Transcript No Slide Title - virtualpharmtox.pharmacy.arizona.edu

Physiological Effects of Nicotine
and Ethanol
Rebecca B R Milholland
Tobacco Plant
•
Grown for its
nicotine containing
leaves which are
smoked, chewed, or
sniffed
Nicotiana tobacum
Nicotine
•
Nicotine is an alkaloid found naturally in
tobacco plants, tomatoes, potatoes, eggplant
and green peppers
Nicotine
•
Nicotine is an alkaloid found naturally in
tobacco plants, tomatoes, potatoes, eggplant
and green peppers
Neuromuscular System
Motorneuron
Neuromuscular
Junction
Muscle Fiber
Neuromuscular System
Signal from
the Brain
Motorneuron
Nerve Terminal
Muscle Fiber
Neuromuscular System
Signal from
the Brain
Motorneuron
Acetylcholine (ACh)
Muscle Fiber
Neuromuscular System
Signal from
the Brain
Motorneuron
Acetylcholine (ACh)
Muscle Fiber
Neuromuscular System
Signal from
the Brain
Motorneuron
Nicotine
Muscle Fiber
Nicotinic Syndrome
•Nicotine produces
tachycardia
and blood pressure
through its action in
the sympathetic
nervous system or
the “Fight or Flight”
system.
Nicotine decreases appetite.
Nicotine’s action on
skeletal muscles
and the diaphragm
to produce paralysis
and asphyxiation
Chronic Effects of Nicotine
•Chronic administration
leads to coronary artery
disease and
hypertension
Nicotine produces peptic
ulcer disease,and esophageal
reflux through its influences
on the Gastrointestinal tract.
•Nicotine enhances
learning and memory
•Nicotine enhances
learning and memory
•Nicotine’s influences
in the brain also
produces its addictive
properties
Most Likely Avenues for
Exposure
•
•
Tobacco Products
Insecticides
– Anti-AChE (Acetylcholine Esterase)
– nAChR activators (like nicotine)
Alcohol
H
OH C
H
H
C H
H
Factors which Influence Ethanol
Movement Though the Body
•
Absorption
Factors which Influence Ethanol
Movement Though the Body
•
•
Absorption
Distribution and Solubility
– Body Fat Percentage
Dose-Response Curve for Acute
CNS Response to Ethanol
Response
Death
Labored breathing
Unconscious
Deep sleep
Sleep
Giddy
No effect
Dose
Chronic CNS Effects of Ethanol
•
Korsacoff’s Syndrome
– Loss of short term memory
– Due to a Thyamine Defficiency
Ethanol
Alcohol
Dehydrogenase
NAD
NADH
Acetaldehyde
Ethanol
Alcohol
Dehydrogenase
NAD
NADH
Acetaldehyde
Aldehyde
NAD
Dehydrogenase
NADH
Acetate
Ethanol
Alcohol
Dehydrogenase
NAD
NADH
Acetaldehyde
Aldehyde
NAD
Dehydrogenase
NADH
Acetate
Citric Acid Cycle
Energy
Ethanol
Alcohol
Dehydrogenase
NAD
NADH
Acetaldehyde
Aldehyde
NAD
Dehydrogenase
NADH
Acetate
Citric Acid Cycle
Energy
Fatty Liver
Fibrosis
Cirrosis
Ethanol
Alcohol
P450 Dehydrogenase
NAD
NADH
Acetaldehyde
Aldehyde
NAD
Dehydrogenase
NADH
Acetate
Citric Acid Cycle
Energy
Fatty Liver
Fibrosis
Cirrosis
Ethanol Interaction with P 450
•
•
Acute Administration -  P 450
Chronic Administration -  P 450
Acetominophen
Detoxication
Sulfation
Glucuronidation
Safe Excretion
by Kidney
and in Bile
Acetominophen
Detoxication
Activation to a
Toxic Metabolite
Sulfation
Glucuronidation
Quinoneimine
Free Radical
Safe Excretion
by Kidney
and in Bile
Liver and Kidney
Damage
Acetominophen
Detoxication
Activation to a
Toxic Metabolite
P450
Sulfation
Glucuronidation
Quinoneimine
Free Radical
Safe Excretion
by Kidney
and in Bile
Liver and Kidney
Damage
Acetominophen
Detoxication
Activation to a
Toxic Metabolite
P450
Sulfation
Glucuronidation
Quinoneimine
Free Radical
Safe Excretion
by Kidney
and in Bile
Liver and Kidney
Damage
Ethanol
Induction
Of P450
Expression
Other Alcohols
•
Methanol
Other Alcohols
•
Methanol
– Induces blindness and death due to formic acid
production
Other Alcohols
•
Methanol
– Induces blindness and death due to formic acid
production
•
Ethylene Glycol
Other Alcohols
•
Methanol
– Induces blindness and death due to formic acid
production
•
Ethylene Glycol
– Kidney damage due to oxalic acid production and
crystal formation in the renal tubules
Other Alcohols
•
Methanol
– Induces blindness and death due to formic acid
production
•
Ethylene Glycol
– Kidney damage due to oxalic acid production and
crystal formation in the renal tubules
Treat Exposures to Both Alcohols
with Ethanol!!
Conclusions: Nicotine
•
Acute
Conclusions: Nicotine
•
Acute
– Acts at acetylcholine receptor in muscle
– Produces asphyxiation and paralysis
Conclusions: Nicotine
•
Acute
– Acts at acetylcholine receptor in muscle
– Produces asphyxiation and paralysis
•
Chronic
Conclusions: Nicotine
•
Acute
– Acts at acetylcholine receptor in muscle
– Produces asphyxiation and paralysis
•
Chronic
– Acts at acetylcholine receptors in the sympathetic
nervous system to coronaroy artery disease and
high blood pressure
– Acts at acetylcholine receptors in the brain to
induce physical addiction.
Conclusions: Ethanol
•
Acute
Conclusions: Ethanol
•
Acute
– Fatty Liver
– CNS Depression
Conclusions: Ethanol
•
Acute
– Fatty Liver
– CNS Depression
•
Chronic
Conclusions: Ethanol
•
Acute
– Fatty Liver
– CNS Depression
•
Chronic
– Korsacoff’s Syndrome
– Cirrosis of the Liver