Pharmacology of Nicotine/Smoking Cessation

Question 1

nicotine - properties and MOA

Answer 1

• lipophillic
• MOA:
  
  • can mimic ACh –> opens ion channels
  • so, it binds to a₄b₂ nicotinic ACh receptors that are located on ventral tegmental area (VTA) cell bodies, which are an aggregation of dopraminergic neurons
    
    • the axon bundles coming from these neurons go to the –> nucleus accubens (NA), where they secrete dopamine
      
      • –> addiction response

Question 2

nicotine - pharmokinetics

Answer 2

• metabolized by the liver
  
  • by CYP-2A6 –> forming & excreting cotinine
    
    • ​note that estrogen indues CYP-2A6, and thus women excrete cotinine faster (men have higher cotinine levels)

Question 3

nicotinine transdermal patch

• MOA
• PK
• dosing
• AEs

Answer 3

• MOA: continuous, low level of nicotine delivery via the veins
• PK: long acting
• dosing: given in 7 / 14 / 21 mg doses (only 21 mg is 24 hr delivery)
  
  • light smoker: 7 mg
  • average smoker: 14 mg
  • heavy smoker: 21 mg
    
    • (24 hr patch; night ddelivery)
• AEs:
  
  • skin reactions
  • night disturbances

Question 4

C/I transdermal patch?

Answer 4

severe dermatological diseases: psoriasis, excema

Question 5

nicotine chewing gum

• MOA
• PK
• dosing
• AEs

Answer 5

• MOA: nicotine absorbed thru basic oral mucosa as patient chews side to side
• PK: short acting
• dosing: 2mg and 4mg
  
  • smokes < pack/day: 2m
  • smokes > pack/day: 4mg* (highly dependent)
• AEs:
  
  • throat irritation / sores
  • hiccups

Question 6

nicotoine lozenges

• MOA
• PK
• dosing
• AES

Answer 6

• MOA: absorbed into basic oral mucosa as patient holds in mouth
  
  • instruct pt to NOT chew or swallow!
• PK: short acting
• dosing: 2mg or 4mg - time dependent
  
  • pts show smoke > 30 min after awaking: 2 mg
  • pts show smoke < 30 min after waking: 4 mg
• AEs:
  
  • hearburn
  • hiccups
  • sore throat

Question 7

nicotine nasal spray

• MOA
• PK
• dosing
• AE

Answer 7

• MOA: directly to nasal septum
• PK: short acting (rapid delivery)
• dosing: only one available
• AEs:
  
  • nasal irritation
  • runny nose / sneezing
  • watery eyes

Question 8

nicotine oral inhalant

• MOA
• PK
• dosing
• AEs

Answer 8

• MOA: treats behavioral aspect of smoking by breaking hand to mouth ritual (4% delivered to lungs)
• PK/dosing/AEs: n/a

Question 9

varenicline

• MOA
• PK
• dosing
• AEs

Answer 9

• MOA: is a partial nicotine agonist
  
  • ​actually binds the a₄b₂ receptors of VTA –> releases dopamine, but less than actual nicotine
    
    • given as a monotherapy
• PK: renal eliminated
• dosing: one dose only, adjust dose for pts with renal impairment
• AEs:
  
  • nausea
  • suicidal ideation
  • vivid dreams

Question 10

what is the most effective smoking cessation agent?

Answer 10

varenicline

Question 11

buproprion

• MOA
• PK
• dosing
• AE

Answer 11

• MOA: NE/dopamine reuptake inhibiton (stimulant)–> keeps dopamine high in the system to sustain those withdrawing from nictone
  
  • possibly also antagonizes A₃B₂ receptors, blocking nicotine in these pts
• PK:
  
  • slow release
  • hepatic metabolism (CYP2B6)
• dosing:
  
  • take 2x/day
    
    • ​morning
    • 3 pm
  • adjusted as:
    
    • pt becomes less nicotine dependent
    • pt with hepatic disease
• AEs:
  
  • insomnia (common)
  • headache
  • weight loss

Question 12

what transdermal patch dosage provides night delivery?