TOXICODYNAMICS Flashcards
Mechanism of action of tetradotoxin
Blocks VG sodium channels of motor neurons causing skeletal muscle paralysis
Mechanism of action of 2,4-dinitrophenol
Collapses mitochondrial proton gradient across the inner membrane causing seizures and hyperthermia
Attributes of target molecule
Reactivity
Accessibility
Critical function
Reaction types
Noncovalent
Covalent
Hydrogen abstraction
Electron transfer
Enzymatic reaction
Target of CCL4
Destroys cytochrome p450 enzymes which catalyzes its own activation
Benefits of plasma cholinesterase binding to organophosphate
Counteracts the phosphorylation of acetylcholinesterase
Examples of noncovalent bonding
Strychnine - Glycine receptor on motor neurons in the spinal cord
TCDD to Aryl hydrocarbon receptor
Saxitoxin to Sodium channels
Phorbol esters to PKC
Warfarin to Vit K 2,3- epoxide reductase
Examples of soft électrophiles
Silver
Mercury
Carbon in polarized double bonds
Examples of hard electrophiles
Lithium
Calcium
Barium
Alkyl carbonizing ions
Benzylic carbonizing ions, nitrenium ions
Électrophiles that are neither hard not soft
Chromium , zinc, lead
Aryl carbonium ions
Examples of hard nucleophiles
Sulfur in thiols
Sulfur in methionine
Examples of hard nucleophiles
Phosphate oxygen in nucleus acids
Oxygen of purines and pyrimidines in nucleus acids
Nucleophiles that are neither hard nor soft
Mostly nitrogen containing
Nitrogen in primary and secondary amino groups of proteins
Nitrogen in amino groups in purine bases in niçois acids
Which toxicants abstract hydrogen
Neutral free radicals
What is the first step in DNA cleavage
Abstraction of H from deoxyribose in DNA to yield the C-4 radical
Toxication reactions that involve hydrogen abstraction
Nitration of tyrosine residues in proteins
Lipid peroxidation
DNA cleavage by hydrogen abstraction
Toxication reactions involving enzymatic reactions
Ricin and Abrin hydrolyse ribisomal RNA and block protein synthesis
Botulinum toxin acts as a Zn-protease and prevent exocytosis of acetylcholine by hydrolysing the proteins responsible for the process
Anthrax also acts as a Zn protease and inactivate MAPKK inducing death
Diphtheria toxin blocks function of elongation factor 2 in protein synthesis
Cholera toxin activates a G protein
Snake venoms
Bacterial toxins that catalyse transfer for ADP-ribose from NAD+ to specific proteins
Diphtheria
Cholera
Toxins that inhibit closure of voltage activated Na channels
DDT
Pyrethroids
Toxins impair tubulin function
Vinblastine
Colchicine
Paclitaxel
Arsénite
Toxins that impair the function of actin
Cytochalasin B
Phalloidin
Difference between sympathomimetic and anticholinergic toxidromes
Sympathomimetics cause sweating but anticholinergics do not
