Chapter 8

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Chapter 8Caffeine Nicotine

• Robert M. Julien
• Presentation By
• Tamyra Frazier Sarah Massamore

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Differentiate CNS Stimulant Actions of Caffeine
From Those of Amphetamine Cocaine.

• Unlike the actions of cocaine amphetamine,
  caffeine does not induce a release of dopamine in
  the nucleus accumbens it leads to a release of
  dopamine in the prefrontal cortex, which is
  consistent with caffeine reinforcing properties.
• It appears that although caffeine fulfills some
  of the criteria for drug dependence shares with
  amphetamines cocaine a certain specificity of
  action on the cerebral dopaminergic system, it
  does not act on the dopaminergic structures
  related to reward, motivation, addiction.

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Mechanism of Action--Caffeine

• 4 different adenosine receptors (A1, A2A, A2B,
  A3) exist in humans, caffeine is most potent in
  blocking A1 A2A.
• The positive stimulatory effects appear in large
  measure to be due to blockade of A2A receptors
  that stimulate GABAergic neurons of inhibitory
  pathways to the dopaminergic reward system of the
  striatum. Caffeine as a competitive antagonist at
  adenosine receptors, may produce its behavioral
  effects by removing the negative modulatory
  effects of adenosine from dopamine receptors,
  thus stimulating dopaminergic activity.

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Panic Attacks Caffeine

• The usually ingested doses of caffeine do not
  induce panic attacks in normal individuals.
  However, in people predisposed to panic
  disorders, the peripheral the CNS effects of
  caffeine are exaggerated.

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Effects of Caffeine in the Cardiovascular System

• Slight stimulant action on the heart. Increases
  both cardiac contractility (workload of the
  heart) cardiac output.
• Raises blood pressure in adults prone to
  hypertension. Dilates the coronary arteries,
  providing more oxygen to the harder working
  heart.
• Constricts the cerebral blood vessels, decreasing
  blood flow to the brain by 30 (migraines).

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Evidence for Against Caffeine Use by Pregnant
or Nursing Women

• Safety during pregnancy is unresolved.
• Caffeine in breast milk equals or exceeds level
  that exists in the mothers plasma
• Heavy consumption (6 cups) is associated with an
  increased risk of spontaneous abortion but
  moderate consumption does not further increase
  the risk.
• Does not appear caffeine is a teratogen, it
  does not appear to affect the course or normal
  labor delivery.
• Relatively safe in moderate doses. Higher
  levelsincreased incidence of intrauterine
  growth. Later study showed low doses in 1st
  trimester increased risk of intrauterine growth
  retardation high consumption, even in month
  before pregnancy, nearly doubled the risk of
  spontaneous abortion.

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Smoking Statistics

• 450,000 smokers die annually 115K (lung cancer),
  30K (cancer of other organs), 200K (heart
  vascular diseases)
• Life span shortened by 14 minutes for every
  cigarette smoked. 2 packs/day20 years 8 years
  of life lost
• Smoking, the greatest public health hazard, is
  ironically the most preventable cause of
  premature death, illness, disability
• 50 million people (1/5) alive today will die
  prematurely from effects of smoking
• 9 million suffer from cigarette-induced
  bronchitis emphysema. 70 of pulmonary diseases
  deaths, 57K emphysema deaths are tobacco
  related
• Of all cancer deaths in the US, 30 (154K) would
  be prevented if no one smoked.

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Nicotine As an Antidepressant

• Several reports note an antidepressant effect of
  nicotine as well as the comorbidity of depression
  with cigarette use. Subjects with depression had
  odds of nicotine dependence that were more than
  4.5x the odds for those w/o depression. This
  begins as early as age 16.
• In nonsmokers, transdermal nicotine patches
  produced improvement in depression. Researchers
  think the high rate of smoking among depressed
  individuals may represent an attempt at
  self-medication to assist in dealing with
  symptoms.

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Addictive or Habit Forming?

• Nicotine clearly induces both physiological
  psychological dependence in a majority of
  smokers.
• In 1988, the surgeon general concluded that
• Cigarettes other forms of tobacco are
  addicting.
• Nicotine is the addictive drug in tobacco.
• The pharmacological behavioral processes that
  determine tobacco addiction are similar to heroin
  cocaine.
• In total, the evidence clearly identifies
  nicotine as a powerful drug of addiction,
  comparable to heroin, cocaine, alcohol.

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Nicotine Replacement Devices

• Nicotine patches, nicotine gum, inhalers, etc.
• Experts identified nicotine replacement therapies
  as the only pharmacotherapy showed to be
  effective as an aid to smoking cessation.
• All methods of nicotine replacement appear to be
  equally efficacious, approximately doubling the
  quitting rate of smokers attempting to quit w/o
  assistance.
• The limitations are in health care workers who
  fail to recommend or monitor their use during
  cessation.

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Nicotine Therapies Antidepressants

• Efficacy of Nortriptyline is reported but
  supra-additive effect of the drug plus
  cognitive-behavioral therapy.
• The antidepressant Bupropion doubled quitting
  rates.
• Combination of Bupropion nicotine patch only
  slightly improved the results over use of only
  Bupropion.
• Bupropion is equally effective whether the smoker
  is or is not clinically depressed, suggesting
  that Bupropions efficacy is not solely due to
  its antidepressant effect.