pt 4 Flashcards
The greater susceptibility may of nervous system to toxicity is attributed to
Partly to:
-the fact that neurons have a (1)—- metabolic rate, with little capacity for (2)——–
-Furthermore, being electrically excitable, neurons tend to lose cell membrane integrity more readily.
-The great length of the axons is another reason why the nervous system is especially susceptible to toxic effects, because the cell body must supply its axon structurally and metabolically
(1) high
(2) anaerobic metabolism
what drugs produce brain anoxia
BARB
Contamination of food products with tricresyl phosphate was shown to produce a delayed neuropathy related to inhibition of “neuropathy target esterase” whereby there is damage to spinal nerves, the spinal cord, brain, and other tissues
This type of neuropathy also occurs following exposure to organophosphorous
insecticides
tricresyl phosphate
The cell body of neurons may be affected directly by toxicants such as ——
methyl mercury
The paraquat-induced neuronal effects resemble the manifestations in ——–disease.
Parkinson’s
—– affects neurons by intercalating with DNA, leading to a breakdown of the helical structures inhibits the synthesis of RNA and neuronal protein
Since this drug does not cross the BBB, it can affect the neurons in the dorsal
root ganglia and autonomic ganglia, but not those in the CNS.
Doxorubicin
Some axons are very long (up to 1 m), and the elements in the axons, such as ——-, are synthesized not locally but in the cell body, and are transported along the axon.
neurofibrils
β, β-Iminodiproprionitrile (IDPN) produces —–
Proximal Axonopathy: typical lesions through impairment of slow axonal transport of neurofilaments (phosphorylation)
what agents lead to CNS mitochontrial swelling
thallium
distal axonopathy is caused by ——
-organophosphates (TOCP (tri-o-cresyl phosphate), EPN, and leptophos) lead to DELAYED NEUROPATHY
-n-hexane and methyl n-butyl ketone
and organic solvents
Tetrodotoxin, the toxic principle of puffer fish, has been shown to block the action potential by blocking the ——–
Na+ channels
-Interference with Impulse Conduction
MOA of Clostridium botulinum: producing paralysis of muscles by impairing the release of (1) ——- from motor nerve endings
Interference with synaptic transmission
(1) acetylcholine
how does Black widow spider venom interfere with synaptic transmission
produces an excessive release of acetylcholine and results in cramps and paralysis
——- produces neurotoxicity by interfering with kinesin-related motor proteins in neurofilaments that are involved in fast antegrade transport of nerve signals between axons
Acrylamide
-This is manifested as hindlimb splay, ataxia, and skeletal muscle weakness
lead affects Schwann cells possibly by interfering with their —- transport
Ca2+
The PNS is affected before the CNS due to lead. In addition, lead affects motor nerves before the sensory, resulting in “wrist-drop” and “foot-drop.”
——- disrupt myelin sheath because of the high (70%) lipid content of myelin.
Hypocholesterolemic agents such as triparanol,
The pesticide ——- produces degeneration of the GANGLION CELL LAYER resulting in a neurodegerative disorder associated with destruction of the MITOCHONDRIA.
-This phenomenon is found in Leber’s optic neuropathy and Parkinson’s disease.
rotenone
Acetyl ethyl tetramethyl tetralin (AETT) causes ——– through a complex mechanism
myelinopathy
Clostridium botulinum, Black widow spider venom, acrylamide. lead to
Interference with synaptic transmission
TRIparanol, Diphtheria toxin, rotenone, Acetyl ethyl tetramethyl tetralin (AETT).
they cause
Glial cells and myelin
lead, mercury, arsenicals, tellurium (in the endonerium), are associated with ——- toxicity
EXTRAcellular edema
Various parts of neurons may become edematous (CELLULAR EDEMA) following exposure to toxicants
-6-aminonicotinamide affects the perikaryon
-cyanide and carbon monoxide affect the axon
-ouabain and methylsulfoxime affect the presynaptic nerve endings.
——— produce, after acute exposure, narcosis, but they induce axonopathy after repeated exposures
n-hexane and TOCP
ammonia, chlorine, arsnicals lead to
lung local irritation
what are toxicants that lead to cellular damage of lungs and edema, and what is their MOA?
Toxic gases, such as ozone and oxides of nitrogen, produce cellular damage, perhaps through generation of reactive oxygen species followed by peroxidation of cellular membranes.
the lung serves as a conduit for chemicals into the circulation followed by activation in other tissues and development of diseases in different organs. such as ——— that enters via the lung, forms reactive intermediates in the liver, and these intermediates react with bone macromolecules subsequently resulting in leukemia
benzene
On heating, such as in volcanic eruption and mining, quartz may become tridymite or cristobalite. Both of these forms are more fibrogenic than quartz.
The toxic effect stems from the ——- in a macrophage. The released lysosomal enzymes digest the macrophage, and this process, in turn, releases the silica from the lysed macrophage.
rupture of the lysosomal membrane
Another major cause of pulmonary —— is asbestos.
Asbestos refers to a large number of fibrous hydrated silicates of magnesium, calcium, and others.
fibrosis
——– is also a debilitating disease. It may be induced by cigarette smoking or exposure to aluminum, cadmium oxide, or oxides of nitrogen, ozone, and others.
Emphysema
It was suggested that the elastic fibers surrounding and supporting the alveoli and bronchi may be damaged by the ———– under certain conditions
elastase released from polymorphonuclear (PMN) granulocytes
Large airborne particles in the inhaled air are mainly deposited in the nasal passages and cause
They may produce hyperemia, squamous- or transitional-cell metaplasia, hyperplasia, ulceration, and, in certain cases, carcinoma.
closely related herbicide to paraquat, ——-, although also toxic to cultured lung cells, is not toxic to the lungs either after inhalation or after ingestion.
diquat
food colors, pesticides (e.g., DBCP), plastics (phthalates), metals (e.g., arsenic, tin, lead, and cadmium), and organic solvents.
A variety of other chemicals affect the ——, such as steroid hormones, alkylating agents, cyclohexylamine, and hexachlorophene.
testis
both
methylmethane sulfonate (MMS) and
busulfan
produce lethal mutations
but MMS affects spermatids and spermatozoa whereas busulfan affects the prespermiogenic cells. These alkylating agents apparently attack the DNA of these cells with different repair mechanisms
Tumors may develop in the testis. For example, the herbicide – may induce Leydig cell tumors.
linuron
—— has been reported to induce prostate cancer in men
Cadmium
Oocytes may be damaged by chemotherapeutic agents such as
nitrogen mustard and vinblastine, and polycyclic aromatic hydrocarbons (PAH) such as 3-methylcholanthrene and benzo[a]pyrene.
- ——– prevents implantation
- ——– may interfere with ovulation and implantation of the fertilized ovum; it may also retard the development of the sex organs of the offspring
-Haloperidol
-Spironolactone
——– suppresses ovarian steroid hormone secretion, interrupts regular cyclicity and inhibits embryo implantation
Gossypol is also toxic in the female.
vitamins and nutrient deficiencies and cobalt, and poisons lead to —— tox
hemato system
Dichloromethane exposure can also cause asphyxia hypoxia as metabolite is ——-
carbon monoxide!
—– will cause oxidation of the haemoglobin to cause methaemoglobin which is unable to carry oxygen
Aniline
