CHEM 183 Lecture 10: Mental Illness Notes
19 Jun 2018
School
Department
Course
Professor
People blame others for having mental illness
-
Mental illness affects 1 in 4 people
There are many categories that fit into the mental illness
scheme
ā
-
There is a stigma associated with mental illness and this is not
associated with other diseases such as cancer, obviously
people are not blamed for having cancer
People tell others to "get over mental illness"
ā
Many conditions that fall into the category of mental
illness but the main ones we will discuss are:
Schizophrenia, depression, mania, anxiety, OCD
Ā§
None of them are curable, but there are
medications to control the conditions
Ā§
ā
-
What causes mental illness?
We do not have a good idea of what causes mental
illness
ā
In most cases there is not a genetic components,
although in some cases there are some
Environmental factors have never been identified
Ā§
ā
It used to be believed that demons took a hold of
people's brain and that caused the mental illness
ā
In the middle ages, people believed there was a (fool?)
stone in the head that caused mental illness (physical
illness)
ā
A belief that the mood had an effect on people (Lunatic
is Latin for Moon)
ā
-
Treatments
When you don't have good treatments, then many
problems arise
ā
At one time it was believed that the demons could be
released by drilling a hole into the head
You can tell by the nature of the hole in the skull,
that the bone healed and people survived the hole
being drilled into the skull
Ā§
Idea of drilling a hole into the skull to relieve
mental illness/relieve consciousness is still with us
(Amanda Feilding - 1970)
The best way to achieve higher level of
consciousness is by drilling a hole in the skull
ā”
She is a high priestess who did experiments
with mental illness
ā”
She believes that this would work from a
Medical student from Denmark - he said the
real problem was that as we evolved and
started to walk upright, there was not
enough blood being pumped to the brain
because the heart is not strong enough. His
idea was if you drill a hole into the skull, it
would be easier for the heart to pump the
blood because there is less pressure.
ā”
Amanda Feilding ran for parliament twice
with a platform of trepanation (drilling holes
in the head because she wanted it covered
under health insurance)
ā”
Ā§
ā
Peter Halvorson is a hole in the head advocate
Drilled hole in head along with followers to make
themselves "smarter"
Ā§
ā
Mentally ill people were thought to be witches and
sometimes heated up to drive the demons out of them
Many of them were burned or chained and put
into asylums
Ā§
Water therapy - water being poured on them from
a higher level
Ā§
ā
Sigmund Freud was the father of psychoanalysis
He introduced the idea that mental illness was a
struggle between the conscious and unconscious
mind
Ā§
Mental illness can be traced to a malfunction in
the central nervous system in the brain
Ā§
ā
-
Luigi Galvani
He was a scientist who was interested in electricity
Static electricity was being introduced as a
phenomenon (devices could be cranked to give off
sparks)
Ā§
One day he was examining a frog, his assistant was
cranking a generator (wanted to see if there was
effect of electricity on frog)
Ā§
He was using a scalpel and there was a spark from
the generator and the frog leg started to twitch
Looked like the dead frog had life generated
from the electricity and he decided to
duplicate the experiment
ā”
Ā§
Wondered what would happen if their was a
bigger charge (could use lightening)
Ā§
Took frog legs and wanted to expose them to
lightening to see what a real charge could do to
them so he left the frog legs in his backyard on a
brass wire and waited for a storm, hoping to
attract lightening because of the brass (didn't
happen because there was no lightening, but
there was wind and the frog legs started to shake
with the wind)
Ā§
Whenever they touched the wire, the legs
quivered with the wind, he thought he was
releasing electricity that was stored within the
animal in the body
Ā§
Thought there was animal electricity locked up in
tissues
Ā§
ā
-
Alessandro Volta from the University of Pavia did not believe
that there was animal electricity
He thought that it wasn't the tissues of the animal
generating electricity, it was the two dissimilar metals,
the animal was just a conductor of the electricity
ā
This gave birth to the idea of the battery (two dissimilar
metals that are able to conduct electricity)
ā
Regarded as one of the fathers of knowledge of
electricity because the battery plays an important role in
our life
ā
-
By the early 1900s it had become apparent that the human
nervous system functioned through electrical impulses
In a living system there is electricity being produced that
causes motion
ā
The brain and central nervous system is made up of a
huge network of cells called neurons
ā
-
How was the electrical signal transformed into physical
action?
Discovered by Otto Loewi in 1920
Carried out an experiment - took the heart of a
frog, isolated it and stimulated with electricity the
vagus nerve
Vagus nerve causes the heart to slow down ā”
Ā§
Found when he stimulated the nerve, the heart
slowed down
Ā§
He then dripped water over the beating heart and
then allowed that solution to flow onto a second
heart that had been isolated
Ā§
The second heart began to respond as well - the
explanation is that there is a chemical being
transferred from the first heart to the second
heart
This was the discovery of neurotransmitters ā”
Ā§
ā
-
Neurotransmitters are the chemicals that connect nerve cells
to each other and to muscle cells (transmission of information)
Acetylcholine caused the heart to slow down
ā
Epinephrine (adrenalin) caused the heart to speed up
ā
Information flows along the axon and stimulate the
nerve cell adjacent
ā
Dendrite is stimulated by neurotransmitters, message
goes down the axon, neurotransmitters are released to
the next cell (how information is passed along
ā
Serotonin, dopamine, norepinephrine, gamma
aminobutyric acid are other neurotransmitters that
were discovered
ā
Neurotransmitters are released into the synapse which
triggers the info to flow down
ā
Both chemical system and electrical system in the cell
End of the cell electricity causes neurotransmitters
to be released
Ā§
ā
"Lock and key effect"
ā
Some of neurotransmitter can be sucked back into the
synapse
Neurotransmitters are synthesized from diet and
are stored in vesicles
Ā§
There are drugs that can prevent or enhance the
release of the NT in the vesicle
Ā§
There are drugs that can prevent the reuptake
Ā§
ā
-
Drugs
Reserpine causes noepinephrine to leak out of the
vesicles
ā
Amphetamines squeeze noephinephrine and dopamine
out of vesicles
Causes rapid stimulation
Ā§
ā
Tricyclics prevent the reuptake of neurotransmitters
Can help with mood elevation
Ā§
ā
MAO inhibitors prevent the breakdown of certain
neurotransmitters by an enzyme
ā
Neuroleptics block receptors for dopamine
ā
-
Schizophrenia
Not dual or multiple personalities, but it is a loss of
contact with reality
ā
They have visual and auditory hallucinations and
delusions of persecution (ie. Neighbours are aliens, etc.)
