nicotine 1 Flashcards
which receptors does nicotine bind/activate
nicotinic acetylcholine
is nicotine relaxing or stimulating
either or, depending on environment or mood (bored - excite or relax - stressed)
can you get euphoria from cigarettes
the first of the day
what % of men smoke globally
47%
what % of women smoke globally
12%
how many cigarettes consumed/day globally
15 billion
how many deaths a year are linked to tobacco (and %)
5.4 million, 9%
is there an increase or decrease in smoking in industrialized nations
decrease
is there an increase or decrease in smoking in developing nations
increase
what percent of all smokers in 2020 will be in developing countries
85%
what % of canadian population smokes
19%
what is contained in tobacco from the plant
nicotine and carotenoids (naturally occuring chemicals)
how many compounds are added to tobacco during tobacco processing
599
how are compounds produced during process
large molecules broken down
how many new chemicals are created by burning tobacco (like the combustion products)
4000
what is nicotine (and why is it found naturally in plants)
addictive substance even though it is a neurotoxin used by plant to kill insects
what are particulates
combustion products, tar
how much particulate matter are in a cigarette that get exposed to lungs
10-40mg per cig
how much tar per day is deposited in heavy smokers
1g
where does the maximal lung damage happen from smoking
closest to tar deposits
what makes tar so bad (what compounds in tar)
polycyclic aromatic hydrocarbons and nitrosamines
per gram of tar, how many reactive species come from tar deposits
1016-1017 (ROS and RNS)
what are the ROS and RNS like from smoke (2 properties)
high density and relatively stable
what is an example of one of the reactive nitrogen species and whats so special about it
nitric oxide and it is relatively stable
what does nitric oxide do to the body
in excess it can react with other radicals to damage cell membranes - key mediator of lung injury
which ROS or NOS is a key mediator of lung injudry
nitric oxide
what is theobromine and its effect (why is it added)
a bronchodilator to maximize nicotine delivery
what is glycyrrhizin and its effect (why is it added)
a bronchodilator to maximize nicotine delivery
comes from licorice
what is bad about added sugar in cigarettes
they get converted into acrolein when burned (modifies DNA and proteins)
what is acrolein
extremely harmful chemical from burnt sugar which modifies DNA and protein
what can sugars turn into when burned (2 things)
acetaldehyde and acrolein
what does acetaldehyde do to nicotine administration and to whom
increases (triples) self administration (if given at low levels, lower than alcohol)
only in YOUNG rats
why would acetaldehyde increase nicotine self adminstration
it may inhibit monoamine oxidases and boost NT levels
what is the role of menthol in cigarettes (general)
counter irritant
how does acrolein cause irritation (mechanism)
TRPA1 (transient receptor potential A1) irritant receptor in airways (ca permeable)
what does TRPA1 allow to flow through when activated
ca
what triggers the coughing reflex in humans
acrolein targeting the TRPA1 receptor
how does menthol stop irritation of lungs / coughing
interacts with TRPA1 receptor and inhibits activation by acrolein and other irritants
what causes the cooling effect from menthol (which receptor is activation)
TRPM8
what can unintentional additives come from (general 3)
growing handling and processing
what are some examples of unintentional additives
conveyor belt fragments, insect parts, pesticide, herbicide, heavy metals, bacterial and mold toxins, radioactive elements from soil
do nicotine plants accumulate radioactive elements well
yes
what is apatite
a mineral often used in fertilization
what does apatite do
fertilizer to starve plants of nitrogen
why do nicotine plant growers use apatite
starting the plants from nitrogen can help create a flavour
what is a negative thing about apatite
contains radium and radioactive isotopes of lead and polonium
how do electronic cigs work (mechanically)
battery power atomizer heats up and vaporizes nicotine containing liquid
what is one of the main concerning compounds from e cigs
propylene glycol
what is the role of propylene glycol
dissolves nicotine in it in e cigs
what are 3 bad compounds found in e cigs
nitrosamines and propylene glycol
diacetyl
what do nitrosamines do
DNA modifications
what compounds causes popcorn lung
diacetyl
what does diacetyl do
popcorn lung- whole pockets of dead obliterated tisue
how do the amount of free radicals from e cigs compare to those in normal cigs
1/100 of what is found in real cig smoke
what does ecig smoke do to lungs (2 physical things!)
