Chem2 Quiz 1

includes TDM, seperation techniques and blood gasses for testing and forensics

What is the best specimen for qualitative testing?

Urine

What type of testing is used for screening drugs/ drug mtabolites?

Immunoassays

What type of testing is the gold standard for confirmation testing?

GCMS ad LCMSMS

What is the difference between clinical toxicology and forensic pathology?

clinical - monitors pt status for treatment

forensic-analysis for medicolegal proceedings

pharmacokinetics

activity of drugs in the body over time (what the bod does to drugs)

pharmacodynamics

study of physiological response to drugs (what the drug does to the body)

pharmacogenomics

The genetic programming for handling drugs

CYP

Cytochrome P450 a generic term for mixed- function, oxidative enzymes (especially secretion)

Steady state

when quantity of drug absorbed at target tissue is equal to quantity being cleared

MEC

The lower level of a drug in the body that will still be effective

MTC

The lowest level at which a drug is toxic

Half life

time required for 50% of an administered drug o be lost throuch metabolism/elimination

What is the range between MEC and MTC? Goal?

the range is called therapeutic range

t he goal is steady state, which occurs at ~ 5.5 half lives.

Why do we test for the peak and trough?

they help determine the dose and frequency of administration to achieve steady state

how many half-lives does it take to reach steady state?

~5.5

How many half- lives does it take to clear the drug when stopped?

~5.5

When should we be doing therapeutic monnitoring?

When steady state is reached

Describe what ADME stands for?

absorption

distribution

metabolism

excretion

what are the differences between passive diffusion, active transport, facilitated diffusion?

Passive diffusion: high concentration to low concentration with no energy

Active: requires energy to transport against a gradient

Facilitated diffusion: Uses carrier molecule in the membrane, combines reversibly and needs no energy

distribution depends on what characteristics?

• molecular size

• degree of ionization

• lipid solubility

• extent of protein binding (albumin)

• body composition

Proteins distribution depend on what characteristics?

only free, uncharged drugs pass through membranes

Ph depends on what characteristics?

acids: bind albumin

Basics bind alpha 1 glycoproteins or lipids, metals/minerals bind globulins

what does phase one metabolisms do?

make the drug more polar by adding functional groups

What three reactions can happen in phase 1?

1. oxidation

2. reduction

3. hydrolysis

What is the most important enzyme involved with this phase?

cytochrome P450

what does phase II do?

Conjugation to link functional groups to make them more soluble

What 3 reactions can happen in phase II?

1. glucuronidation

2. acetylation

3. sulfation

The moieties attached are ______ soluble

water; because most are excreted in the urine

How are these drugs excreted?

urine and bile

What factors can change pharmacodynamics?

• Drug-Drug interactions

• Genetics

• Age

What is the definition of Vd (volume of distribution)?

the total amount of drug in systemic circulation divided by the plasma drug concentration

What is the equation for half-life?

t_1/2=0.7xVd/Cl

Vd=volume of distribution, Cl=clearance

application: Quantity remaining= (original quantity((1/2)ⁿ

• n=number of half lives

Gentamicin, Amikacin, Tobramycin

Aminoglycosides, antibiotics

• monitor toxic ranges to prevent damage to hearing and kidneys

Vancomycin

Glycoprotein, antibiotics

• monitor toxic ranges to prevent damage to hearing and kidneys

Digoxin

antiarrhythmics and cardioactive

• dec. K and Mg

Procainamide

antiarrhythmics and cardioactive

• Must monitor metabolite NAPA

Lidocaine

antiarrhythmics and cardioactive

• short half life

Phenytoin (Dilantin)

Anti-epileptic

Phenobrbitol

Anti-epileptic

Valproic acid

Anti-epileptic

Other common anticonvulsants→

carbamazepine

Tricyclics

Psychotropics

Amptriptyline

Psychotropics

• metabolized to notriptyline

Lithium

Psychotropics

• used to treat bipolar disorder

Theophyline

Bronchodilators

• Caffeine is an active metabolite

• tested through immunoassay

• LC

Caffeine

Bronchodilators

• Caffeine is an active metabolite

• tested through immunoassay

• LC

Cyclosporine and tacrolimus (FK509)

immunosuppressant - Calcineurin inhibitors

• used to prevent rejection

• whole blood specimens

Sirolimus (Rapamycin) and Everolimus

immunosuppressant - mTOR inhibitors

• used to prevent rejection

• whole blood specimens

What is the major difference between Forensic samples and therapeutic drug testing?

• method collection

• looking for toxic compound and drugs

• these analyses and interpretations are conducted in a manner to be defensible in court

What must all forensic samples have to be tested?

