22) Toxic substances Flashcards
father of modern toxicology
Paracelsus
positive screens require drug confirmation method with…
Definitive or reference method (GC-MS or LC-MS)
2 steps of toxic drug test
- screening test; qualitative
- confirmatory test; quantitative
a cutoff value is ———- than the detection limit, but —— enough to detect drug use within a reasonable time frame
higher
low
————– are not always specific for the drug tested.
Immunoassays
significant factors the CLS should be familiar in reference to drug abuse screening
Detection limit
Specificity (lack of)
Cutoff values
Interpreting positive versus negative results
3 types of invalid urine specimens
- adulteration
- dilution
- substitution
A specimen containing a substance that is not a normal constituent or containing an endogenous substance at a concentration that is not a normal physiological concentration
adulterated urine
Creatinine and specific gravity values that are lower than expected for human urine
dilute urine
Creatinine and specific gravity values that are so diminished or so divergent that they are not consistent with normal human urine
substituted urine
A specimen is considered to have been adulterated if it meets specific criteria established by the Substance Abuse and Mental Health Administration (SAMHSA):
- pH…
- nitrite…
- 5 substances present
- pH <3 or ≥11
- Nitrite concentration ≥ 500 ug/mL
- Chromium (VI)
- Halogens (bleach, iodine, fluoride)
- Glutaraldehyde
- Pyridine
- Surfactant
creatinine concentration is <2 mg/dL and the specific gravity is ≤1.0010
OR
≥1.0200 on both the initial and confirmatory tests on two separate aliquots
substituted urine
Creatinine concentration is 2-20 mg/dL
and
Specific gravity is 1.0010-1.0030 on a single aliquot.
dilute urine specimen
urine adulteration test strip reactions
- Creatinine
- nitrite
- glutaraldehyde
- pH
- specific gravity
- bleach
- pyridinium chlorochromate
- oxidants
Intect® 7
AdultaCheck®
Alere Toxicology PLC
urine adulteration test strips
3 major effects of acetaminophen
- anti-inflammatory
- analgesic
- antipyretic
Toxic doses, described as 2-3 times the maximum therapeutic dose, cause a serious and potentially fatal hepatotoxicity.
acetaminophen
mechanism of acetaminophen’s liver toxicity
saturation of enzymes catalyzing the normal conjugation reaction and results in the drug being metabolized by mixed function oxidases which produces a toxic metabolite that causes necrosis in the liver.
Blood samples should be obtained after 4 hours to ensure absorption is complete
acetaminophen
Not useful if the time of ingestion is unknown or unreliable
acetaminophen levels
Most commonly consumed drug in the world
aspirin
indications for aspirin use
- Cardiovascular disorders
- Colonic and rectal cancer
- Alzheimer’s disease
- Radiation-induced diarrhea
Repeated ingestion of fairly large doses
Syndrome associated with tinnitus (a high- pitched buzzing noise in the ears), vertigo, decreased hearing, and occasionally nausea and vomiting
salicylism
Follows an acute viral illness in children
Involves the liver and central nervous system (CNS)
Has a 20-40% mortality outcome.
Reye’s syndrome
(aspirin)
Causes several metabolic changes in the body (3 types of acid-base disorder)
salicylate poisoning
3 ways aspirin can cause acid-base disturbances
- resp alkalosis; hyperventilation
- resp acidosis; respiratory depression, decreased serum bicarb
- metabolic acidosis; accumulation of pyruvic acid, lactic acid, acetoacetic acid
Excessive elevation of body temperature >106.7°F
hyperpyrexia associated with aspirin poisoning
Can increase the effect of warfarin by displacing it from plasma proteins in addition to its effect on platelets
aspirin
Trinder reaction
aspirin
90% metabolized, 5-10% excreted unchanged in expired air and urine
ethanol
Metabolism of ethanol in the liver involves successive oxidations:
- First to acetaldehyde by the enzyme alcohol dehydrogenase
- Then to acetic acid by aldehyde dehydrogenase
- The intermediate metabolite acetaldehyde is a reactive and toxic compound that may contribute to the hepatotoxicity
can barely walk, vomiting, possibility of LOC
0.20 - 0.249%
alcohol poisoning
0.25 - 0.399%
onset of coma, death with alcohol
> 0.4%
The effect of CO on the oxygen dissociation curve is a shift to the ——-, which decreases the release of oxygen in the tissue
left
———- is formed via interaction of CO with nitric oxide (NO) release by platelets
Peroxynitrite
CO normal ranges and criticals
normal: 0-3%
smokers: 5-10%
critical: >60%
treatment of cases when COHb >20%
Hyperbaric oxygen therapy
Act by releasing monoamines from nerve terminals in the brain
amphetamines
effects of amphetamines
- Locomotor stimulation
- Euphoria and excitement
- Anorexia
———- are a class of drugs whose effects mimic those of stimulated sympathetic nervous system.
Sympathomimetics
(amphetamines)
Class of drugs that form the largest group of hypnotics and sedatives
barbiturates
Reversibly depress the activity of all excitable tissues
barbiturates
Anti anxiety properties of ——– are inferior to those exerted by the ————–.
barbiturates
benzodiazepines
Hypnotic doses increase the total sleep time and alter the stages of sleep in a dose-dependent fashion
barbiturates
Can form alcohols, ketones, phenols, or carboxylic acids, all of which may appear in the urine
barbiturates
Represent the most widely prescribed drugs due to their principal pharmacological effects
benzos
Act selectively on GABA receptors, which mediate fast inhibitory synaptic transmission throughout the CNS
benzos
High lipid solubility causes them to accumulate gradually in body fat
benzos