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Azas-azas umum Toksikologi

Nikmatul Ikhrom EJ, MFarmKlin., Apt.


Prodi Farmasi Fakultas Ilmu Kesehatan
Universitas Muhammadiyah Malang
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

A common course is
when a toxicant
delivered to its
target reacts with it,
and the resultant
cellular dysfunction
manifests
It self in toxicity.
Potential stages in the development of
toxicity

PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Development a toxicity
puffer fish
poison
Poison reaches
the voltage-
gated Na
+
channels of
motoneurons
tetrodotoxin
ingestion
results in blockade of Na
+
channels, inhibition of the
activity of motor neurons and ultimately skeletal
muscle paralysis. No repair mechanisms can prevent
the onset of such toxicity
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Development a toxicity
entering the
mitochondrial
matrix space ingestion
collapses the outwardly directed proton gradient
across the inner membrane by its mere presence
there (step 2b)
2,4-
dinitrophenol
mitochondrial dysfunction (step 3) : hyperthermia
and seizures
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Nasib Racun
dalam Tubuh
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Biological membranes
a phospholipid bilayer
Amphipatic : nonpolar
(liphophilic) + polar
(hydrophilic)
Semipermeable
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

senyawa racun melewati membran sel
bergantung pada :
1. sifat fisika-kimia racun
2. ukuran partikel
3. lipofilitas
4. kemiripan dengan molekul endogen
kepolaran/muatan
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Molecules can traverse membranes by three
principal mechanisms:
1. Passive diffusion
2. Facilitated diffusion
3. Active transport
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Absorbtion
Absorption is the
transfer of a chemical
from the site of
exposure, usually an
external or internal
body surface (e.g.,
skin, mucosa of the
alimentary and
respiratory tracts),
into the systemic
circulation
Biology
membrane
K absorbsi
Menentukan toksisitas
sebuah racun
GIT
Three main factors
affect absorption within
the various sites of the
gastrointestinal tract:
1. type of cells at the
specific site;
2. period of time that the
substance remains at the
site;
3. pH of stomach or
intestinal contents at the
site.
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

GIT
Adanya pengaruh dari asam lambung, enzim
yang ada dalam lambung serta flora usus dapat
mempengaruhi potensi ketoksikkan suatu
racun yang diabsorbsi melalui saluran cerna.
Ex : bisa ular yang diberikan secara oral tidak
akan menunjukkan efek toksik sebagaimana
yang ditunjukkan bila diberikkan secara
intravena.


PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Respiratory
Absorption can occur
at any place within the
upper respiratory tract
There are three basic
regions to the
respiratory tract:
1. nasopharyngeal region;
2. tracheobronchial
region;
3. pulmonary region.

PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Respiratory
Chloroform and ether are examples of lipid-soluble
substances with high blood solubility
Non-absorbed foreign material can also cause severe
toxic reactions within the respiratory system
chronic bronchitis, alveolar breakdown (emphysema),
fibrotic lung disease, and even lung cancer.
In some cases, the toxic particles can kill the alveolar
macrophages, which results in a lowering of the
bodies' respiratory defense mechanism.

PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Skin
skin is a complex,
multilayer tissue. For this
reason, it is relatively
impermeable to most ions
as well as aqueous
solutions.
passive diffusion
Ex : organophosphate
pesticides, carbon
tetrachloride causes
liver injury, Hexane
nerve damage
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG


PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Distribusi
During distribution, toxicants reach their site
or sites of action.
Mechanisms Facilitating Distribution to a
Target Distribution of toxicants to specific
target sites :
(1) the porosity of the capillary endothelium,
(2) specialized membrane transport,
(3) accumulation in cell organelles,
(4) reversible intracellular binding
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Distribution
1. How do chemicals move through the body?
2. Does distribution vary with the route of exposure?
3. Is a chemical distributed evenly to all organs or
tissues?
4. How fast is a chemical distributed?
5. Why do some chemicals stay in the body for a long
time
6. Whereas others are eliminated quickly?
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Distribution
Total volume of body fluids which a
toxicant is distributed is known as the volume
of distribution (V
D
)
Protein plasm if toxicant bind protein
DEPO
High lipid DEPO toxicant nonpolar
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Metabolism
Biotransformation is the process whereby a
substance is changed from one chemical to
another (transformed) by a chemical reaction
within the body.
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Metabolism
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Xenobiotics
enzyms
metabolites
active Non active
< polar
> toxic
redistribution
Toxic effect
> polar
< toxic
Excretion
detoxification ???
bioactivation ???
Fase I
Fase II
Metabolism
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG


PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

Excretion
excretion and : the same process whereby a
substance leaves the body.
Toxicants or their metabolites can be
eliminated from the body by several routes.
The main routes of excretion are via urine,
feces, exhaled air and other
PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG


PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG

PROGRAM STUDI FARMASI
FAKULTAS ILMU KESEHATAN
UNIVERSITAS MUHAMMADIYAH MALANG