Chapter 8 Amines

1
Chapter 8Amines
2
Amines and Amides
Amines a class of organic compounds of
nitrogen that may be considered as derived from
ammonia (NH3) by replacing one or more of the
hydrogen atoms -derivatives of Ammonia -number
of "R" groups varies and is attached to
Nitrogen Amides the organic functional group
characterized by a carbonyl group (CO) linked to
a nitrogen atom (N), contain carbonyl Carbon
attached to Nitrogen, so most "R" groups on
Nitrogen is 2. Note Amides in Chap 11, will
cover now!
the organic functional group characterized by a
carbonyl group (CO) linked to a nitrogen atom
(N), or a compound that contains this functional
group (pictured to the right)
3
Amide Facts
-carboxylic derivatives -named after
corresponding acid, with ending of "amide" (see
below) -Cyclic Amides and Barbiturates (see
button for more info)
4
Amine facts
Nomenclature add suffix "amine" to group
5
Nitrite PreservativesProcessed meats and cancer
websiteDanger of processed meats website

• NO2 ion reaches the stomach and converts to HONO
  after reacting with HCl
• HONO 20 amines N-nitrosamines, which
  is a carcinogen.
• Results
• Nitrite disables hemoglobin..infants blood
  contains less hemoglobin than adultsso more
  dangerous
• Lymphatic system cancers detected in lab animals
• Stomach cancer increase
• Nitrites found in bacon, ham, hot dogs, many
  deli meatsfound as sodium nitritegives meat its
  pinkish color and inhibits bacterial growth
  (botulism)

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General Drug Classifications

• Website
• Process/Cost to develop new drugs

7
CNS Stimulants and Depressants

• Increase heart rate
• pulse
• blood pressure
• breathing rate
• reactions
• Dilate bronchioles pupils
• Some will increase blood glucose levelsuse as
  diet pills

• Decrease heart rate
• pulse
• blood pressure
• breathing
• reactions
• Constrict pupils
• Slurred speech
• balance

8
Nicotine and Caffeine -CNS stimulants -nicotine
actually a poison to insects (insecticide
use) -caffeine in chocolate, cocoa, colas,
"No-Doz"
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CAFFEINE
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What is Caffeine?

• Caffeine (C8H10N4O2), or trimethylxanthine,
• is a
• ?CNS stimulant
• ? cardiac muscle stimulant
• ?respiratory system stimulant
• ? mild diuretic.

11
History of Caffeine

• Caffeine is one of the worlds most widely used
  drugs. It was first extracted from coffee in
  1821. It originated in Ethiopia and by the
  fourth century AD it was introduced to Arabia and
  the rest of the east. Nomads saw the effects
  that it had on animals and how it gave them extra
  energy. Therefore it was used in religious
  ceremonies so that people could stay up all night
  and pray.
• Coffee was introduced to the Europeans in 1573
• Tea was introduced in 1657 and became very
  popular.
• Chocolate milk was introduced in Switzerland in
  1873.

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What is Caffeine?

• Caffeine is medically known as trimethylxanthine
• It is a alkaloid and its chemical formula is
  C8H10N4O2
• When isolated in pure form its a crystalline
  powder and tastes bitter.
• It is used as a cardiac stimulant or a mild
  diuretic which flushes out the system
• Many people use this to feel a boost of energy
  or used to stay awake longer
• This is the chemical
• structure of caffeine

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How Caffeine Works

• This drug causes a chemical change in the brain
  in two ways
• First, caffeine mimics adenosine and binds to all
  other adenosine receptors in your brain. This
  prevents the real adenosine from doing its job
  which happens to be the slowing down of nerve
  impulses and the cause of drowsiness.
• Second, caffeine also increases the dopamine (a
  neurotransmitter which activates the pleasure
  center) in your brain? improves the well-being
  and mood. This is also one reason why this drug
  is so addictive.
• Caffeine is mainly found in beans, leaves,
  fruits, and over 60 plants where it acts as a
  pesticide to kill insects.

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An Addictive Drug

• 90 of Americans consume caffeine in one form or
  another every day
• More than ½ of American adults consume more than
  300mg of caffeine every day
• It is addictive because it uses the same
  mechanism that amphetamines such as cocaine and
  heroine use to stimulate the brain
• These drugs close the blood vessels in the brain
  so that the body cannot go to sleep, releasing a
  rush of adrenaline into the body.

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Withdrawal of Caffeine

• Many people that consume caffeine on a daily
  basis will experience these withdrawal effects
• Headaches
• Irritability
• Nervousness
• Restlessness
• Insonmia

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Caffeine Products

• Coffee 80-135 mg of caffeine
• Decaf Coffee 2-3 mg of caffeine
• Espresso 100 mg of caffeine
• Coke/Diet Coke 45.6 mg of caffeine
• Mountain Dew 55 mg of caffeine
• Chocolate 28 mg of caffeine
• Tea 40-60 mg of caffeine

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Where is Caffeine Found?

• Caffeine is present in coffee, tea, soft drinks,
  chocolate, and kola nuts.
• Colas contain relatively low amounts of caffeine,
  but also contain other alkaloids that can enhance
  caffeine reactions.
• Coffee tends to work best for long-lasting
  alertness.

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How Does Caffeine Work?