ā
History of the treatment is very sad, it is a class of
mental illness where it is obvious there is something
wrong
Historically people were locked up in mental
asylums, chained
Ā§
Wasn't until the 1950s where viable treatments
began to emerge - started in France
Ā§
ā
Henri Laborit (1952)
Frightening number of deaths on the operating
table after the administration of anesthesia and
Laborit wanted to know what caused the sudden
death
Ā§
He wondered whether or not it was a sudden
release of histamine that caused the deaths on the
operating table
Ā§
Wanted to see if antihistamines prior to surgery
would be beneficial
Ā§
Promethazine (phenergan) was an antihistamine
being prescribed so he decided to use it, it wasn't
effective in stopping deaths, but it had a calming
effect on patients when they took it before
surgery (told his colleagues)
Ā§
Tried promethazine on schizophrenics, it calmed
them a little bit, but it triggered researched to see
if there were other drugs with similar molecular
structures that worked better
Ā§
ā
Antihistamine (chlorpromazine/thorazine) had a calming
effect on people before surgery and it had a huge
calming effect on schizophrenics, but eventually they
developed Parkinson like symptoms
Already established that Parkinson's disease was a
disease of dopamine defficiency
Ā§
Chlorpromazine was working because it was
blocking dopamine receptors
Ā§
This meant blocking dopamine receptors, it was
blocking the action of dopamine, the conclusion is
that schizophrenia is caused by an excess of
dopamine (need drugs to block dopamine and
would have to deal with effects)
Ā§
ā
Nathan Kline was experimenting with reserpine to treat
Schizophrenia
Was interested in this because of a plant called
snakeroot (contains hundreds of compounds,
there was a compound called reserpine that could
be isolated and could bring down blood pressure)
Ā§
Was looking into this to bring down blood
pressure and it had a tranquilizing effect - he tried
it on his schizophrenia patients and it worked
Ā§
It worked but again induced Parkinson like effects
Ā§
The two drugs that worked had very different
molecular structures
Chlorpromazine blocked dopamine
receptors (wrong key fit into key hole and
blocked right key from working)
ā”
Reserpine caused dopamine to leak out of
vesicles from which is was stored slowly,
when stimulation happened there was not
enough dopamine become release to have
an effect
ā”
Ā§
ā
It is clear that schizophrenia is due to too much
dopamine activity
ā
Perphenazine is more potent than chlorpromazine
ā
There is a legion of meds that have been developed to
intefere with the dopamine system (such as Haliperidol)
Doesn't have as bad Parkinson-like side effects
and a huge calming effects on anyone who is
overactive
Ā§
Clozapine, Risperidone, Olanzapine
Ā§
Possible one medication doesn't work in one
patient but works very well in another patient
Ā§
ā
Eventually 25% of schizophrenics achieve remission with
appropriate medications (can hold a job, go to school,
etc.)
Other 75% are not at the stage where their life can
become completely normal
Ā§
Newer drugs were not significantly effective than
the old ones, pharmacy pushed new ones because
they were more expensive
Ā§
There is talk to introduce new drugs that have a
second criteria
Should have to show that new drug works
better than old drugs that are already in use
ā”
Show that the drug works better than a
placebo
ā”
Ā§
ā
-
Depression
A situation where you feel hopeless, pessimistic and
useless with the reason that there is no reason for you
to feel like that
Every day becomes a challenge to the extent that
you don't want to get out of bed
Ā§
ā
Antidepressants
Highly controversial area
Ā§
First effective drugs are tricyclics
Resulted from a search for an improved
version of chlorpromazine to treat
schizophrenia
ā”
One chemical was looked at was imipramine
because it had a similar chemical structure
to chlorpromazine
ā”
Turned out that imipramine was ineffective
to treat schizophrenia but it had an elevated
mood effect
ā”
This interacted with neurotransmitters that
blocked the reuptake of serotonin and
norephinephrine (happy chemicals)
When they are found in a high enough
concentration in the synapse, they
result in mood elevation
Ā®
These neurotransmitters are
recycled - swim across synapse to be
retaken by original nerve cell
Ā®
If you block reuptake you will increase
concentration of neurotransmitters in
the synapse
Ā®
ā”
Ā§
Anafranil was given by the company that supplies
it
10-15 years where a company can sell the
drug under its trade name, when the patent
is done any one can manufacture it as long
as you show you are making a chemically
similar drug
ā”
Ā§
Side effects
Anticholinergic (dry mouth, blurred vision) ā”
Antiadrenergic (irregular heart beats)
In addition to blocked the reuptake
they also block acetylcholine and
epinephrine receptors
Ā®
ā”
Ā§
ā
-
How do you increase serotonin and norephinephrine in
synapse without the side effects of tricyclics?