• controlled collections

• temperature monitored

• tamper proof seal

• chain of custody

What kind of forensic testing is used for screening?

immunoassay

What kind of testing is used for confirmation?

GCMS and LCMSMS

What three thing validate a urine drug screen?

1. creatinine

2. pH

3. Oxidizing agent

What specimen and testing do we use for drugs of abuse testing?

urine screening by immunoassays

What specimen do we use for ethanol, salicylate and acetaminophen testing?

Salicylates and acetaminophen: Plasma and serum

Ethanol: blood, plasma or serum

what are the 4 main substances that can cause acute poisoning and that we routinely test for?

• acetaminophen

• salicylate

• alcohols

• carbon monoxide

What are the 4 main categories of DOA and what drugs are in those categories?

• sedatives/depressants

• analgesics

• stimulants

• hallucinogens

What is the detection time for opioids?

2 days

What are some examples of opiates?

• morphine

• Codeine

• 6-monoaetyl morphine

• Hydromophone

• Hydrocodone

• oxymrphone

• oxycodone

What are the 2 main sedatives we test for and what are they taken for?

• Barbituates

• Benzodiazepines

What is the other name for Tylenol and aspirin?

tylenol- acetominophen

Aspirin- salicylate

What kind of acid base problems do Tylenol and aspirin cause?

Tylenol- metabolic acidosis

aspirin- respiratory alkalosis→ metabolic acidosis

How do NSAIDS work vs opioids?

block the effects of prostaglandins

what are the effects of cocaine on the body?

• binds dopamine re-uptake transported inhibits re-uptake

• vasoconstriction, hypertension, heart attack, stroke, seizure

What is the metabolite of cocaine?

benzoylegonine

How long can we detect this drug?

2-4days

What effect has meth users feeling like they have super powers?

dopamine reuptake inhibition

What is the active ingredient that is tested for on cannabinoids?

THC derivatives

What are the 2 drugs that cause hallucinations?

PCP and LSD

What is the Ph of adulterated urine?

<3 or >11

key summary slide for DOA and what is detected for specific drugs

Chromatography

physical process whereby the components of a sample mixture are separated as a result of their differential distribution between stationary and mobile phase

mobile phase

a gas or liquid that flows ina chromatographic system and carries the sample past the stationary phase

stationary phase

a solid liquid or gass that interacts with the components of the mobile phase

Eluent

fluid entering the column

Eluate

fluid exiting the column

analyte

mixture whose individual components have to be seperated and analyzed

mass spectrometry

study of matter through the formation of gas-phase ions that are characterized using mass spectrophotometers by their mass, charge, structure, and/or physicochemical properties

adsorption

solutes of a sample are seperated according to their attraction to the stationary phase vs the mobile phase

partition

solutes of a sample are seperated by differences in their distribution

What is the principle of chromatography?

separates mixture into individual components on basis of specific differences in physical characteristics

What is the difference between normal phase and reverse phase?

Normal phase: Stationary phase is polar and mobile phase is non-polar, carries no polar analytes

Reverse: is the opposite, carrier polar analytes

Ion exchange

must identify the charge of the target substance

initial charge inducement-final charge neutrality

thin layer

used to identify drugs, lipids, carbohydrates, and amino acids

Rf value equation

distance compnent traveled/ distance solvent travelled

Rf value and what it means for solute and solvent distance

seperation is based on differences in solubility between two liquid phases

high performance liquid chromatography

aqueous or organic solutions are pumped through columns under high pressure, which allows high resolution with fast and accurate quantitation

what is the difference between the isocratic and gradient in HPLC?

Isocratic: mobile phase is consistent in composition

Gradient: the composition of the mobile phase is altered as the run occurs

HPLC: high pressure error is caused by

Blockage

HPLC:noisy baseline is caused by

Bubbles

HPLC:drifting baseline is caused by

contamination

HPLC:loss of column resolution is caused by

overloading column with sample or degradation of column packing

gas liquid chromatography is the best method to measure…

blood alcohol

gas-liquid chromatography is used as confirmatory testing for what?

GCMS for regulated drugs of abuse

what are the 4 steps in how Mass spec works?

1. ionization of compound

2. sorted by m/z through deflection

3. signal detected/counted

4. results are displayed

How are ions sorted in mass spec?

by size and charge

What applications can we use for mass spec for?

• TDM

• Drugs of abuse

• heavy metals

• metabolic disorders

O2 in the blood is necessary for _______ metabolism

aerobic

What are the three properties of arterial blood?

1. arterial pO2 high enough to create a diffusion gradient

2. O2 binding capacity is normal

3. Hemoglobin can bind O2 in the lungs/ release it in tissues

Methemoglobin

cannot bind to O2

Hgb containing iron oxidized to Fe³⁺