• Nerve cells mistake caffeine for adenosine, a
  hormone that causes drowsiness. So caffeine
  binds to adenosine receptors.
• One of the mechanisms that caffeine addiction,
  cocaine addiction, and heroin addiction share, is
  that they block an adenosine's ability to slow
  the nerve cells' activity in preparation for
  sleep, and instead increase the speed of their
  activity and of the neuron firing in the brain.
  The caffeine causes the blood vessels in the
  brain to constrict, because it has blocked the
  adenosine's ability to open them to allow sleep.
  The ability of caffeine to close the blood
  vessels is why many pain relievers contain
  caffeine. If a person has a vascular headache,
  the caffeine in the medicine will shut down the
  blood vessels, thus easing the pain.
• As a result, nerve cells dont take in adenosine
  and, therefore, begin to speed up.
• Brain activity is increased, which causes the
  pituitary gland to release adrenaline. This
  boosts alertness.
• Caffeine also stimulates the hormone dopamine,
  which makes one happy.
• This is why caffeine is addictive.
• Also, it constricts blood vessels in the brain

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The Benefits of Caffeine

• Caffeine is a vasoconstrictor, so it can
  sometimes relieve headaches caused by dilated
  blood vessels.
• It also promotes alertness and makes one feel
  happy.

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Downsides to Caffeine Use

• After a caffeine-induced adrenaline high, lows
  occur causing tiredness and depression.
• Such lows cause one to consume more caffeine and
  to eventually become caffeine-dependent.
• Caffeine has a half-life of 6 hours. If it is
  consumed late in the day, it hinders deep sleep
  as adenosine (essential for sleep) is blocked.

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Caffeine as Medication

• Caffeine can be taken in powder and tablet form
  to promote alertness.
• Yet caffeine pills should only be taken for short
  periods of time.
• Some symptoms of a caffeine overdose include
• tremors, trouble sleeping, dizziness, rapid
  heartbeat, and nausea.

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Some Side Effects of Normal Caffeine Use

• Caffeine consumption in large amounts has been
  shown to decrease bone mineral density.
• A caffeine-dependent cycle can occur, which
  brings with it severe headaches if a person does
  not get caffeine.
• Deep sleep can be affected.

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Side Effects for Mothers

• During pregnancy, large and daily doses of over
  300 mg (equal to 3 cups of coffee) may hinder the
  development of a fetus or promote miscarriages.
• Caffeine use while breast-feeding may make an
  infant jittery.

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Effects of Amphetamines
Increased talkativeness Increased
aggressiveness Increased breathing
rate Increased heart rate Increased blood
pressure Reduced appetite Dilated
pupils Visual hallucinations
25
Side Effects
Head aches
Stunted growth
Insomnia
Nervous
Coma
Hallucinations
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Long-Term Effects
There are many long term effects due to
amphetamines. Mental illness like paranoid
schizophrenia, malnutrition, violence and
aggression, infections due to IV injections, and
blockage of blood vessels are all long-term
effects of amphetamines.
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Diet Pills
-CNS Stimulant, effects brain spinal cord
-Amphetamines are used as diet pills because they
raise glucose level in blood. Body doesnt need
food, person doesnt eat because stomach feels
full because the glucose is high.
(note amphetamines are not a safe or effective
way to lose weight.)
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Closing Notes
The effects of using amphetamines can be deadly.
Amphetamines are an addictive drug, can cause
serious damage to ones health. The most severe
effect of amphetamines are popping of the blood
vessels in the brain, or heart failure.
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Methylphenidate (Ritalin)

• Website
• Methylphenidate is a medication prescribed for
  individuals (usually children) who have
  attention-deficit hyperactivity disorder (ADHD),
  which consists of a persistent pattern of
  abnormally high levels of activity, impulsivity,
  and/or inattention that is more frequently
  displayed and more severe than is typically
  observed in individuals with comparable levels of
  development.
• Methylphenidate is a central nervous system (CNS)
  stimulant. It has effects similar to, but more
  potent than, caffeine and less potent than
  amphetamines

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How Ritalin works

• Methylphenidate works by affecting some of the
  natural chemicals that are found in the brain. In
  particular, it increases the activity of
  chemicals called dopamine and noradrenaline in
  areas of the brain that play a part in
  controlling attention and behaviour. These areas
  seem to be underactive in children with ADHD. It
  is thought increasing the activity of these
  chemicals improves the function of these
  underactive parts of the brain. We still dont
  fully understand how stimulants work in children
  with ADHD, and they dont work for everyone. But
  they can be very useful at helping some children
  to learn to control their behaviour.

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More Ritalin info

• Doctors aren't really sure how Ritalin works on
  ADHD kids. Ritalin is a stimulant medication.
  When you consider that kids with ADHD are already
  over-stimulated, it is hard to understand how a
  stimulant drug will help to calm them down.
  Doctors think it has to do with some of the
  neurons in the brain. Instead of being balanced
  as they should, some of the neurons work overtime
  while others are under worked. For some reason,
  Ritalin stimulates the neurons that aren't
  working as they should. The area of the brain
  that tells one when to pay attention to certain
  activities and to ignore other ones is "lazy" in
  ADHD sufferers . Ritalin stimulates those neurons
  so that the child can pay attention and focus on
  his activities.

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Tranquilizers
-all have 7 membered ring containing 2
Nitrogens -CNS depressants -Valium (diazapam)
most common/Librium
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TRANQUILIZERS

• Tranquilizers are divided into a Major
  Tranquilizer and Minor Tranquilizer group.
• Major Tranquilizers include phenothiazines,
  indoles, thioxanthenes, butyrophenones,
  piperazine compounds, and piperidine compounds.
  Trade names include drugs such as Thorazine,
  Haldol, Clozaril and Risperdal. These drugs are
  referred to as Neuroleptics and are most commonly
  prescribed as anti-psychotics. This type of
  tranquilizer is not widely abused.
• Minor Tranquiliers are the more common of the
  tranquilizers. These include the Benzodiazepines,
  known by trade names such as Valium, Xanax,
  Serax, Ativan, Klonopin, Librium and Tranxene.
  There are also combination drugs such as Librax.
  These drugs are very commonly prescribed as
  anti-anxiety drugs, or anxiolytics. They are
  often referred to as Sedative/Hypnotics. They are
  central nervous system depressants with specific
  sites of action. Slang references to these drugs
  include Libs, Tranks, Benzos, and Vees.
• The primary route of administration for these
  medications is oral, swallowed as a tablet,
  capsule, or liquid. They are also available in
  solution form for intravenous use.

