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Block 7; Week 3-Michelle > Toxicology-Buxton > Flashcards

Toxicology-Buxton Flashcards

(93 cards)

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1
Q

What are the 2 relationships to think about with toxicology?

A

Conc’n-Effect

Dose-Response

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2
Q

What are some ways to describe a dose-response relationship?

A

local v. systemic
reversible v. irreversible
immediate v. delayed
graded v. quantal

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3
Q

Which do you use to describe an individual & which do you use to describe a population?
Graded, Quantal

A

Graded: individual
Quantal: Population

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4
Q

What is ED50?

A
  • Median Effective Dose 50; the dose at which 50 percent of the population or sample manifests a given effect; used with quantal d/r curves
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5
Q

What is TD50?

A

Median Toxic Dose 50 - dose at which 50 percent of the population manifests a given toxic effect

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6
Q

What is LD50?

A

Median Toxic Dose 50 - dose which kills 50 percent of the subjects (animal studies)

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7
Q

What is the therapeutic index?

A

LD50/ED50

OR TD50/ED50

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8
Q

What is the margin of safety for drugs?

A

LD1/ED99

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9
Q

What is the margin of safety for toxins?

A

NOAEL/Exposure

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10
Q

Which does Buxton like more–NOAEL or MABEL?

A

MABEL: minimal anticipated biological effect level

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11
Q

What makes a good drug: a lower or higher therapeutic index?

A

higher the TI–better the drug

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12
Q

T/F Drugs acting on same receptor or enzyme have the same therapeutic index.

A

True.

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13
Q

What happens if your Vitamin A is too low?

A

blindness
dry skin
increased infections

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14
Q

What happens if your Vitamin A is too high?

A

anorexia
anemia
nose bleeds
muscle & joint pain

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15
Q

Describe the group to which Vitamin A belongs.

A

unsaturated nutritional hydrocarbons

  • *includes retinol, retinal, retinoic acid, beta-carotene
  • *regulates gene transcription at RXR receptors
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16
Q

What is the adequate adult intake of Vitamin A?

A

3 mg/day

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17
Q

Give the time frames for acute, subacute, sub chronic, chronic exposures to a toxin.

A

Acute: 3 mo

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18
Q

What is the purpose of metabolism?

A 
decrease lipid solubility
decrease amt at target
increase ionization
increase excretion rate
**all help make chemical agents more water soluble & easier to excrete
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19
Q

What is paraoxon?

A

parasympathomimetic acetylcholinesterase inhibitor

organophosphate active metabolite of insecticide parathion

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20
Q

What terrible thing happened with Project Coast?

A

South Africa
during apartheid
tried to use paraoxone to sterilize black people

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21
Q

What are the key organs for biotransformation? What are the 2 biotransformation pathways?

A

Liver, Lung, Kidney, Intestine
Phase 1: make the toxicant more water soluble
Phase 2:link w/ a soluble endogeneous agent (conjugation)

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22
Q

What is N-acetyl transferase?

A

enzyme responsible for acetylating & detoxifying many chemicals including aryl amines
some people are slow acetylators & others are fast–>individual susceptibility!

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23
Q

Who are the slow acetylators? Fast?

A

Slow: Me, Scandinavians, Jews, North African Caucasians
Fast: Inuit, Japanese

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24
Q

What’s the problem with being a slow acetylator?

