Toxicology

Let's talk bout drugs -> sorry its forever long I combined medical and forensic

92%

What percent of poisonings happen in the home?

management, detection, source, toxicity

What are the different parts of toxicology?

Poison

Any chemical or physical agents that produce adverse responses in biological organism

toxic

Poisonous or ability to cause harmful or adverse health effects

toxin

A naturally produced poisonous toxic substance capable or causing disease or death

toxicity

Degree or capacity of a substance to induce damage to living tissue under specific conditions

toxicosis

Disease state that results from exposure to poison, poisoning, and intoxication

Detoxify

Body’s ability to change a toxic substance into a less toxic form

tolerance

Decreased sensitivity to a poison

resistance

Complete insensitivity to poison

inhalation, contact, ingestion, injection

Routes of exposure for poisons

ingestion

What route of exposure do we have the most control with

inhalation

What is the most common route of entry?

composition, dose, route of exposure, duration of exposure, distribution, metabolism, excretion, individual factors

What are the factors of toxicity?

composition

Chemical and physical make up -> gases are more toxic

Dose

Amount of a substance taken in, most critical factor in response

Acute exposure

adverse effects after a single or multiple exposure in a short period of time, subtle, violent, often reversible

Chronic exposure

adverse effects after repeated or long term exposure, usually irreversible (cancer, liver damage, behavioral changes)

Local (nonspecific) exposure

action of toxic substance at the site of exposure or portal of entry

remote (systemic) exposure

effects or action is distributed throughout the body; away or distance from the portal of entry

mutagenicity

the ability to cause heritable change in DNA

teratogenicity

ability to cause birth defects

carcinogenicity

ability to cause cancer

mortality

ability to cause death

direct toxic mech

poison itself causes toxic effects

indirect toxic mech

toxicity results from the interaction of the poison with the biological system

patient consent not required, idenitity of specimen is presume, drug concentrations important, sufficient for medical decisions

Characteristics of medical toxicology?

analytical toxicology

Looking for the presence and concentration

blood (ETDA/heparin/red top), body fluids, stomach contents, hair, skin, nails, tissue, feces, teeth, bone, exhaled air, breast milk

What sample types can be used in analytical toxicology?

Iron

What is the most common metallic poisoning in children less than 6 and OD in adults (vitamins, prenatals, supplements, etc)?

>20 mg/kg

What is the toxic dose of iron?

brain, liver, heart, lungs, kidneys, death

What organs does iron poisoning hurt?

Lead

What is the most serious metallic poisoning and is an important environmental health risk (paint, cosmetics, batteries) in children less than 6 - CANNOT BE CLEARED OR EXCRETED?

45 mcg/dL

What is the toxic dose of lead that must be treated or is fatal?

Leads to IQ deficits, encephalopathy, CNS damage in children

What is the end organ damage with lead poisoning?

arsenic

What is dubbed the inheritance powder and is naturally found in the environment and all living things (seafood, contaminated water, pesticides, herbicides, mining, woodwork, smoking) - with chronic poisoning levels go up?

combines with organic and inorganic substances

What are the complications are associated with arsenic poisoning?

chelation therapy

How do you treat arsenic poisoning?

known carcinogen for skin, lungs, liver, bladder

End organ damage for arsenic poisoning?

urine, hair, nails

What is the specimen for arsenic?

Mercury

What is nicknamed “liquid silver” and is the most toxic heavy metal in the environment where people are commonly exposed by eating sea food?

permanent damage to nervous, digestive, immune systems, lungs, kidneys, eyes, teratogenic

What is the end organ damage for mercury poisoning?

cadmium

What heavy metal is used in the manufacture of rechargeable batteries and cigarette smoke?

royal blue top (edta), urine

What is the specimen for cadmium?

Qualitative

What type of testing just says a drug is there or not, usually a urine sample and used for screening in the workplace, management of substance abuse, and clinical/trauma assessment?

confirmation testing

For preliminary results of qualitative assays what needs to be done?

not detected (could be to low, too early, too late)

Concerning drug cut-off levels, what does a negative test mean?

gas chromatography with mass spectrometry

What is considering the gold standard in drug testing but is more time consuming, costly, and training is required (blood sample)?

quantitative (serum concentration)

Determines the concentration level with a serum sample, confirms screening/determines concentration and toxicity

medicalegal situations (EtOH levels)

When are serum concentrations helpful?

the lab cannot report a positive, continue confirmatory testing

If you test below the drug cut off levels on initial screens then

the lab cannot report a positive

If you test above the drug cutoff on initial but below on confirmatory then

Schedule I

What schedule of drugs has no medical use and are highly addictive such as heroin, lsd, ectasy, and weed?