Develop a molecular structure that didnāt fit into the
unwanted receptors and this was the birth of Prozac
Became on of the most popular antidepressants
Ā§
Selective serotonin re-uptake inhibitors (SSRIs) -
blocks serotonin
You want specific activity, not broad
spectrum of activity
ā”
Ā§
Prozac blocks reuptake of serotonin into the
uptake
Ā§
Increased the concentration of serotonin in the
gap and this achieved the mood increase effect
Others: sertraline, fluovoxamine,
maprotiline, paroxetine, trazodone,
citalopram but have different side effect
profiles and depends on individuals
ā”
Ā§
ā
Side effects
Nausea, anxiety, sleep disturbances and sexual
dysfunction
Ā§
Side effects have to be weighed against the
benefits of the medication
Ā§
Even if side effect has only been documented in
one person, it has to be listed therefore it doesn't
mean that it will happen to you
Ā§
ā
Prozac works for many people and brings them out of
depression, but in 1989 there was a huge shooting
incident in Louisville
Joseph Wesbecker shot a store and he had a
history of mental illness and had been on Prozac
Ā§
Prozac was blamed for this
Ā§
The relatives of the victims launched a lawsuit
against the manufacturer for Prozac
Ā§
ā
Allegations that SSRIs cause an increase in suicide
But you don't know if suicides are caused by the
drugs or the condition
Ā§
ā
Since early 2000s there was concern among young
people that Prozac was causing suicide
We have had studies that show in controlled trials
there was no difference in the frequency of
suicidal thoughts in subjects taking Prozac, a
tricyclic or a placebo
It is the disease that causes suicidal
thoughts
ā”
People's conditions are very good in
controlling the illness
ā”
Ā§
ā
Drugs are overprescribed, more widely used than it
should be and should only be used for serious situations
ā
Prozac can also be used for OCD
ā
-
OCD is obsessive compulsive disorder
Affects 2% of the population
ā
Chemistry graduate student who had cats at home and
was constantly worried whenever he was using his
washing machine or fridge that somehow one of the
cats would climb into it and he wouldn't notice it and
the animal would be locked into the machine or fridge
Knew this could not have happened if he
repeatedly opened and closed the washing
machine
Ā§
ā
OCD interferes to a large extent of your life
People cannot leave their house till they have
made sure their door is closed a certain number of
times and this can be up to 350 times
Ā§
People think they need to do a certain number of
sit ups a day or else something horrible would
happen
Ā§
Lady was in a supermarket and saw a cockroach
run across the store, disturbed her so much that
every item of food had to be washed because it
could be cockroach contaminated
Ā§
There are people who are counters who need to
count things (# of light poles, etc) in an obsessive
way, if they think they missed a count they have
to stop, go back and start again
Ā§
ā
Very often highly intelligent people who know full well
their door is locked but they can't get away from the
thought
ā
About 20% of first degree relatives of people with OCD
have the disease (genetic issue)
ā
About 20% of OCD patients have tics and 50% of
patients have Tourettes
ā
-
Tourette Syndrome (Georges Gilles de la Tourette)
Person suffers from involuntary tics and vocalizations
ā
Many people who have Tourette syndrome also have
OCD
ā
-
Obsession: unwanted, unreasonable, intrusive thought that
you can't get away from
They are about contamination concerns, harm to self or
others, symmetry concerns, saving concerns, perfection
concerns
ā
-
Compulsions: rituals performed to gain release from obsessive
thoughts
-
OCD is not due to some deeply rooted emotional imbalance
Injury to the head or seizures, stroke can trigger OCD
which suggests that it is something physical that
happens to the brain and triggers it
ā
Man had a stroke and developed gourmand syndrome
which is an obsession with food
ā
People with OCD have been examined with scans and
there are more parts of the brain that are active with
people with OCD
ā
Evidence that the strep infection in children can trigger
OCD and this has been referred to as PANDA
ā
-
Diagnoses
Really interferes with life
ā
Do you have repetitive thoughts that make you anxious
and that you cannot get rid of no matter how you try?
ā
Do you keep things extremely clean or was your hands
frequently?
ā
-
Anaphranil is given for depression but improved OCD
symptoms
Increases serotonin levels
ā
Side effects:
Dizziness, sedation, etc.
Ā§
ā
40-60% will respond to SSRIs with an improvement in
symptoms of some 30%
ā
At least 10-12 weeks are required
ā
Treatment
Behaviour therapy - forcing the person to do the
thing that they fear; 10-20 sessions can improve
symptoms by 85%
Ā§
Psychoptherapy doesn't work
Ā§
Confrontation therapy - if someone is afraid to sit
on the toilet, force them to sit on the toilet
Ā§
Transcranial magnetic stimulation
Ā§
ā
MAO inhibiters
Tuberculosis is a bacterial infection of the lungs
Ā§
Until the 1950s when antibiotics were developed,
patients were locked up in sanitariums
Ā§
Only treatment for tuberculosis is to be exposed
to the sunshine
Drug iproniazid was developed - first
antitubucular drug
It improved their medical condition
and caused patients to be cheery
Ā®
Nathan Kline tried the drug on his
depressed patients but some of the
patients developed high blood
pressure or strokes
Ā®
There was a dietary component,
patients had taken the drugs had
salami, aged cheese, etc.
Ā®
The drug inhibited an enzyme MAO
(enzyme that breaks down serotonin,
etc.)
