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Pmcol 305 > Nicotine > Flashcards

Nicotine Flashcards

1
Q

forms of tobacco product (8)

A

cigarettes
e-cigarettes
cigars
cigarillos
shisha
smokeless
patches
gum

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2
Q

electronic cigarettes

A

vapourize e-juice containing nicotine (glycerin or PG-based)
no tar “cleaner smoke is healthier”
flavours + additive → severe adverse effects
diacetyl + vitamin E acetate

vapour damages immune system (same as cigarettes)
5-8x more nicotine per puff than cigarettes

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3
Q

diacetyl

A

butter flavour of e-cigarettes
obliterates lung tissue → bronchiolitis obliterans
‘popcorn’ lung in factory workers = holes in lungs

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4
Q

vitamin E acetate

A

antioxidant
severe allergic reactions by inhalation

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5
Q

hookah

A

water cools smoke → less irritating, fewer particulates
- but, increase time of exposure to chemicals
uses shisha

hot air vapourizes chemicals - 11x more CO
elevated CO in blood → increased hr
increased risk of lung disease, oral/lung cancer

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6
Q

shisha

A

most processed, flavoured, tobacco form

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7
Q

smoke

A

an aerosol = particulates + gases

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8
Q

particulates in smoke

A

nicotine
water
tar
PAHs
benzo[a]pyrene
metals

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9
Q

gases in smoke

A

nicotine, CO, CO2, NO, nitrosamines, ammonia, nitrites, sulfur, alcohols, ketones, aldehydes, hydrocarbons

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10
Q

first-hand smoke

A

inhalation of smoke directly from burning tobacco

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11
Q

second hand smoke

A

smoke that has already been inhaled by others

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12
Q

third hand smoke

A

fumes from fingers, clothes, fabric

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13
Q

nicotine

A

alkaloid
uncharged = free base

causes addiction
competitive acetylcholine receptor agonist

protects plants from pests → pesticide

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14
Q

administration

A

inhalation (11-20% bioavailability)
oral - smokeless forms (50-80% bioavailability)

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15
Q

inhalation

A

controlling pH in cigarettes optimizes absorption (free base)
burning generates up to 4000 new chemicals
pyrolysis → lower bioavailability

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16
Q

free base

A

both nitrogens are neutral (no hydrogens)
weak base
easily reduced by plants
pH > 6

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17
Q

monoprotonated

A

one nitrogen is protonated = +1 charge
3 < pH < 9

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18
Q

diprotonated

A

both nitrogens are protonated = +2 charge
pH < 6

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19
Q

1 cigarette

A

~ 8mg nicotine
delivers 0.5-2 mg
occupies 80% of binding sites (nAChRs)

60 mg is lethal

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20
Q

pharmacokinetics + addiction

A

1-2 puffs/min - 2 sec long
1-2 ug nicotine/kg body weight is delivered to the brain
= one pack/day is optimal for brain stimulation

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21
Q

oral - smokeless forms

A

3-4x greater nicotine absorption
slower rate of absorption

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22
Q

distribution

A

blood pH is 7.4 = 70% monoprotonated, 30% unprotonated
<5% is bound to plasma protein

brain, liver, kidney, spleen, lung

least to adipose (less blood supply)

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23
Q

metabolism

A

nicotine → cotinine
in liver
aldehyde oxidases: CYP2A6 + CYP2B6
monooxygenases process small amount

half life = 2hr

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24
Q

CYP2A6 mutation

A

slows metabolism = greater [nicotine] for longer time → off target effects
results in lower tobacco use
aversive

