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Toxicology
Kronzuckers BIOC65
74
Pharmacology
Undergraduate 4
12/06/2010

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Term
[K+]outside
[K+]inside
[Na+]outside
[Na+]inside
[Ca2+]outside
[Ca2+]inside
[Cl-]outside
[Cl-]inside
Definition
=5mM
=140mM
=120mMx
=20mM

=100nM-200nM
=125mM
=9mM
Term
NERNST EQN
Definition
PSI n(nernst potential) of a given Ion (X+)= [(R *T)/(z*F)] * ln ([X+])outside/[X+] inside)
Term
Na channel inhibitors
Definition
Saxitoxin
Brevetoxin
Propofol (anasthetic)
Lidocane (dentist)
Tetrodotoxin
Term
K+ Nernst potential
Na+ potential
Ca2+ potential
Cl- potential
Definition
=-89mV
=+48mV
=+124mV
=-71mV
Term
Nernst
R=
T=
z=
F=
Definition
=gas constant: 8.3143j/k/mol
=temp in K
z=valence state
farrady constant: 96,485 coloumbs/mol
Term
Benzodiazepines
Definition
GABA A receptor to open Cl- channel driving to inhibit AP
Term
Na+ channel inactivation blockage
Definition
Gryanotoxin (rododendron=Sherlock Holmes)
Banana Spider
Scorpion Venom
Term
Na/K ATPase is a
Definition
Primary Transporter
uses 70% of the bodies energy
Moves 2 Na out for 3 K in
is a primary transporter coupled to ATP
Term
Oubain
Digoxin
Definition
Blocks cardiac Na/K ATPase entirely
inhibits cardiac myocytes' ATPase
Term
2ndary Na transport system
Definition
2Na/Ca
makes myocytes more contractile than normal
Term
Ca2+ channel blocker
Definition
Prevents vesicles from fusing with membrane-preventing ACH release
Leads to rapid heart AP in heart
Black Mamba poison
Tarantula Poison
Term
Ca2+ influx causes
Definition
AP plateau-prolongs AP
Channels close after 200ms-responsible for the +ve Inotropy
Term
K+ channel blockage
Definition
Tarantula Poison
Term
Cl- agonist
Definition
Killed Heath Ledger
Ambien
Works on Gaba A receptors
Term
Cl- influx impt for
Definition
inhibition of AP-
-ve charge brought in by Cl-, negates the Na+ +ve charge.
Term
GABA A receptors are
Definition
between A1 and G2 subunit on the Cl- ionotropic channel
brings down AP's, spasms,
is an anxiolytic, anti-depressant
Term
ACH blockers
Definition
Rattlesnake Toxin-prevents vesicle fusion
Botox: prevent fusion
Curare
Cobra- ACH antagonist receptor blocker
Succinylcholine: ACH antagonist
Pancuronium
Term
ACH release stimulators
Definition
a-Latrotoxin (B.widow spider):quicker vesicle fusion
Term
ACH agonist
Definition
Epibatidine: poison dart frog
Nicotine
Muscarine
Term
ACE blocker
Definition
Green mamba:agonist
Organophosphates
Carbamines
Nerve gas
Sarin Gas
Term
Cocaine
Definition
works on DA release-speeds up release and inhibits breakdown/reuptake
Term
MDMA-ecstacy
Definition
similar to tyrosine and DA
creates quicker release of NTRAnsmitters
Serotonin =Ve feedback through input of amines
similar to NE symptoms
Family of amphetamines
Term
Phenethylamine
Definition
DA feel good-same for chocolate reward
Term
Myristicin
COLD FX-ginseng
Resveratrol
Catechins
Liquorice
Definition
MAO inhibiter-not an AMINE
Rise in BPress

