toxicology juju Flashcards
What is therapeutic drug monitoring?
- Measuring conc. of a drug/metabolites in order to optimize the dosing to patient/ assess compliance w dosing schedule
- optimum dosing: improves drug therapeutic effect while avoiding side effects/toxic effects
- check: blood serum/plasma, urine
- Used to find appropriate dosing for conditions such as renal dysfunction, pregnancy, newborns, geriatric pts
Use TDM with drugs with:
- A narrow TI
- significant side effects
- low margin of safety
What are the indications for drug monitoring? clinical, legal, forensic
Clinical:
- Overdose
- Therapeutic Monitoring
Legal: workers comp
Forensic:
- COD
- DUI
- athletic testing
- employment testing
What are the forensic indications for drug monitoring?
- COD
- DUI
- athletic testing
- employment testing
What are trough concentrations used for
To see when due for next dose
Therapeutic Drug monitoring can be done through
Blood serum plasma urine
When are peak concentration of most drugs
30-60 min post dose
Pharmacokinetic Principles
*LADME
*L- Liberation : how the metabolite becomes available in the body
*A- Absorption: movement into circulation
*D- Distribution: body tissues
*M- Metabolism: conversion of drug to active
*E- Elimination
Alcohols description
Can be acute intoxication or chronic abuse (Pancreatic disease, Liver cirrhosis)
- peak is 30-75 min post ingestion
- 1 oz liquor, 4 oz wine, 12 oz beer→25-30 mg/dL
- clearance rate: 15- 25 mg/dL/hour (clear up in an hr in normal body non alcoholic)
- screened for via BREATH TEST AND BLOOD TESTS***
- screen for alcohol in pregnancy: AVOID
- metabolism: differs person to person
What tests for alcohol?
Breath Test & Blood Test
Alcohol peak?
30-75 post ingestion
Alcohols: methanol, ethylene glycol, isopropanol
Methanol
- (MUDPILES)
- moonshine
- washer fluid
- sx: imparired vision - blindness*, seizures, vomit, coma
Ethylene glycol:
- antifreeze
- sx: anuria*, vomit, seizures, coma
isopropanol:
- rubbing alcohol
- sx: hematemesis, melena, abdominal pain, vomit, coma
all of them: vomit, coma
Ethylene Glycol poisoning symptoms
Anuria, vomiting, seizures, coma
Isopropanol poisoning symptoms
Vomiting, abdominal pain, hematemesis, melena, coma
Methanol associated with
Moonshine, washer fluid
sx: impaired vision-blindness, vomitting, seizures, coma
Methanol poisoning
Impaired vision, blindness, vomit, seizure ,coma
Occupational Environmental Toxins + sources of contamination
-Heavy metals
-Gases
-Caustic compounds
contamination sources:
- soil
- ground water
Examples of environmental toxins
-Carbon monoxide
-Mercury
-Cyanide
-Insecticides
-Lead
Carbon monoxide deaths per year?, leading cause of what?
- 4,000 deaths per year, leading cause of accidental & deliberate poisoning (inside the car)
With carbon monoxide poisoning there is binding to?
Binding of Carbon monoxide to oxygen binding sites on hemoglobin
- can have 50% drop
Carbon monoxide poisoning: adults vs kids
Adults:
- headache= MC sx**
- heart: MI
- lungs
- CNS: permanent neurological impairment
- vision
- hearing
- peripheral nerve conduction
Kids: mimics Gastroenteritis**
- diarrhea, N/V
- Fetal hb has different binding capacity so infants may not be as affected as adults
What can children presentation of carbon monoxide poisoning mimic?
gastroenteritis
Carboxyhemoglobin Relative to Total Hemoglobin (%) - ranges: nonsmoker, smoker, sx associated
nonsmoker normal range: 0.1-0.9 smoking: 1.5-10
10-30: increasingly severe headache, dyspnea on exertion
40-50: + tachycardia, may be fatal
60-70: coma, seizure, often fatal
80: rapidly fatal
Lead poisoning primarily effects
- Primarily affects children (greater than 5 µg/dL in blood)
- Pediatric screening :done at 1 year old & 2 years old
- labs shows CBC microcytic anemia-LOW hct
- Impairs cognition and behavior causing: seizures, mental retardation, chronic behavior dysfunction, anemia, renal toxicity, recurrent vomiting and abdominal pain.
What is impaired with lead poisoning?
-Impaired cognitive and behavioral impairment
causing: seizures, mental retardation, chronic behavior dysfunction, anemia**, renal toxicity, recurrent vomiting and abdominal pain.
Lead poisoning monitoring in children
5-44 ug/dL:
- f/u blood lead monitoring
- check iron status
- +/- Hb or Hct
- environmental investigation
- lead hazard reduction
- neurodevelopmental monitoring
- abdominal x-ray with bowel decontamination (if indicated)
45-69:
-f/u blood lead monitoring
- check iron status
- Hb or Hct
- free erythrocyte protoporphyrin
- environmental investigation
- lead hazard reduction
- neurodevelopmental monitoring
- abdominal x-ray with bowel decontamination (if indicated)
- oral chelation therapy
- +/- hospitalization
> =70:
- hospitalize
- oral chelation: binds to iron to excrete it
what lead levels in adults does not require any action
adults: under 25 ug/dL requires no action
children: greater than 5 is poisonous and requires action
What are symptoms of lead poisoning?
Lead exposure = microcytic anemia* -> hypoxemia
- fatigue, lethargy
- lowered IQ: Mental retardation /developmental delays
- renal toxicity
- difficulty concentrating
- hearing impairment
- muscle/joint pain
- abdominal pain/constipation
- vomiting
- encephalopathy: seizures
- lead line (blue -black line) in gingival gums high exposure
What is pediatric and pregnant screening for lead based on
Risk or exposure
- do not screen for lead poisoning if asymptomatic
- only screen if you are exposed: paint, certain areas
Testing for illicit drugs, addictive and harmful therapeutic agents goal is to
*Detect past exposure by detecting metabolites (urine = recent usage)
- hair + nails can show older usage
Can test:
- Urine
- Serum
- Meconium: stool in fetus that forms during 3rd trimester
- breath
- saliva
- hair
- nails
peripheral blood smear: lead poisoning
basophillic stippling of red cells
Detection Window for Commonly Abused Substances Urine Drug of Abuse Testing DAT: Amphetamines, Barbiturates, Benzodiazepines, Cocaine
-Amphetamines 2–4 days
-Barbiturates 1 to >5 days- Depends on barbiturate
-Benzodiazepines 2 to >8 days- Depends on benzodiazepine
-Cocaine metabolite 2 to >7 days- Heavy users may remain positive for 6–10 days using sensitive immunoassays with a 150 ng/mL cutoff
-Methadone 1–4 days
-Opiates 2 to >5 days- Heavy users may remain positive for up to 7–8 days
-Phencyclidine 7–14
-THC (marijuana) 20–30
Detection Window for Commonly Abused Substances Urine Drug of Abuse Testing DAT: Methadone, opiates, PCP, THC
-Methadone 1–4 days
-Opiates 2 to >5 days- Heavy users may remain positive for up to 7–8 days
-Phencyclidine 7–14
-THC (marijuana) 20–30
-Amphetamines 2–4 days
-Barbiturates 1 to >5 days- Depends on barbiturate
-Benzodiazepines 2 to >8 days- Depends on benzodiazepine
-Cocaine metabolite 2 to >7 days- Heavy users may remain positive for 6–10 days using sensitive immunoassays with a 150 ng/mL cutoff
