STIMULANTS

1
STIMULANTS

• Allen Fowler
• Mycheal Scott
• Psyc 472

2
DEFINITION

• Stimulants are a substance which tends to
  increase behavioral activity when administered
• Elevate Mood
• Increase Motor Activity
• Increase Alertness
• Decrease need for Sleep
• Increase the brains metabolic and neuronal
  activity

3
PROCESSES

• While all stimulants increase behavioral activity
  the component processes involved differ.
• Neurotransmitter or receptor processes
• Increase neurotransmitters release
• Block reuptake
• Inhibition of inhibitory neurotransmitters
• disinhibition

4
COMMONLY USED STIMULANTS

• Caffeine
• Nicotine
• Amphetamine
• Cocaine
• Ephedrine
• Ritalin

5
CAFFEINE AND NICOTINE

• Allen Fowler

6
CAFFEINE (picture
courtesy Erowid web site)
7
CAFFEINE

• Most commonly consumed psychoactive drug in the
  world
• Average intake per person per day is between 80
  to 400 milligrams
• Consumption of caffeine is not considered drug
  abuse
• No regulation on sale or use

8
CAFFEINE CONTENT

• Item
• Coffee (5 oz)
• Tea (5oz)
• Cocoa (5oz)
• Chocolate (1oz)
• Chocolate milk (1oz)
• Cola drink (12oz)
• OTC stimulants
• OTC analgesics (aspirin)
• OTC cold remedies

• Average (mg)
• 100
• 50
• 5
• 25
• 5
• 100
• 100
• 35-65
• 30

9
EFFECTS

• Caffeine elicits positive effects such as
• Enhanced mental alertness
• Sustained intellectual effort
• No substantial disruption of coordinated
  intellectual thought or motor activity
• Increased energy
• A sense of well-being
• Faster and clearer flow of thought
• Reduced fatigue
• Need for sleep is delayed

10
Effects

• Caffeine may adversely effect tasks involving
• delicate muscle coordination
• Accurate timing
• Arithmetic skills
• Heavy doses - 1.5 grams
• Agitation
• Anxiety
• Tremors
• Rapid breathing
• Insomnia
• Lethal dose 10 grams
• 100 cups of coffee
• 100 OTC stimulant capsules

11
Effects

• Caffeine causes a slight stimulant action on the
  heart
• Increases the workload
• cardiac contractility
• Increases cardiac output
• Dilates coronary arteries
• More oxygen to the heart

12
Effects

• Caffeine constricts cerebral blood vessels
• Decreases blood flow by about 30
• Can relieve headaches
• Bronchial relaxation
• Increased secretion of gastric acid
• Increased urine

13
Effects

• Chronic use associated with habituation and
  tolerance
• Quitting may cause withdrawal
• Headaches
• Drowsiness
• Fatigue
• Negative mood

14
Reproductive Effects

• Freely crosses the placenta to the fetus
• Consumed by estimated 75 of pregnant women
• Breast milk contains levels equal or higher in
  concentration than mothers plasma
• Safety still unresolved
• One study shows 300 mg relatively safe
• Higher doses increased intrauterine growth
  retardation
• Another study shows 160 mg may cause growth
  retardation
• 300mg intake even in the month before doubled
  the risk of spontaneous abortion
• Recent study shows 6-10 cups per day is
  associated with increased risk of spontaneous
  abortion
• Moderate consumption does not increase the risk

15
Therapeutic Uses

• Asthma
• Bronchial relaxation effects
• Narcolepsy
• To help maintain daytime wakefulness
• Migraine
• Restricts blood flow in the cerebral cortex
• Headache and other minor pain syndromes
• In conjunction with aspirin

16
Pharmacokinetics

• Caffeine is rapidly and completely absorbed
• Significant blood levels reached in 30-45 minutes
• Levels peak in about 2 hours
• Caffeine is freely and equally distributed
  through total body water
• Caffeine can be found in almost equal
  concentrations throughout body and brain

