Rankin- Toxicology- (1)- Leah :) Flashcards Preview

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Flashcards in Rankin- Toxicology- (1)- Leah :) Deck (33):
1

Main principle of toxicology?
Whats an LD50?

-Dose dictates toxicity

LD50, He says: "You might want to know this.*
-lethal dose in 50% of the population
-HIGH LD50 = SAFER
-LOW LD50 = DANGER

2

There are many scales for ranking the toxicity of substances.... what rating do they lack?

-NON-TOXIC; most any substance is toxic in a large dose

3

-#1 cause of poisoning in the US?
-major sources?
-minor sources?

CARBON MONOXIDE
-colorless, odorless, tasteless= you don't know you're being exposed
-major sources: incomplete combustion of fossil fuels
(car exhausts i.e. Shane Gandee from Buckwild/ my high school, kerosine heaters, house fires)

-minor sources: cigarettes; hemolytic anemia, paint removers w/ methylene chloride

4

What two chemicals cause poisoning in house fires?

CO + cyanide

5

How does CO cause poisoning?

-Binds ferrous iron (Fe2+) in Hb = COHb
-Binds 250x tighter than O2-->
-DECREASE O2 carrying capacity of the blood
-INCREASE time to release O2 from Hb--> Tissue

= Anoxia --> main target = globus pallidus --> respiratory failure
= Cherry red mucus membranes

6

How is CO related to forensics?

In shootings, CO binds heme containing proteins (other than Hb) in tissues, when close up.

Short range gun wounds should have cherry range appearance, long range less likely to see red tissue.

(.....I think you would be red and bloody regardless, but whatever. Lol: he was really excited about that and the house fires. Haha)

7

At what level of CO is poisoning symptomatic?

-Mild sx up to 20-30% COHb
(person likely won't know they are sick)

-Moderate symptoms at 40%+ COHb
(i.e. severe headache)

-70%+ COHb
(risk resp failure, death)

8

Treatment of CO poisoning?
-at 10-20%?
-At 20+% and severe H/A?
-At 50%+

-10-20%: remove the source, get fresh air
-20%+: give 100% O2
-50%+: give 100% O2 + hyperbaric O2

9

How are patients exposed to CN? (4)

-occupational exposure (mining, chemical synthesis etc)
-certain drugs (i.e. laetrile for cancer)
-apricot or peach pits
-fires (esp if plastic is burnt)

10

How does cyanide cause poisoning?

-Inhibits electron transport chain
-Binds ferric iron (fe 3+) of cytochrome oxidase

11

Who is especially sensitive to cyanide?

- Children
- LD50 much lower possibly in kids due to less developed cellular machinery

12

Symptoms of CN poisoning

-RAPID progression (esp compared to CO)

-Nausea/ light headedness --> feeling of suffocation (can't use O2 due to screwed up ETC) --> hyperventilation --> resp failure --> death (or severe brain damage)

13

Normal detoxification of cyanide:
-How is it detoxified in the liver?
-How does it get to the liver for detox?

Liver: Make thiocyanate, less toxic metabolite
CN + (S2O3)2- --> SCN- + (SO3)2-
via: *sulfotransferase*

-Binds ferric iron (3+) in methemoglobin in blood for transport to the liver (CN---FeHb complex)

14

How is cyanide poisoning reversed?
(two steps)

1. Use oxidizing agent (i.e. sodium/amyl nitrite) to make more methemoglobin--> sequester CN

2. Administer thiosulfate to ^^ sulfotransferase activity in liver

15

How do you lower methemoglobin levels post treatment for CN poisoning?

methylene blue (reducing agent, reduces Fe3+ to Fe 2+)

16

#1 reason agricultural crops are lost?

-#1- fungal infection of healthy plants

17

DiazinON + malathiON are what kind of insectisides?
Which is most toxic?
Which is still on the market?

-organophosphates
-diazinon is most toxic (lower LD50) (D for Danger/ di for die!)
-malathion is still on the market for home gardeners

18

How do organophosphates poison humans?
insects?
What are the classic symptoms?

