April 21, 2023

Smoking Smoking Cessation Cessation

Prepared by:Prepared by:

Khuloud Khuloud BaghdadyBaghdady

April 21, 2023

Important Notes Cigarette smoking is the chief, single, avoidable cause of

death in U.S.

The recommended treatment for tobacco dependence involves both behavioral counseling and pharmacotherapy.

Pharmacist is the only health care provider who comes in contact with individuals self-treating tobacco use and dependence…WHY??

April 21, 2023

Epidemiology of Tobacco Use and Dependence In Arab world 70% of men and 25% of women are

smokers (1999). In 2003, 1/10 die from smoking in Arab world. In Jordan, the rate of smoking is 43% (18-40 years),

49% (40-60years). (1999) In our university the rate is 79% for men, 21% for women

in the school of nursing!!! 45% of them have started smoking in high school. (2003)

Smoking friends represent 77% of smoking causes, while free time represent 70% of causes.

Design, baseline results of Irbid longitudinal, school-based smoking study.

Mzayek F, Khader Y, Eissenberg T, Ward KD, Maziak W.

Abstract OBJECTIVE: To compare patterns of water pipe and cigarette smoking in an eastern

Mediterranean country. METHODS: In 2008, 1781 out of 1877 seventh graders enrolled in 19 randomly selected schools

in Irbid, Jordan, were surveyed. RESULTS: Experimentation with and current water pipe smoking were more prevalent than

cigarette smoking (boys: 38.7% vs 26.8%; 20.2% vs 9.0%, girls: 21.2% vs 9.5%; and 7.5% vs 2.3%, P<0.05 for all). Parent- and peer-smoking correlated more strongly with water pipe than with cigarette smoking.

CONCLUSION: Water-pipe smoking is more prevalent than cigarette smoking at this early age.

April 21, 2023

Waterpipe tobacco and cigarette smoking among university students in Jordan. Khabour OF, Alzoubi KH, Eissenberg T, Mehrotra P, Azab M, Carroll MV, Afifi RA, Primack BA.

OBJECTIVES: To characterize the relative prevalence of waterpipe tobacco and cigarette smoking among university students in Jordan, and to compare the demographic and environmental factors associated with each form of tobacco use.

DESIGN: We surveyed 1845 students randomly recruited from four universities in Jordan. We used multivariable logistic regression controlling for clustering of individuals within universities to determine associations between demographic and environmental covariates and waterpipe tobacco and cigarette use.

RESULTS: Waterpipe tobacco smoking rates were 30% in the past 30 days and 56% ever, while cigarette smoking rates were 29% in the past 30 days and 57% ever. Past 30-day waterpipe tobacco smoking rates were 59% for males and 13% for females. Females had substantially lower odds than males of being current waterpipe (OR 0.12, 95%CI 0.10-0.15) or cigarette (OR 0.08, 95%CI 0.05-0.14) smokers. Current cigarette smoking was more significantly associated with markers of high socio-economic status (SES) than waterpipe tobacco smoking.

CONCLUSION: Waterpipe tobacco smoking is as common as cigarette smoking among Jordanian university students. While cigarette smoking is consistently associated with high SES, waterpipe tobacco smoking is more evenly distributed across various populations.

April 21, 2023

April 21, 2023

Etiology of Tobacco Use andDependence Nicotine stimulates the mesolimbic dopaminergic

system in the midbrain inducing pleasant rewarding effects that promote continued use of the drug as with other addictive substances (e.g., opiates, cocaine, amphetamine)

Psychological/environmental factors play an important role in establishing and maintaining dependence smokers commonly associate smoking with specific activities such as driving, drinking coffee, etc

April 21, 2023

Pathophysiology of Tobacco Useand Dependence Tobacco smoke is a complex mixture of an estimated

4800 compounds found in gaseous and particulate phases.

Approximately 500 compounds are present in the vapor phase (N2, CO, NH3, HCN, C6H6), the remaining constituents are found in the particulate phase (the most imp one is the alkaloid nicotine, the addictive component).

The particulate phase – (H2O + nicotine) = tar. The tar contain numerous carcinogens (PAHs,

nitrosamine).

April 21, 2023

Pathophysiology of Tobacco Useand Dependence Nicotine is distilled from burning tobacco and carried in

tar droplets small airways of the lung arterial circulation (rapidly) distributed throughout the body.

Nicotine penetrates the CNS bind to receptors in the brain and other organs stimulate the release of neurotransmitters such as NEP, Ach, D, that induce stimulatory effects on CVS.

