Common psychostimulants: Caffeine and nicotine

1
Common psychostimulants Caffeine and nicotine

• Sources
• Pharmacokinetics
• Pharmacodynamics
• Side effects

2
Caffeine

• Most popular drug in the world
• Caffeine is useless since it serveth neither
  Nourishment nor Debauchery. --Anonymous, 1650

Xanthine derivatives or methylxanthines

• Caffeine

• Theophylline

• Theobromine

3
Sources of caffeine

• Plants of 28 genera in 17 families
• Most common sources are coffee, tea, chocolate,
  and kola
• Coffea arabica and Coffea robusta
• Camellia sinensis Green, black, and oolong
• Theobroma cacao
• Kola/cola
• Ilex paraguayensis, Ilex vomitoria

4
Pharmacokinetics

• Oral administration
• Beverages Coffee, tea, cocoa, chocolate milk,
  cola (fortified)
• Chocolate
• OTC preparations
• Stimulants
• Pain-killers (caffeine synergizes acetylsalicylic
  acid)
• Diuretics and cold preparations
• Elimination half-life ranges from 3 to 10 hrs
• Longer late in pregnancy, in utero, elderly
• Concentrated in breast milk
• Shorter in smokers

5
Pharmacodynamics Effects

• Cortex at normal doses (100-200 mg)
• Rewarding effect Feel competent
• Alertness, sustained attention, faster thought
• Reduced fatigue, lower need for sleep
• Fine motor coordination, timing accuracy, and
  arithmetic may be impaired
• Heavy dosing (1.5 grams a day) may produce
  agitation, anxiety, tremors, panting, and insomnia

6
More effects of caffeine

• Spinal cord stimulated at toxic doses (2 - 5
  grams) cardiac arrhythmias at 10 - 20 grams
• Dilates coronary arteries constricts cerebral
  arteries
• Bronchodilation

7
Pharmacodynamics Mechanisms

• Mediated by blockade of adenosine receptor
• A normal dose blockades 50 of receptors
• Adenosine is not a neurotransmitter but a
  neuromodulator or autacoid.
• Adenosine, and thus caffeine, act on NE, DA, ACh
  , glutamate, and GABA
• DA activity is especially increased, but not in
  the nucleus accumbens

8
Side effects of caffeine

• Caffeine-induced disorders from DSM-IV
• Conflicting data on reproductive effects
• May slow growth in utero, especially high dose
• Caffeine may be harmful prior to conception
• May increase the risk of spontaneous abortion
• Withdrawal effects due to increased adenosine
  receptor density and thus increased adenosine
  sensitivity

9
Nicotine

• Source Tobacco
• Administration
• Inhalation Smoking tobacco tars
• Intranasally Snuff
• Oral/buccal Chewing tobacco
• Oral/gastrointestinal Nicotine gum
• Transcutaneous Patches
• All produce comparable blood levels

10
Pharmacokinetics and pharmacodynamics

• Distributes rapidly to all body compartments,
  analogous to smoke
• Stimulates nicotinic ACh receptors
• Enhances cortical activity, including attention
  and memory
• Activates neuromuscular junction and ANS
• Stimulates DA pathways from VTA to nucleus
  accumbens

11
Side effects

• Vomiting and nausea tolerate rapidly
• Otherwise, little tolerance but dramatic
  dependence
• Stimulates hypothalamic ADH and consequent fluid
  retention
• Reduces afferent input from muscles, lowering
  muscle tone Relaxation and flabbiness

12
More side effects

• High toxicity from tobacco and administration
  routes

• Damages unborn children

• Environmental pollution and second-
• hand smoke

13
Therapies

• Standard protocol (Julien, 1995)
• 1. Withdrawal
• 2. Diagnosis
• 3. Treat coexisting conditions
• 4. Reduce drug craving
• 5. Prevent relapse
• Divide and conquer Nicotine replacement and
  reduction clonidine, buspirone, or
  antidepressants to reduce craving
• American Lung Association plan

14

• The Great American Smoke-out Day
• Third Thursday in November
• Began in Randolph, MA in 1971
• Went national in 1977
• More Americans quit smoking this day than any
  other
• Quitting smoking may be a learned behavior
  Repeated failure may lead to success.

15
Cell product exports

• Neurotransmitters
• Effects restricted to cells at synapse
• Neuromodulators or autacoids
• Effects on a few cells or an area of cells
• Hormones and neurohormones
• Effects on area served by circulation system
• Pheromones
• Effects on other organisms

16
How much caffeine?
5oz 5oz 5oz 1oz 1oz 12oz Tab- Anal-
Diur- Coffee Tea Cocoa Choc. C.Milk Cola
lets gesics etics