Stimulants 3 Nicotine

Question 1

Along with caffeine and alcohol, one of the most widely
used psychoactives in the world and routinely rated by addicts as the toughest substance to stop using

Answer 1

Nicotine

Question 2

Nicotine is who’s neurotoxic defense against
insects, works like other ACh-agonist toxins, paralyzing insects that eat the leaves

Answer 2

Tobacco plant

Question 3

Nicotine is a what agonist

Answer 3

ACh

Question 4

admin of nicotine is customarily

Answer 4

inhalation or mucous membrane

Question 5

nicotine can also be absorbed through what (ie transdermal patches)

Answer 5

skin

Question 6

leads to good absorption from intestines
(nicotine is basic)

Answer 6

oral administration

Question 7

this admin is not useful because nicotine undergoes extensive (90%) first pass metabolism

Answer 7

PO

Question 8

passively slips through this with ease

Answer 8

BBB

Question 9

elimination is

Answer 9

fairly quick (T1/2 ~ 2± hours)

Question 10

the most important metabolizing
enzyme, converting nicotine mostly to cotinine

Answer 10

Cytochrome P450 CYP2A6

Question 11

stress accelerates

Answer 11

nicotine metabolism

Question 12

tobacco farmers who handle the leaves (wet) without gloves can have nicotine seep into the skin/clothing, causing them to get sick

Answer 12

green tobacco sickness

Question 13

What does this mean for smokers’ reports that smoking helps them feel less stressed?

Answer 13

nicotine gets metabolized quicker, sends them into a state of nicotine withdrawal, smoking makes the withdrawal go away

Question 14

main route for metabolite elimination

Answer 14

urine

Question 15

Nicotine acts mainly as a direct agonist at what, causing Na+ influx = EPSP

Answer 15

nicotinic Ach receptors

Question 16

The key effect is activation of these excitatory nicotinic receptors located on

Answer 16

VTA dopamine neurons

Question 17

activation of these excitatory nicotinic receptors located on VTA dopamine neurons leads to

Answer 17

increased activity in mesolimbic “reward” circuitry (but not nearly to the extent that cocaine or amphetamines can increase it)

Question 18

activation of these excitatory nicotinic receptors located on VTA dopamine neurons ends up also activating

Answer 18

endogenous opioid systems

Question 19

Curiously, at very high doses, nicotine begins to have what effects on ACh activity (tolerance???)

Answer 19

antagonist

Question 20

among the estimated 4700 chemicals in tobacco smoke,
something appears to work as an MAOI (i.e., slowing the
breakdown of DA, NE, 5-HT), not nicotine itself, but most likely

Answer 20

beta carbolines

Question 21

mesocortical nicotinic receptor activation can lead to

Answer 21

more dopamine activity and attention in frontal lobe

Question 22

Like caffeine, increased alertness, attention/concentration, working memory (overall sharpening of mental functioning), reduced hunger

Answer 22

psychoactive effects of nicotine

Question 23

Many persons have inadvertently discovered it as “self-
medication” for

Answer 23

ADHD

Question 24

Smoking rates are extremely high among

Answer 24

schizophrenic persons

Question 25

However, the data are fewer on the cognitive benefits among

Answer 25

non-patient smokers

Question 26

Equivocal data exist on whether smoking increases

Answer 26

testosterone levels

Question 27

develops quickly (within hours), mostly though desensitization of NAChRs, this tends to keep smokers puffing away throughout the day, lost once the smoker stops smoking for the day, the next day the building starts anew

Answer 27

tolerance

Question 28

this develops – metabolic? (GTS is more common &
severe among nonsmokers)

Answer 28

longer term tolerance

Question 29

But overall, tolerance to nicotine is far less than tolerance to

Answer 29

other addictive drugs

Question 30

craving, grouchiness, ↓ mental sharpness, hunger, frustration, restlessness, anhedonia, beginning within hours of deprivation, weight gain is a common longer-term consequence

Answer 30

withdrawal side effects

Question 31

The role of nicotine-related cues (conditioned stimuli)

Answer 31

cannot be overstated

Question 32

inability to feel pleasure

Answer 32

anhedonia

Question 33

needed to cause nicotine toxicity via PO admin

Answer 33

enormous amounts

Question 34

could be as low as 60mg or as high as >1g

Answer 34

LD50

Question 35

this way of entry is more problematic (e.g., green
tobacco sickness, insecticide exposure; e-cig liquid)

Answer 35

transdermal

Question 36

follows a biphasic pattern

Answer 36

toxicity

Question 37

cholinergic stimulation symptoms predominate: nausea, vomiting, diarrhea, muscle fasciculations, tachycardia and hypertension occur initially

Answer 37

first phase of toxicity

Question 38

symptoms appear to relate to cholinergic inhibition, likely a product of extreme NAChR desensitization, bradycardia, cardiac arrhythmia, hypotension, coma, and respiratory, muscle failure, which typically leads to death if not treated

Answer 38

second phase of toxicity

Question 39

Gums, patches, lozenges, inhalers, etc. provide low dose nicotine so that users can slowly taper their use (wean themselves) without experiencing unbearable withdrawal symptoms.

Answer 39

Nicotine replacement therapies

Question 40

Nicotinic ACh receptor antagonist (Presumably counteracts the effects of nicotine), Also a DA & NE reuptake blocker (Presumably allows mesolimbic DA activity to stay high, thus minimizing withdrawal
symptoms)

Answer 40

Zyban / Wellbutrin (bupropion)

Question 41

“Partial agonist” at nicotinic ACh receptors – competes with ACh and nicotine, binds to receptors and can activate, but is less likely to activate them than ACh or
nicotine is, limits psychoactive effect of nicotine

Answer 41

Chantix (varenicline)