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79 Cards in this Set

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What are the factors that influence toxicity?

1.) exposure variables of toxicant


2.) nature of toxicant


3.) Biological variables of indiv. ingesting intoxicant


4.) Toxicokinetics (major factor of toxicity)

tox of 6

<5 mg/kg

tox of 5
5-50 mg/kg
tox of 4
50-500 mg/kg
tox of 3
0.5-5 g/kg
tox of 2
5-15 g/kg

tox of 1

>15 g/kg

TDM VS Toxicology list them.

1.) assume it's presence 1.) screen for presence


2.)Quantitative 2.) qualitative


3.) Invasive (serum) 3.) noninvasive (urine)


4.)SLOW TAT 4.) Fast TAT


5.) Metabolites may interfere 5.) metabolites =


measured


6.)Expensive 6.) cheap


7.) Dynamic range 7.) min. analyst. sens. =


(therapeutic range) symptomatic (min diag)

is toxic to 50% of population
TD50

Salicylate (aspirin) describe it?


Treatment?

Higher TI


ASA, Active ingredient (Salicylic acid)


analgesic, antipyretic, anti-inflamm.


Interferes w/ platelet aggregation & GI func.


Overdose --> initially reap. alkalosis --> converts pyruvate to lactate, breakdown fatty acids= ketoacids --> metabolic acidosis


Mixed acid base disorder


-Treatment: neutralization/elimation of acid & maintain electrolyte balance

Levels of Aspirin:


1.) serum levels > 100 , 6 hours following ingestion =


2.) > 500 microgram/ml =


3.)Theraputic range?


4.) 40 -50 =

1.) toxic


2.) lethal


3.) 15-30


4.) symptoms

What are ways to measure salicylate (aspirin)?

1.) Trinder rxn - purple color w/ FeCl3 (spectophotometry)


2.) Enzymatic - NADH linked run measure at A 340 nm

Describe Tylenol (acetaminophen)?

-analgesic


-Overdose = severe heptatoxcity, metabolized/conjugated/ eliminated by liver.



What is another name for Tylenol or acetaminophen?

paracetamol

Hepatic damage is indicated when for Tylenol?


Therapetuic range?

-3-5 days after ingestion


-> 150 microgram/ml @ 4 hrs is toxic


Theraputic range: 10-20

Acetominophine overdose results in?

-Inability for the liver to adequately conjugate the metabolite of acetaminophen (acetamidoquinone) = reactive intermediate produced by glutathione.


-excess N-acetylbenzoquinoneimine =hepatic necrosis
-Antidote = N-acetylecysteine (NAC) helps breaks down metabolic product

What is CO, symptoms and treatment?

-colorless, tasteless, odorless gas


-has a 200-250 times more affinity for Hgb


-suffocation, tissue hypoxia, death


Treatment: remove source of CO, admin. O2 mask.

What happens during CO poisoning?


Treatment?

Hgb cannot adequately exchange CO2 for O2 cuz of increased ant of CO --> increases COHB and decreases oxyhemglbin.


-remove source of CO, admins. O2 mask.

List the % COHb & symptoms.

1.)0-5% = city, non-smokers


2.) 15% = smokers = headache, SOB


3.) 30% =severe headaches, SOB, fatigue, impairment of judgement


4.) 40-50% = confusion, loss consciousness


5.) 60-70% = unconciousness, resp. failure, death (cont. exposure)


6.) 70-80% = lethal, immed. fatal

Name three ways to measure CO?Which of the methods is the best to measure CO?

1.) Spot CO check - cherry red appearance ( 5 ml of 40% NaOH + 5ml of 1;20 blood)


-persistence of pink solution => 20% COhb


2.) Spectrophotometry - measure 4-7 wavelength (measure color of blood)


3.) differential spectroscopy (best method)


-Hemolysate of WB, reducing agent to reduce oxyhgb & methehgb --> only COhb & reduced Hb in solution.


-Absorptions spectrum 550 nm ( COhgb & reduced hgb), 541 nm ( only COhgb)


Describe Ethanol.

-Most common toxic exposure, and most common substance of abuse in the ER U.S.


-Associ. w/ trauma, loss of consicouness, other drug exposure


-Involves in medico-legal interventions

Treatment for other alcohols, you use what?

Ethanol

Alcohol dehydrogenase(enzyme) only metabolized to which alcohol?

Ethanol

-Ethanol metabolism occurs where?


-Reaction Equation for it?

-detoxication (liver)


-ethanol + NAD ---> (alcohol dehyrogenase) --->


Acetaldehyde (converts to acetate w/ALDH) +NADH

Legal limit for ethanol?


What level is toxic for ethanol?

-80-100 mg/dL


-0.1 g/dL (100 mg/dL

Ethanol blood levels:


1.) 50-100 mg/dL


2.) 100-200 mg/dL


3.) 200-400 mg/dL


1. reduced inhibitions, disorientation, confusion


2. progressive impairment of motor abilities


3. approaching unconcsiouness

Long term consumption of ethanol may lead to _______ and then ______.

alcoholic (toxic) hepatitis; cirrhosis

Describe methanol?

-methanol --> formaldehyde --> formic acid =


visual impairment, severe metabolic acidosis, pancreas necrossi


-more toxic than ETHANOL cuz metabolite (formaldehyde & formic acid)


-Visual impairment think METHANOL!!

Describe Isopropanol?

-(rubbing alcohol) --> acetone (metabolic product)(not usually toxic amts)

Describe Ethylene glycol or 1,2 ethanediol (antifreeze)?

-ethylene glycol --> formic acid, glycol acid & oxalic acid --> renal failure


-Will see urine has Ca oxalate crystals

name the types of methods for alcohol testing?

