Toxicology Flashcards
(153 cards)
1
Q
What is the difference between a toxin and toxicant?
A
Toxin - natural, toxicant - man made
2
Q
Bioaccumulation
A
The accumulation of a substance within tissues of an organism (distribution exceeds elimination)
3
Q
Biomagnification
A
Process whereby concentration of a substance increases as the substance moves up the food chain
4
Q
How is therapeutic index calculated?
A
LD50/ED50 (lethal dose over effective dose)
5
Q
Categories for dosing (time of exposure) in toxicology
A
Acute lt 24 hr, Subacute repeated exposure for 1 month or less, Subchronic repeated exposure for 1 to 3 months, Chronic more than 3 months
6
Q
When analyzing a toxicants dose-response curve, does a steeper line imply less certainty or more certainty about the toxicants effects?
A
More certainty (a perfectly vertical line would mean the entire population has the same response)
7
Q
When analyzing a toxicants dose-response curve, is the curve with a steeper slope or shallower slope considered more toxic (assuming the same LD50)?
A
Shallower slope (will show more problems at low dose)
8
Q
What toxicant caused problems during World War II and why was this surprising?
A
Diethylene glycol. Sulfanilamide (antibiotic) was put in diethylene glycol, which was not known to be toxic because it has a shallow (unpredictable) dose-response curve
9
Q
What compound was accidentally released in Bhopal, India in 1984?
A
Methyl isocyanate
10
Q
What five pollutants account for 98% of outdoor air pollution
A
Sulfar dioxide (SO2), Particulate matter (PM), Nitrogen Dioxide (NO2), Carbon Monoxide (CO) and Volatile Organic Compounds
11
Q
Which outdoor pollutants are reducing
A
Sulfur dioxide (SO2) and smoke
12
Q
What outdoor poullutants are oxidizing?
A
Hydrocarbons, nitrogen oxides, secondary photochemical oxidants (e.g. ozone)
13
Q
Effects of SO2 exposure
A
Pulmonary irritant, upper airway mucus secretion, bronchoconstriction, thickening of mucus layer in trachea
14
Q
Effects of particulate matter exposure
A
Chronic pulmonary inflammatory conditions and cancers. Mesothelioma (asbestos), pneumoconiosis (blakc lung), aluminosis (Shavers disease, bauxite lung), Byssinosis (cotton dust), Berylliosis (berrylium)
15
Q
What is the relationship between particulate size and deposition in the lung
A
Smaller particulate size, deposition deeper into the lung
16
Q
Effects of exposure to oxides of nitrogen
A
Deep lung irritation, increased respiratory frequency, decreased compliance
17
Q
Effects of exposure to ozone
A
Lung irritation, pulmonary edema (mostly lower respiratory tract), cough, chest tightness, dryness of throat. Long term - chronic bronchitis, fibrosis, emphysematous changes
18
Q
What is the environmental agent responsible for the most deaths each year?
A
Carbon monoxide
19
Q
What is a normal reading for COHb
A
lt 5% in non-smokers, up to 15% in smokers
20
Q
Effects of a low level of carbon monoxide poisoning (10-20% COHb)
A
Headache, cutaneous blood vessel dilation
21
Q
Effects of a medium level of carbon monoxide poisoning (20-40% COHb)
A
Significant headache, dizziness, nausea, vomiting, collapse, potential death
22
Q
Effects of a high level of carbon monoxide poisoning (above 40% COHb)
A
Syncope, Cheyne-Stokes respiration, Convulsions, Decreased CV function, coma, death
23
Q
What is the apperance of a patient who has carbon monoxide poisining?
A
Bright pink skin (due to cherry-red color of COHb)
24
Q
What occurs within 2-3 weeks of CO poisoning?
