Buxton toxicology Flashcards
(208 cards)
1
Q
What is poison?
A
all substances are poisons,
2
Q
What is the science of the adverse effects of chemicals on the living organism?
A
decriptive toxicologist
mechanistic toxicologist
regulatory toxicologist
3
Q
What are adverse effects?
A
Any change from an organism’s norma state
dependent upon the concentration of active compound at the target site for sufficient time.
4
Q
What is a toxicant (poison)?
A
any agent capable of producing a deleterious response in a biological system
5
Q
What are regulatory agencies for toxicology?
A
FDA
EPA
OSHA
CPSC
6
Q
What is EPA for?
A
pesticides and environmental chemicals
7
Q
What is OSHA for?
A
Workplace exposures
8
Q
What is CPSC?
A
for consumer product safety commission
9
Q
What is this:
Medicolegal aspects of chemical/drug exposures
Cause and circumstances of death
A
Forensic toxicology
10
Q
What is this:
Treatment of patients exposed to toxicants
Development of diagnostic tests and treatments
A
Clinical toxicology
11
Q
What is this:
Testing of drugs under specified conditions in animal organ systems looking for toxicity (FUNCTIONAL CHANGES)
A
safety pharmacology
12
Q
As with therapeutic use of chemicals, toxicology references the understanding of the toxic effects of chemicals to (blank) or (blank)
A
concentration: effect
dose: response
13
Q
What is a dose?
A
the amoutn of toxin entering the body
14
Q
What is the dose dependent upon?
A
The environmental concentration Properties of the toxin Pathway of exposure Duration of exposure Frequency of exposure
15
Q
(blank) is all or none
(blank) is some on a scae
A
quantal
graded
16
Q
In an individual you will have a dose response that is (blank)
A
graded
17
Q
In a population you will have a dose response that is (blank)
A
quantal
18
Q
Classically, a quantal dose (concentration) response (effect) is used to determine the (blank)
A
lethal dose
19
Q
T or F
The dose makes the poison
A
T
20
Q
What is ED50?
A
Median effective dose 50; the dose at which 50 percent of the pop or sample manifests a given effect; used with quantal d/r curves
21
Q
What is TD50?
A
Median toxic dose 50- dose at which 50 percent of the popuation manifests a given toxic effect
22
Q
What is LD50?
A
Median toxic dose 50- dose which kills 50 percent of the subjects (animal studies)
23
Q
What is this:
LD50/ ED50
A
Therapeutic index
24
Q
What is the margin of safety for drugs?
A
LD1/ED99
25
What is the margin of safety for toxins?
NOAEL/exposure- no observed adverse effect level (just shows where the death limit)
26
What is the most useful tool for figuring out margin of safety?
MABEL "minimal anticipated biological effect level"
27
What are the 2 ways you can find the therapeutic index?
TD50/ED50 or LD50/ED50
28
THe higher the (blank) the better the drug
Therapeutic index (TI)
29
TI will vary from (Blank) such as antineoplastic drugs to greater than (blank) such as penicillin
1
| 1000
30
Drugs acting on the same receptor or enzyme system often have the same (blank)
TI
| e.g 50 mg of hydrochlorothiazide equates to 2.5 mg of indapamide
31
Some chemicals have both therapeutic and toxic effects such as (blank)
vitamin A
32
WHat happens if you have too low of a dose of vit A?
blindness, dry skin, increased infections
33
WHat happens if you have too high of a dose of vit A?
anorexia, anemia, nose bleeds, muscle and joint pain
34
(blank) is a group of unsaturated nutritional hydrocarbons that includes retinol, retinal, retinoic acid, and beta carotene
Vitamin A
35
What does Vit A do?
as retinoic acid regulates gene transcription at RXR receptors
36
What is the adequate intake for Vit A?
3 mg/day for adults
37
What has a very high lethal dose?
ethyl alcohol
38
What has a very low lethal dose?
botulinim toxin
39
What are the routes and sites of exposure?
ingestion (GI tract)
Ihalation (lungs)
Dermal/topical (skin)
injection (intravenous, intramuscular, intraperitoneal)
40
in order what are the most effective to least effect routes of exposure.