Ā®
ā”
MAO degrades important neurotransmitters ā”
MAOIs increase important
neurotransmitters
Foods contain tyramine that can
elevate blood pressure
Ā®
When MAO is inhibited, the break
down of tyramine is inhibited as well
and causes hypertension (high blood
pressure)
Ā®
ā”
Ā§
Patients on MAO have to stay away from foods
that are high in things that will raise their blood
pressure (beer, wine, chocolate, chicken liver,
herring, aged cheeses and certain drugs like
demerol and decongestants)
Ā§
ā
-
Manic
Periods of being manic, and periods of being depressed
Manic shoppers, engage in more sex
Ā§
Followed by a period of depression
Ā§
ā
Due to a chemical imbalance in the brain
ā
John Cade was imprisoned by the Japanese during the
war
Noted that there were periods of suffering and
periods of them being highly elated
Ā§
Maybe is due to a toxin that builds up in the brain
and is excreted in the urine
Ā§
Took urine from mentally ill patients and injected
into guinea pigs
Found the urine in the manic phase killed
guinea pigs more frequently
ā”
Wondered if it was the concentration of uric
acid in the urine that was the bi product of
something that was happening in the brain
ā”
Wanted to see if injecting uric acid would
have an effect on animals - not very soluble
in water, but salts of uric acids were
ā”
The base he used to neutralize was lithium
oxide
ā”
Made lithium urate and this had a calming
effect on animals, but it was hard to make
so he tried lithium carbonate
ā”
This evened the manic patients and lithium
carbonate became the drug of use to treat
manic patients
Interferes with the synthesis of
inositol (triggers electrical conduction)
Ā®
ā”
Ā§
Side effects: trembling, nausea
Ā§
ā
None of these drugs will cure the disease
ā
-
Some anti-cancer drugs that can cure diseases
-
Antianxiety agents
Feeling of apprehension, uncertainty or fear that is out
of proportion to a stimulus
ā
Sometimes it can result in panic attacks (pounding heart,
hyperventilation, sweating and feeling jittery)
ā
Drugs used in treatment were barbiturates - problem is
they are too sedative and addictive
Became mainstream in the 1950s-60s
Ā§
ā
-
Frank Berger
Tested drugs for antibiotic activity in England
ā
He tested a chemical called mephenesin which was a
muscle relaxant
When he treated animals with this they became
extremely calm
Ā§
This had an anti-anxiety effect
Ā§
Had too many side effects to be used commonly
but lead to meprobamate (miltown)
Extensive search to find substances that had
an antianxiety effect
ā”
Librium was introduced as antianxiety drug,
followed by valium
Increase activity of GABA which is an
inhibitory neurotransmitter
Ā®
Xanax, lorazepam, etc. are given to
people who are anxious or people
who have trouble sleeping
Some people gives rise to bad
dreams so they can't take it
ā
If they are taken with
alcohol/barbiturates it can
cause central nervous system
depression
ā
Ā®
ā”
Ā§
ā
-
What is the role of cannabis?
Use it as medical marijuana
ā
Claims about it helping with depression but also that it
can cause depression
It can help depression but only while it is in your
blood stream
Ā§
It depends on which kind of marijuana you use
because the strains have difference balances of
TCH and CBD
CBD has the antidepressant effect ā”
Ā§
ā
-
Mental Illness Notes
Tuesday, November 14, 2017
5:24 PM
People blame others for having mental illness
-
Mental illness affects 1 in 4 people
There are many categories that fit into the mental illness
scheme
ā
-
There is a stigma associated with mental illness and this is not
associated with other diseases such as cancer, obviously
people are not blamed for having cancer
People tell others to "get over mental illness"
ā
Many conditions that fall into the category of mental
illness but the main ones we will discuss are:
Schizophrenia, depression, mania, anxiety, OCD
Ā§
None of them are curable, but there are
medications to control the conditions
Ā§
ā
-
What causes mental illness?
We do not have a good idea of what causes mental
illness
ā
In most cases there is not a genetic components,
although in some cases there are some
Environmental factors have never been identified
Ā§
ā
It used to be believed that demons took a hold of
people's brain and that caused the mental illness
ā
In the middle ages, people believed there was a (fool?)
stone in the head that caused mental illness (physical
illness)
ā
A belief that the mood had an effect on people (Lunatic
is Latin for Moon)
ā
-
Treatments
When you don't have good treatments, then many
problems arise
ā
At one time it was believed that the demons could be
released by drilling a hole into the head
You can tell by the nature of the hole in the skull,
that the bone healed and people survived the hole
being drilled into the skull
Ā§
Idea of drilling a hole into the skull to relieve
mental illness/relieve consciousness is still with us
(Amanda Feilding - 1970)
The best way to achieve higher level of
consciousness is by drilling a hole in the skull
ā”
She is a high priestess who did experiments
with mental illness
ā”
She believes that this would work from a
Medical student from Denmark - he said the
real problem was that as we evolved and
started to walk upright, there was not
enough blood being pumped to the brain
because the heart is not strong enough. His
idea was if you drill a hole into the skull, it
would be easier for the heart to pump the
blood because there is less pressure.