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Effects of Tranquilizers

• The minor tranquilizers induce a feeling of calm
  and relaxation. Commonly used pre-surgery to
  relax the patient. Depending on the medication
  and dosage this can range from feelings of mild
  euphoria to states of drowsiness, confusion, and
  lightheadedness. Effects can include hostility,
  blurred vision, hallucinations, lethargy,
  headaches, memory loss, disorganized thinking,
  and irritability. Other common effects include
  impaired motor function, dry mouth, nausea,
  vomiting, and sweating. Certain Benzodiazepines,
  including Valium, can produce toxic reactions
  when combined with alcohol.
• The Benzodiazepines (Minor Tranquilizers) can be
  addictive even at prescribed dosages if the
  medication is administered for long periods of
  time. The withdrawal process can be painful and
  even life-threatening with some of the
  Benzodiazepines. Physical withdrawal symptoms can
  include general pain, stomach cramps, diarrhea,
  flu-like symptoms, and heart palpitations. There
  is also the possibility of seizure with certain
  medications. The withdrawal can also produce
  psychosis, hallucinations, delusions, paranoia,
  and depression.

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Sleeping Pills
36
History

• Common type of sleeping pills antihistimines,
  over the counter sleeping pills that contain
  diphenhydramine (benadryl, etc)
• Barbiturates were used to treat symptoms, but
  stopped being used because side effects mirrored
  drunkenness (slurred speech, hangover, etc)
• Benzodiazepines presently used types of pills
• Most commonly abused drug because of easy access

37
Chemistry

• Effect the GABA gating system, central to
  thoughts/brain activity
• Make chloride channel in middle of GABA open so
  chloride can flow through
• Chloride keeps cells from being activated so
  system is quieted, cant promote sleep
• CNS depressant
• Suggested doses no more than 10 mg (adult), 5 mg
  (elderly)

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Uses of Sleeping Pills

• Used as sedatives and tranquilizers
• Treat anxiety help with short-term sleep
  problems
• Help with insomnia, jet lag
• Symptomatic cure, not causal
• Should only be used for brief periods of time (2
  weeks max)
• NOT to be used for sleep apnea
• (obstruction of throat/delay of brain signal
  reminding body to breathe), need to be able to
  wake up

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Side Effects

• Physical dependence- body adapts to the presence
  of the drug
• Hallucinations, sleep walking, sleep driving, etc
• Withdrawal symptoms may include
• anxiety
• restlessness
• insomnia
• irritability
• gastrointestinal problems
• loss of appetite
• trembling/weakness
• increased sensitivity to light, sound, smells

40
Barbiturates
-barbituric acid 1st one and a cyclic
amide -physiological effect of being a CNS
depressant -act as sedatives in small doses or
induce sleep (general anethesia-see next slide
for current drugs used in general anethesia) in
large doses (see specific examples in
text) -synergistic effect with othe CNS
depressants such as alcohol
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Current General Anesthesia

• induction agents
• For 50 years, the most commonly used induction
  agents were rapidly acting, water-soluble
  barbiturates such as thiopental, methohexital,
  and thiamylal. These drugs are not commonly in
  use today.
• Propofol, a nonbarbiturate intravenous
  anesthetic, has displaced barbiturates in many
  anesthesia practices.
• The use of propofol is associated with less
  postoperative nausea and vomiting and a more
  rapid, clear-headed recovery.
• In addition to being an excellent induction
  agent, propofol can be administered by slow
  intravenous infusion instead of vapor to maintain
  the anesthesia.
• Among its disadvantages are the facts that it
  often causes pain on injection and that it is
  prepared in a lipid emulsion, which, if not
  handled using meticulous aseptic precautions, can
  be a medium for rapid bacterial growth.
• Anesthesia can also be induced by inhalation of a
  vapor. This is how all anesthetics were once
  given and is a common and useful technique in
  uncooperative children. It is reemerging as a
  choice in adults. Sevoflurane is most commonly
  used for this purpose.

42
What are they?

• Barbiturates are CNS depressants. There are over
  2,000 known barbiturates.
• Barbiturates are some of the most addictive
  drugs. They are often used to substitute for
  alcohol because similar effects are produced.

43
Physiology Of Barbiturates

• Barbiturates are depressants. They are used as
  medication for the treatment of mental illnesses,
  epilepsy, insomnia, and any type of hyper
  excitement.
• They reduce cranial pressure and
• They also induce sleep and subdue pain.
• Their main uses in this era is a general
  anesthetics they are very effective, they will
  put anyone to sleep in ten seconds.
• They work by enhancing the GABA neurotransmitter
  by bind to the receptor for GABA. Barbiturates
  dissolve easily in fat.

44
Barbiturates History

• In 1864, Adolph von Baeyer added urea to diethyl
  malonate in the presence of ethoxide ion. The
  result of this was a cyclic compound that Baeyer
  called barbituric
• It was later discovered that certain derivatives
  of barbiturate acids , such as Pentothal,
  Pentobarbital, and Sectobarbital have powerful
  psychological effects.

45
When Barbiturates are prescribed

• Treatment of disorders such as insomnia, anxiety,
  tension, and epileptic seizures.
• 50 mg is a normal dosage that may be prescribed
  but because rapid tolerance may occur, up to ten
  times this amount may be needed to produce a
  similar effect.