IV> inhale> ip> im> ingest> topical
41
What is acute exposure?
less than 24 hr usually a single exposure
42
What is subacute exposure?
about 1 month repeated dosese
43
What is subchronic exposures?
1-3 months in repeated doses
44
What is chronic exposure?
greater than 3 months repeated doses
45
Over time what can happen to the drug if you are chronically using it?
the amount of chemical can build up and redistribute or it can overwhelm repair and removal mechanisms
46
Once a living organism has been exposed to a toxicant, the compound must get into the body and to its target site in an (Blank) in order to cause adverse effect
active
47
What are the bodies defenses?
- membrane barriers (passive and facilitate diffusion, active transport)
- biotransformation enzymes, antioxidants
- elimination mechanisms
48
What is this:
| absorption through GI tract stomach (acids), small intestine (long contact time, large surface area - villi)
ingestion
49
What is this:
readily absorb gases into the blood stream via the alveoli. (Large alveolar surface, high blood flow, and proximity of blood to alveolar air)
inhalation
50
What is 1st pass effect?
liver detoxifies and reduces amount of drug
51
What is this:
| absorption through epidermis (stratum corneum), then dermis; site and condition of skin
percutaneous absorption
52
What is this:
| blood carriers the agent to and from its site of action, storage depots, organ transformation and organs of elimination
distribution
53
What is the rate of distribution dependent on?
blood flow and characteristic of toxicant (affinity for the tissue, and the partition coefficient)
54
T or F
| distribution maychange over time
T
| depo storage of toxicant in fat
55
What wil store in fat?
| How can you get rapid release of these drugs?
very lipophylic compounds (DDT)
| Rapid mobilization of the fat (starvation)
56
What drugs will deposit in bone?
chemicals analogous to calcium-fluoride, lead, strontium
57
Whats messed up about drugs that bind to plasma proteins?
they displace endogenous compounds and only free is available for adverse effects or excretion
58
Why is the liver a target organ?
it has high blood flow and participates in oxidative reactions
59
Why is the kidney a target organ?
high blood flow, concentrates chemials
60
Why is the lung a target organ?
high blood flow, site of exposure
61
Why are neurons a target organ?
oxygen dependent and causes irreversible damage
62
Why is the myocardium a target organ?
cuz it is oxygen dependent
63
Why is the bone marrow, intestinal mucosa a target organ?
rapidly dividing cells
64
Where can adverse effects occur?
at the level of molecule, cell, organ or organism
65
TOxins interact with ....?
proteins, lipids, RNA, DNA
66
What do toxins interfere with?
```
receptor-ligand binding
membrane function
cellular energy production
alters membrane ion channels
perturb homeostasis (Ca2+)
```
67
What is filtered by the kidney and excreted in the urine?
water soluble products
68
What are exhaled?
volatile compounds
69
Compounds can be excreted by the liver and excreted into the (blank) which will drain into the small intestine and is eliminated in feces
bile
70
What are the ways you can get excretion?
milk, sweat, saliva, bile, feces, exhalation, urine
71
What is the primary objective of metabolism?
to make chemical agents more water soluble and easier to excrete
72
What will metabolism do?
decrease lipid solubility
decrease amount at target
increase ionization
increase excretion rate=decreased toxicity
73
What is this:
| biotransformation can result in the formation of reactive metabolites
bioactivation
74
What is the major mechanism for activating or terminating the biological activity of chemicals?
metabolism
75
Metabolism is frequently the single most important determinant of the (blank) and (blank) of the pharmacological response to a chemical
duration and intensity
76
Where does biotransformation occur?
in liver, kidney, lung, GI and other organs
77
What is paraoxin?
a parasympathomimetic; acetylcholinesterase inhibitor.
78
What is an organophosphate active metabolite of the insecticide parathion?
paraxon
79
What are the key organs in biotransformation?
Liver (high), lung, kidney, intestine (medium), others (low)
80
What is phase I of biotransformation?
make the toxicant more water soluble
81
What is phase II of biotransformation?
Links with soluble endogenous agent (conjugation)
82
What does pharmacogenomics and toxicogenomics do?
identifiy subsets of people at risk for toxicity to chemicals or drugs
83
Who can get underdeveloped biotransformation enzymes and it will result in gray baby syndrome?
premature infants and infants 6-12 months who get chloramphenicol
84
Why can infants have decreased drug affects compared to adults?
they have greater percentage of water than humans so allows for dilution of drug
85
What leads to greater absorption of heavy metals?
stomach is less acidic and periods between stomach emptying are longer
86
WHen is the most sensitive period of the fetus?
