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Dose-response curve
Mechanism of toxicology
Toxicodynamics is the mechanism of action of a toxic chemical to the body (what chemicals
do to the body). The targets for the toxicodynamic actions of toxic chemicals are
a) Enzymes
b) Membrane receptors
c) Intracellular receptors
d) Ion channel
Toxic effects generally result from adverse cellular, biochemical, or macromolecular changes
which attained by
a) Damage to an enzyme system
b) Disruption of protein synthesis
c) DNA damage
d) Modification of an essential biochemical function
Toxicity
Metals
Mercur
y
of heavy metals
General
Source
OrganicCNS effect (fish)
InorganicKidneys effect (dental amalgam)
Metal
Other exposure:
Occupation such as Miners thimerosal for vaccine storage
Adsorption
a) Pulmonary absorption of mercury vapour is high
b) Gastrointestinal absorption of Hg+1 or Hg+2 is on
the order of 15 %
c) Alkyl mercurial highly absorbed from the
gastrointestinal tract
d) Deposition mainly at kidney
Lead
Source
Manufacturing/Gasoline (organic)/Moonshine/Ayurveda
medication
Adsorption
a) Inorganic Lead via lungs and GIT
b) Organic lead can penetrate skin
c) First adsorbed into soft tissue then redistributed to:
i) Bone major deposit
ii) Others: teeth and hair
iii) Kidney elimination
Lead deposition if high Vit D and Phosphate
Mechanism
a) Bind to sulfhydryl groups Inhibit enymes such as
gamma-aminolevulinic acid dehydratase (ALA-D)
and ferrochelatase in heme synthesis Anemia
b) Inhibition of pyrimidine 5 nucleotidase
Basophilic stippling
c) Inhibit calcium dependent process Neurotoxicity
Toxicity
General symptoms
a) Intention tremor
b) Inflammation of the gums
with excessive salivation
c) Psychiatric symptoms, such
as excitability, insomnia,
irritation, and shyness
d) High pulmonary absorption
can lead to interstitial
pneumonitis
Treatment
Chelators:
a) Peniccilamine
b) Unithiol, DMPS
c) Succimer, DMSA
Calcium EDTA cannot be
used binds weakly
nephrotoxic
Nephrotoxicity symptoms
Nephrotic syndrome
Tubular dysfunction
Acute
a)
b)
c)
d)
exposure
Abdominal pain ("lead colic")
Joint/muscle aches
Short-term memory problems
Difficulty concentrating,
irritability
e) Anemia (sometimes
accompanied by basophilic
stippling on blood smear)
f) Nephropathy
Chronic exposure
a) Hypertension
b) Neuropsychiatric effects
c) Reproductive effects
d) Mortality
e) Kidney and accelerate agingrelated diseases related to
vision, hearing, and dental
health
Remove exposure
Chelators:
a) Succimer, DMSA
b) Ca EDTA
Mild Vitamin C dose
Arsenic
Cadmiu
m
f) Anemia
Acute poisoning
GITNausea, vomiting, abdominal
pain, and diarrhea dehydration,
hypotension, and QTc prolongation
cardiac arrhythmias, shock, acute
respiratory distress syndrome, and
sometimes death
Chronic poisoning
a) Skin lesions
b) Neurologic manifestations
c) Cancer
d) Cardiovascular
Hypertension
e) LiverJaundice
f) Endocrine
g) Respiratory
h) Mortality
i) Reproductive and
developmental
Nephrotoxicity symptoms
Tubular dysfunction
Acute
a)
b)
c)
d)
poisoning
Remove exposure
Nasogastric
Charcoal
Chelator: Dimercarprol/
succimer/ Unithiol
No specific method
Adsorption
a) Ingestion or inhalation
b) Cadmium is transported to the liver where
metallothionein, a cadmium- and zinc-binding
protein, is synthesized
c) Metallothionein = detoxifying protein, transported to
the kidneys
d) Metallothionein enters the lysosomes where it is
degraded by lysozymes, releasing free cadmium
ions into the tubular cell cytoplasm.
Mechanism
Mainly hypothesis which involves accumulation of Cd in
tubules Reduce activation of calcitriol
Glomerular damage
Nephrolithiasis
Bone disease
Venoms
Snake venom
Snake venom has combination of toxic and non-toxic compound.
Type of toxic compound:
a) Cholinesterases
b) Aminoacid oxidases
c) Hyaluronidases Dissolve intracellular and speed the spread of preys tissue
d) Proteinases break down of tissue
e) Phospholipases Harm muscle and nerve cell
f) Adenosine triphosphates
g) Phosphodiesterases
h) Neurotoxin Paralysis with nervous system
i) Cardiotoxin Irrerversible depolarisation of Cardiac muscle
j) Hemorrahagins
k) Haemotoxins
l) Myotoxins
Snake venom can affect presynaptic by inhibiting Ach release or postsynaptic by binding to AchR Neuromuscular blockade paralysis
Pufferfish
Selective block of Na channel in nerve cell
Antivenom
Injected into animals to stimulate antibody, the antivenom is used to treat animal bites
Research
ACE inhibitor from pit viper
Cobroxin (morphine like) from cobra
Nyloxin for arthritis pain from cobra