pharmacology and toxicology

1. Neurotoxicity
Presented by Fatma altalaqani & mysm Namer
Supervised by dr. Ammar Ali Hussein
Higher diploma in toxicology
Baghdad university college of pharmacy

2. Neurotoxicity
Any adverse change in structure or function of the central nervous system
during development or at maturity following exposure to chemical , physical ,
biological agent .

4. Nervous system parts
• The various structures of the nervous system
are intimately interconnected, but for
convenience we divide them into two parts:
(1) the central nervous system (CNS),
composed of the brain and spinal cord; and
(2) the peripheral nervous system (PNS),
consisting of the nerves that connect the
brain and spinal cord with the body’s
muscles, glands, sense organs, and other
tissues.

5. Nervous system parts
• The basic unit of the nervous system is the individual nerve cell, or neuron.
Neurons operate by generating electrical signals that move from one part of
the cell to another part of the same cell or to neighboring cells. In most
neurons, the electrical signal causes the release of chemical messengers
neurotransmitters —to communicate with other cells.

6. Neurotoxicity
( Neuropathies )
• a full understanding of the toxicity
also requires knowledge of the
functional outcomes of those
changes.
• function includes motor, sensory,
autonomic, and cognitive
capabilities.

7. MECHANISMS OF NEUROTOXICITY
• Efforts to understand the mechanism of action of individual neurotoxic
compounds have begun with the identification of the cellular target. In the
NS, this has most often been one of four targets: the neuron, the axon, the
myelinating cell, or the neurotransmitter system .
 Neuropathies,
 Axonopathies,
 Myelopathies,
 Neurotransmitter-associated toxicity

9. Neuropathies
 Certain toxicants are specific for neurons, or sometimes a particular group of
neurons, resulting in their injury or, when intoxication is severe enough, their death.
The loss of a neuron is irreversible and includes degeneration of all of its
cytoplasmic extensions, dendrites and axons, and of the myelin unsheathing the axon
 The initial injury to neurons is followed by apoptosis or necrosis, leading to
permanent loss of the neuron.
 Example : Doxorubicin , Methyl mercury , Trimethyltin .

10. Axonopathies
• The neurotoxic disorders termed axonopathies are those in which the primary site of
toxicity is the axon itself. The axon degenerates, and with it the myelin surrounding
that axon; however, the neuron cell body remains intact.
• Axonopathies can be considered to result from a chemical transection of the axon.
The number of axonal toxicants is large and increasing in number.
• as these axons degenerate, the result is most often the clinical condition of peripheral
neuropathy, in which sensations and motor strength are first impaired in the most
distal extent of the axonal processes, the feet and hands. With time and continued
injury, the deficit progresses to involve more proximal areas of the body and the long
axons of the spinal cord.

11. • The potential for regeneration is great when the insult is limited to peripheral nerves
and may be virtually complete in axonopathies in which the initiating event can be
determined and removed.
• Example : pyridinethion ,
Organophosphorus compounds ,
Acrylamide , carbone disulfide ,
Gamma-diketones

12. Myelopathies,
 Myelin provides electrical insulation of neuronal processes, and its absence
leads to a slowing of and/or aberrant conduction of impulses between
adjacent processes, so-called ephaptic transmission. Toxicants exist that result
in the separation of the myelin lamellae, termed intramyelinic edema, and in
the selective loss of myelin, termed demyelination.
 Intramyelinic edema may be caused by alterations in the transcript levels of
myelin basic proteinmRNA (Veronesi et al., 1991) and early in its evolution is
reversible.

13. • Remyelination in the CNS occurs to only a
limited extent after demyelination
• in general the extent of the demyelination
and whether it is localized within the CNS
or the PNS or is more diffuse in its
distribution. Those toxic myelopathies in
which the disruption of myelin is diffuse
generate a global neurological deficit,
whereas those that are limited to the PNS
produce the symptoms of peripheral
neuropathy.
• Example : Lead , Tellurium ,
Hexachlorophene

14. Neurotransmitter-associated toxicity
• A wide variety of naturally
occurring toxins, as well as
synthetic chemicals, alter specific
mechanisms of intercellular
communication. Some chemicals
that have neurotransmitter-
associated toxicity are : Nicotine ,
Cocaine , Atropine , Amphetamines
..ect

15. • OP and carbamate pesticides produce
their insecticidal actions by inhibiting
AChE, the catalytic enzyme that ends
the postsynaptic action of
acetylcholine. The resultant cholinergic
overstimulation produces signs of
acute toxicity ranging from flu-like
symptoms to gastrointestinal distress,
ataxia, twitching, convulsions, coma,
and death

16. References
• Casarett & Doull’s .TOXICOLOGY the basic science of poisons . 8th
edition .
• VANDER’S HUMAN PHYSIOLOGY 13th edition .