Nicotine Flashcards
Nicotine preperations
cigarettes -allows for self administration and maintenence of consistent plasma levels cigars pipes e-cigs smokeless patches gums
nicotine administration
plant alkaloid base with pka 8.0 Administration -inhalation -Buccal -Nasal -Transdermal
Nicotine absorbtion
cigarettes -via lungs (acidic) cigars/pipes -via mouth (basic) smokeless -via mouth (basic) patches -via skin
Nicotine biotransformation
Nicotine (half life ~2 hours)
-Cytochrome P450 (CYP2A6)
Cotinine (half life ~ 16 hours)
Individual variability in rates of nicotine metabolism
Caucasions > Asians = African-Americans
Females > males
Fast metabolizers consume more
- dependent on level of cytochrome p450 gene
- -metabolizes nicotine
Fast metabolizers less likely to quit
nicotinic receptors (ACh)
Agonist action at receptor - Receptor Desensitization - Receptor upregulation
Locations of nicotinic receptors
Brain Neurons
Autonomic Ganglia
Skeletal muscles
Brain Choinergic Systems
Ventral Tegmental area
cortex/hippocampus
-review photo in slides
Nicotine Acute Cognitive and Physiological effects
arousal
attention
mental acuity
relaxation
increased respiration
anti-diuresis
Toxic effects of nicotine
Dizziness Nausea Vomiting Tremor Respiratory Suppression Seizures Death
Nicotine Therapeutic uses
ZERO
Nicotine Potential treatments
Depression Schizophrenia Alzeimers Touret's Syndrom ADHD Anxiety
Nicotine Tolerance
- Metabolic, Cellular, and Behavioral mechanisms
- Cross Tolerance with Caffeine, Opioids, Antidepressants, Benzodiazepines
- Tolerance leads to withdrawal symptoms
- Acute and Chronic Withdrawal syndromes
symptoms f nicotine withdrawal
irritability Anxiety Distraction Restlessness Insomnia Hunger Weight Gain
Nicotine Physical Dependence
Linked to nicotine tolerance
Withdrawal Sndroms
Dependence
Smoking - Acute Cellular Tolerance
Not Smoking - Onset of Withdrawal
Resume Smoking - Termination of Withdrawal
Cycle repeats
Dependence
(Smoking - Acute Cellular Tolerance)
Smoking Desensitizes Nicotinic Receptors
System Compensates by Increasing Receptors
Dependence
(Not Smoking - Onset of Withdrawal)
During Withdrawal, Receptors are Hyperresponsive
Withdrawal Symptoms Develop
Dependence
(Resume Smoking - Termination of Withdrawal)
Receptors become occupied by nicotine
Withdrawal symptoms dissipate
Nicotine Psychological Dependence
Strong Reinforcer
Acting Via Dopamine Systems
Nicotine and Brain Systems
Dopamine Axons
Cholinergic Cell Bodies
Dopamine Cell Bodies
Nicotine and Brain Systems
Dopamine Axons
Nucleus Accumbens (NA) -Stem out from cell bodies in Ventral Tegmental Area
Nicotine and Brain Systems
Cholinergic Cell bodies
Laterodorsal (LDT)
Pedunculopontine (PPT)
-Communicates with Dopamine Cell Bodies around Substantia Nigra
Nicotine and Brain Systems
Dopamine Cell Bodies
Ventral Tegmental Area
Nicotine and the Dopamine Reward System
Nicotine Stimulates DA Neurons in VTA to Release DA in Nucleus Accumbens and PreFrontalCortex
LDT / PPT
-Release ACh act at nicotinic receptors
VTA
-Releases Dopamine at NA and PFC
Factors in Smoking Addiction
Withdrawal Syndrome
Dopamine Reward System
Conditioning Cues
Smoking Addiction Conditioning Cues
Sensory (Taste, Smell, Touch)
Mood
Social
out of twenty people, how many will smoke, try to quit, actually quit, and fail quitting?
20 people
5 will smoke,
5 will try to quit,
1 will actually quit
4 will continue to smoke
Motivations to smoke
Image
Rebellion
Peer Pressure
Stress Relief
Weight Control
Advertising
Parmacotherapy for Smoking Addiction
Nicotine replacement
Buproprion
Varenicline
Parmacotherapy for Smoking Addiction
Nicotine Replacement
Nicoderm or Nicorette
-occupies nicotinic receptors
Parmacotherapy for Smoking Addiction
Buproprion
Antidepressant blocks dopamine reuptake
Parmacotherapy for Smoking Addiction
Varenicline
Partial Nicotinic Receptor Agonist
Annual US Deaths
Smoking: 430,000
Alcohol: 81,000
Other Drugs: 14,000
AIDS: 17,000
Car Accidents: 41,000
Murders: 19,000
Death by smoking
Lung Cancer: 125,000
Other Cancers: 31,000
Other Diagnoses: 67,000
Secondhand Smoke: 38,000
Chronic Lung Disease: 82,000
Ischemic Heart Disease: 82,000
Stroke:
17,000
Effects of Smoking on the Cardiovascular System
Increases Demand
Reduced Oxygen supply to heart
Effects of Smoking on the Cardiovascular System
Increases Demand
Increases heart rate / Contraction
Increases Blood pressure
Effects of Smoking on the Cardiovascular System
Reduces oxygen supply to heart
Artherosclerosis
Carbon Monoxide reduces affinity of hemoglobin for oxygen
Impairs Pulmonary function
(Chronic Obstructive Pulmonary Disease)
Chronic Obstructive Pulmonary Disease
Combination of:
Emphysema
Chronic Bronchitis
Asthma
Emphysema
The walls of the alveoli are damaged by inflammation. Alveoli can lose their natural elasticity, Become overstretched and rupture.
Several adjacent alveoli may rupture, forming one large space instead of many small ones
Bronchitis
Chronic Brnochitis is a chronic inflammation and thickening of the walls of your bronchial tubes,
Which narrows them. It often induces coughing spells.
Carcinogens in Cigarette Smoke
can cause: skin agin lung disease and cancers infertility incontinence Urinary Tract Disease and Cancers
Gum Disease
Heart Disease
Impotence
Poor Clotting
Cigarette smoke cancers
lung mouth throat stomach bladder