A

you have a higher rate of bladder cancer formation etc. if you are exposed to N-aryl amine & are a slow acetylator

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25
What is thiopurine S-methyltransferase (TPMT)?
enzyme responsible for S-methylation of anti-cancer drugs used in chemo (like azathiopurine & 6-mercaptopurine)
26
What is the individual susceptibility significance of being a person with high TPMT levels?
respond poorly to chemo b/c they conjugate drugs before they can act
27
What's the problem with CO in the air or in smokers?
it forms carboxyhemoglobin which doesn't carry O2 | effects: headache, confusion, vision changes, tachypnea, tachycardia, coma, respiratory failure, death
28
What is SO2?
colorless product of fossil fuel combustion | exposure shouldn't exceed 2 ppm in air pollution
29
What is bad about SO2?
forms acid (H2SO4) on moist membranes irritates the eyes, mucous membranes, skin toxic for the lung causes bronchiolar constriction & bronchospasm at greater exposure levels
30
What is NO2 in air pollution?
brownish gas associated with fire product of fermentation given off in large amounts in grain silos can't exceed 3 ppm without really bad effects
31
What are the bad side effects of having NO2 in the air?
deep lung irritant: irritating to eyes & nose significant toxicity in lung-pulmonary edema can cause pulmonary lesions, pulmonary edema, death
32
What is O3?
ozone is a bluish gas that is a product of electrical equipment & generators of ozone used in water purification can't exceed .5 ppm without bad effects
33
What's the issue with having O3 in your body?
deep lung irritant--pulmonary edema airway inflammation hyper-responsiveness
34
What's the deal with the toxicity of organophosphate & carbamate insecticides?
they are cholinesterase inhibitors organophosphates bind irreversibly carbamates are reversible inhibitors **rapidly absorbed from skin, GI, resp tract
35
Who is at risk for organophosphate toxicity?
workers who are constantly exposed to organophosphates | infants with underdeveloped cholinesterase activity--at greater risk
36
What are the symptoms of organophosphate & carbamate & how do you make the diagnosis?
Symptoms: DUMBELS: diarrhea, urination, miosis, bronchorrhea, bradycardia, excitation with muscle fasciculation, anxiety, seizures, lacrimation can die from resp depression diagnosis: low plasma or red blood cell cholinesterase level
37
What is parathione?
organophosphate insecticide
38
What's the toxicity of parathione?
delayed toxicity once ingested it is converted into paraoxone paraoxone is an inhibitor of cholinesterase
39
What do you do when you treat insecticide poisoning?
atropine (reverse muscarinic effects) pralidoxime (2-pam)--reverses the effects organophosphates (reversal of the phosphorylation of acetylcholinesterase enzyme)
40
T/F Ibuprofen is the Leading cause of toxic drug ingestions in the United States. These can lead to hepatic toxicity and death when ingested in quantities of 150 mg/kg or more. Currently found in over 600 Rx and OTC products.
FALSE | acetaminophen
41
How can acetaminophen lead to liver damage?
when it is metabolized...its toxic intermediate can deplete hepatic gluathione liver damage in infants or adults
42
What is the treatment for acetaminophen poisoning?
Oral activated charcoal 60–100 g mixed in aqueous slurry (if given within 2–3 h of acute ingestion) **Oral N-acetylcysteine (NAC), Mucomyst. 140 mg/kg loading dose, followed by 70 mg/kg Q 4 h for 72 hr. Acetadote® (i.v. N-acetylcysteine), administered intravenously within 8 to 10 hours after ingestion of a potentially hepatotoxic quantity of acetaminophen, is indicated to prevent or lessen hepatic injury (21 hr infusion). Alternate oral treatment end point: may stop NAC if no evident liver injury at 36 h after ingestion Fulminant liver failure may require emergency liver transplantation
43
In general what is the approach for treating poisoning? Note: most toxins don't have specific antidotes-like acetaminophen
