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Nicotine
4.06.07
42
Other
Not Applicable
04/07/2007

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Cards

Term
What are adverse med consequences of smoking?
Definition
Respiratory disease (e.g., COPD) *Pulmonology
Cardiovascular disease (e.g., CHD) *Cardiology
Cancers (e.g., lung, colon, bladder, kidney) *Oncology
Osteoporosis *Orthopedics
Infertility, Pregnancy, Postpartum problems *OB/GYN
Lowers medication blood levels *Psychiatry, others
Prolonged wound healing *Surgery, Infectious Disease
Vision problems (e.g. macular degeneration, cataracts) *Ophthalmology
Term
Why do ppl smoke?
Definition
Psychological – pleasurable, mood and stress management, weight control, aids concentration

Social – heavily marketed, family and friend smoking

Biological – neurobiological and genetic effects linked to nicotine dependence
Term
What neurotransmiter does N alter?
Definition
Nicotine alters the function of neurotransmitters (DA) via acetylcholine receptors (nACH)

Translates into psychological effects such as reduction in negative affect, stress relief, and weight reduction
Term
How addictive is N?
Definition
Pharmacologically, nicotine is as addictive as heroin and cocaine.
Term
Why is tobaccy diff than other drugs?
Definition
Tobacco differs from other drugs of abuse since a greater percentage of those who try it become daily users than those who try other drugs of abuse.
Term
What is general structure of N?
Definition
There are 2 rings in the structure of N, a pyridine and a pyriolidine ring
Term
How is N distilled/
Definition
Nicotine is distilled from burning tobacco and is carried on “tar” droplets and in the vapor phase.
Term
How is N absorbed?
Definition
90% of the nicotine is absorbed in the mainstream cigarette smoke.
Absorption into the pulmonary circulation results in the rapid delivery of nicotine to the arterial system and from there to the brain.
Nicotine reaches the brain in seconds contributing to its reinforcing and addictive properties.
Term
Where is most N metabolized?
Definition
85 - 90% of nicotine is metabolized in the liver and the majority (70%) on the first pass through the liver before it enters into the systemic circulation.
Term
What is N/s half-life?
Definition
half-life of nicotine in the blood is ~ 120 minutes.
Term
Is any N excreted?
Definition
5% - 10% of nicotine is excreted via urine, unchanged (range 2% - 35%).
Term
What systems does it change?
Definition
CV, neural, endocrine, skelatal
Term
does it cross bio membranes?
Definition
yes, and it acts upon specific receptors in brain and periphery
Term
What system does it really affect?
Definition
neuroendocrine
Term
What neurotrans does it affect?
Definition
AChR, dopa, GLUT, GABA, serotonin
Term
what enzyme metabolizes N?
Definition
The CYP2A6 enzyme is responsible for 90% of nicotine metabolism

80% of nicotine becomes cotinine, which becomes 3 hydroxy-cotinine
Term
Tol?
Definition
Tolerance – need more for larger effects, diminished effects with same amount
Term
Withdrawl symptoms?
Definition
Withdrawal symptoms - if longer interval between smoking or in past quit attempt(s).

Repetitive use or loss of control over use.

Use despite health hazards

A great deal of time is spent smoking or trying to smoke
Term
What are commonalites btwn Nic and other drugs?
Definition
lots...
Term
What does N do in the brain?
Definition
When smoke is drawn into the mouth, nicotine molecules flow into the lungs, diffuse into blood vessels, are carried to the heart, and then to the brain. A nicotine molecule inhaled in smoke will reach the brain within 10 seconds.
In the brain, nicotine travels through blood vessels, into capillaries, and into neurons, which transmit electrical impulses throughout the nervous system and underlie our thoughts, feelings, behaviors, and skills.
Term
Wwhat does N do int he brain part 2?
Definition
Nicotine binds to acetylcholine receptors, opening ion channels (> acetylcholine), causing large electrical impulses. Repeated smoking causes adaptation to increased electrical activity and the need for continued nicotine to maintain this effect. In the neuron, nicotine triggers neurotransmitter release, which latch onto other cells to trigger electrical impulses and subsequent releasing of neurotransmitters.
Term
What does N do in the brain, part 3?
Definition
Nicotine stimulates release of dopamine from nucleus accumbens (reward center)
Dopamine enhances feelings of reward and pleasure
Nicotine increases serotonin levels, mostly in the amygdala (brain emotional response center)
Serotonin can relieve depression and anxiety
Term
Is ther a genetic component to becoming addicted?
Definition
Nicotine stimulates release of dopamine from nucleus accumbens (reward center)
Dopamine enhances feelings of reward and pleasure
Nicotine increases serotonin levels, mostly in the amygdala (brain emotional response center)
Serotonin can relieve depression and anxiety
Term
What are initial feelings of smokers?
Definition
Initial experience with smoking causes nausea, dizziness, and/or coughing in some individuals

Initial experience with smoking causes pleasurable experiences in others (e.g., head rush, buzz, dizziness).

