TOXICOLOGY PT 2 Flashcards
Blood specimens for drug monitoring can be taken at two different times: during the drugs highest therapeutic concentration (________), or its lowest (_______). Occasionally called _______, trough levels show sufficient therapeutic levels; whereas peak levels show toxicity.
“peak‟ level ; „trough‟ level ; residual levels
Sample Timing for some important drugs..
Since ______ has a long half-life a single daily dose may be employed and so the timing of concentration monitoring is not critical.
phenytoin
_________: Its half life may be as long as 48 hrs. following a single dose. A trough concentration taken just after a dose together with a peak level 3 hours later is ideal.
Carbamazepine
_______: The measurement must be made at least 6 hours after a dose to avoid inappropriate high levels.
Digoxin
_______: This drug has a narrow therapeutic index and timing of sampling is not critical if the patient is receiving one of the slow release formulations, wherein through levels should be taken.
Theophylline
________: A 12 hrs. sample gives the most precise guide to dosage adjustment
Lithium
_______: Pre dose peak; 0.5 hrs. after i.v and 1hr. after i.m, administration.
Gentamicin
Samples should be _______ and ________ as soon as possible.
collected and centrifuged
Avoid ________ tubes because these may lower drugs concentrations due to the adsorption of drug into the matrix
serum-separator
Storage of samples: _______ tubes are acceptable for most assays
Plastic cryovial type
For CSA: Whole blood to be collected in an ____ tube.
EDTA
________ may be affected by temperature and all variables should be standardized.
Analytical methods
Drug criteria to be suitable for therapeutic drug monitoring:
Narrow target range
Significant pharmacokinetic variability
A reasonable relationship between plasma concentrations and clinical effects
Established target concentration range
Availability of cost-effective drug assay
Antiepileptic Drugs (AEDs) include
valproic acid,
phenytoin,
carbamazepine,
phenobarbital
Newer AEDs (which includes __________) are not widely monitored
lamotrigine,
gabapentin,
topiramate,
levetiracetam,
oxcarbazepine
There is a defined relationship between _______ and ______.
blood concentration and seizure control
_____ individual differences between dose and blood level
Large
______ metabolized, patients on multiple drugs
CYP450
Both under-dosing and over-dosing can result in ______
seizures
Most antibiotics (including…) have a wide therapeutic index and do not require monitoring
B-lactams,
macrolides,
quinolones
________ (gentamicin, amikacin, streptomycin and tobramycin) are bactericidal, it binds to the bacterial ribosome
Aminoglycosides
Aminoglycosides is used for treatment of __________, may cause ________
gram (-) bacterial infection ; hearing loss
_______ has an inhibitory effect on the synthesis of the bacterial cell wall and cytoplasmic membrane. It has a narrow therapeutic index and toxicity may be severe or irreversible (nephrotoxic)
Vancomycin
Vancomycin is used for treatment of __________, administered IV
- Only the trough levels are monitored to ensure drug is within therapeutic range
gram (+) bacterial infection
Acts on gram (-) bacteria by inhibition of protein synthesis, unlike aminoglycosides it can be absorbed in the GIT
Chloramphenicol
Chloramphenicol toxic effect is
blood dyscrasia
Techniques for measurement of TDM Chromatography
HPLC
GC/MS
The separation of a substance depends on the relative distribution of mixture constituents between two phases, a mobile phase (carrying the mixture) and a stationary phase.
HPLC: High Pressure Liquid Chromatography
- a separation method using very high temperatures to cause sample vaporization. In __________ the vaporized fractions are passed through an electrical field.
- The molecules can be separated on the basis of molecular weight. The pattern of separation is unique to each drug and therefore establishes a “________” for identification.
- the gold standard method for the identification of drugs of abuse.
GC/MS ; Mass Spectrophotometry ; fingerprint
uses a non-radioactive enzyme label. The assays are performed in a single step, i.e. only one antibody is used in the procedure
Enzyme Immunoassay
uses radioactivity to detect the presence of the analyte. the sample is incubated with an antibody and a radio-labeled drug. the amount of radioactivity measures is compared to the radioactivity present in known standards which are included in each run. Results are quantitative.
RIA
uses the creation of light scattering particles to measure drug levels.
PETINIA - Particle Enhanced Turbidimetric Inhibition Immunoassay
based on competition for the target analyte antibody binding sites. Provides rapid analyses of blood and urine samples, uses an antibody specifically reactive with a particular drug.