A
Neurologic deterioration (can also get atherosclerotic disease)
25
Treatment for CO poisoning
100% oxygen (and hyperbaric oxygen therapy, which is somewhat controversial)
26
Common signs and symptoms for Sick Building syndrome
Eye nose and throat irritation, headaches, fatigue, reduced attention span, irritability, nasal congestion, difficulty breathing, nosebleeds, dry skin, nausea
27
Common signs and symptoms from solvent exposure
CNS depression (headache, dizziness, anesthesia, asphyxiation, respiratory depression, coma, death). Chronic - cirrhosis and carinogenesis
28
Effects of exposure to halogenated aliphatic hydrocarbons
Acute - CNS depression and adverse cardiac effects (arrhythmias). Chronic - liver problems, cancer, impaired memory, neuropathies, renal issues
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Three toxic halogenated aliphatic hydrocarbons
Carbon tetrachloride, chloroform, trichloroethylene
30
Effects of exposure to aromatic hydrocarbons
Variable, mainly CNS depression, sometimes hematopoietic disturbances (benzene, chronic)
31
Effects of exposure to polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs)
Dermatologic effects (chloracne, erythema, hyperkeratosis), elevated triglycerides, long-term liver problems
32
Effects of endocrine disruptors (such as Diethylstilbestrol (DES))
Genital tract anomalies, clear cell adenocarinoma, epidydmal cysts, hypotrophic testes, low ejaculatory volume, poor semen quality
33
Define TLVs, TWA, STEL, TLV-C, and BEI
Threshold limit values, Time-Weighted Average (allowed time of exposure), Short-Term Exposure Limit, Threshold Limit Value Ceiling, Biological Exposure Index (normal measured biological value)
34
What class of drugs are chemical insectisides in use today?
Neurotoxicants
35
What class of pesticides are no longer used in the west, but still used in third world, and give a few examples
Organochlorine compounds, DDT, Chlordane, Lindane
36
Effects of DDT exposure
Acute - paresthesia, ataxia, CNS disturbances, fatigue, tremor. Chronic - weight loss, mild anemia, muscular weakness, EEG changes, hyperexcitability
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Effects of cyclodiene (e.g. chlordane) exposure
Acute - dizziness, headache, nausea, vomiting, hyperreflexia, myoclonus, convulsions. Chronic - same as acute, psychological disturbances, EEG changes
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Effects of chlorinated benezenes exposure (e.g. lindane)
Acute - same as DDT (paresthesia, ataxia, CNS disturbances, fatigue, tremor), and seizures
39
Mechanism of DDT-type pesticides
Alteration of Na and K transport across axonal membranes. Increased negative afterpotential, prolonged APs, repetitive firing, spontaneous firing
40
Mechanism of action of Cyclodienes (e.g. chlordane)
Antagonists for GABA receptors, partial repolarization of the neuron and a state of uncontrolled excitation
41
What pesticides replaced organochlorines and how do they work?
Organophosphates and Carbamates. They inhibit acetylcholinesterase
42
For the pesticides that replaced organochlorides, which is fast (reversible) and which is slow (irreversible)
Organophosphates react irreversibly w/ body, Carbamates react reversibly
43
Treatment for exposure to organophosphates or carbamate pesticides and give restrictions
Atropine, and/or Pralidoxime (2-PAM). 2-PAM will not work with all Organophosphates (OPs), and will not work long after OP exposure
44
What is contraindicated in carbamate poisoning?
Oxime antidotes
45
Effects of pyrethroid insectiside exposure
Cutaneous paresthesias, dizziness, burning, itching, tingling of skin. Ingestion - epigastric pain, nauesea, vomiting, headache, blurred vision, parasthesia, palpitations, muscle fasciculations, disturbances of consciousness, convulsions
46
Types of pyrethroid pesticides and differences between them
Type I lack an alpha-cyano group as opposed to Type II
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Mechanism of pyrethroid pesticides
Modify gating kinetics of Na channels, resulting in hyperexcitable states
48
Which type of pyrethroids are longer acting
Type II
49
At what COHb point does death occur
Usually around 50% (can be as low as around 25-30%)
50
Effects of exposure to chlorphenoxy herbicides
Persistent chloracne, skin, eye and respiratory tract irritation, dizziness, headache, severe muscle pain in thorax, shoulders and extremities, fatigue, decreased libido, dyspnea, irritability, intolerance to cold
51
What class are paraquat and diquat in?
