Section 3 Pharmacological Interventions in Tobacco Cessation

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Section 3Pharmacological Interventions in
Tobacco Cessation
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Objectives

• Participants will be able to list the 5 FDA
  approved pharmacological interventions for
  smoking cessation
• Participants will be able to list the dosage,
  contraindications, warnings and precautions of
  Zyban
• Participants will be able to list the dosing
  guidelines, contraindications, warnings and
  precautions of Nicotine Replacement Therapy
  (transdermal)

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FDA Approved Pharmaceuticals

• Zyban (Bupropion SR)
• Nicotine Transdermal System
• Nicotine Gum
• Nicotine Nasal Spray
• Nicotine Inhaler

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Investigational Pharmaceuticals

• Clonidine
• Nortriptyline

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Zyban sustained-release tablets 150 mg.

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Category/Action

• Antidepressant CNS miscellaneous
• Marketed by GlaxoWellcome Inc.
• Mechanism of effect is unknown
• Weak blocker of neuronal uptake of serotonin and
  norepinephrine
• Weak inhibitor of neuronal re-uptake of dopamine

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Absorption/Metabolism/Elimination

• Peak plasma levels reached in 3 hrs.
• t1/2 is 8-12 hrs.
• Steady state levels reached in 1.5-5 days
• Extensively metabolized by the liver
• Eliminated in the urine (87) and feces (10)
• Elimination of major metabolites may be altered
  w/renal or hepatic dysfunction

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Clinical Studies

• Two placebo-controlled, double-blind trials using
  non-depressed, chronic smokers
• One dose-response one comparative
• Both showed that pharmacotherapy was
  significantly more effective than placebo

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Indications/Usage/Dosage

• Indicated as a first-line smoking cessation
  treatment.
• Begin while patient is still smoking.
• Treatment should start with one 150 mg. dose
  daily for 3 days.
• Recommended and maximum dose 300 mg. daily in
  two 150 mg. doses.
• Continue treatment for 7-12 weeks

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Contraindications, Warnings, and Precautions
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Contraindications

• In patients with a history of seizure disorder.
• In patients treated with another medication
  containing Bupropion (incidence of seizure is
  dose-dependent).
• In patients with a current or prior diagnosis of
  bulimia or anorexia nervosa.
• In patients treated with a monoamine oxidase
  inhibiter (MAOI) within the last 14 days.
• In patients who have a known allergy to Bupropion
  or its components

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Warnings

• Patients must be made aware that Zyban and
  Wellbutrin are the same medication.
• Studies in laboratory animals have indicated a
  potential for hepatotoxicity.
• There is a risk of seizure associated with
  bupropion (dose-dependent), even w/negative hx.
• Risk of seizure is r/t patient factors, clinical
  situations, and concomitant medications.

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Risk Factors r/t Patients

• Predisposing factors, such as hx. of head trauma,
  prior seizure or CNS tumor.
• Concomitant medications that lower seizure
  threshold, such as antipsychotics,
  antidepressants, Theophylline and systemic
  steroids.

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Risk Factors r/t Clinical Situations

• Excessive use of alcohol
• Abrupt withdrawl from alcohol, sedatives, or
  benzodiazapines.
• Addiction to opiates, cocaine or stimulants, or
  use of OTC stimulants or anorectics.
• Diabetes, treated with insulin or oral
  hypoglycemics.

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Precautions

• Neuropsychiatric phenomena
• delusions, hallucinations, psychosis,
  concentration disturbance, paranoia and confusion
• Activation of mania in bipolar disorder patients.
• Altered appetite and weight
• Allergic reactions
• Pregnancy(class B) lactation
• Renal or hepatic impairment
• Recent MI or unstable cardiac disease

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Drug Interactions

• Drugs metabolized by the CYP2D6 isoenzyme.
• Tricyclics, SSRIs, Antipsychotics, Beta-blockers,
  Type 1C Antiarrhythimics
• MAO inhibitors
• Levodopa
• Drugs that lower seizure threshold
• Nicotine Transdermal System

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Adverse Reactions

• Seizures
• Insomnia, agitation, confusion
• Dry mouth
• Rash
• Sweating
• Tinnitus
• Tremor
• Anorexia/wt. loss

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Overdose

• Limited experience in clinical trials w/bupropion
  SR more w/immediate release.
• Symptoms (early)-confusion, lethergy, seizure,
  nausea, hallucinations (late)-hypotension, muscle
  rigidity, stupor, coma, uncontrolled seizures,
  cardiac failure.

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Nicotine Replacement Therapy
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Category/Action

• Miscellaneous CNS
• Chief alkaloid in tobacco products
• Binds to nicotinic-cholinergic receptors at the
  autonomic ganglia in the adrenal medulla, at
  neuromuscular junctions and the brain
• Two positively reinforcing properties,
  stimulating effect and reward effect.

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Action, continued

• Stimulant effects (in the cerebral cortex)
  predominate at low doses.
• Reward effects (in the limbic system) predominate
  at high doses.
• Nicotine activates neurohormonal pathways,
  releasing acetylcholine, norepinephrine,
  dopamine, serotonin, vasopressin, beta-endorphin,
  growth hormone, and ACTH.