EMIT - Enzyme Multiplied Immunoassay Technique
Method uses a fluorescent molecule as the label instead of an enzyme, making it more sensitive.
FPIA - Fluorescence Polarization Immunoassay
a chemical reaction that emits energy in the form of light. When used in combination with immunoassay technology, the light produced by the reaction indicates the amount of analyte in a sample.
Chemiluminescence
COLORIMETRY..
acetaminophen in urine is detected by boiling to form ______ which reacts with o-cresol to form _______
p-amphenol ; indophenol blue
COLORIMETRY…
Tinder assay for salicylate using ferric nitrate forming a _____
(+) colored complex
study of substances toxic to the body
toxicology
absorption of toxins from the GIT is by ______
passive diffusion
common substances causing toxicity
Alcohol
Carbon Monoxide
Cyanide
Alcohol includes
ethyl, methanol
most common abused rug, it is converted to acetic acid - resulting in acidosis, it causes diuresis by inhibiting ADH
Alcohol
specimen in Alcohol
serum, plasma, whole blood (use of alcohol-free cleanser)
In alcohol the ff are elevated
GGT,
AST,
HDL,
MCV
Alcohol fetal dose
300 to 400 ml of pure alcohol consumed in less than an hour.
Colorless, odorless, tasteless gas produced by incomplete combustion of carbon-containing substances like gasoline.
Carbon monoxide
Carbon monoxide method
co-oximetry (carboxyhemoglobin)
a component of insecticides and rodenticides - common suicide agent, it expresses its toxicity by binding to iron resulting to hypoxia
Cyanide
Metals
Arsenic
Cadmium
Lead
Mercury
component of ant poison, rodenticides, .s and metal alloys. Common homicide or suicide agent. It expresses it toxicity by binding to the thiol groups in proteins
arsenic
a significant environmental pollutant - pigment in paints and plastics poisoning can result from ingestion of acidic foods stored or prepared in metal containers containing _____
cadmium
an enzyme inhibitor, it is a component of household paints. Exposure can result to encephalopathy, birth defects and compromised immunity. Low level exposure may cause behavioral changes such as hyperactivity and attention deficit disorder, low IQ.
Lead
LEAD..
Blocks ______ resulting to anemia
delta aminolevulinic acid synthetase
toxic blood level in lead
> 70 ug/dL
also an enzyme inhibitor which may result to loss of glomerular function. If inhaled or absorbed through the skin it can accumulate in the CNS.
Mercury
DRUGS OF ABUSE/SUBSTANCES OF ABUSE
Amphetamines
Annabolic Steroids
Cannabinoids
Cocaine
Opiates
Sedative Hypnotics
Lysergic Acid Diethylamide - hallucinogen
Acetaminophen
Salicylate
therapeutically used for treating narcolepsy and attention deficit disorder. Increases mental alertness and physical capacity and has anorectic property.
Amphetamines
amphetam-like compounds
Ephedrine, Pseudoephedrine, Phenypropanolamine
recreational abused drug
Methylenedioxymethamphetamine (ecstasy)
chemically associated with testosterone. it improves athletic performance by increasing muscle mass.
Annabolic steroids
most potent psychoactive substance of cannabis satibus. It induces a sense of well being and euphoria.
Cannabinoids (Tetrahydrocannabinol)
derived from coca plant erythroxylon and used as additive to some foods, and as local anesthesia. It is a potent CNC stimulant that elicits a sense of excitement and euphoria. It causes sudden death due to direct toxicity on myocardium.
Cocaine
used as analgesic, sedative and anesthesia, derived from opium poppy
opiates
common tested opiates
morphine and codeine
a derivative of heroin (highly addictive) a strong analgesic
morphine
an antitussive opiate
codeine
CNS depressants, toxicity is initiated by ethanol
Sedative Hypnotics
secobarbital, pentobarbital, phenobarbital
Barbiturates
diazepam (valium), lorazepam (ativan), chlordiazepoxide (librium)
Benzodiazepines
hallucinogen
Lysergic Acid Diethylamide
overdose of this drug can cause hepatocellular injury
Acetaminophen ; analgesic, anti-pyretic
anti-inflammatory, analgesic, anti-pyretic
salicylate
Salicylate..
_______ is metabolized to salicylic acid
aspirin (acetylsalicylic acid)
inhibit enzymes in the krebs cycle causing pyruvate to be converted to lactic acid, lipid metabolism is increased and amino acid is decreased. Accumulation of organic acids causes metabolic acidosis
Salicylate