46
Immediate Effects appear rapidly and may last
from hours to days

• Sleepiness
• Slurred speech
• Trouble walking, balancing, etc.
• Emotional Instability
• floating sensation
• Slowing of heartbeat
• Shallow breathing
• Sense of relaxation
• Reduced attention span

47
Long Term Effects

• Increased aggressiveness
• Severe depression
• Physical dependence
• Withdrawal reactions
• Vision problems
• Chronic tiredness

48
Side Effects

• Skin rashes
• Nausea
• Dizziness
• Increases blood pressure, heart rate, breathing
  rate, and body temp.
• Heart attacks, strokes, and respiratory failure,
  brain seizures.

49
Withdrawal symptoms

• Hallucinations
• Eating disorders
• Disorientation
• Vomiting
• Sleep disorders

50
Barbiturates and other depressants

• When combined with other CNS depressants like
  Demerol, heroin, morphine, and codeine it is
  extremely dangerous. The combination of alcohol
  and barbiturates can often be lethal.
• If one has allergies and takes antihistamines
  along with barbiturates this may cause
  respiratory arrest.

51
Barbiturates and stimulants

• Barbiturates are often used to counteract large
  doses of stimulants such as cocaine or
  amphetamines.
• This mixture may cause increased heart rate and
  coronary arrest.

52
The Chemistry of Depression

• Neurological research has identified over 50
  kinds of neurotransmitters. Scientists have found
  that several neurotransmitters are directly
  related to mental health problems. These specific
  neurotransmitters are Dopamine, Serotonin,
  Norepinephrine, and Gamma Aminobutyric Acid. A
  shortage or excess of these neurotransmitters are
  thought to be responsible for emotional disorders
  like anxiety, depression, ADHD, social anxiety
  and mood disorder.
• There are three basic molecules, known chemically
  as monoamines, which are thought to play a role
  in mood regulation norepinephrine, serotonin and
  dopamine.
• website

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Neurotransmitterswebsite

• How They Work Once the brain's three
  neurotransmitters, known as monoamines
  (serotonin, norepinephrine, and dopamine), have
  played their part in sending messages in the
  brain, they get burned up by a protein in the
  brain called monoamine oxidase, a liver and brain
  enzyme. Antidepressants known as monoamine
  oxidase inhibitors work by blocking this cleanup
  activity. When the excess neurotransmitters don't
  get destroyed, they start piling up in the brain.
  And since depression is associated with low
  levels of these monoamines, it's not surprising
  that increasing the monoamines ease depressive
  symptoms. Unfortunately, monoamine oxidase
  doesn't just destroy those neurotransmitters
  it's also responsible for mopping up another
  amine called tyramine, a molecule that affects
  blood pressure. So when monoamine oxidase gets
  blocked, levels of tyramine begin to rise, too.
  And that's when the trouble starts. While a
  hike in neurotransmitters is beneficial, an
  increase in tyramine is disastrous. Excess
  tyramine can cause a sudden, sometimes fatal
  increase in blood pressure so severe that it can
  burst blood vessels in the brain. Every time
  you eat chicken liver, aged cheese, broad-bean
  pods, or pickled herring, tyramine floods into
  your brain. Normally, MAO enzymes take care of
  this potentially harmful tyramine excess. But if
  you're taking an MAO inhibitor, the MAO enzyme
  can't stop tyramine from building up. This is
  exactly what happened when the drugs were
  introduced in the 1960s. Because no one knew
  about the tyramine connection, a wave of deaths
  from brain hemorrhages swept the country. Other
  patients taking MAO inhibitors experienced severe
  headaches caused by the rise in blood pressure.
  These early side effects were particularly
  disturbing because nobody knew why they were
  happening.

54
Neurotransmitters
55
SSRIs

• Serotonin Re-Uptake Inhibitor Impairing Body
  Serotonin Metabolism SSRI's are "Selective
  Serotonin Re-Uptake Inhibitors." Neuronal
  re-uptake of neurotransmitters is metabolism.
  What serotonin re-uptake inhibitor actually means
  is that the SSRI-antidepressant interferes with
  ones ability to metabolize serotonin, so that
  will build up. In other words, an
  SSRI-antidepressant impairs the ability of cells
  to metabolize serotonin, not only in the brain,
  but -since serotonin is widely distributed
  throughout the body- in the body as well!

56
Serotonin info.

• In the brain, messages are passed between two
  neurons (nerve cells) via a synapse, a small gap
  between the cells. The neuron that sends the
  information releases neurotransmitters (with
  serotonin among them) into that gap. The
  neurotransmitters are then recognized by
  receptors on the surface of the recipient cell,
  which upon this stimulation, in turn, relays the
  signal. About 10 of the neurotransmitters are
  lost in this process, the other 90 are released
  from the receptors and taken up again by
  monoamine transporters in the sending cell (a
  process called reuptake).
• Depression has been linked to a lack of
  stimulation of the recipient neuron at a synapse.
  To stimulate the recipient cell, SSRIs inhibit
  the reuptake of serotonin. As a result, the
  serotonin stays in the synaptic gap longer than
  it normally would, and has the chance to be
  recognized again (and again) by the receptors of
  the recipient cell, which can finally be
  stimulated fully

57
Serotonin Levels

• Serotonin Levels
• General Effects
• "This neurotransmitter regulates
•         the onset of sleep,
•         sensory perception,
•         mood and depression,
•         body temperature,
• Normal Serotonin Levels
•           "Regulates sleep,
•           reduces pain and appetite, and
•            generally calms you down and improves
  your mood.