Bipyridyl herbicides
52
What are the long term effects of bipyridyls (e.g. paraquat and diquat)
Pulmonary toxicity, death (3-4 weeks)
53
Treament for paraquat/diquat exposure
Gastric lavage, Fuller's earth (Kaolin), hemoperfusion
54
Types of fungicides
Hexachlorobenzene (HCB), phthalimides, dithiocarbamates
55
Two widely used fumigants
Phosphine, Ethylene dibromide/dibromochloropropane
56
Most common rodenticides and the effects of each
Zinc phosphide (necrosis of GI tract, liver/kidney damage), Fluoroacetate (intereferes with Krebs ycle by inhibition of aconitase), Anticoagulants (hemorrhage by antagonizing vitamin K)
57
What do aromatic hydrocarbons cause?
Leukemia
58
Essential trace elements
Metals which we require to live (e.g. need chromium in +3 state to regulate glucose)
59
Proteins that help with transport, storage, and elimination of metals
Metallothioneins (Cd, Cu, Hg, Ag, Zn), Transferrin (Fe, Al, Mn), Ferritin (Fe, Cd, Zn, Be, Al), and Ceruloplasmin (Cu)
60
Chronic exposure to cadmium causes increased concentrations of what in urine?
B-2 microglobulin
61
What can be a side effect of chelation therapy
Deficiency of essential trace elements (because chelators are usually not specific for a given metal)
62
Toxicity of various forms of arsenic
Organic arsenicals less than As5+ less than As3+ less than Arsine
63
Selective toxicity
The property of a toxicant (e.g. pesticides) that they kill the intended organism but do not affect others (e.g. us)
64
Long term sequelae of arsenic exposure
Lung, skin, bladder cancers
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Mechanisms of Arsenic
Uncouple Ox Phos (5+), Bind with Sulfhydrl (3+), Interact with hemoglobin to cause hemolysis (Arsine gas)
66
Treatment for arsenic poisoning
Severe cases - chelation with dimercaprol (BAL) or succimer (chelation ineffective for arsine gas exposure)
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How do we monitor patients exposed to arsenic?
Blood and urine arsenic concentrations and hair/nail analysis
68
Mee's lines
Transverse white deposits of arsenic on the nails
69
What class of symptoms are characteristic of posoning with arsenic (arsnicals or arsine gas)?
GI Disturbances (projectile vomiting, diarrhea)
70
Common sources of cadmium exposure
Shellfish, fish from polluted water
71
Smoking a pack a day doubles one's body burden of what metal?
Cadmium
72
Cadmium exposure is correlated with what long term sequelae?
Lung and prostate cancers
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Principally what organs does cadmium end up in?
Lungs (absorbed from air), Kidney, Liver. Most cadmium in GI tract gets excreted in feces
74
In what form is cadmium found in the blood?
In blood cells bound to metallothionein
75
What is the mechanism of action of cadmium
Interaction with functional macromolecules
76
Effects of cadmium exposure (chronic)
Renal problems, chronic pulmonary dysfunction, osteopenia-osteomalacia, yellow teeth lines
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Treatment for cadmium exposure
Vitamin D once osteomalacia evident, chelation controversial, EDTA salts?
78
Biomarkers of effect for cadmium
Renal function related proteins: B-2 microglobulin, retinol-binding protein (RBP), N-acetyl-B-D-glucosaminidase (NAG). These are not SPECIFIC for cadmium
79
Typical means of exposure to lead
Food, also environmental sources (lead paint, etc)
80
Why is speciating arsenic tests important?
The patient may be exposed to organic arsenicals (e.g. from lobster) which is ok, but without speciation it can return a general high As level
81
What are rice water stools a symptom of?
Arsenic poisoning
82
Why are children more at risk for lead poisoning?
They have a much higher absorption percentage (up to 40%)
83
In what form is lead found in the blood?
Bound to hemoglobin
84
Main target organs for lead toxicity
Kidney, liver, brain. Also heavy deposition in long bones
85
Does lead cross the placenta?
