Nicotine Dependence Nicotine Dependence and Smoking Cessation and Smoking Cessation

Presented by: A. Al-Ahdal Presented by: A. Al-Ahdal Therapeutics IIITherapeutics III

Clinical Pharmacy DepartmentClinical Pharmacy DepartmentKAUU- 2006/2007KAUU- 2006/2007

Why Smoking Cessation Why Smoking Cessation is Importantis Important??

More than 500,000 smoking related deaths More than 500,000 smoking related deaths occur per yearoccur per year

Nearly one in five deaths was attributable to Nearly one in five deaths was attributable to smokingsmoking

Tobacco is the leading preventable cause of Tobacco is the leading preventable cause of illness and death illness and death

Fifty billion dollars in medical expenses a year Fifty billion dollars in medical expenses a year can be attributed to cigarette smoking can be attributed to cigarette smoking

Smoking contributes to and exacerbate many Smoking contributes to and exacerbate many age-related diseasesage-related diseases

• • Chronic Obstructive Pulmonary Disease (COPD)Chronic Obstructive Pulmonary Disease (COPD)

•• AsthmaAsthma

• • Hypertension Hypertension

• • Cardiovascular DiseaseCardiovascular Disease

• • StrokeStroke

• • AtherosclerosisAtherosclerosis

• • Peptic Ulcer DiseasePeptic Ulcer Disease

• • Gastroesophageal Reflux Disease (GERD)Gastroesophageal Reflux Disease (GERD)

• • DiabetesDiabetes

• • Impotence Impotence

• • Cancer: Lung, Oral, Larynx, Esophagus, Kidney, Cancer: Lung, Oral, Larynx, Esophagus, Kidney, Bladder, PancreasBladder, Pancreas

Why Smoking CessationWhy Smoking Cessation is Importantis Important??

Why Quit Tobacco UseWhy Quit Tobacco Use??

Benefits Benefits ““Improve Your Health & Lifestyle”Improve Your Health & Lifestyle”

20 minutes: BP, HR, and temperature of hands and 20 minutes: BP, HR, and temperature of hands and feet become normalfeet become normal

8 hours: O8 hours: O22 and CO and CO22 levels in blood return to normallevels in blood return to normal

1 day: risk of heart attack begins to decrease1 day: risk of heart attack begins to decrease

2 days: sense of smell and taste improves. Nerve 2 days: sense of smell and taste improves. Nerve ending starts to regrow.ending starts to regrow.

mucous in airways begins to break up and clear mucous in airways begins to break up and clear out of your lungsout of your lungs

2 weeks to 3 months: Circulation becomes better 2 weeks to 3 months: Circulation becomes better andand

Why Quit Tobacco UseWhy Quit Tobacco Use??breathing improves breathing improves 1 to 9 months: Coughing, sinus congestion, 1 to 9 months: Coughing, sinus congestion,

shortness of breath and fatigue decreaseshortness of breath and fatigue decrease1 year: Risk of heart disease is less then half 1 year: Risk of heart disease is less then half

of one year ago of one year ago 5 years: From five to fifteen years after 5 years: From five to fifteen years after

quitting, stroke is reduced to that of people quitting, stroke is reduced to that of people who have never smokedwho have never smoked

10 years: Risk of lung cancer drops to as little 10 years: Risk of lung cancer drops to as little as one-half that of continuing smokersas one-half that of continuing smokers

15 years: Risk of heart disease is similar to 15 years: Risk of heart disease is similar to that of people who have never smokedthat of people who have never smoked

Saves Money Saves Money $$$$...$$$$...

