SMOKING CESSATION Interactions [P’kinetic] Cigarette smoke induces CYP450 causing increased metabolism and therefore decreased effects of the following:

Caffeine, theophylline, bendamustine, irinotecan, clozapine [P’dynamic] Tobacco affects the following drugs:

Benzodiazepines

β blockers: tobacco ↑HR so need to ↑dose of β blockers

Inhaled corticosteroids: need to ↑dose

Hormonal contraceptives: ↑ risk of serious CV adverse effects like stroke, MI, thromboembolism o Estrogen itself already ↑ risk of clotting; smoking further ↑ the risk o Contraindicated in women >35y/o + smoking 15 cigarettes/day o Not just oral contraceptives, but also anything containing estrogen

[Absorption] Nicotine is a weak base and therefore absorbs best in alkaline media (pH 7.3-7.5)

Therefore, acidic beverages like coffee, juices, & soda interfere with nicotine absorption

Nicotine Withdrawal vs. Toxicity Withdrawal Toxicity

Anxiety, irritability, anger, frustration, lack of concentration, restlessness, cravings

Upset stomach, N/V/D, headaches, dizziness, drooling, cold sweat, blurry vision

(Smoking alleviates these symptoms)

Motivations & Behavioral Techniques 5 A’s for brief intervention

o Ask, advise, assess, assist, arrange

Transtheoretical Model for Behavior Change o Precontemplation, contemplation, preparation, action, maintenance

Telephone quit line: 1-800-QUIT-NOW

Medications Nicotine Replacement Therapy (NRT)

o Patches, gum, lozenges, inhaler, nasal spray

Buproprion SR (Zyban)

Varenicline (Chantix)

Combination therapy [Refer to Dr. Wilkins’ Pharmacologic Product Guide chart]

Patch Taper down: 21mg (4-6wks) 14mg (2wks) 7mg (2wks)

o Not therapeutically different, just psychological success/improvement

Counseling o Location: chest, arm, back o Rotate patch every 24 hours to decrease risk of itchy skin o If experiencing vivid dreams or sleep disturbance, patient can take patch off at bedtime (16 hr wear)

Expectations: only 20% success rate (need to focus on behavioral changes)

Duration: 8-10 weeks

Gum Dosing: 4mg > 1 pack/day 2mg < 1 pack/day

o “Chew & Park” 1 piece q1-2 hrs for 1-3 months o Max: 2mg x 30 pieces or 4mg x 20 pieces

Not for patients with dentures or poor dentition: very tough, hard resin

SE: jaw soreness (if not chewing & parking), hiccups (NaHCO3 coating), N/V (nicotine toxicity if constantly chewing), headaches

Lozenge Dosing: dependent on when is the first cigarette after waking up

o If <30 minutes 4mg o If >30 minutes 2mg

Inhaler 10mg (Rx) Good for patients who smoke menthol cigarettes since it has a menthol flavor

Better for lighter smokers

Helps with hand to mouth motion satisfaction

Dosing: start with 1 cartridge q1-2h; each cartridge delivers 4 mg nicotine

1 cartridge = 20 mins of continuous active puffing

Nasal spray 10mg/ml (Rx) Fast acting, quickest absorption greatest potential for abuse

Lots of side effects (e.g. burning in nostrils) unpopular, limited use

Dosing: 1-2 dose/hour where 1 dose is 1 spray per nostril (max 5 doses/hr, 40 doses/day)

Delivers 0.5 mg nicotine

Bupropion SR (Zyban) Nicotine receptor antagonist: blocks DA and NE reuptake in CNS

Also an antidepressant, so helpful for patients with underlying depression

No weight gain

Dosing: o Days 1-3 150mg qd o Days 4+ 150mg bid Dosing interval: ≥8 hours o Dosing adjustments

Hepatic impairment: 150mg every other day Renal impairment & elderly: 150mg qd Too many side effects: 150 mg qd instead of bid

Counseling: o May cause insomnia: don’t take 2nd dose at bedtime o Patient should continue smoking first 1-2 weeks; select quit date during 2nd week

Contraindicated with MAOI drugs and systemic steroids (e.g. prednisone)

May lower seizure threshold with theophylline, benzodiazepines, systemic steroids, alcohol

Lots of drug interactions

Varenicline (Chantix) Partial agonist and antagonist at nicotinic ACh receptor

o Agonist: stimulates low level of DA release which ↓withdrawal by hitting reward center o Antagonist: blocks nicotine from binding

P’kinetics: absorption not affected by food, minimal metabolism, primarily renal elimination, 24 hr t½

Being vareniciline 1 week before quit date

Titration: to ↓nausea and insomnia o Days 1-3 0.5mg qd o Days 4-7 0.5mg bid o Days 8+ 1mg bid (up to 12 weeks) o Dosing adjustment:

CrCL <30ml/min initial 0.5mg qd, max 0.5mg bid Hemodialysis 0.5mg qd

Side effects: nausea, insomnia, abnormal dreams, constipation, headache, dry mouth, suicide/mood changes

Combination NRT Common but not FDA approved

May be necessary for heavy smokers due to failure of a single agent

Precautions: ↑toxicity, ↑side effects, ↑cost

Long acting + short acting o Long acting: patch relatively constant levels of nicotine o Short acting: gum/lozenge/inhaler/nasal spray acute dose titration for withdrawal sx & flexibility