58
Serotonin Levels

• Low Serotonin Levels
• "Low levels of serotonin are associated with
•         increased carbohydrate cravings
•         depression
•         heightened sensitivity to pain, and
•         troubled sleep patterns
• Very low levels suicide/violent crimes/drug
  abuse/hostility/impulsiveness/OCD/eating
  disorders 
• Higher Serotonin Levels
• "When serotonin levels are increased,
•         carbohydrate cravings subside,
•         mood is elevated,
•         pain tolerance improves, and
•         sleep is more restful.
• Very High Levels schizophrenia/mood
  disorders/psychosis/autism

59
Depression and Serotonin cont

• Low serotonin levels are believed to be the cause
  of many cases of mild to severe depression which
  can lead to symptoms such as anxiety, apathy,
  fear, feelings of worthlessness, insomnia and
  fatigue.  The most concrete evidence for the
  connection between serotonin and depression is
  the decreased concentrations of serotonin
  metabolites in the cerebrospinal fluid and brain
  tissues of depressed people.

60
Dopamine, Depression and Drug Addiction

• A third substance that may play a role in mood is
  dopamine. Dopamine is associated with the reward,
  or reinforcement, that we get which causes us to
  continue participating in an activity. It has
  been implicated in such conditions as Parkinson's
  Disease and schizophrenia. There is also some
  evidence that, at least for a subset of patients,
  dopamine plays a role in depression.6
  Dopaminergic substances and stimulants have been
  used as antidepressants when other measures have
  failed.7 Some studies have investigated
  dopaminergic agents as a rapid method of
  relieving depression (in contrast to medications
  which may take up to six weeks to exhibit their
  full effect).8
• Although agents that work selectively on dopamine
  have the benefit of fast action, they have also
  exhibited some properties which have kept them
  from being as widely used as other
  antidepressants. Dopamine is a neurotransmitter
  that is associated with addiction and it's
  production is stimulated by drugs such as
  cocaine, opiates and alcohol (which may explain
  why depressed persons choose to self-medicate
  with drugs and alcohol
• Dopamine website

61
Alkaloids

• -basic compound obtained from a plant
• -many have physiological effects
• -widespread in nature, structures vary
• (see examples below)

62
Opium based drugs
63
Opium
64
Opium(Papaver somniferum)

• \ô-pë-æm\ n ME, fr. L. fr. Gk. Opion, fr. Dim.
  Of opos sap an addictive narcotic drug that is
  the dried juice of a poppy

65
Opium Please!

• Opium is grown mainly in India and Turkey.
• The legitimate world demand for opium amounts to
  about to about 680 metric tons a year, but many
  times that amount is distributed illegally.

66
Process.

• It is processed into the alkaloid morphine
  which has long served as the chief painkiller in
  medical practice, although synthetic substitutes
  such as meperidine (trade name Demerol) are now
  available. Heroin, a derivative of morphine, is
  about three times more potent. Codeine is another
  important opium alkaloid.

67
Molecules of opiates have painkilling properties
similar to endorphins/enkephalins produced in the
body.
They occupy many of the same nerve-receptor sites
and bring on the same analgesic effect as the
bodys natural painkillers.
68
OUCH!!!

• Narcotic analgesics,aka opioids, include opium
  and the natural opium derivatives codeine and
  morphine synthetic derivatives of morphine such
  as heroin and synthetic drugs such as meperidine
  and propoxyphene hydrochloride. Narcotics relieve
  pain by acting on specific structures, called
  receptors, located on the nerve cells of the
  spinal cord or brain.

69
Give me more!

• In the 1970s scientists isolated substances
  called enkephalins, which are naturally occurring
  opiates in the brain. They discovered what many
  believe is the reason behind physical dependence
  on opioidsthat is, the drugs may mimic the
  action of enkephalins. If true, this hypothesis
  suggests that physical dependence on opioids may
  develop in people who have a deficiency of these
  natural substances.

70
Just Say NO!
Today opium is sold on the street as a powder or
dark brown solid and is smoked, eaten, or
injected. Heroin addicts in the U.S. number close
to half a million people. Although the synthetic
narcotic methadone has been used to offer addicts
some relief from opiates, it is itself addictive.
Complete recovery from opiate addiction requires
years of social and psychological rehabilitation
71
Opium

• "One must not think life withthe mind, but with
  opium"-André Malraux
• "It banishes melancholy, begets confidence,
  converts fear into boldness, makes the coward
  eloquent, and dastards brave. Nobody, in
  desperate circumstances, and smiling under a
  disrelish for life, ever laid violent hands on
  himself after taking a dose of opium, or ever
  will."John Brown(1735 - 1788)

Julie Woods
72
Opium Uses and Physiology

• Opium is prescribed to treat diarrhea or pain.
• Opiates slow respiration and heartbeat, suppress
  the cough reflex, and relax the smooth muscles of
  the gastrointestinal tract
• Opiates act by binding to specific receptor
  melocules for the endorphin/enkephalin class of
  neurotransmitters in the brain. These are among
  the neurotransmitters that control movement,
  moods, and physiology.

73
Chemistry of Opium

• Opium contains over 30 alkaloids. The most
  abundant of which is Morphine, Codeine, and
  Thebaine. The opium alkaloids are largely
  combined with the dibasic acid, meconic acid.
• Morphine
  Meconicacid

74
Effects of Opium

• Euphoria
• sense of emotional detachment
• absence of pain and stress
• altered mood and mental processes
• Sleepiness
• Vomiting
• loss of appetite
• reduced sex drive
• itchy skin
• increased urination
• Sweating
• inability to concentrate
• impaired vision
• death

75
Side/Withdrawal effects

• The most detrimental side-effect of Opium is
  addiction. People have to continue taking opium
  or suffer terrible withdrawal effects like
• Malnutrition
• respiratory complications
• low blood pressure
• mental and physical health problems
• severe constipation
• contracted pupils

• Moodiness
• menstrual irregularities
• lung, liver, kidney and brain damage
• collapsed veins from injecting the drug
• loss of weight
• reduction of sex hormone levels
• frequent infections
• pregnancy complications including still birth
• death

76
Historical Background

• Opium began being used as a medical drug as early
  as 100 A.D.
• Opium Wars- Britain flooded China with opium,
  forcing them into addiction. The Chinese
  Government banned opium, but the trade continued
  illegally.
• This escalated into a trading war in 1839
• Conflict began a long history of Chinese
  suspicion towards the West.

