Toxicology Flashcards
carbon monoxide
Air Pollutant
Asphyxiant (along with cyanide)
Part of EPA six criteria for Air Quality
- CO, SO2, NO2, Ozone, PM, Lead
Source:
- Vehicles»»fire
Acute Respiratory Health Effects
Sulfur Dioxide (SO2)
Source: Fossil Fuel, mostly coal
Environmental Problems: Acid rain, pH change in soil, metal leaching
Health effects:
- Water soluble so damages upper airways
- STRONG association with ASTHMA
Concentration and Effect: 3 ppm: easily detected odor 10 ppm: URI 20 ppm: Irritating toeyes 50-100ppm: max. tolerable
Symptoms:
- Acute:
- Irritation, cough, burning, lacrimation, difficulty
swallowing
- Vomiting, diarrhea, abdominal pain, fever, headache,
vertigo, agitation, tremor, convulsion, pulmonary edema
- Toxicity most severe in patients with lung problems:
asthma, emphysema, bronchitis
- Long term:
- Aggravation of chronic cardiopulmonary disease
(asthma, chronic obstruction, coronary artery disease) - Children: reduced lung function, increased upper
respiratory infections
- Aggravation of chronic cardiopulmonary disease
Pathophysiology:
- SO2 + moisture in airways= SULFUROUS ACID
- Irritation
Nitrogen Oxides
Source:
- Power Plants
- Cars
Major source of Ozone
Not very water soluble
- penetrates deep into lungs
Potent respiratory tract toxin
- Clinical Features
- Bronchitis, pneumonia, hemorrhagic pulmonary
edema, alveolar damage
- Pathophysiology
- May cause lipid peroxidation, decreased ciliary
movement, bronchoconstriction, enzyme inhibition
- May cause lipid peroxidation, decreased ciliary
Toxicity:
- Decomposes in alveoli to nitrous acid (NHO2),
nitric acid (HNO3), and NO (vasodilator) on contact
with moisture
Ozone
O3
Bluish gas, no or slightly pungent odor
Ethanol
EtOH
Produced by yeast
Many Therapeutic Uses
1 unit = 10ml EtOH = 8g EtOh
Absorption:
- Rapid
- Food decreases rate in SI
Transport:
- To liver
Distribution:
- Vd correlates with total body water (40 L)
- Conc. depends on water conc.
- Found in lipids also (brain)
BAC
- Grams of EtOH/100ml blood
- 1 drink results in .03%
- Elimination is 1/2 drink per hour
Metabolism:
- Mostly by ADH in LIVER, stomach
- Aspirin inhibits ADH availability in stomach, and women have less ADH in stomach
ADH follows zero order (saturation kinetics)
- Average rate is 6-8 g EtOH/hr (3/4-1 drink)
Pharmacology
- CNS: Depressant
- Facilitates GABA
- Inhibits NMDA glutamate receptors
- Respiratory: Little effecct until high lvls (depress brainstem drive)
CV: Vasodilation (hypothermia), Increase HDL and decrease LDL (french paradox)
Renal:
- Increase urine flow: diuresis by two mechanisms, volume effect and inhibition of ADH
Sexual Function:
- Frontal lobe dis-inhibitor
- Depressant
- Gonadal toxin
GI:
- Low dose stim appetite
- High dose depress appetite (due to high calories)
Liver:
- Stimulate cytochrome p450
- Produce ROS
- Toxicity
- Fatty liver, toxic hepatitis, cirrhosis
Acute Alcohol Poisoning
- Relaxed– Euphoric– Excited– confused–stupor–COMA–DEATH
Acute may cause HYPOGLYCEMIA due to inhibiting GLUCONEOGENESIS
Chronic Alcohol Abuse: - Loss of appetite - Vitamin and nutrient deficiencies Ketotic (Wernicke- Korsakoff syndrome) - Stomach ailments, ulcers and diarrhea - Cardiomyopathy - Coagulation defects - Sexual impotence
Isopropanol
Alcohol of Therapeutic use
Characteristics
- Burning, bitter taste
- 2nd most ingested alcohol
Source:
- Rubbing alcohol (70%)
- Windshield wiper fluid (50-85%)
- Antifreeze (40-55%)
- Window Cleaner (0-25%)
Kinetics