Tolerance to the aversive effects develops quickly with repeated smoking.
Term
What are major Tx for smoking cessation?
Definition
Non-Pharmacologic:
- self-help materials
- behavioral therapy
- brief advice from a health care provider

Pharmacologic:
- nicotine gum - nicotine lozenge
- nicotine nasal spray - bupropion/zyban
- transdermal nicotine patch
- nicotine inhaler
- new non-nicotine meds
Term
What is physician's advice?
Definition
Advise cessation;
Inform of risks of smoking;
Provide self-help materials, a referral, and possibly pharmacotherapy;
Set agreement for cessation/reduction;
Request follow-up in-person or via telephone
Term
Nicotine gum?
Definition
Nicotine Gum:

Some adverse side-effects such as oral and gastric problems, jaw ache, under-dosing
2mg dose outperforms placebo at 6-month assessment (OR=1.66)
4mg dose more effective than 2mg, particularly among more dependent smokers
tends not to be effective with brief advice
Term
transdermal patch?
Definition
Transdermal Nicotine Patch:

Relatively few side effects, popular form of NRT

21mg/4 weeks, 14mg/2weeks, 7mg/2weeks

Shown to double quit rates achieved by placebo at EOT

Combined with physician advice, quit rates can reach 28% at 12-month follow-up 1

No conclusive evidence to show that the higher, 42 - 44 mg initial dose, produces higher quit rates than 21 - 22 mg dose 2
Term
Nasal spray?
Definition
Nicotine Nasal Spray (NS):

- Faster delivery of nicotine (10-minutes) than patch (5-10 hours) and gum (30 mins)

- Side effects (burning sensation, watery eyes) prevalent in first week of use

- Used at least 8 times per day, but not more than 40

- More than doubles quit rates achieved by placebo
Term
What are special populations for being affected by smoking?
Definition
Women

Pregnant and postpartum women

Psychiatric populations

Adolescents
Term
WHAT ARE OTHER non-N meds?
Definition
MAO Inhibitors (Moclobemide, Selegiline)
Preliminary supporting data

SSRIs (Fluoxetine, Buspirone)
Limited support

Endogenous Opioids (Naltrexone)
Limited support
Results inconsistent

Nicotinic Receptor Antagonists (Mecamylamine)
Limited support in combination
with NRT
Term
Nicotine Vaccine?
Definition
Three under development (TA-NIC, NicVAX, Nicotine-Qbeta)

Induces antibodies against nicotine molecule, which blocks neural receptors that produce rewarding effects from smoking (blocks DA)

Vaccines are safe, well-tolerated, and immunogenic

Could increase smoking since vaccine limits rather than eliminates nicotine that reaches brain
Term
Rimonabant?
Definition
CB1 antagonist

May attenuate the activation of the endocannabinoid system and the mesolimbic DA neuronal pathway

AEs: nausea, dizziness, and upper respiratory tract infections
Term
Varenicline?
Definition
a4b2 nicotinic receptor partial agonist

Agonist function, stimulates DA, reducing craving and withdrawal

Antagonist function, blocks receptors, eliminating reward from “slip”
Term
Bupropion?
Definition
Bupropion
- Initiated 7-14 days before quit date and treatment duration is 7 – 12 weeks.
- 300mg dose shown to outperform patch and placebo at EOT and 1year follow up.
- Reported to reduce relapse rate, especially among African Americans, older smokers, and women.
- side effects (headache, insomnia, constipation, nervousness/restlessness, seizures) and contra-indications (concurrent use of some meds, seizure disorder, past eating disorder, alcohol use).
Term
women
Definition
Women tend to smoke fewer cigarettes per day than men and score lower on measures of nicotine dependence.

However, women have as much difficulty quitting as men.

While women benefit from NRT relative to placebo, they may get less clinical benefit from most NRT products than do men.
Women tend to smoke less for nicotine reinforcement and more for non-nicotine reinforcement (e.g., sensory effects of smoking, management of stress and negative affect, secondary social reinforcement).

Initial studies have shown that women may benefit more from Zyban (bupropion), a drug originally marketed as an anti-depressant, such that women have cessation rates comparable to men.
Term
prewg/post-partum women
Definition
Smoking while pregnant can cause adverse health complications such as intrauterine growth retardation, low birth weight, congenital malformations, pre-mature births, and fetal mortality1.

Approximately 20-30% of women continue to smoke for the duration of their pregnancy despite these risks1,2.

Up to 40% of pregnant women who smoke quit prior to starting prenatal care1.

These women usually quit on their own, unaided.

Others are referred to a variety of interventions with various success (cessation rates up to 30%) 2.

Interventions often do not take into account the unique needs of pregnant women, they tend to be highly dependent on nicotine, and NRT is not usually given to this population as the risk benefit profile is not clear.

Although as many as 40% of pregnant women who smoke quit prior to starting prenatal care1, 60-80% will relapse by 6-months postpartum1

Thus, interventions in the post-partum time period have focused more on relapse prevention.

Relapse prevention interventions have included minimal contact, brief advice, although there have been few more intensive tailored interventions
Term
Psychiatric pts?
Definition
more likely to smoke, be heavy smoker, develop cancer, commit suicide
Term
Does smoking effect effectiveness of antipsychotics?
Definition
Tobacco increases the activity of enzymes that breakdown medications
Higher doses of medication may be required to manage symptoms
Stabilizing blood levels of medication is more difficult
Term
Why else might psychiatrics smoke?
Definition
to self medicate symtoms (n increases stim, decreases Anx, improves attention, improoves mood)
Term
What are 3 new Tx?
Definition
Bupropion (Zyban): Effective for persons with Schizophrenia (depending on type of anti-psychotic treatment) and major depression
Fluoxetine (Prozac): Effective for persons with a history of major depression and current depression symptoms
Naltrexone: Some evidence for efficacy in the general population of smokers; effectiveness in persons with psychiatric illness unknown
Term
adolescents?
Definition
~ 23% of adolescents smoke

Adolescent smoking prevention programs have limited success.

Adolescent smoking cessation program quit rates are poor.

Pharmacological treatment outcomes for adolescent smoking have limited success.
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