Lesson 17: Nicotine/Tobacco

Where does nicotine bind

• nicotinic ACh receptors (nAChR)

  • ionotropic → excitatory effect

  • influx of NA+ and K+ → positive charge inside neuron

  • nicotine binding site on the a subunit

nAChR subunits - where is nicotine most active?

• beta 2 and alpha 4

• 12 kinds of subunits total (a2-a10; b2-b4)

Types of tobacco products

• smoking, chewing, snuff (inhaling), dip (mouth), vaporizer/ecig, dissolvables, cessation products (patch/gum)

When did the smoking rates begin to change

in 1964, after US surgeon general report links smoking to cancer and other diseases

• however, smoking in low to middle income countries has increased

• and rates of vaping have increased, which can completely reverse this progress

Vape regulations in BC

• 19 years old

• max dose of 20 mg/ml

• vapes must contain EITHER nicotine or THC

• flavor only products banned

• cannot be used in public buildings, workplaces, on school property, or near doorways/air intakes

• strict advertising restrictions

• health canada must be aware of all new products

What are the most common reasons for vape use among smokers

• help them quit

• long term replacement of cigarettes

• use in non smoking places

Absorption

• differs depending on the method of intake

  • smoking - lungs; snuff - nasal mucous membrane; patch - skin, etc

• not easily absorbed through the stomach (weak base)

Distribution

• reaches the brain very fast

  • 50% of peak brain concentration within 15 seconds

  • max concentration within 1 minute

    • increases addictive tendencies

  • remains in brain for 15 minutes

• crosses most barriers

  • blood brain barrier, placenta, breast milk

Elimination / metabolism

• broken down by cytochrome P450

• smokers metabolize faster

• females metabolize faster

• more rapid metabolizers show more intense withdrawal symptoms

Nicotine effects in the PNS

• increased heart rate and blood pressure

• vasoconstriction, cooler skin temp, wrinkles

• laxative effects (easily develops tolerance)

Nicotine effects in the CNS

• arousal → brain waves active; similar to when concentrating hard

• increased breathing rate

• vomiting (easily develops tolerance)

• feeling a rush

• cognitive performance effects

  • improved accuracy and speed in attention tasks

  • improved performance in fine motor tasks

  • improved short term episodic memory

2 phases of acute nicotine poisoning

• nausea and vomiting, excessive salivation, abdominal pain, pallor, sweating, hypertension, tachycardia, tremor, and seizures

• hypotension, bradycardia, coma, death

Harms with chronic use

• cancers

• heart and lung disease

• COPD

• reduced reproductive capacity

• also harms with second hand exposure

Nicotine increases NAcc DA in 3 ways

• nAChRs on VTA dopamine neurons directly cause DA release on to the NAcc

  • mesolimbic pathways has dopamine neurons → have nicotinic ach receptors (excitatory) → when activated, make dopamine tracks more effective → more dopamine sent to the nucleus accumbens

• nAChRs on GLU neurons in the VTA stimulate DA neurons in the mesolimbic DA pathway, increasing DA in the NAcc

  • indirectly stimulated (dopamine) by glutamatergic neurons

• nicotine desensitizes nAChRs on GABA neurons in VTA. When nAChRs are desensitized, less GABA is released, leading to more DA release

  • GABA desensitized → inhibited function; more dopamine released

Withdrawal

• 50%

• emerge within 24-48 hrs

  • peak at 1 week

  • dissipation by 2-4 weeks

• cravings may persist longer

• symptoms

  • cravings, insomnia, low mood, anxiety/restlessness, anger/irritability, tremor, headaches, dizziness, nausea, drowsiness

What do graphic warning labels on cigarette packaging actually do

• attract attention better than text only

• elicit stronger emotional reactions

• elicit more negative views of smoking

• increase intentions to quit smoking

• increase intention to not start smoking

Quitting smoking

• very difficult, but most who succeed go cold turkey

  • even going smokeless and/or reducing intake is a worthwhile goal

• various drug aids to help

  • nicotine replacement therapies → patches, gum, etc

  • bupropion → NE + DA reuptake inhibitor; nAChR antagonist

    • reduces reinforcing effects of nicotine and severity of withdrawal

  • varenicline → partial agonist for nAChR with competitive binding (outcompetes nicotine)

    • alleviates withdrawal while blocking nicotine from smoking