Term
|
Definition
1. Efficacy (depends on correct chewing method & retention in mouth for 20-30 min)
• Short-Term: 24% abstinence @ 6 mo
• Long-Term: 18% abstinence @ 1 yr
2. Best if used w/ Buproprion and/or w/ supervised stop-smoking program
3. Suggested termination of use after 6 mo
4. CI: swallowing gum (b/c of 1st pass metabolism), smoking (b/c of additive efx of Nic) |
|
|
Term
Nicotine transdermal patches
(Habitrol, Nicotrol, Nicoderm CQ, ProStep) |
|
Definition
1. Efficacy: 16.8% (double placebo) @ 24 wks
2. Peak plasma conc: Habitrol – 5-6hr, Nicoderm – 4 hr, Prostep – 9hr
3. Side efx: Overall well tolerated; sleep disturbances (remove patch overnight), skin irritation
4. CI: smoking b/c of additive efx of Nic |
|
|
Term
| Nicotine Inhaler/Nasal spray (Nicotrol) |
|
Definition
1. Efficacy: 23% for inhaler, 31% for NS (~ double placebo) @12 wks
2. Goal: disrupt behavioral associations (best if used in combo w/ supervised stop-smoking
program)
3. Side Efx: nasal irritation, mouth/throat iritation
4. Use >3 mo = useless (no further change so switch to diff approach)
5. CI: pts w/ chronic rhinitis, smoking (b/c of additive efx) |
|
|
Term
| Mechanisms of Low- or no-nicotine “cigarettes” (Eclipse, Accord, Quest) |
|
Definition
1. Mech:
• Approx behavior assoc w/ smoking
• Deliver Nic on demand to alleviate withdrawal
• decreased exposure to smoke-related toxins by heating tobacco w/o burning it
2. Ineffective overall (b/c smokers don’t want to use them)
3. Withdrawn PRIOR to FDA rulings on designation as drug delivery device & subsequent reg over
them (could have lead to FDA reg of cigs)
4. CI: cig smoking |
|
|
Term
|
Definition
1. Smokeless tobacco similar to snuff but its positioned under the upper lip & not inhaled
2. Use: in Sweden to maintain steady-state, low plasma Nic levels to eliminate exposure to
harmful components of tobacco smoke
3. Efficacy: not tested in other pop
4. CI: smoking
5. Pasteurized (NOT fermented like smokeless tobacco) " does NOT appear to cause oral cancer |
|
|
Term
Buproprion (Wellbutrin, Zyban)
Non-nicotine cessation compounds |
|
Definition
1. Mech: unknown, may act via NE inhibition or DA reuptake based on ATD axns
2. Efficacy:
• 60% abstinence @ 9 wks (double placebo)
• 24%-30% abstinence @ 1 yr (4x placebo)
• enhances efficacy of other cessation tx (esp when used in combo w/ intensive
behavioral counseling but not sig more effective w/ nic patch)
• has dose efx
3. well-tolerated, low potential for abuse
4. drug interaxns: drugs affecting CYP2A6 (TCAs, SSRIs, BB, Type IC antiarrhythmics,
antipsychotic meds
5. CI: pts w/ hx or current seizure disorder, anorexia nervosa, bulimia
6. No direct additive Nic efx w/ cont cig smoking (combo is counterproductive though) |
|
|
Term
Varenicline (Chantix)
Non-nicotine cessation compounds |
|
Definition
1. mech: partial agonist w/ high affinity at α4β2-containing Nic cholinergic R & mod affinity at
5-HT3 R
2. Uses: 2nd line tx for buporpion resistant smokers who want to quit (diff mech & can use tx in
sequence)
3. PK: max plasma con 3-4 hr after oral admin, steady state in 4 days of multiple dosing, 24hr
half life, renally elim
4. No diff in PK due to age, race, gender, smoking status, meds
5. Side efx: nausea, may be related to changes in behavior, agitiation, depressed mood, suicidal
ideation in adolescents
6. No additive Nic efx w/ smoking (counterproductive) |
|
|
Term
Mecamylamine
Non-nicotine cessation compounds |
|
Definition
1. Mech: non-selective antagonist at non-!7-nicotinic cholinergic receptors, crosses BBB "
affects BOTH central & peripheral (ganglionic) R " potential side efx
2. Efficacy: inconclusive (in Phase II Trials), may be more useful as adjunctive tx or in combo w/
path
3. Also antihypertensive agent
4. Counterproductive w/ smoking |
|
|
Term
Rimonabant
Non-nicotine cessation compounds |
|
Definition
1. Mech: CB1 antagonist
2. Efficacy: yes short term, but not more than other tx
3. Uses: 2nd line of tx in subgroups of smokers, decr wt gain assoc w/ smoking cessation
4. Side Efx: severe depression
5. OFF MARKET! |
|
|
Term
| Nortriptyline Non-nicotine cessation compounds |
|
Definition
| 1. Mech: unconfirmed • Short term: may block NE, 5HT transporters • Chronic use: action at beta adrenergic R • No DA efx 2. PK: lipophilic, plasma half life of 16-90 hrs 3. Uses: TCA 4. Efficacy: highest in depressed pts |
|
|
Term
Vaccines
Non-nicotine cessation compounds |
|
Definition
1. Mech: Abs to Nic " trap drug in plasma " can’t penetrate brain in conc high enough to
