Pharmacological Treatmenttpcrc.sbmu.ac.ir/uploads/pharmacology.pdf · National Research Institute...
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Transcript of Pharmacological Treatmenttpcrc.sbmu.ac.ir/uploads/pharmacology.pdf · National Research Institute...
Pharmacological Treatment
Dr.sh.eslampanah Tobacco Prevention and Control Research Center
National Research Institute of Tuberculosis and Lung Disease Shahid Beheshti Medical University
Pharmacological Treatment for Smoking Cessation
First-Line: Nicotinic drugs Non-nicotinic drugs 1.Bupropion SR 2.Varencline
The cause for pharmacotherapy
Willpower alone
Use of pharmacotherapy
Use of pharmacotherapy can double a smokers’ chances of successfully quitting1,2,3
1. Silagy C, et al. Nicotine replacement therapy for smoking cessation (Cochrane review), Issue 2, 2002 2. Jorenby DE, et al. New England Journal of Medicine 1999; 340:685–691 3. Jarvis M, et al. Abstract presented at 7th SRNT, 2001 Seattle, US.
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Presenter
Presentation Notes
Notes: Using willpower alone is the most commonly tried method of giving up smoking; however, only about 3% of smokers are still cigarette-free after 6 months.4 Part of the problem is that successful quitting needs careful thought and motivation. In clinical trials pharmacotherapy has been shown to double success rates.1,2,3 References: 1. Silagy C, Lancaster T, Stead L, et al. Nicotine replacement therapy for smoking cessation (Cochrane review). In: The Cochrane Libaray, Issue 2 2002. Oxford: Update Software. 2. Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. New England Journal of Medicine 1999; 340:685–691 3. Jarvis MJ, Powell S, Marsh H, et al. A meta-analysis of clincal studies confirms the effectiveness of bupropion SR (Zyban) in smoking cessation. Abstract presented at the 7th Annual Conference of the Society for Research on Nicotine and Tobacco, 2001 23-25 March, Seattle, Washington, USA. 4. Hughes JR, Gulliver SB, Fenwick JW, et al. Smoking cessation among self-quitters. Health Psychology 1992; 11:331–334.
Aim…….
• 1-Give the rationale for using NRT • 2-Describe the existing products • 3-Discuss their efficiency, safety& how
they should be dosed
Nicotine’s action in the brain
•Nicotine binds to nicotinic receptors which stimulate the release of neurotransmitters, such as dopamine and noradrenaline.1,2
•Repeated doses of nicotine from smoking can cause the number of nicotinic receptors to increase by up to 300%, compared with non-smokers.2
Nicotine gum:
•Most common method •Flexible craving relief whenever you need it •Chewing action helps break habit •2 mg, 4 mg
Nicotine patches: •Continuous craving relief during waking hours •Simple, once a day treatment •Discreetly worn on your skin, underneath clothing •3 step: 15 mg, 10 mg, 5 mg
Nicotine inhalator:
l if you miss the “hand-t
Ideal if you miss the “ha
•Flexible craving relief when you need it •Designed to be held like a cigarette-keeps hands busy
Nicotine micro tab:
•Discreet and flexible relief from a tiny tablet •Slowly dissolves under the tongue •Convenient dispenser so it’s always to hand
Nicotine nasal spray:
•No faster relief for strong cravings •Flexible and rapid relief when you need it most •Particularly suitable for heavy smokers
NRT
Dose Character
Gum 2,4 mg common
Patch 5,10,15mg Safe, SR
Micro tab 2 mg Rapid
Inhalator 2 mg/inh Habit
Spray 2 mg/puff Urgent
NRT Contraindications:
• pregnancy • recent heart attack • irregular heart beat • severe or worsening heart pain • stomach ulcers • overactive thyroid • high blood pressure • diabetes requiring insulin
BUPROPION : MECHANISM OF ACTION
• Atypical antidepressant thought to affect levels of various brain neurotransmitters
– Dopamine
– Norepinephrine
• Clinical effects
– ↓ craving for cigarettes
– ↓ symptoms of nicotine withdrawal
Presenter
Presentation Notes
Bupropion is an atypical antidepressant thought to affect the levels of brain neurotransmitters (e.g., dopamine, norepinephrine). By blocking neural dopamine or norepinephrine uptake in the central nervous system, bupropion decreases the craving for nicotine and symptoms of withdrawal (Fiore et al., 2000). Recall that the dopaminergic system is thought to play a role in self-reinforcing behavior (reward pathways) and dependence, whereas noradrenergic effects are thought to prevent the symptoms of nicotine withdrawal. Bupropion SR has been shown to promote long-term abstinence when compared to placebo and to decrease the cravings for cigarettes and symptoms of nicotine withdrawal (Hurt et al., 1997). Fiore MC, Jaén CR, Baker TB, et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health Service. Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997;337:1195–1202.
• Bupropion SR(Zyban:150mg) • Contraindications: • 1. Convulsion • 2. History of MAO use • 3.Head truma
Bupropion
• Side effects:
• 1-Sleep disturbance • 2-Dry mouth • CAUTION in Seizure
Bupropion SR (Zyban) • Week 1: Days 1-7 : 150 mg once daily
• QUIT SMOKING BETWEEN DAY 7 AND DAY 14 OF TREATMENT
• Weeks 2-8(12) : 150 mg twice daily
Varenicline (Chantix) • Varenicline (Chantix) is a non-nicotine prescription drug
developed specifically for smoking cessation. Not an antidepressant. – The “pill” releases dopamine, but substantially less than with
smoking. – Varenicline specifically targets the alpha-4 beta-2 (α4β2)
nicotinic receptors, blocking the binding of nicotine from smoking.
