PHARMACOTHERAPY OF SMOKING CESSATION

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1 PHARMACOTHERAPY OF SMOKING CESSATION Domenic A. Ciraulo, MD Director of Alcohol Pharmacotherapy Research Center for Addiction Medicine Department of Psychiatry Massachusetts General Hospital

2 Disclosure Neither I nor my spouse/partner has a relevant financial relationship with a commercial interest to disclose

3 WHY TREAT? ADDICTIVE NATURE OF COMPONENTS OF TOBACCO NICOTINE, PERHAPS OTHERS SUCH AS ACETALDEHYDE RESPONSIBLE FOR 443,000 DEATHS PER YEAR IN UNITED STATES ANNUALLY

4 SUPPORT FOR NICOTINE AS PRIMARY ADDICTIVE SUBSTANCE SMOKING DELIVERS AEROSOLIZED WHEN SMOKED AND IS RAPIDLY ABSORBED FROM PULMONARY VASCULATURE A 1-3 MG NICOTINE BOLUS IS DELIVERED TO THE BRAIN WITHIN SECONDS OF SMOKING

5 NICOTINE RECEPTOR ACTIVATION INCREASES DOPAMINE NOREPINEPHRINE SEROTONIN ENDOGENOUS OPIOIDS PRODUCES REDUCTION IN ANXIETY, DYSPHORIA, INCREASED ATTENTION AND CONCENTRATION

6 LEVEL 1 EFFICACY MEDICATIONS NICOTINE REPLACEMENT (INCLUDING NRT COMBINATIONS) BUPROPION SR VARENICLINE

7 LEVEL 2 EFFICACY NORTIPTYLINE MECAMYLINE CLONIDINE NALTREXONE MAO INHIBITORS CYTISINE NICOTINE VACCINE

8 PROFILE OF SMOKERS RECENT STUDIES INDICATE THAT SMOKERS PRESENTING FOR TREATMENT HAVE MORE SEVERE DEPENDENCE HIGHER RATES OF CO-MORBIDITY

9 IMPROVING OUTCOMES WITH MEDICATION BEHAVIORAL THERAPIES MOTIVATION (MET) CONTINGENCY MANAGEMENT(EG, FINANCIAL REWARDS)

10 DETERMINING SEVERITY OF DEPENDENCE SMOKING IN FIRST 5 MINUTES AFTER AWAKENING SMOKING DESPITE SEVERE ILLNESS (EG RESPIRATORY INFECTIONS) WAKING UP AT NIGHT TO SMOKE SMOKING TO REDUCE WITHDRAWAL SYMPTOMS SMOKING GREATER THAT ONE PACK PER DAY

11 TREATMENT OPTIONS NICOTINE REPLACEMENT THERAPY FORMULATIONS WITH EQUIVALENT EFFICACY, BUT COMBINATIONS MAY BE BETTER FOR SOME PATIENTS GUM LOZENGES ORAL STRIPS SPRAY INHALER TRANSDERMAL PATCHES

12 VARENICLINE (CHANTIX) ALPHA 4 BETA 2 PARTIAL AGONIST AT NICOTINIC ACETYLCHOLINE RECEPTORS AS A PARTIAL AGONIST IT IS LESS ACTIVE THAN NICOTINE AT THESE RECEPTORS AND BLOCKS NICOTINE BINDING TO RECEPTORS SUSTAINED RELEASE OF DOPAMINE (LOWER AMOUNTS THAN NICOTINE) IN VENTRAL TEGMENTAL AREA

13 SUBJECTIVE EFFECTS REDUCES WITHDRAWAL SYMPTOMS REDUCES URGE TO SMOKE REDUCES REWARD FROM NICOTINE IF LAPSE TO SMOKING OCCURS

14 VARENICLINE CLINICAL USE BEGIN A WEEK OR TWO BEFORE QUIT DATE INITIAL DOSE IS 0.5, AFTER 3 DAYS 0.5 TWICE DAILY, AFTER ANOTHER 4 DAYS 1 MG TWICE DAILY DOSE TOLERATED BEST WITH MEALS, OR FULL GLASS OF WATER USUAL COURSE OF 12 WEEKS, IF NO RESPONSE NICOTINE REPLACEMENT IS ADDED

15 VARENICLINE ADVERSE EFFECTS NAUSEA, HEADACHE, INSOMNIA, ABNORMAL DREAMS,CONSTIPATION, FLATULENCE, COMMON RENAL CLEARANCE USE ALTERNATIVE DRUG OR LOW DOSE DEPENDING ON RENAL FUNCTION RARE BUT SERIOUS AVDVERSE EFFECTS HAVE BEEN REPORTED, BUT DATA DOES NOT CONCLUSIVELY SUPPORT DIRECT RELATIONSHIP WITH VARENICLINE DEPRESSION, AGITATION, SUICIDAL IDEATION AND ACTS

16 BUPROPION ANTIDEPRESSANT AGENT LOWER EFFICACY THAN VARENICLINE SO SECOND LINE AGENT BUPROPION WITH NRT DOES NOT INCREASE EFFICACY APPROACH IS TO START BUPROPION AND SET QUIT DATE AFTER 2 WEEKS

17 BUPROPION MECHANISM OF ACTION IS INCREASES IN BRAIN DOPAMINE AND NOREPINEPHRINE AE: DRY MOUTH, CONSTIPATION, NAUSEA, WEIGHT LOSS, INSOMNIA, INSOMNIA, HEADACHE, ANXIETY, TREMOR, ELEVATED BLOOD PRESSURE RARE BUT SERIOUS: SEIZURES

18 ELECTRONIC CIGARETTES SOME EVIDENCE THAT IT MAY HELP PEOPLE STOP SMOKING BUT NOT SUPERIOR TO APPROVED AGENTS CONCERNS ABOUT SAFETY WHAT IS IN VAPOR TARGETS YOUNGER PEOPLE CAN BE ALTERED WITH OTHER DRUGS

19 COMPARATIVE EFFICACY (COCHRANE REVIEW) NRT VS PLACEBO 1.84 ( ) COMB NRT VS PL 2.04 ( ) BUPROPION VS PL 1.82 ( ) VARENICLINE VS PL 2.88 ( ) VARENICLINE VS NRT 1.57 ( ) VARENICLINE VS BUP 1.59 ( )

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