Nicotine Flashcards
Is nicotine addictive?
Yes, highly
What was nicotine originally used for?
it was an insecticide
What plant does nicotine come from?
Tobacco plant
What is the #1 killer in the world?
Smoking
What did cigarette ads target?
they targeted kids to get addicted and continue using when they got older
How fast does nicotine reach the brain after inhaling it?
7 seconds (as fast as if injected)
How does time of effect, change addiction?
The less time it takes to get to the brain the more addictive a drug is
The cigarette is a delivery system for more than 7,000 other chemicals in cigarette smoke, how many are carcinogens, what type of toxins?
- Carcinogens (70), ciliotoxins (paralyse cilia in lungs, can’t move mucus out), inhibitors
What diseases can be caused by smoking?
Heart disease, stroke, gum infections, bladder cancer
what happens to mucociliary clearance when smoking?
it is decreased, can’t get mucous out of lungs
Smoking combined with asbestos causes?
50-90 times more risk, increase lung cancer deaths.
Asbestos has small fibers that when breathed in can get into the lungs and cause cancer
How many deaths from coronary heart disease are due to smoking
1/3
What is nicotine’s effect on the skin, eyes, hair (does it vasoconstrict or vasodilate)
Nicotine – vasoconstriction
Skin – wrinkles (smoking + sun damage)
Eyes – cataracts
Hair – thinning
20% of smokers die from what lung conditions?
Bronchitis + emphysema
How many people die from second hand smoke each year?
900,000 people
Children exposed to smoke are more at risk of developing what diseases?
Children exposed to smoke have an increased rate of brain tumors, cancers, asthma, infections SIDS
Types of nicotine absorption/administration?
Mouth, lungs, skin (patch)
Does nicotine have a first pass inactivation?
No, bypasses the liver, when inhaled
How do smokers control nicotine bioavailability?
The smoker controls the bioavailability
- If nicotine is higher than 6%, then the smoker puffs less
- If the nicotine level is less than 6%, then the smoker puffs more
- The smoker controls the level of nicotine to be about the same
Nicotine gum (oral administration) causes?
Nicotine gum – rate of absorption is slower less concentration in blood
Why can children die from eating a cigarette?
Nicotine is absorbed very well in the GI tract, so if a child swallows/ eats a cigarette they will get nicotine poisoning and can die
Where is nicotine distributed in the body?
- Everywhere
- Chemoreceptor trigger zone (triggers vomiting before enough gets absorbed, kids) – no blood brain barrier
- Smokers build up tolerance to vomiting, need more nicotine to have the same effect
Which cytochrome P450 metabolizes nicotine?
CYP2A6, CYP2A6 activates procarcinogens that form cytotoxic and genotoxic metabolites (urine is carcinogenic)
What is nicotine’s half life?
2 hours
What effect does a defective CYP2A6 cause?
- Slower removal of nicotine
- Therefore, a smoker needs to smoke less cigarettes to maintain the same blood nicotine levels
- (They can smoke, but end up smoking less)
Excretion of Nicotine?
- Urine is carcinogenic, which is probably why bladder cancer is more common in smokers
- Alkaline urine decreases the excretion of nicotine
What type of receptor is the nicotinic receptor, how many subunits does it have?
it is a ligand gated ion channel, (sodium/calcium channel), it has 5 subunits, alpha (9) or beta (3), receptors in the neurons differ from those in the muscles
What is the effect of acetylcholine binding to nicotinic receptors?
- Ach binds, opens channel – sodium/calcium can now flow through
- Ach comes off, receptor is desensitized for a bit and then regenerates
What is the effect of nicotine binding to nicotinic receptors?
- Nicotine binds – opens channel
- The receptor is desensitized for longer
- More ions get into the brain (Na+, Ca2+)
What cardiovascular effects does nicotine cause?
- Change blood flow, heart rate (increases)
- Hunger contractions of the stomach decrease, less hungry
Is nicotine excitatory or inhibitory?
excitatory
Effects of Nicotine poisoning?
CNS: excitation followed by inhibition
Tremor, convulsions…
Paralysis
Death from respiratory failure
what type of receptors are necessary for dopamine release?
Beta 2 and alpha 4 ach receptors
What is menthol?
It is a channel modulator
What effect does menthol have on smoking?
- Increases the addictive property
- Decreases the ability to stop smoking
- Now banned as an addition in cigarettes
How does nicotine alter dopamine levels in the brain causing addiction?
Nicotine decreases the GABA inhibition (desensitize)
Nicotine stimulates receptors on glutamate excitation
- Increases the amount of dopamine released
What are some withdrawal symptoms from smoking nicotine?
- Depressed mood, steep trouble, irritable, difficulty concentrating, restless, increased appetite, weight gain
- Craving for nicotine peaks at 3 days and then goes down
- Initial distress in first 5 days
- Later there is a sense of well being, but the cravings don’t go away
- Excess nicotinic receptors slowly decline, up to 6-12 weeks for them to go away
Types of nicotine treatments?
- Replacement therapy – patch
- Block nicotinic receptors in the reward pathway – BUP (drug), varenicline, partial agonist, lower effect of dopamine
- Block CYP2A6
- Decrease dopamine release (topiramate tablet
- Nicotine vaccine – being tested, nicotine would have no effect
What are the effects of e-cigarettes?
e-cigarettes have small particles that are absorbed into the lungs and get into the blood, the magnitude of the risk for vaping is not known yet
- Disruption to lung function and gas exchange
- Impaired respiratory immunity and host defence systems
- Respiratory inflammation and injury
