low efficacy stimulants - nicotine

Question 1

what is the major psychoactive component of tobacco?

Answer 1

nicotine

Question 2

what are routes of admin of nicotine?

Answer 2

Buccal (chew)
Intranasal (snuff)
Oral (Lozenge)
Transdermal (patch)
Nasal spray
Inhalation (cigarettes/ vapes) - COMMON

Question 3

what are the different exposures to nicotine?

Answer 3

• first hand - inhaled by smoker
• second hand - exhaled by smoker or released from a burning cig
• third hand - residue that sticks to surfaces and dust after the smoke clears

Question 4

which of different exposures are indirect exposure?

Answer 4

• second hand
• third hand

Question 5

since nicotine is lipid soluble, what does it mean about absorption?

Answer 5

it is readily absorbed by the body through lungs, mucous membrane, skin, & less extent through GI tract

Question 6

is nic administered through IV?

Answer 6

no

Question 7

how much mg of nic is in a cigarette and how much reaches the blood stream?

Answer 7

in cig: 6-11 mg
in blood: 3mg

Question 8

what can the smoker’s do that affects the absorption?

Answer 8

the user can titrate (adjust) dose of nicotine by inhaling more frequently or deeply

Question 9

what is nicotine absorption dependent on?

Answer 9

pH - the environment that nicotine passes through changes the absorption rate

cigarette smoke is acidic, so less nic is absorbed. the pH of mouth can alter absorption nicotine

Question 10

what can nicotine permeate? in how long, and where are peak levels seen?

Answer 10

permeates BBB

reaches brain 7-20 seconds following a puff

reaches peak levels in lungs, blood, and brain in 1o minutes

Question 11

does nic reach the blood as fast as the brain?

Answer 11

no, it reaches brain first and there’s a slow increase in blood concentration

Question 12

what affects plasma nicotine levels?

Answer 12

nicotine concentration in the cartridge, rate of puffing, and puff duration.

Question 13

why is smoking during pregnancy bad for you?

Answer 13

• chemicals in cigarettes pass through placenta and reach all the organs of the developing fetus, including the brain
• prenatal exposure had long lasting effects on neurobehavioral development

Question 14

what metabolizes nicotine, where does it occur, and what is the active metabolite formed?

Answer 14

metabolizing enzyme: CYP2A6
location: liver
metabolite: cotinine, a partial agoninst

Question 15

where do we see increased CYP2A6 and what does that indicate?

Answer 15

it is increased in estrogen, so faster nicotine metabolized in women than men.

Question 16

what inhibits CYP2A6 activity and what does it do?

Answer 16

methanol

it causes a slower conversion to cotinine

Question 17

what is true with individuals with low CYP2A6 activity?

Answer 17

they have slow nic metabolism so..
- they are less likely to be smokers
- smoke less
- have greater success stopping

Question 18

what is the half life of nic and cotinine?

Answer 18

nic: 2hr
cotinine: 16 hr

Question 19

how do individuals avoid withdrawal symptoms?

Answer 19

they smoke repeatedly throughout the day

Question 20

what are the methods of excretion of nic?

Answer 20

urine and breast milk

Question 21

what neurotransmitter does nicotine and cotinine interact with?

Answer 21

acetylcholine

Question 22

what occurs when nic/cotinine interact with the acetylcholine?

Answer 22

1. neurons with cell bodies in BASAL FOREBRAIN projects to neurons in CEREBRAL CORTEX and LIMBIC SYSTEM

affects attention, learning, memory

2. neurons with cell bodies in BRAINSTEM (PPN/LTD) project throughout the BRAINSTEM and CEREBELLUM

affects movement, breathing, heart rate

Question 23

what is the synthesis, storage, and breakdown of the Ach system?

Answer 23

1. choline and acetyl coA are combined by choline acetyltransferase (ChAT) to for acetylcholine
2. Ach is moved into synaptic vesicles for storage by the vesicular Ach transporter (VAchT), embedded in the vesicle membrane
3. The enzyme acetylcholinesterase (AChE), breaks Ach down to choline and acetate.
   Choline is transported back into the cell for reuse
   **There is NO reuptake transport for Ach!

Question 24

Ach binds to 2 families of cholinergic receptors, what are they?

Answer 24

• nicotinic receptors (nAchR)
• muscarinic

Question 25

what are the characteristics of the nicotinic receptors?

Answer 25

- many types but all of them are excitatory - so when they are bound to, an ion channel is opended and positivelu charges cations flow into the postsynaptic neuron

Question 26

what are the characteristics of the muscarinic receptors?

Answer 26

- G proteined coupled - excitatory: M1, M3, M5 - inhibitory: M2, M4

Question 27

what is the mechanism of nicotine at Ach nicotinic receptors?

Answer 27

- acts as a full agonist - produces rapid influx of positively charged ions into the neuron, produces rapid excitatory responses

Question 28

what is the mechanism of cotinine at Ach nicotinic receptors?

Answer 28

- acts as a partial agonist - activates the receptor to a lesser degree than nicotine so less excitatory responses are produced

Question 29

what does high doses of nicotine lead to?