ā”
Amanda Feilding ran for parliament twice
with a platform of trepanation (drilling holes
in the head because she wanted it covered
under health insurance)
ā”
Ā§
ā
Peter Halvorson is a hole in the head advocate
Drilled hole in head along with followers to make
themselves "smarter"
Ā§
ā
Mentally ill people were thought to be witches and
sometimes heated up to drive the demons out of them
Many of them were burned or chained and put
into asylums
Ā§
Water therapy - water being poured on them from
a higher level
Ā§
ā
Sigmund Freud was the father of psychoanalysis
He introduced the idea that mental illness was a
struggle between the conscious and unconscious
mind
Ā§
Mental illness can be traced to a malfunction in
the central nervous system in the brain
Ā§
ā
-
Luigi Galvani
He was a scientist who was interested in electricity
Static electricity was being introduced as a
phenomenon (devices could be cranked to give off
sparks)
Ā§
One day he was examining a frog, his assistant was
cranking a generator (wanted to see if there was
effect of electricity on frog)
Ā§
He was using a scalpel and there was a spark from
the generator and the frog leg started to twitch
Looked like the dead frog had life generated
from the electricity and he decided to
duplicate the experiment
ā”
Ā§
Wondered what would happen if their was a
bigger charge (could use lightening)
Ā§
Took frog legs and wanted to expose them to
lightening to see what a real charge could do to
them so he left the frog legs in his backyard on a
brass wire and waited for a storm, hoping to
attract lightening because of the brass (didn't
happen because there was no lightening, but
there was wind and the frog legs started to shake
with the wind)
Ā§
Whenever they touched the wire, the legs
quivered with the wind, he thought he was
releasing electricity that was stored within the
animal in the body
Ā§
Thought there was animal electricity locked up in
tissues
Ā§
ā
-
Alessandro Volta from the University of Pavia did not believe
that there was animal electricity
He thought that it wasn't the tissues of the animal
generating electricity, it was the two dissimilar metals,
the animal was just a conductor of the electricity
ā
This gave birth to the idea of the battery (two dissimilar
metals that are able to conduct electricity)
ā
Regarded as one of the fathers of knowledge of
electricity because the battery plays an important role in
our life
ā
-
By the early 1900s it had become apparent that the human
nervous system functioned through electrical impulses
In a living system there is electricity being produced that
causes motion
ā
The brain and central nervous system is made up of a
huge network of cells called neurons
ā
-
How was the electrical signal transformed into physical
action?
Discovered by Otto Loewi in 1920
Carried out an experiment - took the heart of a
frog, isolated it and stimulated with electricity the
vagus nerve
Vagus nerve causes the heart to slow down ā”
Ā§
Found when he stimulated the nerve, the heart
slowed down
Ā§
He then dripped water over the beating heart and
then allowed that solution to flow onto a second
heart that had been isolated
Ā§
The second heart began to respond as well - the
explanation is that there is a chemical being
transferred from the first heart to the second
heart
This was the discovery of neurotransmitters ā”
Ā§
ā
-
Neurotransmitters are the chemicals that connect nerve cells
to each other and to muscle cells (transmission of information)
Acetylcholine caused the heart to slow down
ā
Epinephrine (adrenalin) caused the heart to speed up
ā
Information flows along the axon and stimulate the
nerve cell adjacent
ā
Dendrite is stimulated by neurotransmitters, message
goes down the axon, neurotransmitters are released to
the next cell (how information is passed along
ā
Serotonin, dopamine, norepinephrine, gamma
aminobutyric acid are other neurotransmitters that
were discovered
ā
Neurotransmitters are released into the synapse which
triggers the info to flow down
ā
Both chemical system and electrical system in the cell
End of the cell electricity causes neurotransmitters
to be released
Ā§
ā
"Lock and key effect"
ā
Some of neurotransmitter can be sucked back into the
synapse
Neurotransmitters are synthesized from diet and
are stored in vesicles
Ā§
There are drugs that can prevent or enhance the
release of the NT in the vesicle
Ā§
There are drugs that can prevent the reuptake
Ā§
ā
-
Drugs
Reserpine causes noepinephrine to leak out of the
vesicles
ā
Amphetamines squeeze noephinephrine and dopamine
out of vesicles
Causes rapid stimulation
Ā§
ā
Tricyclics prevent the reuptake of neurotransmitters
Can help with mood elevation
Ā§
ā
MAO inhibitors prevent the breakdown of certain
neurotransmitters by an enzyme
ā
Neuroleptics block receptors for dopamine
ā
-
Schizophrenia
Not dual or multiple personalities, but it is a loss of
contact with reality
ā
They have visual and auditory hallucinations and
delusions of persecution (ie. Neighbours are aliens, etc.)
ā
History of the treatment is very sad, it is a class of
mental illness where it is obvious there is something
wrong
Historically people were locked up in mental
asylums, chained
Ā§
Wasn't until the 1950s where viable treatments
began to emerge - started in France
Ā§
ā
Henri Laborit (1952)
Frightening number of deaths on the operating
table after the administration of anesthesia and
Laborit wanted to know what caused the sudden
death
Ā§
He wondered whether or not it was a sudden
release of histamine that caused the deaths on the
operating table
Ā§
Wanted to see if antihistamines prior to surgery
would be beneficial
Ā§
Promethazine (phenergan) was an antihistamine
being prescribed so he decided to use it, it wasn't
effective in stopping deaths, but it had a calming
effect on patients when they took it before
surgery (told his colleagues)
Ā§
Tried promethazine on schizophrenics, it calmed
them a little bit, but it triggered researched to see
if there were other drugs with similar molecular
structures that worked better
Ā§
ā
Antihistamine (chlorpromazine/thorazine) had a calming
effect on people before surgery and it had a huge
calming effect on schizophrenics, but eventually they
developed Parkinson like symptoms
Already established that Parkinson's disease was a
disease of dopamine defficiency
Ā§
Chlorpromazine was working because it was
blocking dopamine receptors
Ā§
This meant blocking dopamine receptors, it was
blocking the action of dopamine, the conclusion is
that schizophrenia is caused by an excess of
dopamine (need drugs to block dopamine and
would have to deal with effects)
Ā§
ā
Nathan Kline was experimenting with reserpine to treat
Schizophrenia
Was interested in this because of a plant called
snakeroot (contains hundreds of compounds,
there was a compound called reserpine that could
be isolated and could bring down blood pressure)
Ā§
Was looking into this to bring down blood
pressure and it had a tranquilizing effect - he tried
it on his schizophrenia patients and it worked
Ā§
It worked but again induced Parkinson like effects
Ā§
The two drugs that worked had very different
molecular structures
Chlorpromazine blocked dopamine
receptors (wrong key fit into key hole and
blocked right key from working)
ā”
Reserpine caused dopamine to leak out of
vesicles from which is was stored slowly,
when stimulation happened there was not
enough dopamine become release to have
an effect
ā”
Ā§
ā
It is clear that schizophrenia is due to too much
dopamine activity
ā
Perphenazine is more potent than chlorpromazine
ā
There is a legion of meds that have been developed to
intefere with the dopamine system (such as Haliperidol)
Doesn't have as bad Parkinson-like side effects
and a huge calming effects on anyone who is
overactive
Ā§
Clozapine, Risperidone, Olanzapine
Ā§
Possible one medication doesn't work in one
patient but works very well in another patient
Ā§
ā
Eventually 25% of schizophrenics achieve remission with
appropriate medications (can hold a job, go to school,
etc.)