77
Morphine
78
The History of Morphine

• Morphine comes from opium which is derived from
  poppy plants. Morphine was first isolated form
  opium in 1805 by Friedrich Serturner.
• It wasnt until almost 50 years later, when the
  hypodermic needle was invented, that morphine was
  widespread.

79
History of Morphine Continued

• Morphine is now the most widely used analgesic
  after almost 200 years of being discovered.

80
Chemistry of Morphine

• Morphine is an alkaloid that is extracted for
  opium. It is used as a pain killer and can be
  taken in many forms such as injected, smoked,
  sniffed or swallowed.

81
Uses of Morphine

• Morphine is primarily used as a very strong pain
  reliever. For both moderately sever to very sever
  pain.It can be used for relief of certain types
  of labored or difficult breathing and is
  sometimes rarely used for sever cough.

82
Uses Continued

• If a person has a chronic or debilitating illness
  morphine may be given regularly but this is still
  being debated by doctors.

83
Uses Continued

• If morphine is abused or taken for a long time a
  profound physical and psychological dependency
  may occur. But even though it is addictive it is
  rarely found as a street drug but is refered to
  as M, morph or Miss Emma.

84
Uses Continued

• Because of the risk of dependency for the drug,
  doctors practice strict regulations on it.
  Overall, Morphine is a very good pain reliever
  but must be treated with respect.

85
Is Morphine in Cheese?

• Morphine, of course, is an opiate and is highly
  addictive. So how did it get into milk? At first,
  the researchers theorized that it must have come
  from the cows' diets. After all, morphine used in
  hospitals comes from poppies and is also produced
  naturally by a few other plants that the cows
  might have been eating. But it turns out that
  cows actually produce it within their bodies,
  just as poppies do. Traces of morphine, along
  with codeine and other opiates, are apparently
  produced in cows' livers and can end up in their
  milk.
• But that was only the beginning, as other
  researchers soon found. Cow's milk-or the milk of
  any other species, for that matter-contains a
  protein, called casein, that breaks apart during
  digestion to release a whole host of opiates,
  called casomorphins. A cup of cow's milk contains
  about six grams of casein. Skim milk contains a
  bit more, and casein is concentrated in the
  production of cheese.
• If you examined a casein molecule under a
  powerful microscope, it would look like a long
  chain of beads (the "beads" are amino
  acids-simple building blocks that combine to make
  up all the proteins in your body). When you drink
  a glass of milk or eat a slice of cheese, stomach
  acid and intestinal bacteria snip the casein
  molecular chains into casomorphins of various
  lengths. One of them, a short string made up of
  just five amino acids, has about one-tenth the
  pain-killing potency of morphine.
• What are these opiates doing there, hidden in
  milk proteins? It appears that the opiates from
  mother's milk produce a calming effect on the
  infant and, in fact, may be responsible for a
  good measure of the mother-infant bond. No, it's
  not all lullabies and cooing. Psychological bonds
  always have a physical underpinning. Like it or
  not, mother's milk has a drug-like effect on the
  baby's brain that ensures that the baby will bond
  with Mom and continue to nurse and get the
  nutrients all babies need. Like heroin or
  codeine, casomorphins slow intestinal movements
  and have a decided antidiarrheal effect. The
  opiate effect may be why adults often find that
  cheese can be constipating, just as opiate
  painkillers are.

86
Cheese and Morphine continued

• It is an open question to what extent dairy
  opiates enter the adult circulation. Until the
  1990s, researchers thought that these protein
  fragments were too large to pass through the
  intestinal wall into the blood, except in
  infants, whose immature digestive tracts are not
  very selective about what passes through. They
  theorized that milk opiates mainly acted within
  the digestive tract and that they signaled
  comfort or relief to the brain indirectly,
  through the hormones traveling from the
  intestinal tract to the brain.
• But French researchers fed skim milk and yogurt
  to volunteers and found that, sure enough, at
  least some casein fragments do pass into the
  bloodstream. They reach their peak about 40
  minutes after eating.
• Cheese contains far more casein than other dairy
  products do. As milk is turned into cheese, most
  of its water, whey proteins, and lactose sugar
  are removed, leaving behind concentrated casein
  and fat.
• Cheese holds other drug-like compounds as well.
  It contains an amphetamine-like chemical called
  phenylethylamine, or PEA, which is also found in
  chocolate and sausage. And there are many
  hormones and other compounds in cheese and other
  dairy products whose functions are not yet
  understood. In naloxone tests, the
  opiate-blocking drug eliminates some of cheese's
  appeal, just as it does for chocolate.