Yes
86
Mechanism of action of lead
Binds sulfhydryl groups, interfering with many important enzymes (ALA-D, Ferrocheletase, others), also affect DNA transcription factors and calcium-related activity
87
Effects of acute lead poisoning
GI disturbances, CNS effects (paresthesias, pain, muscle weakness), and renal damage. Death in 1-2 days
88
Effects of chronic lead poisoning (plumbism)
CNS - ataxia, falling, headache, clumsiness, iritability, confusion, visual disturbances, delirium, convulsions, coma, MR, EEG changes, seizures, cerebral palsy. Neuromuscular - muscle weakness, fatigue. Heamtologic - basophilic stipling in RBCs, hypochromic microcytic anemia. Other - renal tubular disorder, nephropathy, ashen color of face, lead-lines along gums, reproductive problems
89
Which form of lead crosses the BBB particularly well?
Organic lead (tetraethyl- and tetramethyl- forms are lipid soluble)
90
Treatment for lead poisoning
Chelation with CaNa2EDTA or dimercaprol (BAL) and D-penicillamine
91
For which types of lead poisoning is chelation therapy used?
Inorganic lead. Do not use chelation for organic lead exposures
92
Useful biomarkers for lead exposure
Zinc protoporphyrin (ZPP) and free protoporphyrin (FEP) in blood, ALA in blood and urine
93
How do you measure lead in organic vs inorganic exposures?
Organic - urine lead, Inorganic - whole blood lead
94
Why are ALA and ZPP not good biomarkers for ORGANIC lead exposure?
Because organic lead compounds do not affect heme synthesis
95
At what blood level of lead is treatment recommeded to begin (retesting, lead prevention activities)
Above 10 mcg/dL
96
At what blood level of lead should chelation first be considered?
Above 20 mcg/dL. Recommended above 45 mcg/DL
97
Most common sources of exposure to mecury
Contaminated food (e.g. fish)
98
Three toxic forms of mercury
Elemental, inorganic and organic mercurials
99
Mechanism of action of mercury
Bonds with sulfur (e.g. Sulfhydryl groups)
100
Absorption and transport of elemental mercury
Not well absorbed (skin or GI), transported by RBCs
101
Where does elemental mercury tend to end up in the body?
Lungs, fistulas, diverticula, brain. Does cross BBB
102
Effects of acute exposure to elemental mercury
GI distrubances, metallic taste in mouth, cough, chest tightness, pulmonary toxicity (residual fibrosis)
103
Effects of chronic exposure to elemental mercury
Asthenic vegetative syndrome (micromercurialism) - neurasthenia, gingivitis, thyroid disturbance (e.g. goiter), tremor, psychological changes, perspiration, erethism (blushing)
104
Classic triad of mercury vapor exposure
Excitability, tremors, gingivitis
105
Absorption and transport of inorganic salts of mercury
Some GI, some skin. Transported by RBCs and plasma. Generally does not cross BBB
106
In what organs do inorganic salts of mercury end up?
Kidney, liver
107
Acrodynia
An idiosyncratic reaction to chronic mercury - erythema, photophobia, diaphoresis, anorexia, tachycardia, irritability, milarial rash
108
Absorption and transport of organic mercurials
Oral, skin, inhalation. Transported by RBCs, does cross BBB
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Organs in which organic mercurials tend to end up
Liver, kidney, brain, hair, and epidermis
110
What type of mercury is subject to enterohepatic recirculation?
Organic mercurials
111
Most toxic form of organic mercurials and their effects?
Alkyl mercurials (used as fungicides) - paresthesia, ataxia, neurasthenia, vision and hearin loss, tremor, spasticity, coma, death
112
Treatment for mercury exposure
Chelation with BAL, D-penicillamine (do not use BAL with organic mercury)
113
In what case of mercury exposure should chelation not be used?
Organic mercurials (may redistribute the mercury). In these cases use N-acetylcysteine or cysteine followed by succimer
114
Absorption of Thallium
Oral, inhalation, derm
115
Where is most of the absorbed thallium in the body found?
The kidneys
116
What is the mechanism of action of thallium?