Other 75% are not at the stage where their life can
become completely normal
Ā§
Newer drugs were not significantly effective than
the old ones, pharmacy pushed new ones because
they were more expensive
Ā§
There is talk to introduce new drugs that have a
second criteria
Should have to show that new drug works
better than old drugs that are already in use
ā”
Show that the drug works better than a
placebo
ā”
Ā§
ā
-
Depression
A situation where you feel hopeless, pessimistic and
useless with the reason that there is no reason for you
to feel like that
Every day becomes a challenge to the extent that
you don't want to get out of bed
Ā§
ā
Antidepressants
Highly controversial area
Ā§
First effective drugs are tricyclics
Resulted from a search for an improved
version of chlorpromazine to treat
schizophrenia
ā”
One chemical was looked at was imipramine
because it had a similar chemical structure
to chlorpromazine
ā”
Turned out that imipramine was ineffective
to treat schizophrenia but it had an elevated
mood effect
ā”
This interacted with neurotransmitters that
blocked the reuptake of serotonin and
norephinephrine (happy chemicals)
When they are found in a high enough
concentration in the synapse, they
result in mood elevation
Ā®
These neurotransmitters are
recycled - swim across synapse to be
retaken by original nerve cell
Ā®
If you block reuptake you will increase
concentration of neurotransmitters in
the synapse
Ā®
ā”
Ā§
Anafranil was given by the company that supplies
it
10-15 years where a company can sell the
drug under its trade name, when the patent
is done any one can manufacture it as long
as you show you are making a chemically
similar drug
ā”
Ā§
Side effects
Anticholinergic (dry mouth, blurred vision) ā”
Antiadrenergic (irregular heart beats)
In addition to blocked the reuptake
they also block acetylcholine and
epinephrine receptors
Ā®
ā”
Ā§
ā
-
How do you increase serotonin and norephinephrine in
synapse without the side effects of tricyclics?
Develop a molecular structure that didnāt fit into the
unwanted receptors and this was the birth of Prozac
Became on of the most popular antidepressants
Ā§
Selective serotonin re-uptake inhibitors (SSRIs) -
blocks serotonin
You want specific activity, not broad
spectrum of activity
ā”
Ā§
Prozac blocks reuptake of serotonin into the
uptake
Ā§
Increased the concentration of serotonin in the
gap and this achieved the mood increase effect
Others: sertraline, fluovoxamine,
maprotiline, paroxetine, trazodone,
citalopram but have different side effect
profiles and depends on individuals
ā”
Ā§
ā
Side effects
Nausea, anxiety, sleep disturbances and sexual
dysfunction
Ā§
Side effects have to be weighed against the
benefits of the medication
Ā§
Even if side effect has only been documented in
one person, it has to be listed therefore it doesn't
mean that it will happen to you
Ā§
ā
Prozac works for many people and brings them out of
depression, but in 1989 there was a huge shooting
incident in Louisville
Joseph Wesbecker shot a store and he had a
history of mental illness and had been on Prozac
Ā§
Prozac was blamed for this
Ā§
The relatives of the victims launched a lawsuit
against the manufacturer for Prozac
Ā§
ā
Allegations that SSRIs cause an increase in suicide
But you don't know if suicides are caused by the
drugs or the condition
Ā§
ā
Since early 2000s there was concern among young
people that Prozac was causing suicide
We have had studies that show in controlled trials
there was no difference in the frequency of
suicidal thoughts in subjects taking Prozac, a
tricyclic or a placebo
It is the disease that causes suicidal
thoughts
ā”
People's conditions are very good in
controlling the illness
ā”
Ā§
ā
Drugs are overprescribed, more widely used than it
should be and should only be used for serious situations
ā
Prozac can also be used for OCD
ā
-
OCD is obsessive compulsive disorder
Affects 2% of the population
ā
Chemistry graduate student who had cats at home and
was constantly worried whenever he was using his
washing machine or fridge that somehow one of the
cats would climb into it and he wouldn't notice it and
the animal would be locked into the machine or fridge
Knew this could not have happened if he
repeatedly opened and closed the washing
machine
Ā§
ā
OCD interferes to a large extent of your life
People cannot leave their house till they have
made sure their door is closed a certain number of
times and this can be up to 350 times
Ā§
People think they need to do a certain number of
sit ups a day or else something horrible would
happen
Ā§
Lady was in a supermarket and saw a cockroach
run across the store, disturbed her so much that
every item of food had to be washed because it
could be cockroach contaminated
Ā§
There are people who are counters who need to
count things (# of light poles, etc) in an obsessive
way, if they think they missed a count they have
to stop, go back and start again
Ā§
ā
Very often highly intelligent people who know full well
their door is locked but they can't get away from the
thought
ā
About 20% of first degree relatives of people with OCD
have the disease (genetic issue)
ā
About 20% of OCD patients have tics and 50% of
patients have Tourettes
ā
-
Tourette Syndrome (Georges Gilles de la Tourette)
Person suffers from involuntary tics and vocalizations
ā
Many people who have Tourette syndrome also have
OCD
ā
-
Obsession: unwanted, unreasonable, intrusive thought that
you can't get away from
They are about contamination concerns, harm to self or
others, symmetry concerns, saving concerns, perfection
concerns
ā
-
Compulsions: rituals performed to gain release from obsessive
thoughts
-
OCD is not due to some deeply rooted emotional imbalance
Injury to the head or seizures, stroke can trigger OCD
which suggests that it is something physical that
happens to the brain and triggers it
ā
Man had a stroke and developed gourmand syndrome
which is an obsession with food
ā
People with OCD have been examined with scans and
there are more parts of the brain that are active with
people with OCD
ā
Evidence that the strep infection in children can trigger
OCD and this has been referred to as PANDA
ā
-
Diagnoses
Really interferes with life
ā
Do you have repetitive thoughts that make you anxious
and that you cannot get rid of no matter how you try?