87
Morphine and Codeine
88
Morphines structure
HO
O
N
CH
HO
3
89
Morphine facts

• Morphine is a naturally occurring substance in
  the opium poppy, Papayer somniferum.
• It is a narcotic analgesic, used primarily for
  pain
• After Heron, it has the highest dependency for
  these type of drugs
• Taken by Injection, smoking, sniffing or
  swallowing

90
More Morphine fact

• Produces euphoria and a general state of
  relaxation
• Also used to relieve breathing problems, and
  severe coughs

91
With the invention of the hypodermic needle
during the American Civil War, the injection of
morphine became indispensible in treating
patierts who had to undergo some sort of surgery.
Physicians of that time hoped that injecting
morphine directly into the blood stream would
avoid the addictive effects of smoking or eating
opium, but instead it proved more addictive.
92
Codeines structure
CH O
3
O
N
CH
HO
3
93
Codeine facts

• Also a painkiller made from the poppy plant, or
  synthetically produced
• When mixed with Aspirin or acetaminophen, pain
  relief will increase
• Can be arrested for possession, for trafficking,
  producing or prescription shopping

94
Effects of short term use of Codeine

• Besides pain relief, can cause nausea and
  vomiting, blurred vision and loss of night vision
• can lower heart rate, blood pressure and
  breathing, disorientation, convolutions and
  hallucination
• Overdose could cause coma or death

95
Effects of long term use of codeine

• Depression, having difficulty concentrating or
  sleeping
• Combining with Aspirin can cause bleeding in
  stomach combining with Tylenol can cause kidney
  and liver damage
• body stops making natural pain killins

96
HEROIN

• Diacetylmorphine
• C21H23NO5

97
Types of Heroin

• Heroin 1-4
• Brown Heroin
• Black Tar Heroin
• Powdered
• Pill form

98
Heroin is an opiate

• Opiates are derived from the dried milk of the
  opium poppy
• The opium poppy contains morphine and codeine
• Opioids can be swallowed,
  or dissolved in water and
  injected
  poppy plant
  
  

99
Chemistry of Heroin

• Name Diacetylmorphine
• Alternate Chemical Names
  
  
  
  Heroin, Diamorphine, Acetomorphine
• Chemical Formula C21H23NO5
• Molecular Weight 369.42
• Melting Point 243-244
  

100
Intended Short-Term Effects

• Kills pain
• Dialates blood vessels - produces a feeling of
  warmth
• Surge of pleasurable sensation, known as a rush
• Little interference with muscle coordination,
  sensation or intellect
• Relieves stress and discomfort by creating a
  detachment from pain, desires and activity

101
Side-Effects

• Dry-mouth, heavy feeling in extremities, nausea,
  vomiting, severe itching, drowsiness
• CNS depressant - cardiac and pulmonary functions
  are slowed
• Mental functions are clouded
• Reduces bowel activity - causes constipation

102
Long-Term Side-Effects

• Addiction - the positive pleasure from taking the
  drug is replaced by relief at taking the drug to
  maintain normality
• Collapsed veins
• Bacterial infections
• Abscesses
• Infection of heart lining and valves

103
More Long-Term Side-Effects

• Arthritis and other rheumatologic problems
• Symptoms similar to the flu - aches, sweating and
  chills, tremors, sneezing and yawning
• Liver and kidney disease
• Lung complications - pneumonia and tuberculosis

104
Heroin can be

• Swallowed
• Dissolved in water and injected
• Sniffed
• Fumes from heated powder can be inhaled (chasing
  the dragon)

105
Treatment for Heroin Addiction

• Detoxification
• Methadone Programs
• LAAM
• Naloxone and Naltrexone
• Buprenorphine

106
Detoxification

• Objective To relieve withdrawal symptoms while
  patients adjust to a drug-free state
• Used in conjunction with medications
• Best form of detoxification
  Therapeutic community residential
  programs lasting at least 3-6
  months residential treatment
  facility

107
Methadone Programs

• Not intoxicating or sedating - effects do not
  interfere with ordinary activities, i.e. driving
• Taken orally
• Suppresses narcotic withdrawal for 24-36 hours
• Patients are able to perceive pain
  and have emotional reactions
• Relieves the cravings associated
  with heroin addiction
  
  liquid methadone

108
Prescription Pain Relief

• Oxycodone (oxycontin) (oxycodone
  hydrochloride)-semisynthetic opiate derived from
  opioid alkaloid similar to codeine (called
  thebaine)
• Vicodin-acetaminophen and hydrocodone
• Percocet-acetaminophen and oxycodone
• All are narcotics, addictive, moderate to high
  pain relief, CNS depressants,

109
Pain relief medication

• website

110
Oxycodone

• is a central nervous system depressant
• stimulate opioid receptors in central nervous
  system that cause responses from respiratory
  depression to euphoria
• tolerance and resistance can develop
• patients seek to gain the euphoric effects,
  mitigate pain, and later avoid the withdrawal
  symptoms of heroin and oxycodone
• comes from the alkaloid codeine found in opium.

111
Side Effects / Overdose

• Side Effects dryness of the mouth, confusion,
  sedation, light-headedness, respiratory
  depression, nausea, vomiting, headache, sweating
• Overdose slow breathing, seizures, dizziness,
  weakness, loss of consciousness, coma, confusion,
  cold or clammy skin, small pupils

112
Legal Uses

• oxycodone is combined with
• - aspirin to make the drug Percodan
• - acetaminophen to make Percocet(Vicodan)
• - OxyContin is oxycodone along with
  time-release tablets.
• All are prescription pain-killers used for high
  pain relief.

113
What is the difference between percocet and
percodan?

• Answer BOTH CONTAIN THE NARCOTIC OXYCODONE,
  BUT ONE HAS ASPIRIN, AND THE OTHER ACETAMINOPHEN
  (TYLENOL)Percodan is the brand name for the
  combination of acetylsalicylic acid (aspirin) and
  oxycodone. Percodan is prescribed for moderate
  to moderately severe pain. Oxycodone binds to the
  pain receptors in the brain so that the sensation
  of pain is reduced. Acetylsalicylic acid halts
  the production of prostaglandins which otherwise
  cause pain. It is available in tablet, capsule,
  and liquid form and is taken every 6 hours by
  mouth. Since oxycodone can be habit forming, care
  must be taken to follow the doctor's instructions
  when taking PercodanÂ. Do not take a larger
  dose, or take it more frequently, or take it for
  longer than the doctor has prescribed. nothing
  Percocet has a narcotic (oxycodone) combined with
  acetaminophen (Tylenol) Percodan combines the
  same narcotic with aspirin. Percocet contains
  Oxycodone and Acetominophen (Tylenol). Percodan
  contains Oxycodone and Aspirin

114
Illegal Uses

• Street Names OC, OX, Oxy, Oxycotton, Blue,
  Hillybilly Heroin, Kicker
• The time-release tablets of OxyContin, are
  crushed and then the powder is snorted. The
  powder is also water soluble and is dissolved and
  then injected.
• The full 12-hour dose of oxycodone is taken in
  one hit.
• Unless prescription, it is illegal to have the
  substances.
• Oxycodone related drugs have high dependency and
  have been abused for close to 30 years. A sharp
  raise in abuse rates occurred when OxyContin was
  introduced in 1996.