``` Treat the patient not the poison emesis (ipecac) *not for strong acids or bases, petrol or stimulants Gastric lavage activated charcoal urinary excretion (thru alkalination) dialysis ```
44
Once again, what is the antidote for organophosphate poisoning?
quaternary ammonium oxime (2-pam) | **reconstitution of cholinesterase activity
45
what is the antidote for formaldehyde poisoning?
ammonia | **Forms hexamethylenetetramine
46
What is the antidote for mercury poisoning?
formaldehyde sulfoxylate
47
What is the antidote to convert ferrous ion to ferrous carbonate?
sodium bicarb
48
What are some common heavy metal poisonings?
Lead Arsenic Mercury Iron
49
What is the MOA that makes lead poisonous?
interferes protein function where carboxyl, phosphate, sulfhydryl binding occurs where calcium, zinc, iron binding are important
50
What is the result of lead poisoning?
widespread dysfunction possible binds to erythrocytes & can be deposited in bone children: mental retardation, peripheral neuropathy, nephrotoxcity, anemia
51
What is the treatment for lead poisoning?
metal chelators | calcium, EDTA, dimercaprol
52
What are some chelators that are in use to treat heavy metal toxicity?
``` Chelators in use are: Dimercaprol (British antilewisite) Succimer (dimercaptosuccinic acid) EDTA (general) Penicillamine (copper poisoning) Deferoxamine (iron poisoning) ```
53
Why can methanol be toxic? Why are people usu exposed?
exposed when it is used as an ethanol sub 30-200 mL is toxic methanol-->formaldehyde via alcohol dehydrogenase formaldehyde-->formic acid via aldehyde dehydrogenase formate=acidosis & blindness
54
What is the metabolism of methanol like compared to ethanol? What is the toxicity timeline for methanol?
1/10 the metabolism of ethanol | toxicity 6-30 hrs after ingestion
55
What is the treatment for methanol poisoning?
Supportive measures, airway etc. Correct acidosis with bicarbonate Administer fomepizole to block the alcohol dehydrogenase (also used in ethylene glycol poisoning) Administer folic acid to enhance breakdown of formic acid
56
The Ginger Jake drink during prohibition caused Jake leg. What toxin was in it? What is this Jake paralysis now called?
Toxin was TOCP (an organophosphate) neurotoxin--axonal damage to spinal cord neurons delayed paralysis by 1-3 weeks called organophosphate induced delayed neuropathy (OPIDN)
57
Where is dioxin found? this is the Times Beach toxin.
concentrated inf at & thymus
58
what are the symptoms of dioxin exposure?
Acute exposure causes eye, skin and mucous membrane irritation, nausea, vomiting and muscle pain Polyneuropathies, sensory impairment and lower extremity weakness and motor problems present after a period of weeks
59
What is the treatment for dioxin?
There is no antidote | Administration of olestra can promote elimination decreasing the T1/2 of dioxins from 7 to 1-2 years
60
What is risk?
known impacts & known probabilities
61
What is uncertaintY?
known impacts & unknown probabilities
62
What is ignorance?
unknown impacts & unknown probabilities
63
What are some important human carcinogens to keep in mind?
``` aflatoxins alcoholic beverage consumption analgesic mixtures containing phenacetin cyclosporin A environmental tobacco smoke estrogens (steroidal) ```
64
What are some drugs that can cause bradycardia?
``` PACED propranolol, poppies anticholinesterases clonidine, CCBs Ethanol Digoxin ```
65
What are some drugs that can cause tachycardia?
``` FAST freebase anticholinergics/antihistamines amphetamines sympathomimetics solvents theophylline ```
66
What are some drugs that can cause hypothermia?
``` COOLS carbon monoxide opiates oral hypoglycemics liquor sedatives/hypnotics ```
67
What are some drugs that can cause hyperthermia?
``` NASA NMS, nicotine antihistamines salicylates sympathomimetics anticholinergics antihistamines ```
68
What are some drugs that can cause hypotension?
``` CRASH clonidine, CCBs reserpine antihypertensives antidepressants aminophylline sedative/hypnotics heroin (opiates) ```