Mimics potassium ions, uncouples Ox Phos, affects protein synthesis, and interferes with several enzymes
117
Effects of acute thallium poisoning
Gastroenteritis, convulsions, confusion, collapse, neuropathy
118
Effects of chronic thallium poisoning
Non-descript ill health, paresthesias, neuropathies, loss of hair, Mee's lines
119
Chronic poisoning with what metal is often misdiagnosed sa Guillain-Barre syndrome?
Thallium
120
Treatment for thallium poisoning
Gastric lavage, emesis, Prussian blue. Chelation is ineffective and may redistribute Thallium
121
What proportion of poisonings and fatalities involve children under age 6?
Half of poisonings, 3% of fatalities
122
What is implied about a drug by a large or small Vd?
Large Vd - Lipophilic, Small Vd - Lipophobic
123
What general effect do most toxins result in?
CNS depression leading to obtundation or coma
124
How do patients who die from poisoning typically die?
From airway obstruction by flaccid tongue, aspiration of gastric contents, or respiratory arrest
125
Examples of cardiotoxic drugs
Ephedrine, amphetamines, cocaine, tricyclics, digitalis
126
Some drugs that cause cellular hypoxia
Cyanide, hydrogen sulfide, carbon monoxide
127
Some drugs that cause seizures
Tricyclics, isoniazid (INH), diphenhydramine, antipsychotics, cocaine, amphetamines
128
What does the coma cocktail do?
Reverse depressed mental status and respiratory rate
129
What is in the present day coma cocktail?
Oxygen, dextrose, naloxone (narcan), and thiamine
130
Why is dextrose part of the coma cocktail?
In case the patient is hypoglycemic (a common cause of altered mental status)
131
What does naloxone (narcan) do?
It is an opioid antagonist that reverses respiratory and CNS depression due to opioids
132
What is the relationship between naloxone half life and half life of many opioids?
Naloxone has a much shorter half life (may require more naloxone)
133
What might naloxone administration result in and what is the result of this?
Catecholamine surge, can lead to cardiac sensitization and dysrhytmias
134
Why is thiamine part of the coma cocktail?
In case the patient is malnourished or alcoholic (Wernicke's, Korsakoff's)
135
Signs and symptoms of Wernicke's
Depressed mental status, ataxia, nystagmus, opthalmoplegia
136
Signs and symptoms of Korsakoff's
Short-term memory loss, confabulation
137
What are the only lab tests required for most poisoned patients?
Acetaminophen level, ECG and SMA7
138
What does the ECG pickup in the case of poisoned patients?
Evidence of Na channel blockade from medications like tricyclics, atypical antipsychotics and Type I antidysrhytmics
139
What does the SMA7 lab test identify in the poisoned patient?
Xenobiotics that cause anion gap metabolic acidosis
140
Give the calculation for anion gap
(Na + K) - (HCO3 + Cl)
141
What is the normal anion gap?
12-16 meq/L
142
Three poisons that are suggested by a negative anion gap
Bromism, Lithium, paraproteins
143
Common causes of anion gap metabolic acidosis
Methanol, uremia, DKA, paraldehyde, iron, isoniazid, lactic acidosis, ethylene glycol, salicylates
144
Give the calculation for osmolar gap
Measured serum osmolality (blood test) - calculated osmolarity
145
Give the calculation for calculated osmolarity
2 x Na + Glucose/18 + BUN/2.8 + ETOH/4.6
146
What are the normal measured osmolality and osmolar gap?
Osmolality: 280-290 mosm/L and mosmolar gap: 0-15 mosm/L
147
What substances cause an elevated osmolar gap?
Ethanol, ethylene glycol, methanol, isopropanol
148
What is the single most useless test the physician can order on a poisoned patient?
Urine drug screen
149
The two primary mechanisms for removing toxins
Orogastric lavage and activated charcoal
150
Orogastric lavage should be considered in patients who present within one hour and ingested one of these substances
calcium channel blockers, beta blockers, tricyclics, antineoplastic agents, colchicine, paraquat/diquat, pdophyllin
151
What seriously toxic substances are not absorbed by activated charcoal?
Cyanide salts, potassium supplements, metals, and alcohols
152
What proportion of gastric contents can orogastric lavage remove?
40% at most
153
What is a risk of administering activated charcoal by NG tube?
Aspiration