Neurochemistry of Nicotine Neurochemistry of Nicotine AddictionAddiction

Inhalation of nicotine Inhalation of nicotine to the to the

brain Stimulating the release ofbrain Stimulating the release of

Dopamine in the midbrainDopamine in the midbrainNicotine activates the dopamineNicotine activates the dopamine

reward pathway (a networkreward pathway (a network

of nervous tissue in the middle of nervous tissue in the middle ofof

the brain that elicits feeling ofthe brain that elicits feeling of

pleasure/arousal in response topleasure/arousal in response to

stimuli)stimuli) key pathway area key pathway area

in the brain responsible for in the brain responsible for thinking, & judgmentthinking, & judgment

Neurochemistry of Nicotine Neurochemistry of Nicotine AddictionAddiction

Chronic administration of Chronic administration of nicotine increases number nicotine increases number ofof

nicotine receptors in specific nicotine receptors in specific regions of the regions of the brainbraintolerancetolerance

Continous smokingContinous smoking more more tolerance, & dependencetolerance, & dependence

Dependant Dependant smokers smokers consumeconsume 10-40mg 10-40mg of of nicotin/day to minimize nicotin/day to minimize symptomssymptoms of of withdrawal withdrawal

Pharmacology Pharmacology of Cigarette Smokeof Cigarette Smoke

More than 4000 substances including some that More than 4000 substances including some that are pharmacologically active, antigenic, are pharmacologically active, antigenic, cytotoxic, mutagenic, and carcinogenic have cytotoxic, mutagenic, and carcinogenic have been identified in cigarette smokebeen identified in cigarette smokeThe two cigarette components thought to cause The two cigarette components thought to cause greatest risk are nicotine and carbon monoxidegreatest risk are nicotine and carbon monoxide

ΔΔ ClearClear Highly toxic weak baseHighly toxic weak base ΔΔ Ganglionic stimulant and depressantGanglionic stimulant and depressant ΔΔ Effects mediated by catecholamine releaseEffects mediated by catecholamine release ΔΔ Increased serum conc. of glucose, cortisol, free Increased serum conc. of glucose, cortisol, free

fatty acids, fatty acids, and vasopressin and vasopressin

11..NicotineNicotine

Pharmacology Pharmacology of Cigarette Smokeof Cigarette Smoke

11..Carbon Carbon

MonoxideMonoxide

ΔΔ Interferes with oxygen transport and utilizationInterferes with oxygen transport and utilizationΔΔ leads to elevated carboxyhemoglobin levelsleads to elevated carboxyhemoglobin levelsΔΔ Chronic carboxyhemoglobin levels lead to mild Chronic carboxyhemoglobin levels lead to mild polycythemiapolycythemia

MetabolismMetabolism – liver, & to a lesser extent kidney, lung. – liver, & to a lesser extent kidney, lung. (70-80%) of(70-80%) of

NicotineNicotine T1/2= (2hrs),T1/2= (2hrs), CCotinineotinine T1/2 =18-20hrsT1/2 =18-20hrs inactive inactive metabolite, a marker of tobacco use, and exposure to metabolite, a marker of tobacco use, and exposure to 22ndnd hand smoke hand smokeExcretionExcretion – PH dependent, acidic urine – PH dependent, acidic urine excretion excretion nicotine and metabolites, found in breast milk, blood, nicotine and metabolites, found in breast milk, blood, & urine of nursing infants& urine of nursing infants

Assessment of Nicotine Assessment of Nicotine DependenceDependence

Number, type (high vs. low nicotine)Number, type (high vs. low nicotine)Fagerstrom ScoreFagerstrom Score

How soon after you wake up do you smoke How soon after you wake up do you smoke

your 1your 1stst cigarette? cigarette? > >1hr1hr

-½-½11 hrhr

66 to to 3030mimi

nn

5mi5minn

or or lessless

Do you find it difficult to refrain from smoking Do you find it difficult to refrain from smoking

in places where its forbidden?in places where its forbidden? NoNoYesYes

Which cigarette would you hate to give up Which cigarette would you hate to give up most?most?

AnyAny

otheotherr

11stst one one in AMin AM

How many cigarettes do you smoke per day? How many cigarettes do you smoke per day? <<101011-2011-2021-21-3030

>>3030

Do you smoke more frequently during 1Do you smoke more frequently during 1stst hr hr after waking than during the rest of the day?after waking than during the rest of the day?

NoNoYesYes

Do you smoke if you are so ill that you are in Do you smoke if you are so ill that you are in bed most of the day?bed most of the day?

