Transcript File amines chap 8 drug ppt. (1).

Chapter 8
Amines
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 (C=O) 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!
-carboxylic derivatives
-named after corresponding acid, with ending
of "amide" (see below)
-Cyclic Amides and Barbiturates (see button
for more info)
Nomenclature:
add suffix "amine" to group
Nitrite Preservatives
Processed meats and cancer website
Danger 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 adults…so more dangerous
– Lymphatic system cancers detected in lab animals
– Stomach cancer increase
– Nitrites found in: bacon, ham, hot dogs, many deli
meats…found as sodium nitrite…gives meat its pinkish
color and inhibits bacterial growth (botulism)
General Drug Classifications
• Website
• Process/Cost to develop new
drugs
CNS Stimulants and Depressants
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Increase heart rate
…pulse
…blood pressure
…breathing rate
… reactions
Dilate bronchioles
…pupils
• Some will increase blood
glucose levels…use as
diet pills
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Decrease heart rate
…pulse
…blood pressure
…breathing
…reactions
Constrict pupils
Slurred speech
balance
Nicotine and Caffeine
-CNS stimulants
-nicotine actually a poison to insects
(insecticide use)
-caffeine in: chocolate, cocoa, colas, "NoDoz"
What is Caffeine?
• Caffeine
(C8H10N4O2), or
trimethylxanthine,
• is a:
• CNS stimulant
•  cardiac muscle
stimulant
• respiratory system
stimulant
•  mild diuretic.
History of Caffeine
• Caffeine is one of the world’s 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.
What is Caffeine?
• Caffeine is medically known as trimethylxanthine
• It is a alkaloid and its chemical formula is C8H10N4O2
• When isolated in pure form it’s 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
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.
An “Addictive Drug”
• 90% of American’s 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.
Withdrawal of Caffeine
Many people that consume caffeine on a daily
basis will experience these withdrawal
effects:
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Headaches
Irritability
Nervousness
Restlessness
Insonmia
Caffeine Products
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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
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.
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 don’t 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
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.
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.
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.
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.
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 breastfeeding may make an infant
jittery.
*Increased talkativeness
*Increased aggressiveness
*Increased breathing rate
*Increased heart rate
*Increased blood pressure
*Reduced appetite
*Dilated pupils
*Visual hallucinations
Head aches
Stunted growth
Insomnia
Nervous
Coma
Hallucinations
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.
-CNS Stimulant, effects
brain & spinal cord
-Amphetamines are used as diet pills
because they raise glucose level in blood.
Body doesn’t need food, person doesn’t eat
because stomach feels full because the
glucose is high.
(note: amphetamines are not a safe or effective way to lose
weight.)
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.
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
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
don’t fully understand how stimulants work in children
with ADHD, and they don’t work for everyone. But they
can be very useful at helping some children to learn to
control their behaviour.
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.
-all have 7 membered ring
containing 2 Nitrogens
-CNS depressants
-Valium (diazapam) most
common/Librium
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.
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,
• 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
• 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,
can’t promote sleep
• CNS depressant
• Suggested doses: no more than
10 mg (adult), 5 mg (elderly)
• 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
• Physical dependence- body adapts to the presence
of the drug
• Hallucinations, sleep walking, sleep driving, etc
• Withdrawal symptoms may include:
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anxiety
restlessness
insomnia
irritability
gastrointestinal problems
loss of appetite
trembling/weakness
increased sensitivity to light, sound, smells
-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
Current General Anesthesia
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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.
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.
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.
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.
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.
Immediate Effects: appear rapidly
and may last from hours to days
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Sleepiness
Slurred speech
Trouble walking, balancing, etc.
Emotional Instability
“floating” sensation
Slowing of heartbeat
Shallow breathing
Sense of relaxation
Reduced attention span
Long Term Effects
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Increased aggressiveness
Severe depression
Physical dependence
Withdrawal reactions
Vision problems
Chronic tiredness
Side Effects
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Skin rashes
Nausea
Dizziness
Increases blood pressure, heart rate,
breathing rate, and body temp.
• Heart attacks, strokes, and respiratory
failure, brain seizures.
Withdrawal symptoms
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Hallucinations
Eating disorders
Disorientation
Vomiting
Sleep disorders
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.
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.
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
Neurotransmitters
website
•
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.
Neurotransmitters
SSRI’s
• 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!
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
Serotonin Levels
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Serotonin Levels
General Effects
"This neurotransmitter regulates
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the onset of sleep,
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sensory perception,
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mood and depression,
·
body temperature,
Normal Serotonin Levels
·
"Regulates sleep,
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reduces pain and appetite, and
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generally calms you down and improves your mood.
