TOXICOLOGY PT 2 Flashcards by Sharmaine Madjid

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

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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

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_________: 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

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_______: The measurement must be made at least 6 hours after a dose to avoid inappropriate high levels.

Digoxin

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_______: 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

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________: A 12 hrs. sample gives the most precise guide to dosage adjustment

Lithium

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_______: Pre dose peak; 0.5 hrs. after i.v and 1hr. after i.m, administration.

Gentamicin

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Samples should be _______ and ________ as soon as possible.

collected and centrifuged

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Avoid ________ tubes because these may lower drugs concentrations due to the adsorption of drug into the matrix

serum-separator

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Storage of samples: _______ tubes are acceptable for most assays

Plastic cryovial type

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For CSA: Whole blood to be collected in an ____ tube.

EDTA

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________ may be affected by temperature and all variables should be standardized.

Analytical methods

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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

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Antiepileptic Drugs (AEDs) include

valproic acid,
phenytoin,
carbamazepine,
phenobarbital

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Newer AEDs (which includes __________) are not widely monitored

lamotrigine,
gabapentin,
topiramate,
levetiracetam,
oxcarbazepine

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There is a defined relationship between _______ and ______.

blood concentration and seizure control

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_____ individual differences between dose and blood level

Large

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______ metabolized, patients on multiple drugs

CYP450

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Both under-dosing and over-dosing can result in ______

seizures

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Most antibiotics (including…) have a wide therapeutic index and do not require monitoring

B-lactams,
macrolides,
quinolones

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________ (gentamicin, amikacin, streptomycin and tobramycin) are bactericidal, it binds to the bacterial ribosome

Aminoglycosides

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Aminoglycosides is used for treatment of __________, may cause ________

gram (-) bacterial infection ; hearing loss

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_______ 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

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Vancomycin is used for treatment of __________, administered IV

Only the trough levels are monitored to ensure drug is within therapeutic range

gram (+) bacterial infection

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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

TOXICOLOGY PT 2 Flashcards

(74 cards)