toxicology ch3 test Flashcards
1
Q
cardiovascular
A
critical to our life
composed of heart, blood vessels, blood, and blood cells
2
Q
Arrhythmias
A
irregularities in heartbeat
3
Q
Tachycardia
A
fast heartbeat
4
Q
Bradycardia
A
slow heartbeat
5
Q
Beta-adrenergic receptors
A
- found in membranes in tissues
- binds epinephrine (as well as drugs and toxicants)
- action mediated by cAMP messenger system
- PKA phosphorylates myosin light chain kinase which causes smooth muscle relaxation
- vasodilation and bronchodilation
6
Q
cAMP messenger system
A
a nucleotide generated from ATP through the action of the enzyme adenylate cyclase.
7
Q
epinephrine (adrenaline)
A
speeds up the heart
8
Q
Isoproterenol
A
beta-receptor agonist (treats bradycardia)
9
Q
ephedrine
A
slows heart down
increases blood pressure
10
Q
digoxin
A
belongs to a class of medications called cardiac glycosides
eliminated via kidneys
Na+, K+ ATPase inhibitors
11
Q
foxglove plant (digitalis lanata)
A
derives heart medicine digoxin and digitoxin
12
Q
digitoxin
A
also part of cardiac glycosides
eliminated via liver
Na+, K+ ATPase inhibitors
13
Q
cardiomyopathies
A
apotosis and necrosis commonly seen in toxicant damaged heart
14
Q
Mitogen-activated protein kinases (MAPKS)
A
initiates apoptosis
15
Q
Cobalt
A
blocks calcium channels (voltage-gated channels)
hypertension can be treated with calcium channel blockers (therefore cant contract)
16
Q
alcohol cardiomyopathy
A
kills myocytes (muscles cells) inhibits protein synthesis- either alcohols or acetaldehydes
17
Q
Doxorubicin (adriamycin)
A
antitumor drug for leukemias, lymphomas, sarcomas, carcinomas
- P450 metabolized it to a free radical (oxidative stress)
- intercalates into DNA (wedges into bases)
- apoptosis
- leads to congestive heart failure-up to 36% of patients
18
Q
Hemmorrhage
A
snake venom (hemotoxins)
complex mixture of proteins ("zootoxins")
19
Q
Hemotoxins
A
toxins affect blood
20
Q
metalloproteinases (digests proteins)
A
(hemorrhagins)
catalytic site has a metalion (Zn, Co)
-carboxypeptidases
enzymes found in snake venom:phospholipase A2, proteinases, nucleotidases, L-amino ancid oxidase
seperate endothelial cells from basement membrane- capillaries
-cause platelet aggregation
21
Q
vasoregulation
A
changes in vascular smooth muscle tone
adrenergic receptors
22
Q
alpha 1 receptors
A
blood vessels
23
Q
beta 1
A
heart
24
Q
beta 2
A
lungs
25
aldosterone
```
main role is to regulate salt and water in the body
mineralocorticoid hormone (adrenal cortex)
•Renin-angiotensin-aldosterone control system
```
26
nitric acid
vasodilation
27
nitrates
nitric acid which activates guanylate cyclase(enzyme GTP to cGMP) (relaxes smooth muscle= vasodilation)
28
Cadmium (5 ppm), lead, mercury
hypertension in rats
29
atherosclerosis
disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls.
30
carbon disulfide
colorless, volatile, corrosive liquid
insecticide
direct injury to endothelial cells
increase blood cholesterol and atherosclerosis
31
pancytopenia
caused by to damage bone marrow
| decrease in numbers to red blood cells, white blood cells, platelets
32
aplastic anemia
no new blood cells (ex. benzene, lindane, chloramphenicol)
33
sideroblastic anemia
reduction to RBCs due to too much iron in bone marrow (ex. lead)
34
hemolytic anemia
decrease in RBC due to loss of circulating RBCs (cells destroyed)
•oxidants such as phenylhydrazine or aniline
•heavy metals – lead, mercury
35
carbon monoxide
binds to hemoglobin and is irreversible
36
Nitrites, nitrates, aromatic amines
Oxidizes ferrous iron to ferric iron (cannot bind oxygen)
37
methemoglobin
clinical symptoms -10-20%
death 70%
turns skin blue
Also caused by procaine, lidocaine, dapsone
38
Ch 10 general principle one
very vulnerable because of specific critical voltages of the neuron membranes
39
2.
tissue is very metabolically active so loss of energy metabolism is detrimental
40
3.
loss of communication between the parts of the system easily happens
41
4
Tissue controls the basic functions of life
42
5
damage to nervous tissue is more or less permanent
43
6
blood brain barrier is key protection mechanism
44
blood brain barrier
prevents most substances from entering nervous tissue
-chemicals that can pass =small, highly lipid soluble, nonpolar
Specific transport systems transport some chemicals – glucose, amino acids, etc.