3-8 weeks
87
What is an enzyme responsible for acetylating and detoxifying many chemicals including aryl amines?
N-aceytlytransferase
88
Who has slow acetylation (due to lack of n acetyltransferase)?
jews, scandanavans, N. African caucasians
89
Who are fast acetylators?
Inuit and japanese
90
Whats scary about slow acetylators?
greater rates of bladder cancer
91
What is this:
| Enzyme responsible for S-methylation of some anticancer drugs used in chemotherapy (azathiopurine and 6-mercaptopurine)
Thiopurine S-methyltransferase (TPMT)
92
People with (high/low) TPMT levels respond poorly to chemo, since htey conjugate the drugs before they can act (need high dose).
high
93
If you have low TPMT can you use chemo?
no, it will be toxic to them
94
Why are the elderly suscpetible to drug toxicity?
- imparied renal/respiratory function
- inefficient metabolizers
- more fat
- lower water content
- lower cardiac output/perfusion
- low albumin
95
What is bioactivation?
compounds to reactive metabolites
96
What is this:
| colorless, tasteless, odorless-0.1ppm in aire but reaches 100 ppm in heavy traffic.
CO
97
(blank) is formed which does not carry oxygen and decreased O2 transfer of O2-heamoglobin
Carboxyhemoglobin
98
Cigarette smokers have (blank) saturation of Hb by CO.
5-10%
99
What are the effects of hypoxia?
headache, confusions, vision changes, tachypnea, tachycardia, coma, respiratory failure, death
100
How do you treat CO?
removal of CO and treatment of O2
101
What is SO2?
colorless product of fossil fuel combustion, should be 0 ppm; expsoures NOT TO EXCEED 2 ppm
102
What does SO2 do to they body?
Forms acid (H2SO4) on moist membranes-irritant in eyes, mucous membranes, skin (has signif toxicity in the lungs-causes bronchiolar constriction and bronchospasm at great exposure levels
103
What amount of SO2 results in bronchiolar constriction and bronchospasm?
5 ppm
104
How do you treat SO2?
supportive respiratory care
105
What is NO2?
brownish colored gas associated with fires and is a product of fermentation ang given off in large amounts in gran silos (silo-fillers disease)
106
What is considered too much exposures of NO2?
3 ppm
107
What does NO2 toxicity cause?
deep lung irritation- irritating to eyes and nose. has signif toxicity in the lung-pulmonary edema.
108
Exposure to NO2 in high levels for even short periods can cause (blank), (blank), and (blnk)
pulmonary lesions, pulmonary edema, death
109
How do you treat NO2?
supportive respiratory care, use of antibiotics and bronchodilators
110
What is O3?
ozone is a bluish gas that is the product of electrical equipment and generators of ozone use in water purification
111
Exposures of O3 should not exceed (blanK)
0.5 ppm
112
What does O3 toxicity do?
deep lung irritante-irritates eyes and nose -signif toxicity in lung -pulmonary edema
*****causes airway inflammation and hyper-responsiveness*******
113
What is the treatment of O3?
respiratory care, use of antibiotics and bronchodilators
114
Cholinesterase inhibitors include so called (blank) agents
nerve gas (VX, sarin, and soman)
115
What are the symptoms of organosphate and carbamate insecticide poisoning?
DUMBELS (Diarrhea, Urination, Miosis, B(bradycardia); Excitation with muscle fasciculation, anxiety, seizures, Lacrimation, and Seizures)
116
How do you diagnose organophosphate and carbamate insecticide poisoning?
with low plasma or RBC cholinesterase level
117
Organophsphates bind (blank), whereas carbamates are (blank) inhibitors
irreversibly
| reversible
118
How are organosphostates and carbamate insecticides absorbed?
from skin, GI tract and respiratory tract
119
What is parathione?
an organosphosphate insecticide
120
How does parathione work?
if ingested or absorbed, it is converted to paraoxone, an inhibitor of cholinesterase
*****delayed toxicity******
121
How do you treat insecticide poisoning?