NoNoYesYes

Score >5 is Score >5 is high nicotine high nicotine dependencedependence

Nicotine WithdrawalNicotine Withdrawal Diagnostic Criteria for Nicotine WithdrawalDiagnostic Criteria for Nicotine Withdrawal

American Psychiatric Association . DSM-IVAmerican Psychiatric Association . DSM-IV

A. Daily use of nicotine for at least several weeks A. Daily use of nicotine for at least several weeks

B. Abrupt cessation of nicotine use, or reduction in the B. Abrupt cessation of nicotine use, or reduction in the amount of nicotine used, fallowed within 24hrs by > or =4 amount of nicotine used, fallowed within 24hrs by > or =4 of the following signs:of the following signs:• Dysphoria or depressed moodDysphoria or depressed mood• InsomniaInsomnia• Irritability, frustration, or angerIrritability, frustration, or anger• AnxietyAnxiety• Difficulty concentratingDifficulty concentrating• RestlessnessRestlessness• Hunger/ weight gainHunger/ weight gain• Significant distress or impairment in social, Significant distress or impairment in social, occupational, and other important areas of occupational, and other important areas of functioning functioning

General Steps in Smoking General Steps in Smoking Cessation InterventionCessation Intervention

Agency for health care policy and research (AHCPR) Agency for health care policy and research (AHCPR) Clinical Practice GuidelinesClinical Practice GuidelinesStep 1. Step 1. AskAsk-Identify all tobacco users at every visit-Identify all tobacco users at every visitStep 2.Step 2. AdviseAdvise-Strongly advise all smokers to quit-Strongly advise all smokers to quit Step 3. Step 3. IdentifyIdentify-all patients willing to quit -all patients willing to quit (history)(history) Step 4.Step 4. Assist Assist-the patient in quitting-the patient in quitting

--Anticipate challenges to planned quit attemptAnticipate challenges to planned quit attempt- - Set a quit dateSet a quit date

- - Provide advice on how to successfully quitProvide advice on how to successfully quit --All patients should be offered nicotine replacement All patients should be offered nicotine replacement

therapytherapy

Step 5.Step 5. ArrangeArrange-Schedule follow-up contact-Schedule follow-up contact

Discuss Potential ProblemsDiscuss Potential Problems

This smoke contains many This smoke contains many irritants and poisons. It is irritants and poisons. It is especially dangerous for especially dangerous for babies and young children. babies and young children. Their lungs are delicate. Their lungs are delicate. Children who breathe this Children who breathe this smoke are more likely than smoke are more likely than other children to get sick. other children to get sick. They may have more They may have more mucus. The fluid in their mucus. The fluid in their middle ears may build up middle ears may build up and cause ear infections. and cause ear infections. They may develop They may develop pneumonia, bronchitis and pneumonia, bronchitis and other lung infections. If they other lung infections. If they have asthma, it may get have asthma, it may get worse.worse.

Patient Management OptionsPatient Management Options

Behavioral TherapyBehavioral Therapy Used to teach patients the problem-solving Used to teach patients the problem-solving skills neededskills needed

To deal with the cessation To deal with the cessation (Clinical Practice (Clinical Practice Guidelines)Guidelines)

- Barriers/concerns - Coping skills- Barriers/concerns - Coping skills

- Dealing with triggers- Dealing with triggers - - OthersOthersIncrease long-term cessation rates by Increase long-term cessation rates by

1.5 to 2 fold over pharmacotherapy 1.5 to 2 fold over pharmacotherapy alonealone

Should be strongly encouraged Should be strongly encouraged

Pharmacologic TherapyPharmacologic Therapy

Nicotine Replacement Therapy (NRT)Nicotine Replacement Therapy (NRT)NRTNRT Increases success for quitting by reducing Increases success for quitting by reducing

the physicalthe physical

Withdrawal symptomsWithdrawal symptoms associated with nicotine associated with nicotine cessationcessation

along with adjusting to behavioral changes, along with adjusting to behavioral changes, coping skills coping skills

and physiological aspects of quitting, plus NRT and physiological aspects of quitting, plus NRT slow onsetslow onset

of action vs. smoking nicotine of action vs. smoking nicotine

Nicotine GumNicotine GumOTCOTC (Nicorette(Nicorette®®)) DosageDosage Adverse Adverse

