MLAB 2401: CLINICAL CHEMISTRYKERI BROPHY-MARTINEZAgents of Toxicology

ALCOHOL

Symptoms Disorientation,

slurred speech, confusion, euphoria, paralysis

CNS depressant Metabolizes to

acetic acid

After a few drinks…

ALCOHOL CLASSES Ethanol

Liver most effected Chronic exposure leads to toxic hepatitis and

cirrhosis GGT, AST, HDL, MCV all increased with abuse

Methanol Found in homemade liquor and commercial

products Isopropanol

Rubbing alcohol Ethylene Glycol

Antifreeze and hydraulic fluid Causes metabolic acidosis and renal tubular

damage Sweet taste attracts children

DETERMINATION OF ALCOHOLS

Specimen Serum, plasma,

whole blood Avoid use of alcohol

in preparation of site Keep sample capped Legal alcohol, chain

of custody

MEASUREMENT OF ALCOHOL

MethodsEnzymaticGC: reference methodOsmometry

CARBON MONOXIDE

Produced by an incomplete combustion of carbon containing substances

Colorless, odorless, tasteless gas

Sources Gasoline engines Wood/plastic fires Improperly ventilated furnaces

CARBON MONOXIDE

Actions Binds tightly to hemoglobin and does not allow

O2 to attach to hgb, forming carboxyhemoglobin

Decreases O2 delivery to the tissues= HYPOXIA

Specimen Type Whole blood

Methods GC: reference method Differential spectrophotometry

CYANIDE

Component of insecticides and rodenticides Common suicide agent

Action Binds heme iron and prevents the cells from

using oxygen

Measured by ISE

METALS

Arsenic Found in the environment Binds to proteins to change their structure and function Affects cellular and organ systems

Mercury Contaminated foods major source of outbreaks Protein binding to change the structure or function,

especially enzymes Measured by AAS

Cadmium Found in mining and industrial processes Binds to proteins to change their structure and function

Lead Review previous lecture notes from Chemistry and

Hematology

THERAPEUTIC DRUGS Salicylates (NSAID)

Aspirin Decreases thromboxane and prostaglandin formation

through inhibition of cyclooxygenase which interferes with platelet aggregation

Interferes with GI function

Overdoses associated with: Acidosis Formation of ketones due to fatty acid metabolism Hyperventilation due to stimulation of respiratory

system

Methods GC Immunoassay

THERAPEUTIC DRUGS

Acetaminophen (NSAID) Overdose causes

Hepatotoxicity Tylenol is the brand name

Methods HPLC Immunoassay

DRUGS OF ABUSE: URINE Qualitative screening

Uses urine Problems

Only detects recent drug use

Detects drug metabolites Detects drug classes A positive result can not

discriminate between a single and chronic use

Overdose can occur with prescription, OTC or illicit drugs

DRUGS OF ABUSE: URINE

Important to detect specimen adulteration How can we tell an altered specimen?

Urinary pH Specific gravity Creatinine

Chain of custody

Important to monitor specimen collection

DRUGS OF ABUSE

Methods Two-Tiered

Screening Simple and rapid spot test

Immunoassay (Ab-Ag Rxn.) Good sensitivity, marginal specificity Detects the class of drugs

Confirmation High sensitivity and specificity GC reference method Immunoassay methods also used

DRUGS OF ABUSE Amphetamines

Stimulant used to treat narcolepsy and attention deficit disorder

Related compounds Ephedrine Pseudoephedrine “Ecstasy”/ MDMA

Overdose symptoms Hypertension Convulsions Cardiac arrthymia

DRUGS OF ABUSE Anabolic steroids

Effect muscle mass; improves athletic performance

Chronic use causesToxic hepatitisAtherosclerosisAbnormal platelet aggregationHeart enlargement

DRUGS OF ABUSE

Cannabinoids THC

Tetrahydrocannabinol most potent

Psychoactive compounds

Often used in cancer treatment regimens

Half-life 1 day after single use 3-5 days after

chronic use

DRUGS OF ABUSE Cocaine

CNS stimulator and local anesthetic

Dose and route of administration important factor in serum concentration

Half life 0.5-1 hour Primary metabolite is benzolecgonine

Overdose symptoms Hypertension, arrhythmia, seizure, MI

Detection Urine: up to 3 days post single use Urine: 20 days post for chronic users

DRUGS OF ABUSE

Opiates Derived from opium

poppy Includes opium, heroin,

morphine, codeine, Dilaudid, Percodan, Demerol, methodone, Darvon

Overdose symptoms Respiratory acidosis Myoglobinura Cardiac damage

DRUGS OF ABUSE

Phencyclidine or PCPStimulant, depressant, anesthetic and

hallucinogen

Overdose symptomsStupor, coma

DetectionChronic users: 7-30 days post use

DRUGS OF ABUSE

Sedatives/ HypnoticsCNS depressants

TypesBarbituates

phenobarbital, secobarbitalBenzodiazepines

Valium, Ativan

Overdose symptomsSlurred speech, lethargy, coma

“DESIGNER” DRUGS

Bath Salts- “Vanilla Sky” Produce

stimulant/hallucinogenic effects Euphoria Increased sex drive

Can be swallow, inhaled, or injected

Can result in life-threatening effects

Mimics cathinone Found in khat plant

“DESIGNER” DRUGS

Krokodil Synthetic form of desomorphine Similar to heroin highs Named for the effect it has on skin

o Salviao “Magic mint”o Salvinorin A is the active ingrediento Produces hallucinogenic effects

DESIGNER” DRUGS

Synthetic Cannabinoids “Spice” or K2 Produce euphoria Difficult to detect

REFERENCES Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry:

Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins.

Eden, M. P. R. (2014, March). An overview: drugs-of-abuse testing in the clinical laboratory today. MLO, 46(3), 22-24.

Crews, B. O. (2013, February). Synthetic cannabinoids. Clinical Laboratory News, 39(2), 8-10.

http://www.alcoholrehabsandiego.com/drug-tests/ http://www.becksgf.com/index.php?main_page=product_info&cPath

=9_106&products_id=71 http://www.canadianhempco.com/index.php?main_page=product_i

nfo&cPath=4_69&products_id=618 http://daly-tribe.com/Humor/Alcohol_effects.htm http://www.healtylifeblog.com/2009/11/anabolic-steroids-in-sports/

REFERENCES http://www.prostatespecificantigen.net/products.htm http://signsofcocaineuse.com/ http://vyssute.com/downloads/demotivational/ McDaniel, G. (2014, January). Drus of Abuse Testing: Old &

New. Advance for Administrators of the Laboratory , 23(1), 24-27.

Moran, J., & Seely, K. (2014, March). Bath Salts. Clinical Laboratory News, 40(3), 8-10.

Neuroscience for Kids- Bath Salts. (1996-2012). Retrieved from https://faculty.washington.edu/chudler/salts.html

Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson.

Wikipedia. (2014). Retrieved from http://en.wikipedia.org/wiki/Synthetic_cannabis