1 Introduction, history and principles
Paracelsus is one of the founding fathers of toxicology
- notion of dose: everything is toxic but it depends on the amount
Percivall Pott
- relation between work and disease of people
2 Mechanisms
delivery to site of action: ADME (absorption, distribution, metabolism, excreted)
,directly toxic:
- some metals
- strong acids/bases
- nicotine
- CO
molecular interactions
- non covalent binding
- with or without structural similarity with the natural ligand
- covalent binding (permanent): reactions with macromolecules
- reactive oxygen species (hydrogen abstraction)
- damage/inactivation of proteins and DNA
- lipid peroxidation disturbs the membrane structure
3 Absorption, Distribution, Excretion
absorption
passive diffusion/filtration is influenced by lipophilicity, ionization and blood flow
passive diffusion takes place when particle is uncharged/nonionized
,blood stream plays role in maintaining a concentration gradient
in active transport, the transport system is selective > potential for competitive inhibition
facilitated diffusion is similar to simple diffusion: not requires energy and transport goes
down a concentration gradient
- carrier proteins and ion channels
phagocytosis
- cell eating: ingestion of particles; only specialized cells (neutrophils, macrophages)
pinocytosis
- cell drinking: ingestion of drops or small particles; almost all cells
, liver can change chemicals (make more or less harmful)
distribution
4 Biotransformation
Paracelsus is one of the founding fathers of toxicology
- notion of dose: everything is toxic but it depends on the amount
Percivall Pott
- relation between work and disease of people
2 Mechanisms
delivery to site of action: ADME (absorption, distribution, metabolism, excreted)
,directly toxic:
- some metals
- strong acids/bases
- nicotine
- CO
molecular interactions
- non covalent binding
- with or without structural similarity with the natural ligand
- covalent binding (permanent): reactions with macromolecules
- reactive oxygen species (hydrogen abstraction)
- damage/inactivation of proteins and DNA
- lipid peroxidation disturbs the membrane structure
3 Absorption, Distribution, Excretion
absorption
passive diffusion/filtration is influenced by lipophilicity, ionization and blood flow
passive diffusion takes place when particle is uncharged/nonionized
,blood stream plays role in maintaining a concentration gradient
in active transport, the transport system is selective > potential for competitive inhibition
facilitated diffusion is similar to simple diffusion: not requires energy and transport goes
down a concentration gradient
- carrier proteins and ion channels
phagocytosis
- cell eating: ingestion of particles; only specialized cells (neutrophils, macrophages)
pinocytosis
- cell drinking: ingestion of drops or small particles; almost all cells
, liver can change chemicals (make more or less harmful)
distribution
4 Biotransformation