activate the reward pathway (suppress Nic-elicited DA release in NC) " Ag-Ab complexes are
cleared by kidneys
2. Efficacy: related to Ab titer & will depend on individuals immune responsiveness
• Titer doesn’t stay suff elevated for months " greatest use in achieving INITIAL
abstinence & reducing relapse
• 16% abstinent after 12 mo |
|
|
Term
Non-Pharm Tx for smoking cessation
BRIEF PHYSICIAN COUNSELING |
|
Definition
1. one of the strongest msgs to motivate smokers to make a quit attempt
2. 70% of smokers see physician annually
3. only half of pts report ever being told to quit by a physician
• <60% of physicians address smoking in context of related dz
• physicians only counseled pts on smoking on 21-37% of their visits
formal smoking cessation programs – most successful but few attend |
|
|
Term
|
Definition
1. neuroprotection/neurorescue - req ability to target nicotine/analogs to specific R subtypes in specific brain
regions at exact doses for precise amounts of time
• Uses: Parkinsonism, AD, Schizophrenia, Tourette’s, alleviation of pain, decr body wt gain
• Epibatidine – for pain reduction? |
|
|
Term
| Facts about smoking cessation |
|
Definition
1.The more often you try to quit the more likely you will eventually quit (NOT true w/ EtOH abuse)
2. Abstinence rates have great success in the 1st wk " diminish throughout yr
3. 70% of smokers relapse within 1 yr REGARDLESS of therapy |
|
|
Term
| Types of Nicotine Replacement Therapy |
|
Definition
Nicotine Gum (Nicorette)
Nicotine Transdermal Patches (Habitrol, Nicotrol, Nicoderm CQ, ProStep)
Nicotine Inhaler/Nasal Spray(Nicotrol)
Low-or-no-nicotine cigarettes (Eclipse, Accord, Quest)
SNUS |
|
|
Term
Effects of Nicotine
(what it does and then info about tolerance, dependence withdrawal, intoxication) |
|
Definition
1.Provides neuroprotection & neurorescue
2. Has addictive potential (smoking will eventually make you sick or kill you before any benefits from
chronic nicotine exposure are achieved)
- Highest level of dependence (nicotine>heroin>cocaine>alcohol>caffeine)
- Difficulty achieving abstinence (nicotine = heroin = cocaine = alcohol > caffeine)
- Tolerance develops (nicotine = alcohol = heroin > cocaine > caffeine)
- Physical withdrawal is not as severe as alcohol (DTs which are the worst) or heroin but is worse
than cocaine & caffeine)
- Intox is not really a concern for adults b/c nicotine triggers an emetic response
3. No evidence that it is carcinogenic itself!!! |
|
|
Term
Effects of Nicotine
(what it does and then info about tolerance, dependence withdrawal, intoxication) |
|
Definition
1.Provides neuroprotection & neurorescue
2. Has addictive potential (smoking will eventually make you sick or kill you before any benefits from
chronic nicotine exposure are achieved)
- Highest level of dependence (nicotine>heroin>cocaine>alcohol>caffeine)
- Difficulty achieving abstinence (nicotine = heroin = cocaine = alcohol > caffeine)
- Tolerance develops (nicotine = alcohol = heroin > cocaine > caffeine)
- Physical withdrawal is not as severe as alcohol (DTs which are the worst) or heroin but is worse
than cocaine & caffeine)
- Intox is not really a concern for adults b/c nicotine triggers an emetic response
3. No evidence that it is carcinogenic itself!!! |
|
|
Term
| Mortality related to smoking |
|
Definition
o 4x that of all other drugs of abuse combined
o more deaths from smoking than suicide, homicide, MVA, alcohol, AIDS, etc |
|
|
Term
Cigarette smoking
• Irritants & toxins
o Chronic irritation " metaplasia
o Disables resp cilia
o CO " decr availability of Hb
• Carcinogens & angiogenic factors – nitrosamines, aldehydes, polycyclic aromatic hydrocarbons, trace heavy metals
Most effective mode - 10 puffs/cig over 5 min x 1.5 packs/day (30 cigs) = 300 “hits” of nicotine
to the brain/day! |
|
Definition
|
|
Term
| Bolus hit of nicotine while smoking (what it does) |
|
Definition
1.bolus “hit” of nicotine reaches the brain rapidly (<10s) and has no 1st pass metabolism
• CNS levels are 5-10x higher than venous levels
• Activates addiction pathway
o Based on natural rewards (food, water, sex, nuturing) necessary for survival
o Nicotine mimics Ach
o " increased DA transmission from VTA ---> incr DA release at prefrontal cortex (incr cognition) & NA (incr intention/motivation) --> addiction |
|
|
Term
Other modes of nicotine delivery
Why don't they "work"? |
|
Definition
1. don’t achieve high enough conc in CNS rapidly to activate addiction pathway ---> NOT ADDICTIVE!