1.)ADH method (enzymatic alcohol dehyrogenase)
2.) estimation from Osmolalal gap


3.)GLC (gas liquid chromatography) reference/standard method.

Describe Ezymatic alcohol dehydrogenase (ADH) method?

-Sample serum


-clean venipuncture w/ alcohol free disinfectant


-sample capped avoid evaporation


-Ethanol + Nad (enzyme ADH) --> acetaldehye + NADH


-Measure NADH at 340 nm


-Methanol & isopropanol produces a Neg. or low result


Describe osmolal gap method?

-measure osmolal using freeze pt (osmometer)


-calc osmolal gap: measured - calculated


-Normal value: up to 10 mOsm/Kg


-Serum osmolaltiy increases by ______ for each _________ of ethanol increase.

10 mOsm/Kg; 60 mg/dl

For alcohols other than ethanol use what formula?

Calc osmo = 1.86 Na + gluc/18 +BUN/2.8 + ETOH/5

Osmolal gap will increase for only ________ .

non-ethanol alcohols or other compounds

toxic at 300 mg/dL
Ethanol
toxic at 200 mg/dL
Isoprpanol
toxic at 50 mg/dL
Methanol and EG

increase osmolality
normal pH
no acetone

Ethanol

increase osmolality
normal pH
acetone

Isopropanol

increase osmolality
decrease blood pH

Methanol

increased osmolal gap
metabolic acidosis
increased Anion Gap

Ethylene glycol

with carrier gas

mobile phase

what is pre-column>?

wad of glass wool to collect cooked particles of protein, lipid, glucose & salt.

-oven column and high temp is called?

liquid stationary phase

name of the detector.

FID

time from injection of dample to peak vol in FID

Rt (retention time)

Qualitative (identification) of alcohol is made by...

comparing to the calibrator Retention time

Quantitate peak is made by?

comparison btw calibrator peak and sample voltage peak in order to calculate the concentration of alcohol.

What is used to correct the problems of the GLC?

IS (internal standard) which is pure liquid, analyzed by same characteristics as analyte of interest, never found in pt's sample .

errors in GLC

change in flow rate (mobile), oven temp (liquid), null voltage of FID, precise volume of sample

Every ________, ________, ________ & _______ is mixed with same amount of What?

sample, standard, qc & patient

The ratio of IS in ________ run and IS in ______ are used in GLC.

calibrator; patient

alcohol effects from Ethanol

hypoglycemia if fasting
>ketoacidosis
hepatomegaly due to trig accuml from metab of ethanol instead of fa

diag of chronic alcohol abuse?


poor nutrition in chronic alcoholics =?

1.) increase plasma uric acid


2.) increase GGT


3.) increase triglyceride


-Plasma:


decrease folate, Mg, Ca, Phosphate, ATP

methanol gives what metabolic product?

formaldehyde>formic acid
severe metab acidosis, pancreatic necrosis and visual

isopropanol gives what metabolic product?

acetone

Ethylene glycol gives what metabolic product?

formic acid, glycolic acid, oxalic acid
renal failure

poor nutrition in alcoholics >

decr folate
decr Mg and Ca
decr phosphate


decrease ATP

1 unit of alcohol =

10 ml ETOH = 8g ETOH

Barbiturates

-sedative,


-depressantCNS
-Phenobarbital-epilepsy, slow acting


-Toxic: cardiac arrest/respiratory
-Treatment: aid respiration and cardiac output
-replaced by benzodiazepine (metabolite is oxazepam)

Narcotics?

-aka Opiates/opioids


-opium, morphine, codeine
-sleep and pain relief (analgesic)
-supress CNS,


Toxic: respiratory & coma


-Examples: heroin, morphine, codeine & methadone


Treatment: Naloxone, narcotic antagonist

Heroin is metabolized by the _____ to form _____ and excreted by the _____ as ________.

liver; morphine; kidney; morphine glucuronide

Morphine is a metabolite of?


-Methadone is a commercially modified form of what?

-opium/opiode


-heroin

Pesticides?

-organophosphates
-inhibits acetylcholinesterase>effects heart and lungs, cramps, CNS.

Pesticides can be measured by?

-measure pseudocholinesterase (isoenzyme of acetylcholinesterease)

what is the largest group of pesticides?

organophosphates

Amphetimines?

-CNS stimulants


-blocks dopamine receptors of brain
-treats narcolepsy and ADD
-metabolism in liver = benzoic acid
-Toxic: hypertension, cardiac arrythimias, death

Cocaine

-CNS stimulant (high dose) = euphoria & excitement


-Local anesthetic


-1/2 life = 0.5 - 1hr


-Toxicity: hypertension, arrythmia, seizure, AMI

Cocaine is metabolized by ______ to ______ which excreted by the kidney.

cholinesterase; benzoylecognine

The metabolite of cocaine is measured in the ______ and confirmed by?

urine; GCMS ( gas chromatography )

Cannabinoids?

-psychoactive compounds found in Marijuana ( HASHISH)


-THC (tetrahydrocannabinol) = potent & abundant


-produces physchological effects ( euphoria, sense of well being, short term memory = stored in fat cells (lipophilic) stays awhile in system


-1/2 life = 1 day

THC is excreted in urine over an______.

extended period of time

Major urinary metabolite of THC?

TCH-COOH

PCP (phencyclidine)

anesthetic illegally used as a hallucinogen


-effects; violence, seizures, reparatory, death


ID of PCP occurs by the detection of what?

parent drug in the urine

Which of the groups are CNS depressants?

Barbiturates, Narcotics, alcohols

Which of the groups are CNS stimulant?

amphetamines, cocaine, PCP (phencylcidine)