```
atropine IV to reverse the muscarinic effects (continue until wheezing and bronchorrhea are gone)
OR
Pralidoxime (i.v.) 2-Pam to reverese the effect of organophosphates at all sites (early, within 24 hours)
```
122
How does pralidoxime work?
chemical phosphorylation reverese the AChE enzyme
123
What is the leading cause of toxic drug ingestions in the US?
acetaminophen (can lead to hepatic toxicity and death w/ greater than 150mg/kg)
124
Acetaminophen is metabolized to a toxic intermediate that can deplete (blank). In infants and adults, this can lead to liver damage. Adults are better at making the metabolite.
hepatic glutathione
125
What is the treatment for acetaminophen poisoning?
oral activated charcoal (w/in 2-3 hr of ingestion)
oral N-acetylcysteine (NAC)
Acetadote (IV n-acetylcysteine) administered IV within 8-10 hrs after ingestion
126
When can you stop giving NAC in acetaminophen poisoning?
if no evident liver injury after 6 hours after ingestion
127
T or F
| Most toxins do not have specific antidotes
T
128
What is the generic name for NAC for acetaminophen poisoning?
Mucomyst
129
When should you not induce emesis with ipecac?
for strong acids, or alkali petrol or stimulants
130
What is the most important treatment for poisons?
activated charcoal
131
What are ways to treat poisons?
```
Dialysis
urinary excretion (alkalinization)
activated charcoal
gastric lavage
emesis (ipecac)
```
132
What is the antidote for organophosphate?
quaternary ammonium oxime (2-PAM) (to reconstitute cholinesterase activity)
133
What is the antidote for formaldehyde poisoning?
ammonia ( to form hexamethylenetetramine)
134
What is the antidote for mercury poisoning?
formaldehyde sulfoxylate
135
What is the antidote for ferrous ion poisoning?
sodium bicarbonate (to convert it to ferrous carbonate)
136
What are the causes of heavy metal poisonings?
lead
arsenic
mercury
iron
137
What is this:
Widely used in manufacturing; [ex. batteries; glass; as an additive to corrosion-resistant paints, binder in plastics, hair dyes]
Children susceptible to inhalation of paint dust, oral contamination by paint chips
Exposure to certain ceramic glazes and gasoline both contact and air pollutant
Lead
138
Why is lead sucky?
intereres with protein function where carboxy phosphate and sulfhydryl binding occurs and where calcium, zinc, and iron binding are important
139
What is the result of lead poisoning?
wide spread dysfuntion;
low level in children-> decreased development and mental retardation. Peripheral neuropathy, nephrotoxicity, anemia
(multi-system effects)
140
Pb both inhaled and ingested binds to (blank) and is deposited in bone/
erythrocytes
141
How can you detect lead?
blood and urine and with imaging
142
How do you treat lead poisoning?
w/ metal chelators such as calcium EDTA and dimercaprol (to enhance Pb excretion)
143
What are the chelators used to treat heavy metals?
```
Dimercaprol
Succimer
EDTA
Penicillamine
Deferoxamine
```
144
What is penicillamine used for?
copper poisoning
145
What is deferoxamine used for?
iron poisoning
146
How do you often get methanol intoxication?
as a result of its use as an ethanol substitute (30-200ml is lethal)
147
Why is methanol bad?
metabolized to ADH to formaldehyde-> metabolized to formic acid by aldehyde dehyrogenase-> formate and formate/formic acid causes acidosis and blindness
148
Toxicity for methanol is delayed (blank) hours
6-30
| metabolism is slow 1/10th that of ethanol
149
How do you treat methanol intoxication?
Supportive measures, airways etc.
- bicarb (for acidosis)
- administer fomepizole to block the alcohol dehydrognase (also used in ethylene glycol poisoning)
- folic acid (to breakdown formic acid)
150
What is TOCP?
an organophosphate found in boot leggers drinks that was a neurotoxin and created paralysis
151
What is dioxin?
mutagen that is toxic and concentration in fat and thymus
152
What are the effects of dioxin?