ā
Do you keep things extremely clean or was your hands
frequently?
ā
-
Anaphranil is given for depression but improved OCD
symptoms
Increases serotonin levels
ā
Side effects:
Dizziness, sedation, etc.
Ā§
ā
40-60% will respond to SSRIs with an improvement in
symptoms of some 30%
ā
At least 10-12 weeks are required
ā
Treatment
Behaviour therapy - forcing the person to do the
thing that they fear; 10-20 sessions can improve
symptoms by 85%
Ā§
Psychoptherapy doesn't work
Ā§
Confrontation therapy - if someone is afraid to sit
on the toilet, force them to sit on the toilet
Ā§
Transcranial magnetic stimulation
Ā§
ā
MAO inhibiters
Tuberculosis is a bacterial infection of the lungs
Ā§
Until the 1950s when antibiotics were developed,
patients were locked up in sanitariums
Ā§
Only treatment for tuberculosis is to be exposed
to the sunshine
Drug iproniazid was developed - first
antitubucular drug
It improved their medical condition
and caused patients to be cheery
Ā®
Nathan Kline tried the drug on his
depressed patients but some of the
patients developed high blood
pressure or strokes
Ā®
There was a dietary component,
patients had taken the drugs had
salami, aged cheese, etc.
Ā®
The drug inhibited an enzyme MAO
(enzyme that breaks down serotonin,
etc.)
Ā®
ā”
MAO degrades important neurotransmitters ā”
MAOIs increase important
neurotransmitters
Foods contain tyramine that can
elevate blood pressure
Ā®
When MAO is inhibited, the break
down of tyramine is inhibited as well
and causes hypertension (high blood
pressure)
Ā®
ā”
Ā§
Patients on MAO have to stay away from foods
that are high in things that will raise their blood
pressure (beer, wine, chocolate, chicken liver,
herring, aged cheeses and certain drugs like
demerol and decongestants)
Ā§
ā
-
Manic
Periods of being manic, and periods of being depressed
Manic shoppers, engage in more sex
Ā§
Followed by a period of depression
Ā§
ā
Due to a chemical imbalance in the brain
ā
John Cade was imprisoned by the Japanese during the
war
Noted that there were periods of suffering and
periods of them being highly elated
Ā§
Maybe is due to a toxin that builds up in the brain
and is excreted in the urine
Ā§
Took urine from mentally ill patients and injected
into guinea pigs
Found the urine in the manic phase killed
guinea pigs more frequently
ā”
Wondered if it was the concentration of uric
acid in the urine that was the bi product of
something that was happening in the brain
ā”
Wanted to see if injecting uric acid would
have an effect on animals - not very soluble
in water, but salts of uric acids were
ā”
The base he used to neutralize was lithium
oxide
ā”
Made lithium urate and this had a calming
effect on animals, but it was hard to make
so he tried lithium carbonate
ā”
This evened the manic patients and lithium
carbonate became the drug of use to treat
manic patients
Interferes with the synthesis of
inositol (triggers electrical conduction)
Ā®
ā”
Ā§
Side effects: trembling, nausea
Ā§
ā
None of these drugs will cure the disease
ā
-
Some anti-cancer drugs that can cure diseases
-
Antianxiety agents
Feeling of apprehension, uncertainty or fear that is out
of proportion to a stimulus
ā
Sometimes it can result in panic attacks (pounding heart,
hyperventilation, sweating and feeling jittery)
ā
Drugs used in treatment were barbiturates - problem is
they are too sedative and addictive
Became mainstream in the 1950s-60s
Ā§
ā
-
Frank Berger
Tested drugs for antibiotic activity in England
ā
He tested a chemical called mephenesin which was a
muscle relaxant
When he treated animals with this they became
extremely calm
Ā§
This had an anti-anxiety effect
Ā§
Had too many side effects to be used commonly
but lead to meprobamate (miltown)
Extensive search to find substances that had
an antianxiety effect
ā”
Librium was introduced as antianxiety drug,
followed by valium
Increase activity of GABA which is an
inhibitory neurotransmitter
Ā®
Xanax, lorazepam, etc. are given to
people who are anxious or people
who have trouble sleeping
Some people gives rise to bad
dreams so they can't take it
ā
If they are taken with
alcohol/barbiturates it can
cause central nervous system
depression
ā
Ā®
ā”
Ā§
ā
-
What is the role of cannabis?