– Reduces the urge to smoke and reduces the pleasure derived from smoking.
– Works equally well for men and women.
• Vareniclin(Chantix): • Selective partial agonist a4B2 Nicotinic
Acetylcholynic Receptor. • Should be take with one glass of water • The most prevalence Side Effect:Nausea • Other Side Effects: • Constipation. Headache .dry mouth.sleep disorder.
Tasting diorder .eating disorder
• Vareniclin(Chantix): • Contraindications: • age < 18 • pregnancy • caution if psychiatric disorder, renal impairment, insulin
dependent diabet
VARENICLINE: DOSING
Patients should begin therapy 1 week PRIOR to their quit date. The dose is gradually increased to minimize
treatment-related nausea and insomnia.
Treatment Day Dose
Days 1–3 0.5 mg qd
Days 4–7 0.5 mg bid
Day 8 – Week 12
1 mg bid
Initial dose titration
Presenter
Presentation Notes
Treatment with varenicline should be initiated one week BEFORE the patient stops smoking. This dosing regimen allows for gradual titration of the dose to minimize treatment-related nausea and insomnia. The recommended dose of varenicline is 1mg bid (taken as one 1mg tablet in the morning and one 1mg tablet in the evening) following a 1-week titration as follows: Treatment DayDose Days 1–30.5 mg qd Days 4–70.5 mg bid Day 8 through end of treatment1 mg bid The manufacturer recommends that the dosage may be lowered temporarily or permanently for patients experiencing intolerable treatment-associated adverse effects. Patients should be treated with varenicline for 12 weeks. For patients who have successfully quit smoking at the end of 12 weeks, an additional course of 12 weeks may be appropriate to increase the likelihood of long-term abstinence. ♪ Note to instructor(s): Per the manufacturer’s prescribing information, the recommended dosage of varenicline for children, elderly patients, and individuals with impaired renal or hepatic function is as follows: Use in children Safety and effectiveness in pediatric patients have not been established; therefore, varenicline is not recommended for use in patients under 18 years of age. Dosing in elderly patients and patients with impaired hepatic function No dosage adjustment is necessary for patients with hepatic impairment. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Patients with impaired renal function No dosage adjustment is necessary for patients with mild to moderate renal impairment. For patients with severe renal impairment (estimated creatinine clearance <30 mL/min), the recommended starting dose is 0.5 mg once daily. Patients may then titrate as needed to a maximum dose of 0.5 mg twice a day. For patients with end-stage renal disease undergoing hemodialysis, a maximum dose of 0.5 mg once daily may be administered if tolerated well. Pfizer, Inc. (2006, May). Chantix Package Insert. New York, NY.
Second line: • 1-Nortriptyline 75-150 mg • 2-Clonidine
NORTRIPTYLINE (second-line)
DISADVANTAGES – Seizure risk is increased as in
all antidepressants – May require blood level
monitoring and EKG – Dangerous in overdose – Side-effect profile: • Dry mouth, orthostatic
hypotension, cardiac arythmia, constipation, urinary retention, sexual dysfunction, sedation, etc.
ADVANTAGES n Effective treatment for
smoking cessation and depression
n Can combine with NRT
n Useful in patients with chronic pain, insomnia, and anxiety
n Inexpensive
n One of the best tolerated TCAs
Presenter
Presentation Notes
Advantages of nortriptyline include the following: Effective treatment for smoking cessation and depression Can combine with NRT Useful in patients with chronic pain, insomnia, and anxiety Inexpensive One of the best tolerated TCAs Disadvantages of nortriptyline include the following: Seizure risk is increased as in all antidepressants May require blood level monitoring and EKG Dangerous in overdose Side-effect profile: Dry mouth, orthostatic hypotension, cardiac arythmia, constipation, urinary retention, sexual dysfunction, sedation, etc.
CLONIDINE (second-line)
DISADVANTAGES – Fewer efficacy studies
– Medication interactions
– Side-effect profile:
• Decreased HR, sedation, orthostatic hypotension, dizziness, dry mouth
ADVANTAGES n Inexpensive
n Good for patients who are anxious or have insomnia
n Consider for patients with contraindications to antidepressants
n Consider for patients with hypertension
n Second-line treatment for ADHD and opioid withdrawal
Presenter
Presentation Notes
Clonidine is a drug used to lower blood pressure, but it may also reduce drug and alcohol withdrawal symptoms. Advantages of clonidine include the following: Inexpensive Good for patients who are anxious or have insomnia Consider for patients with contraindications to antidepressants Consider for patients with hypertension Second-line treatment for ADHD and opioid withdrawal Disadvantages of clonidine include the following: Fewer efficacy studies Medication interactions Side-effect profile: Decreased HR, sedation, orthostatic hypotension, dizziness, dry mouth A 2004 meta-analysis by Gurley and colleagues of randomized trials of clonidine for smoking cessation concluded: clonidine can lead to a small increase in the number of people likely to quit smoking. Adverse effects of clonidine included a dry mouth and sedation. Clonidine may not be the best option for people trying to quit smoking, but it might be useful for people who are not helped by nicotine replacement therapy or antidepressants. Gourlay SG, Stead LF, Benowitz N (2004). Clonidine for smoking cessation. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD000058. DOI: 10.1002/14651858.CD000058.pub2.
Key point:
• NRT is the treatment of choice, but non-nicotine drugs are also available as an alternative
• Bupropion is the most commonly used non-nicotine treatment
• Bupropion is the generally safe and well tolerated
• Bupropion is as effective as NRT and doubles quit rates when given alongside intensive behavioral support
• Bupropion must not be given to patient at increased risk of seizures
