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Lecture 5

Lecture 5-Toxicology.docx

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Biochemistry 3386B
L.Graham Smith

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Lecture 5: Toxicology Purpose: to detect, identify and possibly measure, in various biological fluids, drugs and poisons which may or may not be suspected to be present Patients: 1. Emergency: altered state of consciousness (drug/medical) 2. Babies and new mothers: mother is an addict, baby may be affected (opiates vs. methadone treatment) 3. Psychiatric: drug use is important to note (are they compliant with their program) 4. Pain Clinic: patients addicted to opiates (post-surgical) – chronic pain (oxycodone, hydromorphone) 5. Sexual Assault Center: women exhibiting symptoms of sexual assault – no memory, drugged or alcohol amnesia 6. Inpatients (ICU): patients in a coma (medical or drug induced)  Induced comas barbituates: in brain dead organ donor, in children with epileptic seizures Analytical Approach 1. Tests for specific drugs or poisons (eg. Drugs of abuse) when clinical information points directly to them 2. General analyses of all drugs or poisons when information is limited Interpretation of Drug Analysis Serum/Plasma  Specimen of choice for drug levels  Can measure levels of intoxication  Contains parent drug and some metabolites (liver is consistently working to metabolize)  Analysis rather involved because there are large amounts of lipids and proteins (making it hard for chromatography)  Drugs can be present in low concentrations  There can be a very narrow detection time Urine  Indicates what drugs have been taken, not when (can’t back calculate)  Cannot measure the level of intoxication (not quantitative) o Accumulated over a varying amount of time o Can give a “ballpark estimate”  Mostly drug metabolites o Only some parent drug excreted o The liver modifies and conjugates the metabolites to an H 2 soluble group – the drug is then filtered out in the kidney  Common conjugated molecule is glucuronic acid – makes it more water soluble o Metabolites are still characteristic of the drug from which they came  Simple analysis because of small amounts of lipid and protein is less (unable to bypass the glomerulus) o Some trace proteins can be from the epithelial cells of the bladder/ureters  Generally there are higher concentrations in the urine than in the serum because they have had more time to concentrate Gastric Fluid  Relatively infrequently tested  Invasive (risky)  No advantage over serum or urine Hair/Meconium  Meconium: first bowel movement of life, benign sample o Advantage: window of detection 0-20 weeks before birth vs. urine which is only days  Hair: blood circulates through hair follicles o Disadvantage: not as long a window of detection, some babies have hair and some don’t (sampling problem)  Tests are requested in neonates concerning long term exposure to drugs of abuse before birth  Not clinically useful  turn around time is too long (weeks)  baby is home  Requested by CAS (only- intervention) Types of Drugs/Poisons 1. Alcohols  (ethanol, methanol, isopropanol (rubbing alcohol), acetone and ethylene glycol (anti- freeze) 2. Drugs of Abuse  Canniboids, opiates (codeine, morphine, hydrocodone, oxycodone), cocaine, amphetamines (metamphetamines), PCP, ecstasy 3. Over the Counter Drugs  Salicylate, Acetaminophen, pseudophedrine (pseudophed – decongestant), diphenhydramine (gravol) 4. Prescription Drugs  Antidepressants, benzodiazepines (lorizapan), barbiturates (codeine and fentenol) 5. Sexual Assault Drugs  often induse amnesia  Gamma-hydroxybutyrate  used to be used as an anesthetic, caused delirium  Flunitrazepam (Rhohypnol  Benzodiazepine  no LOC  prevents memory formation) ** Not common**  Ketamine (Special K)  used as a veterinary anesthetic  floating feeling  no memory  no LOC  Ecstasy is not considered a S.A.D 6. Heavy Metals (Pb, As, Hg) Alcohols  Metabolites are the most harmful part  Ethanol is the most common drug tested o Usually by an alcohol dehydrogenase method (automated) o This is a good, specific test that is fast and convenient o Can get a false positive due to hepatic failure (leak), increases NADH (this is what is measured in ethanol method)  Methanol, isopropanol and ethylene glycol can only be positively identified and measured by Gas Chromatography (GC) – reference method, measures the molecule o Methanol: windshield washer, antifreeze in gas lines  Metabolizes to formaic acid  acidosis leads to optic nerve damage o Isopropanol: in rubbing alcohol  Metabolizes to acetone  ketone  excreted  Increases lactic acid o Ethylene Glycol: antifreeze  Aldehyde  metabolic acidosis  oxalic acid  kidney failure  GC is also used to monitor treatment (ethanol therapy and or hemodialysis) except for isopropanol and acetone treatment which only requires supportive treatment o Small amounts of methanol  treat with ethanol (that we can metabolize)  Liver alcohol dehydrogenase prefers ethanol but will metabolize the others, leading to problems o Over 15 – dialyze o Under 15 – ethanol, competitive  When methanol or isopropanol is suspected the serum osmolality gap (OGAP) is determined first [ ] [ ] [ ] Unexplained Residual = OGAP = OGAP – Ethanol (patient consumed alcohol) OGAP> 10mmol/L  something other than ethanol (methanol, isopropanol, acetone etc. or something with Ethanol) OGAP<10mmol/L can’t rule it out SD ± 6 (lots of variation here – accumulation of the errors of all of these tests)  Ethylene Glycol is toxic at 3.2 mmol/L and therefore wouldn’t show up on the screen
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