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25
excretion
kidneys
26
nicotine concentration vs time
plasma [nicotine] peaks in the evening receptors re-sensitize over night = first daily cigarette is most pleasant
27
acute effects
sympathomimetic affects heart rate, bp, GI movement, motor commands, focus, + mood
28
mechanism of action
affects ACh, DA, GABA, Glu binds + depolarizes cells via nAChRs
29
biphasic mechanism
at high doses high affinity → inactivation of receptor
30
acetaldehyde
from burning may inhibit monoamine oxidases and boost NT levels
31
nAChRs in CNS
cortex, basal forebrain, hippocampus, basal ganglia, thalamus, cerebellum, brainstem presynaptic nAChRs depolarize terminals → prolonged DA, glu, GABA release
32
mechanism of reinforcement
presynaptic receptors on GABA, DA, + glu neurons = more GABA released → disinhibition of DA neuron = more DA release = more glu released → increased firing of DA more dopamine = pleasure, reward, addiction
33
acute adverse effects
stimulation of vomiting centre - common in first time users (area postrema - dorsal brainstem) headaches, nausea, disrupted ANS functioning alternating tachy- and brachycardia severe intoxication → seizures, hypotension, respiratory depression
34
nAChRs
heteropentameric receptors 9 a + 3 b subunits conduct cation influx to depolarize neurons - Na+, Ca2+
35
presynaptic nAChRs
increase NT release
36
postsynaptic nAChRs
depolarize cell
37
high affinity
continuous exposure to agonist (nicotine) inactivates receptor
38
receptor subunit composition
affects reinforcement + reward determine inactivation rates
39
a6
modulate locomotor responses
40
a7
facilitate glutamate release not inactivated
41
b2
subunit knockout in mice prevents DA release self-administration stops = important in reward
42
a4b2
antagonists block reward most important for DA reinforcement main functional nAChRs on VTA DA-ergic soma activation drives DA release and reinforcement govern GABA release - inactivate quickly and for a long time
43
a6b2
mainly on DA-ergic terminals in NAc do not release DA after systematic nicotine administration
44
single dose of nicotine injected into NAc
elevates DA levels for 80 minutes 3x baseline
45
first use
unpleasant targets brain regions/circuits for dizziness, nausea, sweat
46
tolerance
little or no decrease in heart effects, tremor, peripheral vasoconstriction = no change in physical effects
47
metabolic tolerance
increased enzyme activity
48
cellular tolerance
receptor inactivation affects reward nAChR expression increases in PFC - a4b2 enhances sensitivity to nicotine effects
49
behavioural tolerance
mindset stages experience ritual of smoking
50
withdrawal
physiological: headache, drowsiness, insomnia, increased appetite + weight gain, GI upset psychological: craving, mood changes, irritability, anxiety, restlessness, depression, difficulty concentrating, poor judgement + psychomotor performance
51
dependence
addicted if have to smoke within 30 min of waking occurs within days of habit physical + psychological quick metabolism → withdrawal → seek more cue-driven habit
52
long term adverse effects
cancer (lung, liver, colorectal) accelerate skin aging due to peripheral vasoconstriction sexual dysfunction - impaired NO signaling type 2 diabetes → stressed vasculature is insensitive to insulin
53
cancer
benzo(a)pyrene initiates cancer = intercalating agent nicotine enhances growth/metastasis (not initiation) - inhibits apoptotic signaling by binding a7 nAChRs on mitochondria → allows cells with damaged DNA to replicate
54
nicotine → in vitro
enhances cancer cell growth experiment - mice given cancer treated with nicotine/saline for 2 weeks removed tumours continued treatment → nicotine treated mice regrew tumours
55
long term adverse effects - tobacco
cataracts, macular degeneration tooth decay, periodontitis, IBS, Chrohn's infection rheumatoid arthritis, osteoporosis cardiovascular disease - CHD, MI, ischemic stroke COPD → emphysema, chronic bronchitis
56
COPD
inflammation of airways covered in tar + ash deposits cilia function is impaired by PAH + ketones in smoke
57
smokers' cough
when quitting indication of recovery of cilial function
58
pregnancy
constriction of umbilical arteries → reduced oxygen increased addiction risk higher risk of stillbirth, premature or miscarriage, low birth weight cleft palate + lip - higher risk
59
smoking cessation
alternate form of nicotine to ease withdrawal and cravings reduce use instead of complete elimination 3 day hump (withdrawal) → clearance from bloodstream harder to quit smokeless forms - higher doses
60
pharmacological cessation aids
bupropion varenicline
61
bupropion
antidepressant nAChR antagonist - blocks channel even when nicotine is present (competitive) DAT + NET inhibition → decrease sympathomimetic helps reduce cravings
62
varenicline
partial nAChR agonist reduces reward and cravings
63

Pmcol 305 (18 decks)

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