Answer 29

it causes persistant activation of nicotinic receptors (nAChR) and continuous depolarization of the cell. Continous depolarization results in a DEPOLARIZATION block, so the cell cannot reset after the action potential occurs and it can't fire again until nicotine is removed. so instead of stimulant actions, it produces depressant actions

Question 30

how does nicotine alter the activity of dopamine neurons?

Answer 30

it increases dopamine release in the mesolimbic pathways which accounts for its addictive properties

Question 31

where does the mesolimbic pathway start and end, what role does it play in addiction, and what occurs when nicotine is present?

Answer 31

starts: VTA ends: nucleus accumbens key role: reinforcement Binding of nicotine to High-affinity nicotinic receptors in the VTA stimulates burst firing of DA neurons, increasing DA release in the nucleus accumbens

Question 32

what is seen in tobacco smoke? what does this cause

Answer 32

chemicals that inhibit mao which causes the dependence from chronic use

Question 33

why is the mao inhibition so critical?

Answer 33

MAO is the enzyme that breaks down neurotransmitters like dopamine, serotonin, and NE. This means you have a double-hit or even greater increase in mesolimbic dopamine because nicotinic receptor stimulation increases DA release, and MAO inhibition/ blockade prevents that DA signal from ending. Thus DA exists in the synapse for longer!

Question 34

where are nicotinic receptors found?

Answer 34

CNS: hippocampus, cerebral cortex, basal ganglia, VTA & nucleus accumbens PNS: at neuromuscular junctions

Question 35

what systems does smoking activate?

Answer 35

sympathetic and parasympathetic systems (autonomic nervous system)

Question 36

what does release of NE and EPI from adrenal glands contribute to?

Answer 36

the arousing effects of nicotine

Question 37

in non smokers, what behavioral effects do we see after nicotine use?

Answer 37

arousal anxiety tension lightheadedness dizziness nausea.

Question 38

in smokers, what behavioral effects do we see after nicotine use?

Answer 38

- calm/relaxed state - relief from withdrawal mild euphoria

Question 39

what are the acute effects of nicotine?

Answer 39

- General stimulant/ arousal effects a. Increased heart rate and blood pressure, alertness, appetite suppression - Carbon monoxide (in smoked form) reduces oxygen transport to heart and other organs - Vasoconstriction -Can have calming (anxiolytic) effects in some individuals - Mild euphoria (relief?) - Cognitive enhancements - Antidepressant effects

Question 40

what are the benefits of nicotine in learning, memory, and attention>

Answer 40

Abstinent smokers given nicotine show enhanced cognitive & motor performance Nicotine has positive influence on cognition & motor function, even in non-smokers

Question 41

in what diseases does nicotine reduce symptoms in?

Answer 41

- ADHD - tourette's

Question 42

how is nicotine benefital to alzeimer's?

Answer 42

- Acetylcholine neurons die in Alzheimer's disease - Patients showed increased capacity for learning verbal material following nicotine use

Question 43

how is nicotine benefital to parkinson's?

Answer 43

- Dopamine neurons die in Parkinson’s disease - Nicotine users have lower incidence of Parkinson’s disease - Nicotine is neuroprotective for dopamine neurons

Question 44

is nicotine a scheduled drug?

Answer 44

nooo

Question 45

what does chronic exposure to nicotine do?

Answer 45

induces depended and tolerance

Question 46

what is true about nicotine acute tolerance?

Answer 46

it can occur DAILY During the night, individual undergoes mild withdrawal symptoms. At the same time, tolerance from the previous day dissipates. Individual wakes in the morning with strong urge to use tobacco products. Acute Tolerance reflects desensitization of nAchR

Question 47

what does chronic nicotine use do in the synapse?

Answer 47

causes downregulation of nAchR in the synapse

Question 48

what is nicotine seen to be in terms of addictiveness?

Answer 48

be one of the MOST addictive drugs! chronic uses results in tobaco use disorder

Question 49

what type of dependence do we see for nicotine chronic users?

Answer 49

Physical dependence occurs, where body expects (and “needs”) nicotine to avoid unpleasant withdrawal effects

Question 50

what does a long withdrawal from nicotine result in and is the most intense?

Answer 50

abstinence syndrome

Question 51

what are the 3 types of symptoms associated with trying to quit?

Answer 51

- affective symptoms a. anxiety, irritability, depressed mood, anhedonia, insomnia, restlessness, hyperalgesia. - somatic symptoms a. tremors, bradycardia, nausea, hunger and weight gain - cognitive symptoms a. difficulty concentrating (attention issues) & impaired memory

Question 52

when does abstinence syndrome occur>

Answer 52

symptoms peak 24–48 hr after quitting and subside within 2–4 weeks.

Question 53

what prevents withdrawal symptoms?

Answer 53

- nicotine replacement gum - patches

Question 54

what causes abstinence syndrome, from a biological perspective?

Answer 54

1. Resensitization of the desensitized nAChRs (no more depolarization block) 2. Return to normal levels of nAchR 3. Nicotine withdrawal leads to hyperactivity of the habenula, a brain region that shuts down the mesolimbic dopamine system!