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PYB260 > Week 6 - Nicotine > Flashcards

Week 6 - Nicotine Flashcards

1
Q

What is nicotine?

A

comes from the plant form nicotiana tabacum
- smoking tobacco
- smokeless tobacco

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2
Q

Inhalation of nicotine

smoking

A
  • nicotine in smoke and ash
  • 90% absorbed through the mucous membrane in the lungs
  • directly to the heart and reaches the brain in ~ 7 seconds
  • amount absorbed is determined by how a cigarette is smoked and volume of smoke
  • some nicotine is absorbed through the mouth
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3
Q

Inhalation of nicotine

snuff

A

most nicotine absorbed through nasal cavity membrane

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4
Q

Inhalation of nicotine

nasal spray

A

most similar to smoking route of administration and absorption

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5
Q

Inhalation of nicotine

electronic nicotine delivery system (ENDS)

A

similar to smoking (vapours absorbed in lungs), but variable (many factors)

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6
Q

Oral administration

chewing

A

tobacco absorbed through mouth membranes

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7
Q

Oral administration

ingestion

A
  • tobacco rarely swallowed
  • poorly absorbed
  • most metabolised via liver
  • usually induces vomiting
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8
Q

Oral administration

nicotine gum

A
  • nicotine levels rise and fall with chewing
  • peak approx 1/3 that of smoking
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9
Q

transdermal administration

patches

A
  • slow build up of nicotine
  • constant level of nicotine mainted for hours
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10
Q

distribution

A
  • depends on route of administration and time of administration
  • nicotine leaves the brain ~30 min and concentrates in the liver kidneys, salivary glands and stomach
  • nicotine crosses most barriers and is found in sweat, saliva, breast milk and placenta
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11
Q

Excretion

A

Kidneys:
- depends on pH i.e. 30-40% excreted if pH<7
Liver:
- Metabolised to cotinine (~80%), nicotine-1-N-oxide
- half-life ~90-150 mins in adults
- minimal day-to-day accumulation
- metabolism depends on gender, smoker vs non-smoker, genetics (CYP2A6 gene)

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12
Q

physiological effects of nicotine

A
  • increased heart rate
  • increased blood pressure
  • vasoconstriction in skin (skin temperature, cold touch, aging/wrinkles, blushing)
  • inhibits stomach secretion
  • stimutes bowel activity - laxative effect
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13
Q

2 types of cholinergic receptor sites

A

Mucarinic: stimulated by muscarine; blocked by atropine
Nicotinic (NacHr): mainly ionotropic, stimulated by nicotine and blocked by curate (neuromuscular), mecamylamine (neuronal)

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14
Q

3 main configurations of nicotonic

A
  1. Basal state: closed ion channel at rest; high affinity for antagonists
  2. Active state: open channel; low affinity for agonist & antagonists
  3. Desensitised state: closed channel; insenesitive to agonists/antagonists
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15
Q

dosage effect on receptors

A

low doses: nicotine stimulates nicotinic cholinergic receptors
high doses: blocks nicotinic cholinergic receptors

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16
Q

nicotonic receptors in synapses of the brain

A

use dopamine and noradrenalin and release when stimulated
- nicotine also releases serotonin, beta-endorphine and hormones

17
Q

Nicotine and the PNS

A
  • nicotonic receptor sites located at neuromuscular junctions of striated muscles
  • nicotine stimulation = muscles tremors
  • nicotine causes release many neurotransmitters that affect the PNS e.g. adrenaline/epinephrine
18
Q

Nicotine and the CNS

A
  • direct effect on synapses
  • release of adrenalin from various sites (synapses and adrenal glands)
  • stimulation of reticular activating system
  • all result in increased arousal
19
Q

neurophysiological effects of nicotine

A
  • stimulation of medulla - increased respiration
  • inhibition of reflexes due to stimulation of inhibitory cells in spinal cord
  • vomiting centre also stimulated
  • release of norepinephrine and dopamine & stimulation of systems that use these neurotransmitters
  • serotonin systems also affected - antidepressant action
20
Q

effects on mood

A

subjective effects
- acute effects - pleasurable (by smokers)
- chronic effects - stress, well being ratings

21
Q

effects on sleep

A
  • I.V. nicotine - REM sleep in cats but not humans
  • withdrawal may affect sleep (increased REM)
22
Q

effects on performance

A

depends on:
- smokers vs non-smokers
- withdrawal
General effects:
- increased speed and accuracy of vigilance, attention & information processing (only on ST)
- faster motor reaction time e.g. finger tapping speed

23
Q

effects on cognitive functioning

A
  • effects of smoking similar to arousal - thus has effect on learning
  • immediate recall impaired, but later recall improved
  • alzheimer’s disease
  • contentious area of research: many other studies show null or negative effects of nicotine on cog function
24
Q

animal studies

A

spontaneous motor activity in rats usually depressed intially but increases after 7 days
- initial SMA due to increase ACh - then tolerance
- increased adrenalin produces SMA similar to amphetamines

25
Q

conditioned responses

A

nicotine & amphetamine effects on conditioned behaviour are similar
- slows high rates of behaviour and increases low rates of behaviour
- does not increase punished responses
- withdrawl can disrupt shock-avoidance behaviour
may be due to catecholamine release associated with nicotine

26
Q

self-administration

animals

A
  • most animals do not self-administer
  • reinforcement depends on forced consumption, paired stimuli, reinforcement schedules which impose abstinence between administration
  • nicotine can also serve as a punisher
27
Q

self-administration

humans

A
  • reinforcing in humans
  • self-administration is less frequent with higher doses & more frequent with lower doses
28
Q

theories for higher self-administration with lower doses

A
  1. maintain constant nicotine level
  2. trying to achieve high doses
  3. situation & expectations
  4. dual reinforcement model
29
Q

discriminative properties

A
  • 0.2mg/kg can be successfully discriminated - does not generalise to adrenalin, pentobarbital , caffeine
  • may partially generalise to amphetamines and cocaine
  • low doses of ethanol blocks nicotine discrimination in rats but not humans
  • humans can discriminate different doses
30
Q

tolerance

A

develops to nausea produced by stimulating the vomit centre of the brain

31
Q

withdrawal symptoms

A
  • decreased heart rate
  • excessive eating
  • lower levels of concentration
  • distrubed sleep
  • cravings
  • anxiety
  • depression
  • agression
  • headaches
  • nausea
32
Q

withdrawal

A
  • develops over 1st 3 days of abstinence, peak at ~1wk then decreases
  • most symptoms disappear >1 month; cravings may persist and triggered by cue exposure
  • severity not related to dose, length of smoking, previous attempts to quit, age, gender, alcohol or caffeine
  • fast metabolisers: more severe withdrawal
33
Q

treatment

A
  • 2/3 adult smokers want to quit; only 1/10 attempters succeed
  • nicotine replacement therapy includes patches gum and nasal spray
  • pharmacotherapies include buproprion (Zyban) and varenicline (champix)
  • future is looking at nicotine vax

PYB260 (10 decks)

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