Serotonin Levels
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Low Serotonin Levels
"Low levels of serotonin are associated with
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increased carbohydrate cravings
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depression
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heightened sensitivity to pain, and
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troubled sleep patterns
Very low levels: suicide/violent crimes/drug
abuse/hostility/impulsiveness/OCD/eating disorders
Higher Serotonin Levels
"When serotonin levels are increased,
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carbohydrate cravings subside,
·
mood is elevated,
·
pain tolerance improves, and
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sleep is more restful.
Very High Levels: schizophrenia/mood disorders/psychosis/autism
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.
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
Alkaloids
• -basic compound obtained from a plant
• -many have physiological effects
• -widespread in nature, structures vary
• (see examples below)
Opium based drugs
Opium
Opium
(Papaver somniferum)
\ô-pë-æm\ n {ME, fr.
Opion, fr. Dim. Of
addictive narcotic
the dried juice of
L. fr. Gk.
opos sap} : an
drug that is
a poppy
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.
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.
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
body’s natural painkillers.
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.
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 opioids—that 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.
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
"One must not think life with
the 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)
Opium
Julie
Woods
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.
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
Effects of Opium
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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
Side/Withdrawal effects
• The most detrimental sideeffect 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
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.
Morphine
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 wasn’t until almost 50 years later,
when the hypodermic needle was
invented, that morphine was
widespread.
History of Morphine Continued
• Morphine is now the most widely used
analgesic after almost 200 years of being
discovered.
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.
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.
Uses Continued
• If a person has a
chronic or debilitating
illness morphine may
be given regularly but
this is still being
debated by doctors.
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.
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.
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.
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.
Morphine and
Codeine
Morphine’s structure
HO
O
N
HO
CH 3
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
More Morphine fact:
• Produces euphoria and a general state of
relaxation
• Also used to relieve breathing problems,
and severe coughs
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.
Codeine’s structure
CH O
3
O
N
HO
CH 3
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
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
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
HEROIN
Diacetylmorphine
C21H23NO5
Types of Heroin
•
•
•
•
•
Heroin #1-4
Brown Heroin
Black Tar Heroin
Powdered
Pill form
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
Chemistry of Heroin
• Name: Diacetylmorphine
• Alternate Chemical Names:
Heroin, Diamorphine, Acetomorphine
• Chemical Formula: C21H23NO5
• Molecular Weight: 369.42
• Melting Point: 243-244°
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
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
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
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
Heroin can be:
• Swallowed
• Dissolved in water and
injected
• Sniffed
• Fumes from heated
powder can be inhaled
(“chasing the dragon”)
Treatment for Heroin Addiction
•
•
•
•
•
Detoxification
Methadone Programs
LAAM
Naloxone and Naltrexone
Buprenorphine
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
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
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,
Pain relief medication
• website
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.
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
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.
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 Percodan®. 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
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.
Short Term Effects
• Analgesia, sedation, euphoria, feelings
of relaxation, respiratory depression,
cough suppression
• Behavioral effects last 5 hrs. Controlled
time release tablets, OxyContin, lasts 812 hrs.
• When abused, the high (a sedate,
euphoric feeling) lasts up to 5 hours
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.
Cocaine
• Alkaloid substance and CNS stimulant
pure cocoa leaves are harvested
and lime water and kerosene
are added; this is left to sit for
1- 4 days
ammonium hydroxide is then
added, and the substance is dried
again, creating what is called
“cocaine base”
this paste is taken and sulfuric
acid is added; mixture is then
filtered and dried
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
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”).
~Hey! A Cocaine Timeline!~
Early
Civ.
1800s
The Incas in South America chewed
coca leaves to increase energy,
strength, and stamina.
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...
1900s
Documents arise concerning cocaine
dependency, and associating the
stimulant with various psychological and
physical ailments.
In 1902, 92% of all the cocaine
used in America could be found
in tonics at one’s local
pharmacy, among these was
the energizing drink Coca Cola, which originally contained
the stimulant.
Cocaine use is restricted
in 1908 from medicines
entirely.
-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
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) alter
neurotransmitters (substances in the brain which respond
to 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 - governed
impulses to muscles and glands) is elevated and this
causes the “rush” associated with cocaine
-While using cocaine, one may
experience anxiety, paranoia,
depression, loss of ambition,
confusion, and overconfidence
-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
-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
-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 one’s high with each use
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 1982’s 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 world’s 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
Chemistry Of The Drug
Barbiturates contain a balance of 2,4,6-pyrimidinetrione ring
structures and 5,5’-substituents.