Acute: eye, skin, and mucous membrae irritation, nausea, vomiting and muscle pain
After a few weeks:polyneurpathies, sensory impairment, lower extremity weakness, motor problems,
153
Is there an antidote for dioxin?
no but you can use olestra to promote elimination decreased half-life from 7 years to 1-2 years
154
What is a more common name for dioxin?
agent orange
155
What substance is most commonly involved in human poison exposure?
least likely?
analgesics
| chemicals
156
What substance causes the largest number of deaths?
| Least?
analgesics
| pesticides
157
Benzes exposure is linked with (blanK0
leukemia and aplastic anemia
158
Mercury interferes with (blank)
development
159
What are some known carcinogens?
```
aflatoxins
alcohol
analgesics w/ phenacetin
cyclosporin A
tobacco smoke
estrogens, steroidal
```
160
Initial management of the poisoned patient begins with the (blank).
Then use (blank)
Then (blank)
ABC’s.
ACLS algorithms
consider bioavailability and H and P
161
Besides the usual vitals what else should you get from the patient?
blood glucose
162
(blank) are key to your initial managament of the patient
vitals
163
If you smell bitter almonds what is the poison?
cyanide
164
If you smell mothballs what is the poison?
camphor
165
If you smell garlic what is the poison?
organophosphates, arsenic
166
If you smell peanuts what is the poison?
rodenticide
167
If you smell carrots what is the poison?
water hemlock
168
If you smell rotten eggs what is the poison?
sulfur dioxide, HS
169
If you smell wintergreen what is the poison?
methyl salicylates
170
If you smell gasoline what is the poison?
hydrocarbons
171
If you smell fruity what is the poison?
DKA, isopropanol
172
If you smell pears, what is the poison?
chloral hydrate
173
The most commonly reported poison?
analgesics
174
The least commony reported poison?
alcohol
175
The most commonly associated posion with death?
analgesics
176
What poison is least associated with death?
hydrocarbons
177
What is the number one poisonous killer?
carbon monoxide
178
Why do you want to get an EKG?
look for conduction delay and ischemia
179
Why do you want to get CMP?
to calculate anion gap and osmolality
180
Why do you want to check tylenol and aspirin levels?
frequency of abuse and co-ingestionn
181
What do serum volatiles tell you?
quantitative amounts of alcohols (for people with altered mental state of unknown etilogy)
182
WHy check the urine?
screening (rarely changes management)
183
What check the blood?
for quantitative info regarding spec. ingestants
184
What is the coma cocktail and what is it for?
Dextrose, Narcan, Thiamine
cuz the three most likely reasons for being unconscious in the ER are:
ketoacidosis (diabetes)-> dextrose
Opoid overdes-narcan
Too much alcohol (thiamine deficiency)-> thiamine (malnourished)
185
When do you give flumazenil?
For people who we overdose with benzos
186
Do we still use ipecac?
no!!
187
What do you use to manage GI decontamination?
gastric lavage: use with "moderate to severe overdoses" within an hour of ingestion
****variable outcome*****
Activated charcoal
188
When should you not give lavage?
contraindicated with ingestion of corrosives
189
Which is better gastric lavage or charcoal?
charcoal (used within an hour of ingestions)
190
What is the dose for charcoal?
1g/kg or 10: 1 ration of charcoal to poison
191
When do you give cathartics?
with charcoal to enhance elimination
192
When should you use whole bowel irrigation?
- for things not absorbed by charcoal
| - used for body stuffer/packers
193
What is the antidote to anticholinergics?
physostigmine
194
What is the antidote for anticholinergics?
physostigmine
195
What is the antidote for arsenic/lead?
BAL chelation
196
What is the antidote for beta-blockers?
glucagon
197
What is the antidote for benzos
flumazenil
198
What is the antidote for CO?
O2, HBO
199
What is the antidote for cyanide?
Nitrites
200
What is the antidote for digoxin?
digibind
201
What is the antidote for ethylene glycol/methano?
fomepizole/ethanol
202
What is the antidote for iron?
deferoxamine
203
What is the antidote for INH?
B6/pyridoxine
204
What is the antidote for Lead/mercury?
succimer/DMSA
205
What is the antidote for methemoglobinia?
methylene blue
206
What is the antidote for opoids?
naloxone
207
What is the antidote for organophosphates?
atropine
208
What is the antidote for Tricyclic Antidepressants's?
sodium bicarbonate