69
What are some drugs that can cause hypertension?
``` CTSCAN Cocaine thyroid supplements sympathomimetics caffeine antichoinergics amphetamines nicotine ```
70
What are some drugs that can cause hypoventilation?
``` SLOW Sedative/hypnotics liquor opiates weed (marijuana) ```
71
What are some drugs that can cause hyperventilation?
``` PANT PCP Pneumonitis Noncardiogenic pulmonary edema toxic metabolic acidosis ```
72
What are some drugs that can alter mental status?
``` AEIOU TIPS Alcohol Endocrine/Epilepsy intoxication oxygen uremia trauma/tumor infection psychological shock/strokes ```
73
What are some drugs that can cause seizures?
``` OTIS CAMPBELL Organophosphates Tricyclics INH/Insulin Sympathomimetics Camphor/Cocaine Amphetamines Methylxanthines PCP Benzo withdrawal Ethanol Lead/Lithium LIdocaine LIndane ```
74
What are some things that can cause miosis?
``` COPS Cholinergics Clonidine Opiates Organophosphates Pontine bleed Phenothiazines Sedatives/hypnotics ```
75
What are some things that can cause mydriasis?
``` AAAS Antihistamines Antidepressants Anticholinergics (Atropine) Sympathomimetics (Cocaine) ```
76
What are some things that can cause diaphoresis?
``` SOAP sympathomimetics organophosphates ASA PCP ```
77
What are some drugs that can cause red skin?
CO Boric Acid Anticholinergics
78
What are some things that can cause blue skin?
cyanosis | MetHB
79
What are some substances that can cause blistering?
barbituates CO sedative hypnotics snake/spider bites
80
``` What creates the smell in the following? Bitter Almonds Mothballs Garlic Peanuts Carrots Rotten Eggs Wintergreen Gasoline Fruity Pears ```
``` Bitter almonds: Cyanide Mothballs: Camphor Garlic: Organophosphates, Arsenic Peanuts: Rodenticide Carrots: Water hemlock Rotten eggs: Sulfur dioxide, HS Wintergreen: Methyl salicylates Gasoline: Hydrocarbons Fruity: DKA, Isopropanol Pears: Chloral hydrate ```
81
``` Most commonly reported poison? Least commonly reported? Associated with the most deaths? Associated with the least deaths? Number one poisonous killer? ```
``` The most commonly reported poison? Analgesics! The least commonly reported? Alcohol! Which is associated with the most deaths? Analgesics! Which is associated with the least deaths? Hydrocarbons! The number one poisonous killer? Carbon monoxide! ```
82
When would you need an EKG after a poisoning?
``` to look for conduction delays & ischemia sympathomimetics Beta blockers TCAs digoxin CCBs CO ```
83
When would you need a comprehensive metabolic panel after a poisoning?
To calculate anion gap and osmolality
84
Why might you need a chest X-ray after a poisoning? Which agents are we talking?
``` Pulmonary Edema MOPS Meprobamate Methadone Opiates Phenobarbital Propoxyphene Salicylates ```
85
What is diaphoresis?
perspiring profusely
86
When would you need a KUB (kidney ureter, bladder X-ray) after a poisoning?
``` COINS Chloral hydrate cocaine packets opiate packets iron (heavy metals) neuroleptics sustained release/enteric coated tabs ```
87
When is flumazenil used?
used for people who are overdosed on benzos
88
What is the coma cocktail?
dextrose narcan thiamine
89
When is gastric lavage contraindicated?
after ingestion of corrosives
90
Use multiple doses of charcoal as treatment after ingesting which drugs?
``` antimalarials aminophylline ASA barbiturates Beta blockers carbamazepine dapsone dilantin ```
91
When do you not need multiple doses, but rather a single dose, of charcoal to treat?
``` CHARCOAL Caustics/Corrosives Heavy Metals Alcohols Rapid Onset Cyanide Chlorine/Iodine Other insolubles aliphatic laxatives ```
92
When are cathartics used?
given with charcoal to enhance the elimination of the poison
93
When do you use hemodialysis to treat a poisoning?
``` ISTUMBLE Isopropranolol salicylates theophylline uremia methanol barbiturates lithium ethylene glycol ```

Block 7; Week 3-Michelle (6 decks)

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