Schedule II

What schedule of drugs is highly addictive but have some medical uses like cocaine and opiates?

schedule III

What schedule of drugs have less abuse potential compared to II but can lead to moderate physical dependence or high psychosocial dependence?

schedule IV

What schedule of drugs have a lower potential for abuse than Schedule III but the abuse of the drug may lead to limited physical and psychological dependence and include substances like benzodiazepines and certain sleep medications?

Schedule V

What schedule of drugs has the lowest potential for abuse with limited risk of physical/psychological dependence and includes medications like cough preparations with less than 200 mg of codeine?

delta 9 THC

What is the active ingredient in weed?

11-OH-THC, 11-COOH-THC

What are the metabolites of weed?

24-48 hr, 3 days (6 weeks in heavy users)

What is the t1/2 of weed and how long can you pick it up in the urine?

CYP enzymes in the liver

How is delta 9 THC metabolized?

Benzoylecgonine

What is the metabolite of cocaine?

2-3 hours, 3-14 days

What is the t1/2 life of coke and how long can you pick it up in the urine?

mannitol, lactose, cafeine, PPA, epherdrine

What might cocaine be cut with?

endogenous phenylethylamine (PEA), amphetamine

What is Meth derived from and what is the metabolite?

7-14 hours in acidic urine, 18-34 hours in basic urine

What is the detection window for meth?

ADHD, obesity

What is meth approved to treat?

opium, morphine, codeine, heroine

What are the natural opiates?

oxycodone, hydrocodone, methadone, fentanyl

What are the synthetic/semi-synthetic opiates?

6-MAM, morphine

Heroine is metabolized into

most panels only pick up natural forms

What are the limitations for opiate testing?

CO

What is the most common cause of gaseous poisoning and is product of incomplete combustion?

cellular hypoxia and anoxia

What is the primary toxic effect of CO

decreased mental effectiveness, visual acuity, and fine motor coordination, HA LOC,

What are the symptoms of a CO poisoning?

get them out of the area, O2

treatment of CO poisoning?

whole blood (EDTA/heparin)

What specimen is used for CO?

GC, Co-oximeter

What assay is used for CO?

Ethanol

What is the most commonly abused drug and the #1 date rape drug that is categorized as a CNS depressants?

diminished breathing, heart rate, body temp, gag reflex, mental confusion, unresponsiveness, snoring/gasping for air, emesis, erratic breathing, LOC, cyanosis

What are signs of alcohol poisoning?

isopropyl (rubbing EtOH), methanol (antifreeze), acetone (ketones)

Other than ethanol what are the other forms of alcohol?

processed by the liver at a pretty consistent rate

How is ethanol metabolized?

proof/2

How do you determine % ethanol in alcohol?

0.015

What is the clearance rate for BAC per hour?

BAC (most common/accurate, detects 12 hr after drinking), urine test, brethalyzer (converts BAC using 2100 BrAC:1 blood)

What are the different alcohol testing methods?

Biomarkers (EtG, EtS, peth), Gas/liquid chromatography (ideal)

What are the different direct assays for alcohol testing?

LFTs, MCV

What are the indirect assays for alcohol testing?

superficial injuries (protected by the alkaline environment and coagulative necrosis)

How is the esophagus affected by acid ingestion?

deeper injury (can’t neutralize)

How is the stomach affected by acid ingestion?

major injury (eschar) protects from further damage

How is the oropharynx and esophagus affected by alkali ingestion?

minimal damage (neutralized by the acid)

How is the stomach affected by alkali ingestion?

tinnitus, hyperthermia, tachycardia, hyperventilation, multiple organ failure, associated with Reye syndrome

What are the symptoms of ASA toxicity?

stabilize ABCs, limit absorption, enhance elimination, supportive care, serial monitoring

How are we treating ASA toxicity?

Glucuronidation, sulfation, CYP2E1 oxidation forms NAPQI (toxic metabolite), reacts with glutathione

Tell me about the metabolism of Tylenol

7+ grams in adults, 150+ mg in children

What is the toxic dose of tylenol?

ABD pain, N/V, dyspnea, hematuria, jaundice

What are the S/S for tylenol toxicity can appear within 2 - 24 hr?

N-acetylcysteine

What is the antidote to Tylenol toxicity?

less than 4 hours, 2-3 hours

When does tylenol peak in the blood and what is the half-life?

drugs with narrow TI, therapeutic failures, drugs taken on chronic basis, drugs with slow/fast metabolism, assessment of DDIs, if dose-plasma drug concentration is weird

When are we using peaks and troughs

chronic basis

Trough levels are taken on a ________

net charge on drug, protein binding, state of drug ionization, pharmokinectic properties

What factors affect drug distribution?