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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
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MLAB 2401: Clinical ChemistryKeri 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 • 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 • 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 • 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 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 • Salvia • “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_106&products_id=71 • http://www.canadianhempco.com/index.php?main_page=product_info&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