Toxicology Flashcards
1
Q
drug steady state
A
- amount of drug leaving body = amount of drug entering body
- reached after 5 halflives (i.e., after 5 doses given at intervals of 1 halflife)
- in steady state drug concentration is lowest right before a dose (trough) and highest shortly after (peak)
2
Q
Free versus bound drug
A
- free drug is therapeutically active component
- small molecules compete for binding spots and a 2nd drug may displace the first leading to inceased free drug concentrations
3
Q
Volume of distribution
A
- drug size and solubility influence how widely the drug is distributed
- Hydrophilic drugs remain confined within vascular space
- Others distribute into extravascular and intravascular spaces (aqueous)
- Hydrophobic drugs go into adipose
- Volume of distribution (Vd) defined as theoretical volume in which drug is distributed
- Hydrophilic drugs have low Vd, while hydrophobic drugs have high Vd
- Vd expressed in L/kg
- D is the administered IV dose and C is the plasma concentration:
- Vd = (D/C) / (body weight in kg)
4
Q
Drugs of abuse screening (forensic toxicology)
- places of testing
- specimen type
- assay type
- specificity
- additional testing
- adulterant characteristics
A
- refers to testing in workplace, in a drug treatment program, or in legal settings
- urine is usual specimen
- screening drug tests are usually based on immunoassay
- specificty is low
- crossreacting substances cause false positives
- positive tests often require confirmation (gas chromatography/mass spectrometry)
- witnessed collection required to ensure that urine sample has not been altered
- specimen divided into 2 aliquots so that retesting can be performed if positive result is obtained
- check for adulterants:
- color
- odor
- temperature (suspicious if cool)
- pH (suspicious if <4.5 or >8)
- specific gravity (suspicious if < 1.005)
- creatinine (suscpicious if < 20 mg/dl)
- nitrite (suspicious if > 500 ug/mL)
- chain of custody precautions needed for a test that may have implications in criminal case
- duration that agent may be detected depends on range of variables including
- dose
- methodology
- sample type
5
Q
Window of detection
A
6
Q
Ethanol
- metabolism
- specimen
- legal limits
- markers of alcohol consumption
A
- metabolized by hepatic alcohol dehydrogenase to acetaldehyde, which is converted by acetaldehyde dehydrogenase to acetic acid
- specimen
- overdose evaluation, usually serum or plasma is measured
- in forensic testing whole blood or breath alcohol measured (ratio of blood: breath alcohol is 2100:1)
- Legal limit for operation of a car: 80-100 mg/dL (0.08%-0.1%) in whole blood
- whole blood ethanol tends to run lower than serum or plasma ethanol concentration
- legal definitions usually in terms of whole blood
- Markers of alcohol consumption
- gamma glutamyl transferase (GGT) is increased in heavy consumers; 4 weeks of abstinence required for normalization of GGT
- carbohydrate deficient transferrin (CDT) is at least as sensitive and more specific than GGT
7
Q
Clinical effects of blood alcohol
A
8
Q
A
9
Q
These signs and symptoms are associated with what toxic agents?
A
10
Q
The National Academy of Clinical Biochemistry (NACB) guidelines advises ____
A
Tier 1 testing for all labs that support an ED
11
Q
Laboratory evaluation of apparently intoxicated patient
A
- Urine toxicology screening
- serum/plasma toxicology tests
- assessment of anion gap, osmolar gap, and oxygen gap
- abnormally high venous oxygen content (arterialization of venous blood) is seen in cyanide and hydrogen sulfide poisoning
12
Q
Significance of anion gap in tox screening
A
- anion gap > 20 mEq/L is significant (note: hypoalbuminemia may falsely lower the gap)
- toxins that cause anion gap metabolic acidoses include (SAFE CHEAPEN)
- acetaminophen
- salicylates
- ascorbate
- hydrogen sulfide
- ethylene glycol
- methanol
- ethanol
- formaldehyde
- carbon monoxide
- nitroprusside
- epinephrine
- paraldehyde
13
Q
signficance of osmolal gap in toxicology and calculation
A
- osmolal gap > 10 mOsm is significant
- osmolal gap is the difference between the calculated osmolarity by the following formula:
14
Q
significance of oxygen saturation gap in toxicology
A
- O2 sat gap is the difference between saturation given by cooximetry and the saturation given by the pulse oximeter
- normally the difference is < 5%
- causes of increased gap:
- CO poisoning
- methemoglobin
- hydrogen sulfide poisoning (sulfmethemoglobin)
- cyanide poisoning
15
Q
Toxic alcohol poisoning
- substances
- gaps they cause
- metabolism
- treatment
A
- Substances
- ethylene glycol (antifreeze)
- methanol (windshield washer fluid, paint removers, wood alcohol)
- isopropyl alcohol (rubbing alcohol)
- Ingestion suspected if osmolal gap > 10
- Gaps caused by these agents
- ethanol is often present in conjunction with toxic alcohol ingestion and can itself widen the osmolal gap
- ethylene glycol and methanol cause
- increased anion gap
- increased osmolal gap
- isopropyl alcohol does not cause acidosis, like ethanol, but does cause osmolal gap
- Metabolism of these agents
- ethylene glycol is metabolized to oxalate; oxalate crystals can be found in urine where they appear envelope shaped, translucent, and birefringent
- methanol is metabolized to formaldehyde and then to formic acid
- isopropyl alcohol is metabolized to acetone
- treatment of methanol or ethylene glycol poisoning c/o inhibiting activity of alcohol dehydrogenase since the metabolites are toxic
- used to give ethanol to do this
- now give fomepizole
16
Q
Calculated osmolality in presence of ethanol with toxic alcohol ingestion
A
17
Q
A
22
Q
Carbon monoxide poisoning
- sources
- lab testing
- treatment
- clinical effects
A
- Sources:
- incomplete combustion of fossil fuels
- produced endogenously from breakdown of heme resulting in normal Hb-CO <= 1%
- CO bind with great affinity to Hb forming Hb-CO; has even greater avidity for fetal Hb
- CO directly toxic to intracellular oxidative mechanisms
- Lab testing
- Nonspecific:
- lactate
- anion gap
- cardiac markers
- cyanide levels
- Specific:
- cooximetry with levels correlating with clinical effect
- pulse oximetry may give falsely reassuring O2 sat
- Nonspecific:
- Treatment: 100% O2
23
Q
Acetaminophen poisoning
- clinical manifestations
- Prognosis determined by
- toxic dose
- metabolism
- Treatment
A
- manifestations are polyphasic
- Phase I: mild nausea and abdominal discomfort; abates within hours
- Phase II: usually after 24 hours, progressive liver injury
- Phase III: fulminant hepatic failure
- Phase IV: resolution in the form of recovery, liver transplant, or death
-
Rumack-Matthew nomogram
- majority of poisonings do not result in significant hepatic necrosis
- Rumack-Matthew nomogram may be used to predict risk
- approximate time of ingestion must be known; initial blood sample is drawn >= 4 hours following ingestion
- stratifies patients into probable hepatic toxicity, possible hepatic toxicity, and no hepatic toxicity
- potentially toxic dose is > 150 mg/kg in healthy people
- Most acetaminophen is conjugated with glucuronide or sulfate to form nontoxic metabolites; some is metabolized by p450 system into toxic N-acetyl-P-benzoquinone imine (NAPQI) which induces centrilobular necrosis
- Treatment: N-acetylcysteine (Mucomyst)