17
Pharmacokinetics

• Caffeine has 3.5 to 5 hours half life
• Extended half life for
• Elderly
• Pregnant women
• Up to ten hours
• Infants
• Decreased half life for smokers

18
Pharmacokinetics

• Caffeine is metabolized in the liver by the
  CYP1A2 subgroup of enzymes into three metabolites
• Theophylline
• Bronchial relaxation
• Paraxanthine
• Theobromine
• Theophylline and Paraxanthine act similar to
  caffeine
• About 10 is excreted unchanged

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Mechanism of Action

• Major site of action
• Adenosine receptors
• Most potent at adenosine A1 and A2A
• Caffeine works as an antagonism agent
• Blocks the adenosine receptor

20
Mechanism of Action

• Adenosine is a neuromodulator
• Modulatory effect increasing or decreasing the
  rate at which neurons fire
• Works in conjunction with the G protein processes
• Adenosine appears to exert sedative, depressant,
  and anticonvulsant actions
• Works to slow down the system
• Important to sleeping
• Adenosinergic neurons form a diffuse system
• No exclusively adenosinergic pathways
• Adenosine stimulates GABAA inhibitory neurons

21
Mechanism of Action

• Adenosine is created from the process by which
  the body breaks down ATP for energy
• ATP is used throughout the body for energy
• Used for high energy bursts such as exercising
  and running
• Phosphates form a high energy bond
• Cells break the phosphate bond to extrapolate the
  energy
• When the phosphates are pulled off the adenosine
  is now free to have an effect in the body

22
Mechanism of Action

• A1 receptors inhibit excitatory neurons
• Dopamine, glutamate, and ACh secreting neurons
• Reduces production of cAMP
• Slows the activity of the kinase
• Reduces occurrence of the action potential
• A2A receptors stimulate inhibitory neurons
• GABAA neurons
• Stimulates production of cAMP
• Increases activity of the kinase
• Increases occurrence of the action potential
• picture courtesy The Brain
  a Neuroscience Primer

23
Mechanism of Action

• Adenosine A1 receptors
• Inhibit the release of dopamine and glutamate
• Limit the release of acetylcholine
• Blockade of A1 receptors
• Modest reward
• Increased vigilance and mental acuity
• Creates arousal effect

24
Mechanism of Action

• Adenosine A2A receptors
• Stimulate GABAA neurons of inhibitory pathways
• Inhibit dopamine activity
• Blockade of A2A receptors
• Increases the potency of endogenous dopamine

25
Mechanism of Action

• Caffeine facilitates a disinhibition process at
  adenosine receptor sites
• Caffeine removes the negative effects of
  adenosine from dopamine receptors increasing
  dopamine activity
• Caffeine does not stimulate dopamine release

26
NICOTINE (picture
courtesy Erowid web site)
27
NICOTINE

• Primary active ingredient in tobacco
• One of the three most widely used psychoactive
  drugs
• Caffeine
• Alcohol
• Few or no therapeutic applications
• Important because of widespread use and toxicity

28
Background Information

• Indigenous to the Americas
• 1492 Columbus beaches in West Indies
• Natives offer them tobacco as gift
• 1556 first plants taken to Europe
• 1571 believed to have curing properties for 36
  different ailments
• 1575-1600 becomes duty of every man of fashion
  worth its weight in silver

29
Background Information

• 1881 Cigarette rolling machine invented
• 1889 2.4 billion cigarettes produced annually in
  U.S.
• 1904 3 billion cigarettes sold in U.S.
• 1912 13 billion cigarettes sold in U.S.
• WWII through mid-1960s smoking considered cool
• Now beginning to be shunned as unhealthy and
  unwise

30
Background Information

• Responsible for the deaths of 1100 Americans
  every day
• Each day
• 6000 American teenagers try their first cigarette
• 3000 children become regular smokers
• 1000 of these will die from smoking related
  disease
• 9 in 10 smokers become addicted before age 21

