Xenobiotics and the Nervous System

Question 1

List the ways xenos can alter the NS

Answer 1

1. Xenos can alter [neurotransmitter] in the synapse
   
   2. Xenos that interfere with post syn receptors
      
      3. Xenos that interfere with action potentials

Question 2

list the xenos that can alter [NT] in the synapse

Answer 2

organophosphates; insectisides; botulinum toxin; cocaine; SSRIs; black widow spider venom

Question 3

how do OPs affect the NS?

Answer 3

i. Inhibit acetylcholine-esterase

ii. Ach doesn’t get degraded to acetate + choline–>constant stimulation

Question 4

how does botulinum toxin affect the NS?

Answer 4

i. Blocks ACh release–!!

ii. Most toxic xeno we know of

Question 5

how does cocaine affect the NS?

Answer 5

i. Blocks NE uptake into presyn membrane
ii. Blocks the “stop signal”–>which is the reuptake by enzymes
If reuptake is blocked, will have a similar effect to OPs–> heart beats so fast that it exhausts

Question 6

how do SSRIs affect the NS?

Answer 6

i. Selective serotonin reuptake inhibitors
ii. Antidepressant (Prozac, Paxil)
iii. Serotonin binds to serotonergic receptors
1) Blocking the receptors gives higher conc of ser in the synapse–>elevation in mood
iv. Selective
1) Old drugs would also inihibit reuptake of NE

Question 7

how does BW spider venom affect the NS?

Answer 7

Empty the storage vesicles of ACh

Question 8

what xenos interfere with the postsyn membrane receptors?

Answer 8

1. gamma amino-butyric acid (GABA); b. 2. Glutamate is the major stimulatory NT in our CNS
2. Alpha-bungarotoxin

Question 9

what interacts with GABA receptors,

Answer 9

Barbiturates–sedatives (early types); Benzodiazepines-sedatives; Ethanol activates GABA receptors; GHB –gamma hydroxybutryic acid

Question 10

how do barbiturates affect the NS?

Answer 10

1) Synergistic effect w alcohol–sedation n death

2) Depress CNS–>respiratory collapse

Question 11

how do Benzodiazepines affect the NS?

Answer 11

1) GABA agonist

a) Subs that mimic ligand, bind to receptor GABA and produce a calming, sleepy effect

Question 12

how does ethanol affec the NS?

Answer 12

activates GABA receptors

1) Allosteric effector-->binds at allosteric site, makes GABA have more effect on GABA receptor
2) Happens after several drinks

Question 13

how does GHB affect the NS?

Answer 13

1) “date rape” drug

Causes sedation, same as sleeping pills

Question 14

how does glutamate affect the NS?

Answer 14

overstimulates – become excited

Question 15

what is Alpha-bungarotoxin and how does it affect the NS?

Answer 15

i. Produced by cobra
ii. Cobra venom
1) Binds irreversibly (covalently) to cholingernic receptors–nicotinic specificly
Suicide inhibition

Question 16

what xenos interfere with APs?

Answer 16

tetrodotoxin; DDTs

Question 17

how does tetrodotoxin affec tthe NS?

Answer 17

i. Puffer fish

Blocks Na channels in the nerves

Question 18

how does DDT affect the NS?

Answer 18

• -insecticide (nonspecific–works on humans)
  i. Overstims of Na channel in nerves
  ii. Channels remain open, lots of Na goes in–>v depolarized

Question 19

what are the substances that reverse OP poisoning?

Answer 19

atropine, pralidoxone, benzodiazepene

Question 20

how does atropine reverse OP poisoning?

Answer 20

antagonist of muscarinic receptor (blocker)–

Question 21

how does pralidoxine/2-PAM reverse poisoning?

Answer 21

○ OPs Bind to ACh-esterase–inactivate

○ 2-PAM Reactivates enzyme –pulls OP off of enzyme

Question 22

how does benzodiazepene reverse OP poisoning?

Answer 22

OP poisoning leads to excitement/anxiety–BDZ relaxes them