Smoking Cessation

Question 1

How does the addictive process work at the Ventral Tegmental Area (VTA)?

Answer 1

VTA:
• GABA neurons => reward through the tegmental pedunculopontine (TPP) nucleus in mesolimbic system

• Dopamine neurons => aversion signals through nucleus accumbans
• Normally GABA inhibits dopamine release

Addiction:
• When you smoke you undo the inhibition of GABA on dopamine and dopamine gets released
• Overstimulation causes a decrease in dopamine production
• when you stop smoking you produce so little dopamine that you feel cravings and withdrawl

Question 2

What receptors are associated with reward?
• which are associated with reward and aversive effects?

Answer 2

• Presynaptic alpha7 receptors lead to TPP stimulation (pure reward)
• Post-synaptic alpha4beta2 receptors are associated with BOTH reward and adverse effects

Question 3

How much is your risk of dying of a smoking related disease reduced if you quit smoking before 40?

Answer 3

90% reduction

Question 4

Varenicline
• MOA
• Side Effects
• Contraindications

Answer 4

aka chantix

MOA
• Partial agonist at alpha4-beta2 nicotinic Ach receptor
• Blocks additional nicotine from being effective
• Release Mesolimbic Dopamine

Side Effects:
• Self-limiting nausea; depression, suicidal ideation, CV death, MI and Stroke

Contraindications:
• none listed

Question 5

Bupropion
• MOA
• Side Effects
• Contraindications

Answer 5

Wellbutrin
MOA:
• Inhibit re-uptake of NE and Dopamine
•decreases cravings, depression, and withdrawl

Side Effects:
• Insomnia, dry mouth, nausea; suicide ideation

*note insomina and dry mouth are not features of varenicline

Contraindications:
• None listed

Question 6

Nicotine replacement therapy
• MOA
• Side Effects
• Contraindications

Answer 6

MOA:
• attain Nicotine levels high enough to prevent withdrawl but not enough to produce dependence

Side Effects:
• Patch: application site rxns, headaches, cold and flu-like symptoms

• Gum: jaw pain, headache, addition transference
• Spray: local irritation, heartburn, hiccups

Contraindications:
• with patch watch out for: underlying CV disease (especially if you smoke while on the patch), diabetes, hepatic impairment, peptic ulcers, pheochromocytoma

Question 7

Clonidine
• MOA
• Side Effects
• Contraindications
• Other

Answer 7

MOA:
• Alpha-2 adrenergic agonist or imidazoline receptor agonist

Side Effects:
• Sedation (good for anxiety), dry mouth, dizziness

Contraindications :
• none listed

Other:
• Also can be used to treat HTN

Question 8

Mecamylamine
• MOA
• Side Effects
• Contraindications
• Notes

Answer 8

MOA:
• Nicotine antagonist (ganglionic blocker)

Side Effects:
• Orthostatic HypOtension, fatigue, sedation, constipation, dry mouth, N/V

Contraindications:
• Coronary or Renal insufficiency, glaucoma, uremia

Other:
• Moderates smoking cue-induced emotional responses

Question 9

Naltrexone
• MOA
• Side Effects
• Contraindications

Answer 9

MOA:
• Opiate antagonist