- Rapid, complete uptake from GI tract
- Metabolism to acetone
- Slow elimination in kidneys (20-50%)
- Lungs acetone breath
Toxicity
Twice as potent CNS depressant as EtOH
Methanol
CH3OH
Characteristics
Ethylene Glycol
Characteristics
Arsenic
Metal
AsIII most toxic
Bioaccumulate: NO
- Half Life: 3 days
- Major route of exposure: lung, GI
Major target organ
- Short Term:
- Liver
- Kidney
- Heart
- Lung
- Long term:
- Hair, nails, skin (KERATIN), binds to sulfhydryl groups in hair and nails
Major source
- Pesticide, Medicine (chemo), Glassware paint
- FOOD/Water
- Occupational inhalation
2nd most common Heavy-Metal induced Death in USA (CHILDREN)
Pathophysiol
- Inh. mito enzymes (lower ATP, higher ROS
- Inh. SH enzymes
Symptoms:
- 70-180 mg: LETHAL
- Nausea, GI discomfort, Gastric bleeding, vomiting
- Hepatosplenomegaly
- Cardiac arrhythmia, vasodilation
- Constriction of throat, difficulty swallowing
- Shock, hypoxic convulsion, coma, death
Treatment:
- Fluid replacement, BP support (dopamine)
- Chelation
Current EPA Acceptable LVL:
- 10 mcg/L= 1/5000 cancer
Cadmium
Metal
Bioaccumulate: YES!!!
- Half life 10-30 years
Major target organ
- Lung: COPD, bronchitis, emphysema
- CV: Systolic HTN
- BONE: Itai-Itai (osteomalancia, Ca metabolism disrupted by vit D metabolism decrease in kidneys
- Cancer
KIDNEY!!!!!, renal tubular disease, proteinuria, Fanconi’s syndrome in 50% of patients with 300 mcg/g kidney
Major source
- FOOD: plants uptake from soil, shellfish, meats (liver, kidney)
- SMOKING 1mgCD/year
- Normal daily intake: 10-40 mcg/day
Pathophysiol - GI absorption: 5-8 % - RESPIRATORY: 15-30% - Transport: - Blood - Liver - Kidneys BODY BURDEN MOSTLY IN KIDNEYS
Lead
Metal
Bioaccumulate: YES
- Oral uptake: 5-15 adult (41% child)
- RETENTION: (5% adults)(32% children)
- Inhalation is very efficient at absorption/retention
Major target organ
- CNS
- Bone
- GI
- LOWERS IQ
- Blood
Major source
- FOOD
- ENVIRONMENT: paint/lead dust
- Recreational shooting (blood Pb level >30%)
- 3 million tons of lead applied to older occupied housing
- Crawling children are exposed to lead from dust and peeling paint
- 1 million children at risk of lead poisoning (blood level >10 mcg/dl)
Pathophysiol
- > 90 percent of lead sequestered in blood
- Storage
- 95% adults skeleton
- 70% children skeleton
- Soft Tissue
- 5% adult skeleton
- 30% children
Excretion in breast milk puts baby at risk
Crosses placenta so places the Fetus at risk also
Binds sulfhydryl groups
Disrupts mito function and interferes with oxphos
Neurotoxicity: Disrupts Ca dependent intracellular messengers and brain protein kinase C
Stimulates formation of inclusion bodies containing lead-protein
Higher intake in children, higher blood levels, higher risk for CNS toxicity
Mercury
Metal
Bioaccumulate: YES
- T1/2: 70 days
Major target organ
- CNS
- Kidney
- CV health damage
- Prenatal: retardation, blindness, cerebral palsy-like syndromes (fetal Minamata disease)
Major source
- Natural but exposed due to coal burning, (2-3x increase of atmospheric Hg)
- Biomagnification: Incremental increase in conc. of a contaminant at each level of the food chain
- Do not eat, shark, swordfish, king mackerel, or tilefish
Pathophysiol
- Organic (alklmercury) most toxic over inorganic
- Body burden: 15-35 g (50g)
- Daily intake 3-7 mg/kg
Dentistry: Amalgam contains mercury and is controversial for use
Dimercaprol
Chelator
Penicillamine
Chelator
Cyclodienes
POPs:
Dieldrin
Chlordane
Toxaphene
POPs are