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Action, continued

• Can increase circulating cortisol and
  catecholamines tolerance to this effect does not
  develop.
• Produces cardiovascular effects
• peripheral vasoconstriction, tachycardia, and
  elevated B/P

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Absorption/Metabolism/Elimination

• Absorption varies among products (NTS doses
  correlate with amt. absorbed)
• Primary urinary metabolites are cotinine and
  trans-3-hydroxycotinine.
• Major site of metabolism is the liver also
  metabolized in the kidney and lung.
• 10 of absorbed nicotine is excreted unchanged in
  the urine may be increased to 30 in high urine
  flow rates and low urine pH.

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Clinical Studies

• Numerous studies
• Results show statistically significant increase
  in abstinence rates using all four methods of
  NRT, when compared to placebo at 6 weeks, 3 mos.,
  6 mos., and 12 mos.
• Adjunct group or individual counseling in
  addition to NRT resulted in higher success rates
  overall.

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Contraindications

• In patients with known hypersensitivity or
  allergy to nicotine or its components
• In patients with recent MI , worsening angina and
  uncontrolled HTN

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Warnings

• Nicotine from any source can be toxic and
  addictive.
• The risk of using NRT in any form, should be
  weighed against the risk of continued smoking,
  and the likelihood of achieving abstinence
  without NRT.

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Pregnancy Warning

• FDA Class D
• Studies in pregnant animals have shown that
  nicotine is harmful to the fetus.
• Tobacco smoke has been shown to be harmful to the
  human fetus single studies on nicotine have not
  been performed presumption is that of harm.
• Breastfeeding

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Safety Warning

• Amounts of nicotine tolerated by adults can be
  harmful or fatal to children or pets.
• Patients should be cautioned to use safe storage
  and disposal techniques to prevent accidental
  ingestion of any form of NRT

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Precautions

• Smoking during NRT
• Allergic reactions
• contact dermatitis
• bronchspasm
• Cardiovascular or peripheral vascular disease
• hx. of recent MI, serious arrhythmias,
  vasospastic disease, severe angina (should not be
  used)
• NTS was shown to be well tolerated in a
  controlled trial of patients w/CAD (no increase
  in angina freq., no arrhythmias)

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Precautions continued

• Renal or hepatic insufficiency
• Endocrine diseases
• IDDM, Pheochromocytoma, hyperthyroidism
• Peptic ulcer disease
• nicotine delays healing
• Accelerated hypertension

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Drug Interactions

• Smoking cessation as an indicator alone, may
  alter the pharmacokinetics of certain drugs.
• Decrease in induction of hepatic enzymes
• increase in SQ insulin absorption
• decrease in circulating catecholamines
• Prescribing provider should be made aware of
  smoking cessation, so that dosage alterations can
  be considered

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Adverse Reactions

• Difficult to distinguish between withdrawal
  symptoms and drug itself
• Causal relationship probable
• diarrhea, dyspepsia, dry mouth
• arthralgia, myalgia
• abnormal dreams, insomnia, nervousness
• sweating, skin irritation (NTS), mouth and throat
  irritation (inhaler, gum), nasal irritation
  (spray) reported with higher frequency
  

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Abuse/Dependence

• NTS therapy has a low abuse potential.
• Slower absorption, smaller flucuations in blood
  levels, lower blood levels, less frequent use
• Abuse has been reported with gum, inhaler and
  nasal spray
• Nasal spray has the highest abuse potential
• 15-20 of patients report using the spray longer
  that recommended
• 5 use higher doses than recommended

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Overdose/Toxicity

• Can occur with
• smoking while use NRT
• applying several NTS, ingesting cartridge from
  inhaler or large amounts of gum, overuse of nasal
  spray or ingesting contents
• Signs and symptoms
• pallor, cold sweat, nausea, salivation, vomiting,
  abd. pain, diarrhea, HA, dizziness, disturbed
  hearing and vision, tremor, mental confusion,
  weakness

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Routes of Administration/Dosage

• Transdermal (patch), gum, inhaler, nasal spray
• Patch and gum available OTC
• Nicoderm CQ 21mg., 14mg., 7mg.,
• Labeled mg. equal to amt. of nicotine absorbed in
  24 hrs. (21mg. patch 1 ppd.
• Heavy smokers should cut down/switch brands prior
  to starting patch
• Weight lt100 lbs. or smokeslt 1/2 ppd., start on
  14mg. patch

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Investigational Pharmaceuticals

• Clonidine
• Categorized as an antihypertensive
• not approved by the FDA for smoking cessation
• Studies have shown abstinence rates twice those
  of placebo
• Second-line agent
• Significant side effects
• Cannot abruptly discontinue

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Investigational Pharmaceuticals, cont.

• Nortriptyline
• Categorized as a tricyclic antidepressant
• Not approved by the FDA for use in smoking
  cessation
• Limited studies have shown abstinence rates over
  twice those of placebo
• Many side effects
• Second-line agent

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Combination Therapy

• Zyban and Nicotine Transdermal System
• Studies have shown increased abstinence rates,
  higher long term abstinence rates
• Especially successful in highly
  nicotine-dependent, long term smokers
• Careful screening is necessary
• Treatment-emergent hypertension has been seen
• Patients with hx. of HTN, Consult with PCM
• B/P checks weekly
• SOP protocols

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Conclusion

• Attain competency
• Assess completely
• Consult with peers/PCM
• Re-assess frequently
• Stay informed of the latest developments
• Maintain competency