damage =big problems
45
Key brain enzymes
Contain monoamine oxidase (MAO) and catechol-O-methyltransferase – modify chemicals that enter
-contain low levels of P450
- MAO inhibitors
used in depression treatment
selegiline- irreversible MAOI (treats parkinsons)
46
resting membrane potential
-70 mV
47
action potential
voltage gated channels -NA+ and K+
| Na+, K+ ATPase pump reestablishes ions
48
tetrodotoxin
blocks generation of action potential by binding to the outside of Na channel
49
saxitoxin
```
found in dinoflagellates
Food source for various shellfish – paralytic shellfish toxin (PST)
-50 versions
-found in clams, oysters, scallops
-sodium channel blocker
```
50
batrachotoxin
in south american frogs (dart frogs)
- steroid alkaloid
- increases permeability of neuron membrane to sodium- prevents closing of Na channel
51
neuroreceptor types
excitatory (generates action Potential)
| inhibitory (prevents)
52
Acetylcholine
sends signals to other cells
| key to autonomic NS
53
biogenic amines
dopamine, epinephrine, norepinephrine
54
amino acids
glutamates, aspartate, glycine, GABA
55
neuropeptides
endorphines
56
gases
nitric acid, carbon monoxide
57
botulinum
stops the release of ACh
produced by bacterium clostridium botulinum
-botox
58
Nicotinic and Muscarinic receptors
-ACh binds to both
| Nicotine and muscarine are cholinergic agonists (mimic ACh)
59
nicotinic
found on sympathetic and parasympathetic neurons
60
Atropine
muscarinic blocker
Atropa belladonna (deadly nightshade) & Datura stramonium (Jimson weed)
-used to treat some pesticide and nerve agent poisonings
61
muscarinic
found only on parasympathetic neurons (smooth muscles and glands)
62
biogenic amines
catecholamines
| -alpha and beta adrenergic receptors
63
alpha
alpha agonists constrict blood vessels of the nose(nasal decongenists)
-treat hypertension
64
beta
used to treat asthma (enlarge bronchial airways)
65
propranolol
used to treat cardiovascular disorders-dec. heart rate and BP
66
neuroactive peptides
```
enkephalins & endorphins
-opium
morphine,codeine
sedative pain relief
-heroine=chemical derivative of morphine
-naloxene =opioid receptor antagonist treat addiction
- tolerence occurs over time
```
67
Axonopathies
damage to axons-peripheral nervous system
68
proximal axonopathy
swelling of the proximal axon causes atrophy of distal axon
69
synthetic aminonitriles
- inhibits ACh
- bladder problems
- amyotrophic lateral sclerosis(weakening of muscles)
70
Acrylamide
- gels
- some food
- carcinogen group 2A
- inhibits fast axon transport process
71
myelinopathies
Damage to myelin sheath can be significant – inhibits or blocks nerve impulses
72
Triethyltin
France (1954)
| headache, nausea, vomiting, random muscle contractions
73
hexachloroprene
-disenfectant, soaps, toothpaste, fascial scrubs
premature infants washed with this showed myelin damage
-prescription only
-interferes with ion movement&energy in neurons
74
Glutamate
-MSG
-overstimulation=cell death
NMDA receptor CNS
75
calmodulin
protein that Ca2+ binds to which activates the enzyme nitric oxide synthase which produces nitric oxide
76
Mercury
very neurotoxic
- peripheral neuropathy
- most toxic form -dimethylmercury
77
lead encephalopathy
peripheral and central NS effects
children much more susceptible especially under 6
levels accumulate
5mcg/dl =too high 45mcg/dl= treated
78
ch11 general principle 1
everything absorbed by the GI tract goes to the liver
79
principle 2
liver is highly perfused organ
80
principle 3
because liver has phase 1 and phase 2 metabolism hepatocytes are exposed to bioactivated metabolites
81
principle 4
enterohepatic cycling occurs
82
principle 5
multifunctional role of liver means there are multiple potential targets
83
principle 6
more than 900 chemicals known to cause hepatoxicity
84
hepatic steatosis
fatty liver
chronic exposure to ethanol
5 to 50 % is fat
involves interference with normal regulation of lipoprotein synthesis
85
two categories of fatty liver
nonalcoholic and alcoholic
86
cholestasis
stoppage of bile flows
caused by steroids, phenothiaines, tricyclic antidepressants, gold salts, erythromycin
jaundice,pale stool, dark urine
87
acetominophen
Stimulates formation of nitric oxide in hepatocytes which damages the cells
88
fibrosis
excess production and accumulation of collagen fibers
- significant disruption of blood flow in river
- generally thought to be irreversible but recent studies show regeneration
89
cirrhosis
long term exposure leads to fibrosis and scar formation
-ethanol
not reversible
90
halothane
a general anesthetic
91
enzyme test
can indicate liver damage -leakage from cells
92
ratio of AST/ALT
less than one means liver damage
| greater than 2 means alcoholic liver disease
93
reyes syndrome
encephalopathy and hepatic dysfunction in children
| -aspirin being used to treat viral infections