Ph. Dynamic effects of nicotine include: ↑HR, ↑BP, ↑myocardial contraction, vasoconstriction of coronary and peripheral blood vessels, pleasure, arousal, enhanced task performance, appetite suppression.

April 21, 2023

Signs and Symptoms of Tobacco Useand Dependence The majority of chronic smokers develop tolerance to the

effects of nicotine abrupt cessation precipitates symptoms of nicotine withdrawal (anger, irritability, anxiety, difficulty concentrating, drowsiness, fatigue, sleep disturbances, hunger, and strong craving for tobacco).

The physiologic nicotine withdrawal symptoms manifest within 24hr of tobacco abstinence, peak 24 to 48hr later, dissipate gradually over the following 2 to 4 weeks, completely resolve within 1 month of quitting.

April 21, 2023

Complication of Complication of TobaccoTobacco Use and Use and DependenceDependence

April 21, 2023

Cardiovascular Disease 20% of the deaths due to IHD that occur in US each year

are attributable to smoking. Smoking accelerate the process of atherosclerosis,

leading to CHD, cerebrovascular disease, and aortic aneurysm.

Acute CV events that are more likely to occur in smokers include: MI, stroke, sudden death.

Smokers have lower HDL, higher LDL and TG than nonsmokers.

April 21, 2023

Cancer Cigarette smoking is the most imp risk factor in the

development of lung cancer, the leading cause of cancer-related death in US.

Exposure to second hand smoke also ↑ the risk of death due to lung cancer.

Many other cancers occur in tissues that come in direct contact with tobacco, including cancer of the oral cavity, pharynx, larynx, and esophagus.

Other cancer occur at distant sites, such as pancreas, bladder, stomach, kidney, colon and cervix.

April 21, 2023

Cancer There are at least 69 known carcinogens present in

tobacco smoke, including PAHs, nitrosamines, benzene, vinyl chloride, formaldehyde, and arsenic.

Low tar and low nicotine cigarettes don’t decrease the risk of cancer.. WHY??

1. More frequent smoking.

2. More deep inhalation.

April 21, 2023

Pulmonary Disease Cigarette smoking is the principal risk factor for

developing COPD (Emphysema, Chronic Bronchitis).

Tobacco smoke is a potent irritant capable of inducing asthma exacerbations.

In adults, regular exposure to secondhand smoke has been found to ↑ the risk of lower respiratory symptoms such as: wheezing and bronchitis.

April 21, 2023

Pregnancy/Perinatal Complications Women who smoke are more likely to experience

delayed conception and infertility. Women who smoke during pregnancy are at increased

risk for preterm delivery and are more likely to deliver babies of lower birth wt.

Nicotine-induced vasoconstriction in placenta may induce labor, and nicotine and CO may retard fetal growth.

April 21, 2023

Drug Interaction with Tobaccosmoke The majority of Ph.Kinetic interactions are the result of

induction of hepatic CYP 450 enzymes (primarily the CYP 1A2 isozyme) by PAHs present in tobacco smoke.

Induction of the CYP 1A2 can ↑ the hepatic metabolism of Fluvoxamine, Theophylline, Olanzapine, resulting in a reduced therapeutic response or need for higher dosages in smokers.

April 21, 2023

Benefits of Tobacco Cessation Within 1 to 9 months after quitting, ciliary

function in lung epithelial cells is restored, enhancing the lung’s ability to eliminate accumulated tar and respiratory secretions.

1 year after quitting, the excess risk of CHD is ↓ to ½ that of continuing smokers, after 5-15 years, the risk of stroke is ↓ to a rate similar to that of people who have never smoked.

It is very imp to stress to tobacco users that it is never too late to incur many of the benefits of quitting.

April 21, 2023

Treatment of Treatment of TobaccoTobacco Use and Use and DependenceDependence

April 21, 2023

The primary goal for any patient who use

tobacco is complete, long term abstinence from

all nicotine-containing products. Three imp ingredients for successful quitting include:

1. practical counseling (problem solving, skills training).

2. support from a health care provider.

3. support from others (family, friends, co-workers). The use of pharmacotherapy approximately doubles a

patient’s chances of quitting cessation interventions should combine pharmacotherapy with behavioral counseling.

April 21, 2023

Pharmacologic Therapy Clinicians should encourage all smokers preparing for a

quit attempt to incorporate a pharmacotherapy as a component of their ttt plan.

There are 6 FDA approved agents for smoking cessation, including 5 formulations of NRT and sustained release bupropion.

3 of NRT (gum, lozenge, patch) are available OTC, the rest (nicotine inhaler, nicotine nasal spray, bupropion) require a prescription.

