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

Motorneuron

Muscle Fiber

Neuromuscular Junction

Neuromuscular System

Motorneuron

Muscle Fiber

Signal fromthe Brain

Nerve Terminal

Neuromuscular System

Neuromuscular System

Motorneuron

Muscle Fiber

Signal fromthe Brain

Acetylcholine (ACh)

Neuromuscular System

Motorneuron

Muscle Fiber

Signal fromthe Brain

Acetylcholine (ACh)

Neuromuscular System

Motorneuron

Muscle Fiber

Signal fromthe Brain

Nicotine

Nicotinic Syndrome

•Nicotine produces tachycardiaand blood pressurethrough its action in the sympatheticnervous 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 administrationleads to coronary artery disease and hypertension

Nicotine produces peptic ulcer disease,and esophageal reflux through its influences on the Gastrointestinal tract.

•Nicotine enhanceslearning and memory

•Nicotine’s influences in the brain also produces its addictive properties

•Nicotine enhanceslearning and memory

Most Likely Avenues for Exposure

• Tobacco Products

• Insecticides– Anti-AChE (Acetylcholine Esterase)

– nAChR activators (like nicotine)

Alcohol

C C

H

H H

H

HOH

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

Dose

Response

Giddy

Labored breathingUnconscious

Sleep

Deep sleep

Death

No effect

Chronic CNS Effects of Ethanol

• Korsacoff’s Syndrome– Loss of short term memory

– Due to a Thyamine Defficiency

Ethanol

Acetaldehyde

NAD

NADHAlcohol Dehydrogenase

Ethanol

Acetaldehyde

Acetate

NAD

NADH

NAD

NADH

Alcohol Dehydrogenase

Aldehyde Dehydrogenase

Ethanol

Acetaldehyde

Acetate

Citric Acid Cycle

NAD

NADH

NAD

NADH

Alcohol Dehydrogenase

Aldehyde Dehydrogenase

Energy

Ethanol

Acetaldehyde

Acetate

Citric Acid Cycle

NAD

NADH

NAD

NADH

Alcohol Dehydrogenase

Aldehyde Dehydrogenase

Energy

Fatty Liver

Fibrosis

Cirrosis

Ethanol

Acetaldehyde

Acetate

Citric Acid Cycle

NAD

NADH

NAD

NADH

Alcohol Dehydrogenase

Aldehyde Dehydrogenase

Energy

Fatty Liver

Fibrosis

Cirrosis

P450

Ethanol Interaction with P 450

• Acute Administration - P 450

• Chronic Administration - P 450

Acetominophen

SulfationGlucuronidation

Safe Excretionby Kidney and in Bile

Detoxication

Acetominophen

SulfationGlucuronidation

Safe Excretionby Kidney and in Bile

Detoxication

Quinoneimine Free Radical

Liver and Kidney Damage

Activation to a Toxic Metabolite

Acetominophen

SulfationGlucuronidation

Safe Excretionby Kidney and in Bile

Detoxication

Quinoneimine Free Radical

Liver and Kidney Damage

Activation to a Toxic Metabolite

P450

Acetominophen

SulfationGlucuronidation

Safe Excretionby Kidney and in Bile

Detoxication

Quinoneimine Free Radical

Liver and Kidney Damage

Activation to a Toxic Metabolite

P450

Ethanol InductionOf P450Expression

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