31
Background Information

• ½ of all people who have smoked have quit
• American adults who smoke has fallen from 50 in
  1965 to 25 in 1998
• Smoking identified as the major preventable
  cause death and disability
• As far as 30 years ago

32
Background Information

• Nicotine is only one of about 4000 compounds
  released by burning tobacco
• Adverse cardiovascular, pulmonary, and
  carcinogenic effects are from the other compounds

33
Effects

• Nicotine exerts powerful effects on
• Brain
• Spinal cord
• Peripheral nervous system
• Heart
• Various other body structures

34
Effects

• Stimulation of the vomit center in the brain stem
  and sensory receptors in the stomach
• Nausea in early stages of smoking
• Tolerance develops rapidly
• Reduces weight gain
• probably by suppressing appetite

35
Effects

• Stimulates release of ADH (antidiuretic hormone)
  causing fluid retention
• Reduces activity of afferent nerve fibers from
  muscles
• Reduction in muscle tone
• May be partially involved with relaxation effect
• Higher doses
• Can induce nervousness and tremors
• Seizures in toxic overdose
• Smoking associated with increased occurrence of
  panic attacks and panic disorders

36
Effects

• In the CNS nicotine increases
• Psychomotor activity
• Cognitive functioning
• Sensorimotor performance
• Attention
• Memory consolidation

37
Effect

• Nicotine can improve performance on vigilance and
  rapid information processing
• Effects are greater for working memory rather
  than long term memory
• Nicotine exerts an antidepressant effect
• High smoking rates among depressed individuals
  may be an attempt at self medication

38
Effects

• Nicotine exerts a potent reinforcing action
• Indirect activation of midbrain dopamine neurons
• Greatest in early phases
• Diminishes over time
• Smoking is continued to avoid withdrawal symptoms

39
Reproductive Effects

• Smoking during pregnancy increases rates
• spontaneous abortion
• Stillbirth
• Early postpartum death
• Preterm deliveries
• Intrauterine growth retardation is increased 40
• 2000 infant deaths per year attributed to smoking

40
Reproductive Effects

• Smoking reduces oxygen delivery to the fetus
  resulting in varying degree of fetal hypoxia
• Fetus does not receive as much oxygen
• Smoking may result in irreversible intellectual
  and physical deficiencies
• Increased prevalence of ADHD
• Lower IQ scores

41
Tolerance

• Nicotine does not appear induce a pronounced
  degree of biological tolerance
• Increased use in early stages which usually
  levels off as smoking is continued
• Smokers adjust nicotine intake to maintain 20 to
  40 nanograms per milliliter of plasma
• Does induce physiological and psychological
  dependence
• Habituation
• Rebound effect

42
Withdrawal Symptoms

• Intense nicotine craving
• Irritability
• Anxiety
• Anger
• Difficulty concentrating
• Restlessness
• Impatience
• Increased appetite
• Weight gain
• Insomnia

43
Therapy

• Nicotine replacement therapy doubles successful
  quit rates
• Skin patches
• Gum
• Nicotine nasal spray
• The use of Zyban has also been shown to increase
  successful quit rates

44
Pharmacokinetics

• Easily absorbed in the body
• Lungs
• Buccal and nasal mucosa
• Skin
• Gastrointestinal tract
• Nicotine is suspended in the minute particles
  (tars) in smoke
• Orally administered blood levels of nicotine are
  comparable to smoking

45
Pharmacokinetics

• Only about 20 of the nicotine in a cigarette is
  inhaled and absorbed into the bloodstream
• Nicotine which is not immediately absorbed is
  rapidly metabolized by the hepatic enzyme CYP2A6
• Inhalation allows controllability of dose
• Frequency of breaths
• Depth of breaths
• Time in lungs
• Number of cigarettes

