MLAB 2401: CLINICAL CHEMISTRY KERI BROPHY-MARTINEZ Agents 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 Found in homemade liquor and commercial products Rubbing alcohol Antifreeze and hydraulic fluid Causes metabolic acidosis and renal tubular damage Sweet taste attracts children Methanol Isopropanol Ethylene Glycol 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 Methods Enzymatic GC: reference method Osmometry 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 causes Toxic hepatitis Atherosclerosis Abnormal platelet aggregation Heart 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 Overdose symptoms 0.5-1 hour Primary metabolite is benzolecgonine 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 PCP Stimulant, depressant, anesthetic and hallucinogen Overdose symptoms Stupor, coma Detection Chronic users: 7-30 days post use DRUGS OF ABUSE Sedatives/ Hypnotics CNS depressants Types Barbituates phenobarbital, secobarbital Benzodiazepines Valium, Ativan Overdose symptoms Slurred 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 Salvia o o o “Magic mint” Salvinorin A is the active ingredient 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_10 6&products_id=71 http://www.canadianhempco.com/index.php?main_page=product_info&cP ath=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