EffectsEffects NNAppropriate Appropriate

useuse2mg,4mg;regular,mi2mg,4mg;regular,mint,orangent,orange

≥≥2525 cig/ day: cig/ day: 4mg4mg

<<2525 cig/ day: cig/ day: 2mg2mg

Week 1-6: 1 Week 1-6: 1 piece Q 1-2hrspiece Q 1-2hrs

Week 7-9: 1 Week 7-9: 1 piece Q 2-4hrspiece Q 2-4hrs

Week 10-12: 1 Week 10-12: 1 piece Q 4-8hrspiece Q 4-8hrsDurationDuration

Up to 12wksUp to 12wks

• • Mouth/jaw Mouth/jaw sorenesssoreness

• • HiccupsHiccups

• • DyspepsiaDyspepsia

• • incorrect incorrect chewingchewing

- N/ V- N/ V

- - lightheadednesslightheadedness

- throat & - throat & mouthmouth

irritation irritation

- Fixed schedule- Fixed schedule- No > 30pc/day No > 30pc/day (2mg gum)(2mg gum)-No > 20pc/day No > 20pc/day (4mg gum)(4mg gum)-Chew slowly Chew slowly tingling sensation, tingling sensation, park between park between cheeks (1pc. For cheeks (1pc. For 30’)30’)-Wait 15’ Wait 15’ øø food/drinkfood/drink-No any nicotine No any nicotine useuse

Transdermal NicotineTransdermal NicotineOTCOTC

Heavy SmokerHeavy Smoker Light smokerLight smoker [<10-15 cigs/day][<10-15 cigs/day]

Nicoderm CQNicoderm CQ®® (16 to 24hr) (16 to 24hr)

7mg, 14mg, 21mg7mg, 14mg, 21mg

-21mg x 6 weeks 21mg x 6 weeks

-14mg x 2weeks-14mg x 2weeks-7mg x 2 weeks7mg x 2 weeks

HabitrolHabitrol® ® (24hr)(24hr)

-21mg x 6 weeks 21mg x 6 weeks

-14mg x 2-4weeks-14mg x 2-4weeks-7mg x 2-4 weeks7mg x 2-4 weeks

[[≤ ≤ 10-15 cigs/day]10-15 cigs/day]

Nicoderm CQNicoderm CQ® ® or or

HabitrolHabitrol®®

-14mg x 2weeks-14mg x 2weeks

- 7mg x 2 weeks- 7mg x 2 weeks

[[≤ ≤ 5 cigs/day]5 cigs/day]NRT not necessaryNRT not necessary

DurationDuration 8-10wk8-10wk

Transdermal NicotineTransdermal NicotineOTCOTC

ProductProduct AdvantagesAdvantages DisadvantagesDisadvantages

Nicoderm CQNicoderm CQ®®One step processOne step process No oral S.ENo oral S.E..

Easy to useEasy to use

Few non-Few non-compliancecompliance

Can not titrate Can not titrate dosedose

24hr release 24hr release systemsystem

Allergy to Allergy to adhesive adhesive Longer onset to Longer onset to peak plasma peak plasma conc. conc. (6-12hr)(6-12hr)

HabitrolHabitrol®®Provide 24-hr SS Provide 24-hr SS concconc..

No oral S.ENo oral S.E..