46
Pharmacokinetics

• Nicotine is thoroughly distributed in the body
• No barriers to nicotine distribution
• Rapid brain penetration
• Crosses placental barrier
• Appears in all bodily fluids
• The liver metabolizes 80 to 90 before excretion
  to the kidneys
• Primary metabolite is cotinine
• The elimination half life in chronic users is
  about 2 hrs

47
Mechanism of Action

• Nicotine activates specific acetylcholine (ACh)
  receptors known as nicotinic receptors
• Nicotinic receptors are located throughout the
  body
• Skeletal muscle
• Sympathetic and parasympathetic neurons
• CNS

48
Mechanism of Action

• ACh is released, broken down, and reabsorbed very
  quickly (microsecond) allowing the receptor to
  respond to new Ach
• ACh receptors work as a fast first messenger
  system
• Attached directly to ion channels
• Binding has an immediate response

49
Mechanism of Action

• 
  picture courtesy pharyngula.org
• Nicotine replaces ACh at nicotinic receptor
• Beats out the ACh at the binding site
• Works as an agonist
• Opens ion channel allowing depolarization to
  occur
• 
  

50
Peripheral Nervous System

• Activation of nicotinic receptors in the PNS
• Increases blood pressure and heart rate
• Causes the release of epinephrine from the
  adrenal glands
• Increases the tone, secretions, and activity of
  the gastrointestinal tract

51
Central Nervous System

• Nicotinic receptors are widely distributed and
  may be present at the presynaptic terminals of
  neurons which secrete
• Dopamine
• Acetylcholine
• Glutamine
• Activation by nicotine facilitates the release
  and increases the action in the brain of these
  neurotransmitters

52
Central Nervous System

• Dopamine levels are increased in the
• Ventral tegmentum
• Nucleus accumbens
• Forebrain
• Stimulation of these areas account for the
  behavioral reinforcement, stimulant,
  antidepressant, and addictive properties of
  nicotine

53
Central Nervous System

• Increases in acetylcholine contribute to the
  cognitive potentiation and memory facilitation
  properties of nicotine
• Facilitation of glutaminergic neurotransmissions
  contribute to the improvement in memory
  functioning

54
Smoking Diseases

• Smoking accelerates the depositing of fat in the
  arteries
• Increased risk of heart attack and stroke
• Smoking weakens the immune system
• Smoking irritates the lining in the lungs
  impairing respiration
• Smokers cough
• Emphysema
• picture
  courtesy quantumclinic.com

55
Smoking Diseases

• Lung cancer
• 90-95 of male deaths
• 70-75 of female deaths
• Cancer of the mouth and throat
• Chewing tobacco
• Picture courtesy quantumclinic.com

56
Smoking Diseases

• Cardiovascular disease
• Carbon monoxide decreases amount of oxygen
  delivered to the heart while nicotine increases
  the workload
• Carbon monoxide and nicotine increase narrowing
  (atherosclerosis) and clotting (thrombosis) in
  the coronary arteries
• Increased risk of coronary heart disease

57
Smoking Diseases

• About 4000 Americans per year die from lung
  cancer caused by second-hand smoke
• 37000 deaths per year from heart disease caused
  by second hand smoke

58
Sources

• Julien, Robert M. (2001). A Primer of Drug Action
  (ninth ed.). Caffeine and Nicotine (pp 220-248).
  NY, New York Worth Publishers.
• Tompson, Richard M. (2000). The Brain A
  Neuroscience Primer (third ed.). NY, New York
  Worth Publishers.
• http//www.erowid.org/psychoactives/psychoactives.
  shtml
• http//home.howstuffworks.com/caffeine.htm
• http//www.nida.nih.gov
• http//pharyngula.org/pzmyers/neuro/synapse/index
  .php?print
• http//www.quantumclinic.com/quitsmoking/quit-smok
  ing-stop-addiction-cigarettes-nicotine-lung-cancer
  -photos.htm
• http//www.ccc.nottingham.ac.uk/mqzwww/adenosine.
  html
• http//www.pbs.org/wgbh/nova/cigarette/nicotine.ht
  ml