April 21, 2023

Nicotine Replacement Therapy Nicotine gum and patches were switched to OTC in

1996, nicotine lozenge were released to the market directly as OTC product in 2002.

The rational for using NRT during a quit attempt is to provide smokers with non-tobacco source of nicotine.. WHY??

1. To relieve the symptom of nicotine withdrawal. 2. Enable quitters to focus their effort on breaking

the behavioral habit of smoking.

NICOTINE

April 21, 2023

Pharmacokinetics Nicotine is well absorbed from many sites, including the

lung, skin, nasal and buccal mucosa. Absorption of nicotine is pH-dependent, lower systemic

conc is achieved under acidic condition. Nicotine is well abs from GIT but undergoes extensive

first-pass metabolism negligible systemic level. The major difference between the various NRT is the site

and the rate of nicotine absorption. All NRT deliver nicotine less rapidly and achieve lower

serum level than do cigarette or other forms of tobacco.

April 21, 2023

General Precautions/warnings Don’t smoke or use other form of tobacco (cigars, pipes,

chewing tobacco) while you use NRT. Use with caution in patients with serious CVD such as a

recent MI, arrhythmia, angina, un-controlled HTN. It is classified by FDA as Pregnancy Category D the

use of NRT during pregnancy is reserved for women who are un-able to quit using non-pharmacologic methods alone.

Nicotine is excreted in breast milk can be detected in the blood and urine of the infants of nursing smokers.

The use of NRT should be under supervision of a medical provider in smokers <18 year, pregnant, nursing women.

April 21, 2023

Nicotine Polacrilex Gum It is a resin complex of nicotine and polacrilin in a sugar-

free (contains sorbitol) chewing gum base. It is available as 2mg and 4mg strength in regular, mint,

and orange flavors. {Nicorette®} It contain buffering agents (NaHCO3, Na2CO3) ↑

salivary pH ↑ absorption across the buccal mucosa. When the 2mg strength gum is used properly, 1mg of

nicotine is absorbed from each dose, peak conc within 30min, slowly decline over 2-3hrs.

It is OTC product.

April 21, 2023

Dosage ≥25 cigarette/day4 mg

< 25 cigarette/day2 mg

Weeks 1-61 piece q1-2hr

Weeks 7-91 piece q2-4hr

Weeks 10-121 piece q4-8hr

April 21, 2023

Proper Use/ Interactions/ AE/ Precautions Usage guideline for nicotine gum is shown in Table 50-6. The effectiveness of it ↓ by acidic beverages such as

coffee, juice, or soft drink. The most common SE include mouth irritation, fatigue,

unpleasant taste, hypersalivation, and dyspepsia, these can be ↓ or prevented by using proper technique.

If excessive sticking or damage to dental work occurs stop using the gum and consult a dentist.

In temporomandibular joint D don’t use gum. In stomach ulcer, DM, contact medical provider b4 use.

April 21, 2023

Nicotine Polacrilex Lozenge It is a resin complex of nicotine and polacrilin in sugar-

free (contains aspartame), lightly mint-flavored lozenge.

It is available as 2mg and 4mg dime-sized tablets used as other medical lozenges (sucked and rotated within the mouth until it dissolves). {Commit®}. It is OTC product.

It delivers 25% more nicotine than an equivalent dose of gum due to complete dissolution.

It contains NaHCO3, Na2CO3 as in gum.

April 21, 2023

Dosage1st cigarette ≥ 30 min

after waking4 mg

1st cigarette > 30 min after waking

2 mg

Weeks 1-61 lozenge q1-2hr

Weeks 7-91 lozenge q2-4hr

Weeks 10-121 lozenge q4-8hr

April 21, 2023

Proper Use/ Interactions/ AE/ Precautions Usage guideline for lozenges is shown in Table 50-7.

S/E include mouth irritation, nausea, hiccups, cough, insomnia, and headache, heartburn.

The effectiveness of it ↓ by acidic beverages such as coffee, juice, or soft drinks

In stomach ulcer, DM, contact medical provider b4 use.

April 21, 2023

Nicotine Patch Nicotine transdermal system deliver continuous, low

levels of nicotine across the skin over 16 or 24hr. The patch consist of a water-proof surface layer, a

nicotine reservoir, an adhesive layer, and a disposable protective liner.

Currently, there are 4 marketed products, three of them deliver the labeled dose of nicotine continuously over 24hr, while the 4th deliver the dose over 16hr.

This patch, which approximates typical smoking patterns, is applied in the morning and removed at bedtime, and it is an OTC product.

April 21, 2023

Dosage Heavy smokers will require higher strength formulations

for a longer duration of therapy.