2. Includes: Gum, Nasal spray, Inhaler, Patch |
|
|
Term
| Nicotinic Cholinergic Recepetors in CNS |
|
Definition
o Activated by Nic bolus
o Pentameric ligand gated ion channels w/ diversity in subunit comp & diff subunits than muscle receptors (N1)
- Diff in subunit comp ----> diff in affinity for agonists/antag & diff in rates of desen/re-sen
- Diff subtypes are in diff brain regions & on diff parts of neurons so Nic has multiple efx on diff neurons in reward pathway
• heteromeric
o Major brain form is (alpha4)2(Beta2)3 & has high affinity for nicotine
o Major ganglion subtype is (Alpha3)2(Beta4)3
• Homomeric
o (Alpha7)5 is presynaptic |
|
|
Term
|
Definition
o variability in Nic cholinergic R (subunit combos, number, location)
o alteration of interacting neuronal sys - mice lacking 5-HT1B R do not self admin drugs of abuse
o metabolic variants - CYP2A6----> decr nic metabolism ----> decr # of cigs smoked------> decr addictive
potential (more prevalent variant in NON-smokers) |
|
|
Term
| Influences on smoking cessation |
|
Definition
Genetic
Adolescence and smoking
Environmental
Gender diff in withdrawal sx.
Psychiatric population
Reasons for smoking |
|
|
Term
| Genetic Influences on smoking |
|
Definition
1. accounts for 50% of smoking initiation, 70% of maintenance of smoking behavior, 80% of
variation in # of cigs smoked
2. chromosomal correlations (ie portion of chromosome 11 is linked to smoking in AA & EA |
|
|
Term
|
Definition
! 1st symptoms of Nic dependence occur in days/wks of onset of occasional use b/c adolescent
brain is very plastic
! 1/3 of smokers began before 14 (80% before 18)
! adolescent prevention and cessation programs have poor success rates |
|
|
Term
|
Definition
Peer pressure
Concern over weight gain (females)
Close associated with daily lifestyle (environmental cues which are difficult to break) |
|
|
Term
| Gender differences in withdrawal symptoms |
|
Definition
1. Severity & duration of withdrawal are gender dependent
2. Symptoms in F start at a higher level & stay higher longer
• Incr susceptibility to smoking & relapse in F
• At 8 wks the symptoms equal the INITIAL symptoms in M
• Lower cessation success rates in F |
|
|
Term
| Psychiatric Population and smoking |
|
Definition
1. Incr risk of smoking
2. Smoking " altered effectiveness of anti-psychotic meds
• Tobacco " incr activity of enzymes that breakdown meds " req higher doses to manage symptoms
• Stabilizing blood levels of meds is more diff
3. May use Nic to self medicate (Nic " decr anxiety, improved mood, improved attention, incr stim) |
|
|
Term
|
Definition
1. To prevent/diminish withdrawal symptoms
• Only 1st cig of the day " “buzz”
• Other cigs are to prevent withdrawal symptoms (maintain steady state)
2. To enhance focus, conc (efx on hipoocampus, cortex, etc)
3. To reduce anxiety/enhance coping (efx on hypothalamic CRH, brainstem CA, amygdaloid CRH) |
|
|
Term
Nic therapy
o focuses on smoking dependence/cessation & is designed to alleviate withdrawal/craving to prevent
relapse
o NO tx in use that addresses efx on cognition/anxiety |
|
Definition
|
|
Term
|
Definition
1. Mech: alpha2 agonist - inhibits sympathetic outflow & tone
2. Uses: antihypertensive agent, sedative, tx for refractory pain, smoking cessation
3. PK: lipid soluble, CSF elim half life of 1.3 hr, admin w/ transdermal patch |
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