Easy to useEasy to use

Few non-Few non-compliancecompliance

Allergy to Allergy to adhesive adhesive Longer onset to Longer onset to peak plasma peak plasma conc. conc. (6-12hr)(6-12hr)

NAdverse Effects- Vivid Dreams, Local skin reactions

Nicotine Nasal SprayNicotine Nasal SprayRxRx

Product Product DosageDosage AdvantagAdvantage e

Concerns Concerns

Nicotrol NSNicotrol NS®®

NASAL sprayNASAL spray

0.5mg nicotine in 0.5mg nicotine in 50UL aq. Nicotin 50UL aq. Nicotin solsol

Duration: 3-6 Duration: 3-6 momo

1-2 doses/hr (8-1-2 doses/hr (8-40 doses/day)40 doses/day)

One One dose=2sprays dose=2sprays (one in each (one in each nostril)nostril)

Start 8 doses/dayStart 8 doses/day

No> 5doses/hr No> 5doses/hr

40 doses/day 40 doses/day

--Dose easily Dose easily titratedtitrated

--Use to respond Use to respond to cravingsto cravings

--Hot/Peppery Hot/Peppery sensation in sensation in nose/throatnose/throat

Sneezing/Sneezing/coughingcoughing

--watery eyeswatery eyes

--runny noserunny nose

--DependenceDependence

NicotrolNicotrol®®

Oral InhalerOral Inhaler

10mg cartridge 10mg cartridge delivers 4mg delivers 4mg inhaled nicotine inhaled nicotine vaporvapor

Duration: up Duration: up to 6 moto 6 mo

6-166-16 cartridges/daycartridges/day

Depleted after Depleted after 2020’’

Open cartridge Open cartridge retains potency retains potency for 24hrsfor 24hrs

Use @ least Use @ least 6/day6/day

-Dose easily -Dose easily titratedtitrated

-Mimics act of -Mimics act of smoking smoking

--Use to respond Use to respond to cravingsto cravings

- -Ø Ø Break habitBreak habit

- -DependenceDependence

- -Bad taste, Bad taste, coughcough

-hiccups, HAhiccups, HA

--DyspepsiaDyspepsia

--RhinitisRhinitis

--nasal/throat nasal/throat irritirrit . .

Bupropion SRBupropion SRRxRx

ZybanZyban®®

Sustained-release tablet, Dose: 150mg PO Q AM x3 daySustained-release tablet, Dose: 150mg PO Q AM x3 day , ,

then then to 15omg po BID, 8-12 wk to 15omg po BID, 8-12 wk

- Set quit date 1-2 weeks after initiation of therapy.- Set quit date 1-2 weeks after initiation of therapy.- Do NOT exceed 300mg/day Do NOT exceed 300mg/day

- Allow at least 8 hours between doses- Allow at least 8 hours between doses- Avoid bedtime dosing to minimize insomniaAvoid bedtime dosing to minimize insomnia

MOA:MOA: unknown, but thought Neurochemistry, enhancing unknown, but thought Neurochemistry, enhancing dopamine level in themesolimbic system (pleasure dopamine level in themesolimbic system (pleasure center), nicotine addiction is due to dopaminergic center), nicotine addiction is due to dopaminergic

S.E.S.E. Dry mouth, Insomnia, Nervousness/difficulty Dry mouth, Insomnia, Nervousness/difficulty concentratingconcentrating

Duration: up 6 moDuration: up 6 mo

BupropionBupropion

Cont. side effects:Cont. side effects: Anxiety, restlessness and Anxiety, restlessness and insomnia. At high doses, it may cause seizures, insomnia. At high doses, it may cause seizures, so it is not a good choice for individuals with so it is not a good choice for individuals with epilepsy or brain injuriesepilepsy or brain injuries..

Usage:Usage: You must take Bupropion two or three times You must take Bupropion two or three times a day to limit its side effects, although an a day to limit its side effects, although an extended-release form is available that can be extended-release form is available that can be used once or twice a day. This drug may cause used once or twice a day. This drug may cause seizures when taken in large amountsseizures when taken in large amounts..

Smoking and pregnancySmoking and pregnancy

It is well known that smoking during It is well known that smoking during pregnancy can damage the baby and even pregnancy can damage the baby and even cause a miscarriage. Compared with non-cause a miscarriage. Compared with non-smokers, smoking during pregnancy can smokers, smoking during pregnancy can cause:cause:

Reduced birth weight Reduced birth weight

Increased risk of the baby dying Increased risk of the baby dying

just before or just after birthjust before or just after birth

Urinary Urinary