115
Short Term Effects

• Analgesia, sedation, euphoria, feelings of
  relaxation, respiratory depression, cough
  suppression
• Behavioral effects last 5 hrs. Controlled time
  release tablets, OxyContin, lasts 8-12 hrs.
• When abused, the high (a sedate, euphoric
  feeling) lasts up to 5 hours

116
Long Term Effects

• Abuse may lead to dependence and tolerance
• Chronic use leads to tolerance
• The body can adapt to the presence of the drug
  and withdrawal symptoms will occurred if use is
  stopped
• If taken exactly as prescribed, opioids can be
  used to manage pain effectively.

117
Cocaine

• Alkaloid substance and CNS stimulant

118
Cocaine Production
pure cocoa leaves are harvested and lime water
and kerosene are added this is left to sit for
1- 4 days
this paste is taken and sulfuric acid is added
mixture is then filtered and dried
ammonium hydroxide is then added, and the
substance is dried again, creating what is called
cocaine base
this base is dissolved into a pool of acetone and
pool acid is added over time, a white substance
will form at the bottom which is filtered and
dried for shipment
119
Chemistry and Production
Extracted from the leaves of the cocoa plant
(erthroxylon coca) which is located primarily in
Southern America.
The stimulant is formed by adding specific
amounts of various chemicals to enhance potency
and form the well known white powder substance
which is sold illegally (in solid form cocaine is
called crack).
120
Hey! A Cocaine Timeline!
The Incas in South America chewed coca leaves to
increase energy, strength, and stamina.
Early Civ.
1800s
German chemist Albert Niemann identifies the
South American Erythroxylon coca bush and uses
it in an elixir to treat his patients. It is
also used as an anesthetic for surgery and taken
by many for energizing effects.
Psychiatric pioneer Sigmund Freud cites cocaine
in various essays as a potential cure for a
myriad of ailments.
Continued on Next Slide...
121
Documents arise concerning cocaine dependency,
and associating the stimulant with various
psychological and physical ailments.
1900s
In 1902, 92 of all the cocaine used in America
could be found in tonics at ones local pharmacy,
among these was the energizing drink Coca - Cola,
which originally contained the stimulant.
Cocaine use is restricted in 1908 from medicines
entirely.
122
Effects on the Body
-Cocaine is a central Nervous System stimulant
which is ingested through the nose, smoked in its
solid form, and seldom injected -Cocaine
provides the user with a rush,or an increase in
energy which causes chemicals in the brain to
synthetically provide pleasure to the user
-After ingested, the effects of cocaine are
short - term and usually in 15 - 20 minutes,
disappearing after 1 hour -Once cocaine is
taken, one can expect to experience an increased
heart rate and breathing, dilated pupils,
constricted blood vessels, increased blood
pressure and the shakes -Over time, a frequent
cocaine user may experience weight loss,
ulceration of the nasal membrane, cardiac arrest
(overdose), and seizures
123
The physiological components of a human combined
with the potent chemicals of cocaine produce the
popular rush that some 3.7 million Americans
today have felt the reasons for this energizing
high are as follows
-cocaine hydrochloride (white crystalline powder)
alterneurotransmitters (substances in the brain
which respondto nerve impulses) -cocaine
specifically enhances the neurotransmitter
dopamine at its receptor sites (located in the
midbrain), which is thought to be involved in
emotional responses -the autonomic nervous
system (where nerve impulses from the central
nervous system transmit self - governedimpulses
to muscles and glands) is elevated and this
causes the rush associated with cocaine
124
Physiological Effects
-While using cocaine, one may experience anxiety,
paranoia, depression, loss of ambition,
confusion, and overconfidence
-Due to the fact that cocaine is an addictive
substance, a user will inevitably have withdrawal
symptoms when he decides to stop using these
symptoms include irritability, loss of
motivation, nausea, and unclear thinking
-Studies have shown that a regular cocaine user
can (after a period of discomfort and withdrawal)
successfully quit using the drug and redeem his
health over time. For some, however, the highly
addictive nature of the drug can overcome any
desire to quit
-It is very hard for some to quit using cocaine
because of the kindling effect, where a user
will become more sensitive to the drug with
prolonged use, thereby intensifying ones high
with each use
125
Due to the fact that cocaine is not only
available in metropolitan cities but suburbs as
well, its use is still widespread and highly
illegal
-3.7 million American were reported to use
cocaine in 1999 this is drastically lower than
1982s report of 10.2 million
-4.7 of eighth graders in 1999 report using
cocaine at least once
-the average age of a first time cocaine user is
20.6 years
-over 75 of the worlds cocaine is produced in
high altitude rainforests of Columbia, and
smuggled over borders
-cocaine is responsible for over 150,000
emergency room incidents and 3,500 deaths per
year on average
126
Chemistry Of The Drug
Barbiturates contain a balance of
2,4,6-pyrimidinetrione ring structures and
5,5-substituents.