TOXICOLOGY Flashcards

(96 cards)

1
Q

• Branch of science which deals with the study of the effect of drugs on biologic systems

A

PHARMACOLOGY

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2
Q

biologic systems

A

o Routes of drug administration
o Pharmacokinetics
o Drug actions
o Drug interactions

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3
Q

I. ROUTES OF DRUG ADMINISTRATION

A
  1. Oral
  2. Sublingual
  3. Rectal
  4. Intravenous
  5. Intramuscular
  6. Subcutaneous
  7. Inhalation
  8. Topical
  9. Transdermal
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4
Q

– below the tongue; in cases of cardiovascular diseases

A
  1. Sublingual
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5
Q

– suppository: drug delivery system inserted in the rectum

A
  1. Rectal
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6
Q

– IV fluid, anti-fungal, antibiotic

A
  1. Intravenous
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7
Q

– insulin shots

A
  1. Subcutaneous
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8
Q

– asthmatics

A
  1. Inhalation
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9
Q
  • Vicks
A
  1. Topical
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10
Q

• Fate of an administered drug

A

PHARMACOKINETICS

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11
Q

– movement of drugs into the bloodstream after administration

A
  1. Drug absorption
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12
Q
  • movement of drugs to and from the blood and other tissues or organs of the body
A
  1. Drug distribution
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13
Q
  • biotransformation mainly occurring in the liver
A
  1. Drug metabolism
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14
Q

– metabolites of drugs move out of the body through urine; happens in the kidneys

A
  1. Drug excretion
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15
Q

– rate of excretion of drugs and its metabolites

A
  1. Drug clearance
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16
Q

Drug response depends on both the affinity of a drug for its receptors and the drug’s efficacy

A

RECEPTOR THEORY

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17
Q
  • strength of binding between a drug and its receptor
A

• Affinity

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18
Q
  • the degree to which a drug is able to induce maximal effects
A

• Efficacy

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19
Q

– addition of multiple drugs produces different effect for each

A
  1. Addition
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20
Q

– combination of multiple drugs produces singular effect for all

A
  1. Synergism
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21
Q

– addition of one drug will increase the effect of another

A
  1. Potentiation
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22
Q
  • addition of one drug will reduce/block the effect of another
A
  1. Antagonism
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23
Q

• Study of exogenous clinical compounds that profoundly influence bodily functions, either in a deleterious way or for therapeutic benefits

A

TOXICOLOGY

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24
Q

CLINICAL TOXICOLOGY LABORATORY 3 Functions :