-Phosphorylate AchE--> inhibit acetylcholinesterases in both humans and insects

-Get anticholinergic ADRs (parasympathetic effects)
-SLUDE BBB

19

What are the nicotinic effects of organophosphate poisoning?***

KNOW: organophosphates classically cause "parasympathetic sx" but they ALSO have nicotinic effects:
- ^^ HR/ BP
- muscle twitching

(I HAD A QUESTION ON THIS AND WAS CONFUSED BECAUSE I ONLY KNEW ORGANOPHOSPHATES CAUSE SLUDE BBB!!! Know that they also cause nicotinic effects!!!)

20

How do you treat organophosphate poisoning? (2)

-atropine
-pralidoxime (2PAM) to regenerate AchE
(removes phosphate group if administered prior to 'aging'--give fast)

21

How do you determine the severity of organophosphate tox?
Problem with this method?

measure levels of serum cholinesterase

*Some genetic polymorphisms naturally cause lower cholinesterase levels.

22

Carbaryl (Sevin Dust) is what kind of pesticide?
Who uses it? For what plant?
How does it kill humans?
How does it cause toxicity?

-carbamate
-easily purchased by home gardeners; used on tomatoes to kill tomato worms
-respiratory failure

23

How does carbaryl cause toxicity?
How does it compare to organophosphates?

-same mechanism as organophosphates (AchEi) but carbamylates instead of phosphorylating

-will reverse itself more quickly than phosphorylation in organophosphate poisoning

24

How do you treat carbaryl/ carbamate poisoning?***

-atropine only; **no 2PAM**
(will get WORSE if you use 2PAM)

He says: "You might want to know this."

25

Paraquat is what kind of compound?
For what is it used in the US?
Then what happens?
How is this used in Japan?

-herbicide

-THE COPS USE IT TO KILL A BUNCH OF MARIJUANA!
(They get in a helicoper and spray this shit all over the field when they find your field of weed.)
-The marijuana farmers rush out, grab their precious harvest and then they smoke paraquat (poison) laced marijuana.... and they die.

-#1 suicide method in Japan

26

How does paraquat cause toxicity?

-quaternary ammonium compound, accepts electrons.
-generates superoxide anion radical
-lipid peroxidation and leaky cell membranes ensue

27

What are the symptoms of:
-inhaled paraquat
-ingested paraquat
-skin/ eye contact w/ paraquat

-inhaled: SOB --> pulm edema/ fibrosis if chronic

-oral: ulceration of mucus membranes in GI tract --> absorb paraquat --> systemic toxicity

-dermal/ ocular: skin ulcers, corneal lesions, cataract

28

How to reverse paraquat toxicity?

-gastric lavage if oral
-hemodialysis/ hemoperfusion

29

How do determine presence of paraquat in patient?

- sodium dithionite is added to urine or plasma
-look for blue color change
- blue color = paraquat present
- green color= probably "diquat" whatever that is.

30

Benzene:
-where is it found?
-structure?
-type of toxicity acutely?
-chronically?

-gasoline
-simple aromatic ring
-CNS depressant acutely
-Anemia/**leukemia/lymphoma** chronically

(reason our gas pumps have a little plastic shield around them)

31

How does benzene cause cancer?

-benzene --> phenol (intermediate = reactive epoxide benzene oxide)
-phenol --> quinol (an ALKYLATING moiety)

**Normally: quinol detoxified
-Individuals with polymorphisms in "DT Diaphorase" don't detoxify these quinols --> alkylation --> leukemia and lymphomas


32

Toluene and xylenes:
-replaced what compound?
-What are they used in?
-What does acute tox cause?

-replaced benzene as solvent in many cases, due to benzene's carinogenic properties
-found in glues and paint thinners
-acute tox (paint huffing, glue sniffing) --> CNS depression

**BUT NO CANCER!

33

Toluene and xylenes:
how does their structure differ from benzene?
why don't they cause cancer?

-simple aromatic ring + methyl group
-No quinol (alkylaying agent) formation
-Get side chain methyl groups in their metabolic pathways instead of adding hydroxyl groups to make phenol --> quinol