Serotonin syndrome=too much SE can increase diastole to ~120mmHg from 80mmHg
Term
Cheese syndrome
Definition
TYRAMINE-similar to DA
Can require ER trips if on MAO's as well
Term
OD TREATMENTS:
Definition
Nitric Oxide: rapid blood vessel dilation
Nitroglycerin-large dose needed
Nitroprusside
VIAGRA
Niacin & arginine
ICARRIN-epimedium-HORNY GOAT WEED: used to lower blood pressure, produces NO, and raises CGMP
Term
Clostridium Tetani
Definition
Inhibits GABA & glycine= tetanic spasm
Term
Glycine& GABA blocker
Definition
Stychnene=excitatory tetanic spasm
Term
Gustave Maeler
Definition
died via Step. Viridians from heart valve infection via Hemolysin production which oxide hemoglobin
Term
Staph Aureus
Definition
Superantigens: B-barrel proteins creating superpermeable membranes
CAuses EXPLOSIVE WBC multiplication= necritizing faciitis
Term
RICINus COMMUNIS
Definition
Protein production:
Hydrolase(makes cell like water/damages protein) finds large 60S rRNA subunit and causes depurination of ribosomes (purine liberation-requires injection of toxin
Lectin makes cells permeable to hydrolase
Term
CN- affects
Definition
Cytochrome C oxidase-
as does azide and CO
Term
H+ concentration is kept similar to Ca2+ in cytosol @
Definition
=100nM
Term
With acid burns, treatment is
Definition
wash with flowing water, constrict peripheral blood vessels and minimize inflammatory response
Term
Henderson hasselbalch is and used for
Definition
pk= pH-log [A-]/[HA]
use for derivation of pH and measure of acidity
Term
Hansch coefficient
Definition
§ The HANSCH coefficient = log10 [X]octanol/[X]water
□ Looks at the solubility of any compound in a solvent
Term
High K ow compounds
Definition
Trazodone
Lofepramine-gets worse if liver tries to detox (tri-cyclic)
Term
Toxicological Potentiation
Definition
When the liver tries to detox a compound and makes it even more dangerous i.e. lofepramine
Term
BPA mimics
Definition
Estradiol-can affect fetus and cell division
Term
DDT hansch =
Definition
6
Silent springs looked at DDT making the shells of Ospreys extremely brittle preventing Ca2+ deposition
Term
All metals are Lewis
Definition
acids
have partially empty orbital
with potential to react with Lewis Bases
Term
Most metals are toxic in their ____state
Definition
Charged
Term
Vanadium has these states and this is most biologically toxic
Definition
3+ and 5+
5+ is most toxic as Vanadate after loss of the 2 4s electrons
Term
Name for a partially empty orbit
Definition
Lewis Acidic center-highly reactive with Lewis Bases
6 available centers is the most unstable metallic state
Term
the most stable bonding form is the____with the arrival of ____bonding partners
Definition
The octahedron with 6 bonding partners
The tetrahedron with 4 partners is also stable(less)
Term
Iron has __ and __ states found in __ and __
Definition
2+ and 3+, found in hemoglobin and myoglobin
Fe2+ is the more dangerous form due to rapid GI uptake
Fe3+ is eliminated
Term
Fe2+ overload leads to ___
Definition
The Fenton Reaction:
Fe2+ and H2O2 creates Fe3+ and OH radicals
Then OH- and Fe3+ reacts with another H2O2 and produces the lethal OOH- radical
Term
As Fe2+ is, it would bond best to
Definition
CN-, when compared to H2O, CO and NH3+.
6 CN- would bind to Fe2+ creating [Fe(CN)6]4-.
Term
arsenic's _ state is more toxic than it's _ state
Definition
5+ more toxic than 3+
Term
Blue baby syndrome
Definition
when babies eat food high in NO3--> converts to NO2 which displaces O2 and suffocates babies
Term
Blue baby syndrome
Definition
when babies eat food high in NO3--> converts to NO2 which displaces O2 and suffocates babies
Term
N displaces__ in Fe complexes
Definition
displaces the O coordination spot making it tougher for O to bind
Term
EDTA
Desferal
Catechins
EGCG
Definition
is a true chelator with 6 lewis base centers
Is used for metal poisoning
Term
Too much Catechins or chelators in diet leads to
Definition
loss of Ca2+ in bones and osteoporosis
Term
Kf
Definition
equilibrium for the formation of products
higher Kf means more stable products
CN can displace Oxalate from Fe ~^32 orders
Use CN to extract metals from Ores
Term
Detox for CN- poisoning
Definition
Hydroxo-cobalamine
with 4 N groups with cobalt used to hold CN- in place of the -OH group--> cyano-cobalamine
Term
Langmur Isotherm
Definition
Indicates that the higher the concentration: the greater the coverage of a surface would occur up until a saturation point
Term
Heavy Metals and metal ions enter cells via
Definition
Piggybacking onto integral membrane protein channels, and mimicking naturally occuring healthy and normal cations
Term
How to determine the health of organs
Definition
Through studying their efflux kinetics
Term
CYP 450 contains
Definition
An oxygenase and a cytochrome with an Fe3+ heme center- with 6 coordination spots with 1 that is not occupied
Term
CYP450 renders hydrophobic compounds hydrophillic via
Definition
attachment to a substrate binding site across from the heme center and exposes the toxicant to the O group in the heme center
Term
Dangerous disadvantage of Phase 1 detox via CYP P450
Definition
Formation of Aldehydes after oxygenation makes hydrophobic toxicant a little less hydrophobic
Aldehydes can go on to form epoxides through condensation with a schiff base if meeting an amine
Term
Epoxides are dangerous
Definition
due to their affinity to cross link(forms an ADDUCT) with guanine in DNA and upset the helical structure leading to transcription errors and eventually mutations
Term
___is a key element in a key compound for Phase 2 detox
Definition
Sulfur is needed for glutathione formation
Used for the thiol group to kick out a H and bind to the toxicant R group.
Term
GSh cannot be absorbed by the body well-other ways of ingesting are through intake of
Definition
Garlic, Onions, Cauliflower, Broccoli, N-acetylcysteine (NAC)
Term
Rapid medical detox, heavy metal reactions can be used by
Definition
NAC , n-acetylcysteine
and metallothioneines-found in AD patients who have had exposure to Aluminium forming amy-B
Term
Pre-exposure to____allows the body to prepare for metal toxicity
Definition
Zinc Gluconate
Term
4 examples needed for phase 2 detox
Definition
GSH, ortho-sulfates, Taurine & GLucaronic Acid
Term
phase 1 stimulants:
Definition
brassica foods, citrus
Term
phase 1 inhibitors:
Definition
grapefruit juice, capcaisin, tumeric, onion, antihistamines
Term
phase 2 stimulants:
Definition
brassica foods, citrus peels, cysteine, NAC, taurine, fish oils
Term
effect of small doses of metals to benefit the body medically____
Definition
Hormesis-primes the body to fight stressors in the long run
Term
SER is
Definition
Selectivity ratio- how effective a compound is against its' target and how comparatively dangerous it is to humans through division of LD50 for target divided by LD50 for rats=gives effectiveness against mammals
Term
DDT cannot be detoxed by phase 1 because
Definition
CYP P450 can only add the oxygen in the para-position, which is occupied in DDT
+ Hansch ~6
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