin-layer Chromatography (TLC)
- Gas Chromatography (GC)
- Gas Chromatography/Mass Spectrometry (GC/MS) - Reference Method*******
- Inductively Coupled Plasma-Mass Spectrometry (ICP-MS)
- Atomic Absorption (AA)
Lab Procedures for the Detection of Drugs - Immunoassay
•Can be specific to detect a single drug (LSD) or can detect several drugs within a class (opiates)
- Easy to perform
- Can be automated
- Some provide semiquantitative results
- Method of choice for most drugs of abuse screening
•Must be confirmed by a more sensitive method***
Lab Procedures for the Detection of Drugs - GC and HPLC
Gas chromatography
•Relatively rapid
•Capable of resolving a broad spectrum of drugs
•Provides greatest accuracy of identification when coupled to a mass spectrometer (GC-MS)
HPLC
•Useful in analyzing:
- Polar compounds without derivatization (morphine)
- Thermally labile drugs
Toxicology of Specific Agents
Alcohols
General toxic effects:
•Disorientation, confusion, euphoria
•Pprogress to unconsciousness, paralysis and even death
Common Alcohols: •Ethanol •Methanol •Isopropanol •Ethylene Glycol
Ethanol
- Widely available and often abused
- Most common toxic substance encountered in the clinical chemistry lab
- Top ten causes of hospital admissions
•Ethanol is a teratogen- consumption of ethanol during pregnancy can lead to fetal alcohol syndrome
- Delayed motor and mental development in the child
•Consequences of chronic consumption/alcohol abuse:
- Compromised function of various organs, tissues and cells - especially the liver
- Accumulation of lipids in the hepatocytes
- Toxic form of hepatitis
- Liver cirrhosis
Depresses central nervous system (CNS)
- Effect varies depending on blood ethanol concentration and individual’s tolerance
•Metabolized by alcohol dehydrogenase (ADH) to acetaldehyde in the liver.
Ethanol - methods of analysis
•Osmometry can help screen for ethanol
- Increased osmolal gap if ethanol is present
- Difference between measured and calculated osmolality - Gas chromatography - Reference method****
- Alcohol dehydrogenase (ADH)
- Enzymatic method
- Most common method
Ethanol - ADH Method
Ethanol + NAD Acetaldehyde + NADH + H
Measure increase absorbance @ 340nm due to NADH
Increased concentrations of LD, lactate and other alcohols can falsely increase results.
Interpretation:
11 - 22 mmol/L Intoxication
> 32 mmol/L 50% of people Grossly intoxicated
65 mmol/L Coma may occur
86 mmol/L D`eath may occur
Ethanol - Legal Limit
Blood Alcohol Content - BAC
- Legal limit in Canada:
- < .08% = ‹ 80 mg/dL (< 17 mmol/L)
- Legal limit in NL:
- < .05% = ‹ 50 mg/dL (<11 mmol/L)
- Toxic level:
- > 100 mg/dL = > 22 mmol/L
why is NL lower :
•Impairment begins at 0.02
•BAC of 0.03 associated with 2-3 times increased risk of crash
•BAC of 0.05 is associated with 6-17 times increased risk of crash resulting in death of the driver. (MADD)
Specimen Collection for Ethanol
- Specimen – serum, plasma and whole blood
- Serum/ plasma values 20% higher than in whole blood; so important to state actual specimen
- Keep capped to prevent evaporation
- Stable 14 days @ RT or 4 C with or without preservative
- Sodium fluoride used for longer storage or postmortem specimens
•DO NOT clean venipuncture site with alcohol swabs
- Use alcohol-free antiseptic (benzalkonium chloride)
Methanol
- Common solvent; also found in household cleaners
- Constituent in windshield wiper fluid, copy machine fluids, fuel additives, varnishes, etc.
•Ingestion causes:
- Severe metabolic acidosis - can lead to tissue injury and death
- Optic neuropathy that can lead to blindness
- Metabolized by ADH to formaldehyde in the liver
- Formaldehyde is oxidized by aldehyde dehydrogenase to formic acid
Methanol–Alcohol dehydrogenase (ADH)–> Formaldehyde—Aldehyde dehydrogenase–> Formic acid
isopropanol
- Rubbing alcohol
- Found in cleaners, disinfectants, cosmetics, ink, etc.
•Ingestion causes:
- Severe acute-phase ethanol-like symptoms
•Metabolized by ADH to acetone
- Acetone is a CNS depressant similar to ethanol ( eliminated slowly from body)