Patients with strong morning cravings for cigarettes have better success with a 24hr patch.

Patients experiencing withdrawal symptoms or cravings should ↑ the dose, while those who experiencing S/E (dizziness, nausea, vomiting, headache) should ↓ the dose.

April 21, 2023

Proper Use/ Interactions/ AE/Precautions Usage guideline for patch is shown in the following slide.

The most common S/E are local skin reactions (erythema, burning, and pruritus), and they tend to occur more commonly with the 24hr products.

Skin reactions can minimized or prevented by rotating the patch application site on a day basis.

Patients with dermatologic conditions (psoriasis, eczema, atopic dermatitis should not use the patches.

If the person smokes more than 10 cigarettes per day:

Start with 25 mg Patch for eight weeks

Switch to 15 mg patch for 2 weeks

Lower the dose to 10 mg for 2 more weeks

If the person smokes less than 10 per day

Start with 15mg patch for 8 weeks

Cut down to 10 mg for 4 weeks

April 21, 2023

April 21, 2023

Prescription products Nicotine Inhaler: it consists of a plastic mouthpiece and a

nicotine containing cartridge that delivers 4mg of nicotine as an inhaled vapor, which is absorbed across the oropharyngeal mucosa, its S/E include: mouth and throat irritation, cough, and rhinitis.

Nicotine Nasal Spray: it is an aqueous solution of nicotine for administration to the nasal mucosa, each actuation deliver a 0.5mg bolus of nicotine that is absorbed rapidly (within 10-15min) it is used for patients who prefer a medication to rapidly manage withdrawal symptoms.

April 21, 2023

Prescription products Sustained-release Bupropion: it is the 1st pharmaceutical

aid not contain nicotine that approved for smoking cessation, it was marketed originally as antidepressant.

Seizures have been reported in 0.1% of patients it is C/I in patients with history of seizure.

It can be used in combination with NRT.

Clonidine, and Nortriptyline have been found to be effective and should be reserved for patients unable to quit using NRT or Bupropion, because it is not approved by FDA and have more A/E.

Varenicline

Varenicline acts as a partial agonist/antagonist with affinity and selectivity for alpha(4) beta(2) nicotinic acetylcholine receptors

A number of studies point to the a4b2 subtype of the nAChRs as important to the dependence-producing effects of nicotine

FDA approved for use as a smoking cessation aid (2006) The drug provides some nicotine effects to ease the

withdrawal symptoms and blocks the effects of nicotine from cigarettes if they resume smoking

April 21, 2023

Chantix It is taken orally. For the first three days,

the dosage is 0.5 mg once daily (the 0.5 mg tablet is white). For days four to seven, the dosage is 0.5 mg twice a day. From day eight until the end of the treatment, the dose is 1 mg twice a day (the 0.5 mg tablet is blue).

12-24 weeks treatment

April 21, 2023

Varenicline in combination pharmacotherapy

None of the available first-line medications for treating tobacco dependence have labeled indications for use in combination with another .

Combination therapy with varenicline has only been studied in small clinical trials to date. Co administered with sustained-release bupropion. At six months, combination therapy continued to appear more effective than monotherapy,

Combination therapy with varenicline and nicotine replacement therapy has also been evaluated. Heavier smokers might benefit from this combination because varenicline might not fully saturate nicotinic receptors during dose escalation.

April 21, 2023

Adverse effects of vareniclineThe most commonly reported adverse events experienced by subjects on varenicline in clinical trials were nausea, headache, insomnia, and abnormal dreams

In November 2007, the FDA disclosed post-marketing surveillance data indicating reports of suicidal ideation, mood and behavior disturbances, and depression emerging in patients shortly after commencing treatment

with vareniclineز

April 21, 2023

April 21, 2023

Pharmacotherapeutic Comparison All approved agents double the long-term quit rates

compared to placebo.

Adherence to therapy was: Patch > Gum > Inhaler > Nasal Spray, but all have similar efficacy.

The estimated long-term abstinence rates after quitting are 20% for Gum, 14% for Patch, 17% for Inhaler, 24% for Nasal Spray, 17% for lozenge.

April 21, 2023

Product Selection Guideline The choice is based on patients preference and

tolerability of the available dosage forms. For patients who smoke continuously throughout the day

nicotine patch is the better. For patients reporting a negative experience with

pharmacotherapy (poor adherence, S/E, cost.. etc) different regimen should be considered.

For patients who have experienced numerous failed attempts using mono-therapy use combination between long-term and short-term therapy.

April 21, 2023

Conclusion Tobacco use treatment include both

behavioral and pharmacologic therapy.

If you are a smoker, be strong enough to quit, now..