A
  1. Therapeutic drug monitoring (TDM)
  2. Identification of drugs in acute intoxication
  3. Urine testing for drugs of abuse
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25
- enables physicians to adjust and optimize the dosage on an individual basis
1. Therapeutic drug monitoring (TDM)
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- identify the offending drug/s
2. Identification of drugs in acute intoxication
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- establish diagnosis, assess level of intoxication, suggest course of therapy
2. Identification of drugs in acute intoxication
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- pre-employment and medico-legal cases
3. Urine testing for drugs of abuse
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Vol for urine drug testing: --
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Patient:
Donor
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Freshly voided urine sample temp: --
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Analytes tested: --
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: Evidences
Chain of Custody
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Most common drugs of abuse measured in the Ph/Two-parameters:
Marijuana, Methamphetamine
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4 areas :
1. drugs of abuse 2. therapeutic drugs 3. environmental carcinogens 4. toxins
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• Toxicity of chemicals is determined in the [?]
laboratory
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• The normal procedure is to expose test animals 1. By [?], or some other method which introduces the material into the body 2. By placing the test material in the [?] of the test animals' environment
ingestion, application to the skin, by inhalation, gavage water or air
38
Toxicity is measured as clinical "endpoints" which include:
o Mortality (death) o Teratogenicity (ability to cause birth defects) o Carcinogenicity (ability to cause cancer), and, o Mutagenicity (ability to cause changes in the DNA)
39
(death)
o Mortality
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(ability to cause birth defects)
o Teratogenicity
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(ability to cause cancer), and,
o Carcinogenicity
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(ability to cause changes in the DNA)
o Mutagenicity
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• The amount (dose) of a chemical which produces death in 50% of a population of test animals to which it is administered by any of a variety of methods mg/kg
LD50
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• Normally expressed as mgs of substance per kg BW of animal
LD50
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• The concentration of a chemical which produces death in 50% of en. exposed population of test animals in a specified time frame mg/L
LC50
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• Normally expressed as mgs of substance per liter of air or water (or as ppm)
LC50
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OPTIMAL TIME FOR BLOOD SPECIMENS
Steady state concentration Trough or pre-dose period Peak or post-dose level
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• Received regular maintenance doses of the drug for about five half-lives of the drug
Steady state concentration
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• Just before the next dose
Trough or pre-dose period
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• For most orally taken drugs
Trough or pre-dose period
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• Shortly after receiving the drug
Peak or post-dose level
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Peak or post-dose level IV -
30 minutes after infusion
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Peak or post-dose level IM -
60 minutes after injection
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• For patients who exhibit toxic symptoms
Peak or post-dose level
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TECHNIQUES FOR DRUG ANALYSIS
Immunologic Chromatographic Spectrophotometry
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Ab-antigen
Immunologic
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Separation technique
Chromatographic
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Absorbance
Spectrophotometry
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Immunologic:
• Enzyme immunoassay systems • Fluorescence immunoassay • Radioimmunoassay
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Chromatographic:
• HPLC • GLC • TLC
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Spectrophotometry:
• Visible spectrum, ultraviolet spectrum and fluorescence
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• Serum + antibody + enzyme-labelled drug + substrate
ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
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• Measured enzyme activity : drug concentration (directly proportional)
ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
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• More rapid than RIA ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
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• 1st homogenous Enzyme Immunoassay
ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
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: most useful; less likely to be affected by serum constituents
• MDH & G-6-PD
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• Measures drugs (mg/L) & drug metabolites in biological fluids
ENZYME MULTIPLIED IMMUNOASSAY TECHNIQUE (EMIT)
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• Some drugs detected:
Cocaine & metabolites, cannabinoides, opiates & barbiturates
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• Drug to be measured is the hapten
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
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• Specific antibodies bound to a solid state carrier
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
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• Separation of the bound drug from the unbound
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
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• Digoxin and digitoxin tests
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
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• Principle: Sandwich Immunoassay
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA)
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• Drug bound to a fluorogenic substrate :
umbelliferyl-ßgalactoside
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(Enzyme:)
B-galactosidase
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• Fluorogenic reagent + antibody + beta-galactosidase --- incubated w/ serum sample
FLUORESCENCE IMMUNOASSAY
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• Drug and DFS compete for binding
FLUORESCENCE IMMUNOASSAY
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SUBSTRATE-LABELED FLUORESCENT IMMUNOASSAY (+)
Flourescence
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• Fluorescent product
UMBELLIFERONE
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formed when the substrate is cleaved by Bgalactosidase
UMBELLIFERONE
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Enzyme cannot cleave the DFS when it is reacted with the specific antibody
UMBELLIFERONE
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• Separation of free from antibody bound drug
RADIOIMMUNOASSAY
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• Counting the radioactivity in either free or antibody bound fraction
RADIOIMMUNOASSAY
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• Calculating amount of drug in serum from a standard curve of % antibody bound vs drug concentration
RADIOIMMUNOASSAY
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• Incubation of serum + antibody + radiolabeled drug (competition for antibody binding sites)
RADIOIMMUNOASSAY
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• Adsorption of drug to a solid support and elution by means of a mobile, liquid phase
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- screening for drug identification
• Thin Layer Chromatography
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- primarily for quantitating serum drug levels in TDM and also for confirming drug identification
• High-Performance Liquid Chromatography and Gas-Liquid Chromatography
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: gold standard for drug testing
• Gas Chromatography-Mass Spectrometry
90
: NRL for drug testing
• East Avenue Medical Center (Q. C.)
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: tentative identification of tentative
Spectral scan
92
Quantitative analysis:
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1. Visible spectrum –
salicylate
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2. Ultraviolet spectrum
barbiturates
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Fluorescence –
quinidine
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Visible spectrum Wavelength: Ultraviolet spectrum Wavelength:
340 to 700 nm < 340 nm