increases membrane lipid damage (peroxidation)
macrophage infiltration into lungs (like with tobacco smoke)
how did scientists test the effects of e cig smoke on immunity (what general experiment)
2 weeks of exposure to smoke, then exposed to different levels of influenza virus
out of the 4 groups, rank them based on survivability (most to least) (exposure to e cig smoke)
no cig + high virus
no cig + low virus
cig + high virus
cig + low virus
no cig + low virus
cig + low virus
no cig + high virus
cig + high virus
why can e cigs be good for quitting (2)
because they have the same behavioural aspects of cigarette use like the “throat catch”
they can help comtrol cravings
what do lots of people in the medical field think about e cig availability
they should be tighly regulated and not available OTC until there is more evidence on safety
what is in hooka
shisha (tobacco base with added ingredients) wieh water pipes
what is shisha
tobacco base with added ingredients
how is the hookah smoke not hot
it is cooled as it passes through piped in water
how does tobacco shisha compare to cigarette tobacco in carbon monoxide
shisha makes 11 times more CO than in cigarette
how does tobacco shisha compare to cigarette tobacco in carcinogen levels
same or higher
what does hooka do to BP
raise
what does hooka do to HR
raise
can hooka affect lungs long term
yes it can cause lung disease and cancer
can hooka affect mouths long term
yes it can cause oral cancer
does water remove irritants from hooka
some of them
is the shisha nicotine burned in hooka
no just really high heat
what is the average smoking time with cigarettes + number of puffs + inhaled smoke per puff
5-7 mins, 8-12 puffs, 0.5-0.6L
what is the average smoking time with hookah + number of puffs + inhaled smoke per puff
28-80 mins, 50-200 puffs, 0.15 L
where does nicotine bind on receptor relative to ACh
same site
at which pH ranges is nicotine charged
at low pH (positive_
does nicotine cause cancer
no but it may enhance growth
if nicotine doesnt cause cancer, how do cigs give you cancer
tar, CO, metals, hydrocarbons etc
what is the protonation state of nicotine at low ph
mostly diprotonated
what is the protonation state of nicotine at mid ph
monoprotonated
what is the protonation state of nicotine at high ph
nonprotonated / free-base
what does free-base form of nicotine mean / when does it happen
nonprotonated, most at high pH
does the diprotonated form of nicotine happen when smoking
no
which form of nicotine is the most volatine
free base / non protonated
why is the free base / non protonated state most easily absorbed
it is volatile so more easily released from tobacco and increases ease of absorption
what form of nicotine is linked with highest rates of adoption
free base / non protonated
what happens to free base / non protonated nicotine once its in the blood
converted to monoprotonated
how much nicotine on the tongue would kill an adult
60mg
how much nicotine in 1 cigarette
0.5-2mg
what is pyrolysis of nicotine
when nicotine gets destroyed due to burning
why do smokers only get a fraction of nicotine from cigs (3)
because of sidestream smoke, pyrolysis and filter
do most smokers smoke the same way
yes
how many puffs per min in the average smoker
1-2
how long does each puff take in the average smoker
2s
what is the ug/kg of weight that is optimal for brain stimulation
1-2ug/kg
how many puffs do you have if you smoke a pack a day
100-200 puffs
when do nicotine levels in body peak
at the end of the smoking day
why is the first smoke of the day the best
because receptors resensitize overnight
what causes drug accumulation throughout the day
because more smoking throughout the day causes accumulation (new drug added before previous drug is removed)
which receptor is most tied to the effects of nicotine/ most quickly saturated
alpha4beta2
how did they find out that it was the alpha4beta2 receptor which were most saturated with nicotine
they did tracer binding before and after. after it couldnt bind anymore because nicotine already occupies the same site
how many puffs are required to sufficiently occupy 50% of alpha4beta2 receptors
1-2
how much % alpha4beta2 receptors are occupied with 1 cigarette
80%
how does the relapse rate compare with people taking nicotine replacement therapy to quit
honestly no improvement in relapse compared to quitting without NRT
why doesnt nicotine replacement therapy work very well
things like the gum, patch, nasal spray, dont give the same peak height in concentration
what 3 things metabolize nicotine
monooxygenases and CYP2A6 and aldehyde oxidase
what does CYP2A6 turn nicotine into
cotinine
what is the half life of nicotine
2hrs
what is the half life of cotinine
16 hours
what % of nicotine is turned into cotinine
80%
what % of nicotine is turned into nicotine-1’ - N oxide
4-7%
what does monooxygenases turn nicotine into
nicotine-1’ - N oxide
what happens with a mutation in CYP2A6
slows metabolism, so less tobacco use
what does CYP2A6 do to ease of quitting
makes it easier because less metabolism and high nic levels are aversive
what is structurally different with nicotine and cotinine
cotinine has a ketone which makes it more soluble and willing to be excreted
which 2 things can induce enzymes to break down nicotine
nicotine and tar
what may play a role in nicotine tolerance
the enzymes that break it down
what is a good way to test for direct and second hand smoking
test for cotinine