Use it as medical marijuana
ā
Claims about it helping with depression but also that it
can cause depression
It can help depression but only while it is in your
blood stream
Ā§
It depends on which kind of marijuana you use
because the strains have difference balances of
TCH and CBD
CBD has the antidepressant effect ā”
Ā§
ā
-
Mental Illness Notes
Tuesday, November 14, 2017 5:24 PM
People blame others for having mental illness
-
Mental illness affects 1 in 4 people
There are many categories that fit into the mental illness
scheme
ā
-
There is a stigma associated with mental illness and this is not
associated with other diseases such as cancer, obviously
people are not blamed for having cancer
People tell others to "get over mental illness"
ā
Many conditions that fall into the category of mental
illness but the main ones we will discuss are:
Schizophrenia, depression, mania, anxiety, OCD
Ā§
None of them are curable, but there are
medications to control the conditions
Ā§
ā
-
What causes mental illness?
We do not have a good idea of what causes mental
illness
ā
In most cases there is not a genetic components,
although in some cases there are some
Environmental factors have never been identified
Ā§
ā
It used to be believed that demons took a hold of
people's brain and that caused the mental illness
ā
In the middle ages, people believed there was a (fool?)
stone in the head that caused mental illness (physical
illness)
ā
A belief that the mood had an effect on people (Lunatic
is Latin for Moon)
ā
-
Treatments
When you don't have good treatments, then many
problems arise
ā
At one time it was believed that the demons could be
released by drilling a hole into the head
You can tell by the nature of the hole in the skull,
that the bone healed and people survived the hole
being drilled into the skull
Ā§
Idea of drilling a hole into the skull to relieve
mental illness/relieve consciousness is still with us
(Amanda Feilding - 1970)
The best way to achieve higher level of
consciousness is by drilling a hole in the skull
ā”
She is a high priestess who did experiments
with mental illness
ā”
She believes that this would work from a
Medical student from Denmark - he said the
real problem was that as we evolved and
started to walk upright, there was not
enough blood being pumped to the brain
because the heart is not strong enough. His
idea was if you drill a hole into the skull, it
would be easier for the heart to pump the
blood because there is less pressure.
ā”
Amanda Feilding ran for parliament twice
with a platform of trepanation (drilling holes
in the head because she wanted it covered
under health insurance)
ā”
Ā§
ā
Peter Halvorson is a hole in the head advocate
Drilled hole in head along with followers to make
themselves "smarter"
Ā§
ā
Mentally ill people were thought to be witches and
sometimes heated up to drive the demons out of them
Many of them were burned or chained and put
into asylums
Ā§
Water therapy - water being poured on them from
a higher level
Ā§
ā
Sigmund Freud was the father of psychoanalysis
He introduced the idea that mental illness was a
struggle between the conscious and unconscious
mind
Ā§
Mental illness can be traced to a malfunction in
the central nervous system in the brain
Ā§
ā
-
Luigi Galvani
He was a scientist who was interested in electricity
Static electricity was being introduced as a
phenomenon (devices could be cranked to give off
sparks)
Ā§
One day he was examining a frog, his assistant was
cranking a generator (wanted to see if there was
effect of electricity on frog)
Ā§
He was using a scalpel and there was a spark from
the generator and the frog leg started to twitch
Looked like the dead frog had life generated
from the electricity and he decided to
duplicate the experiment
ā”
Ā§
Wondered what would happen if their was a
bigger charge (could use lightening)
Ā§
Took frog legs and wanted to expose them to
lightening to see what a real charge could do to
them so he left the frog legs in his backyard on a
brass wire and waited for a storm, hoping to
attract lightening because of the brass (didn't
happen because there was no lightening, but
there was wind and the frog legs started to shake
with the wind)
Ā§
Whenever they touched the wire, the legs
quivered with the wind, he thought he was
releasing electricity that was stored within the
animal in the body
Ā§
Thought there was animal electricity locked up in
tissues
Ā§
ā
-
Alessandro Volta from the University of Pavia did not believe
that there was animal electricity
He thought that it wasn't the tissues of the animal
generating electricity, it was the two dissimilar metals,
the animal was just a conductor of the electricity
ā
This gave birth to the idea of the battery (two dissimilar
metals that are able to conduct electricity)
ā
Regarded as one of the fathers of knowledge of
electricity because the battery plays an important role in
our life
ā
-
By the early 1900s it had become apparent that the human
nervous system functioned through electrical impulses
In a living system there is electricity being produced that
causes motion
ā
The brain and central nervous system is made up of a
huge network of cells called neurons
ā
-
How was the electrical signal transformed into physical
action?
Discovered by Otto Loewi in 1920
Carried out an experiment - took the heart of a
frog, isolated it and stimulated with electricity the
vagus nerve
Vagus nerve causes the heart to slow down ā”
Ā§
Found when he stimulated the nerve, the heart
slowed down
Ā§
He then dripped water over the beating heart and
then allowed that solution to flow onto a second
heart that had been isolated
Ā§
The second heart began to respond as well - the
explanation is that there is a chemical being
transferred from the first heart to the second
heart
This was the discovery of neurotransmitters ā”
Ā§
ā
-
Neurotransmitters are the chemicals that connect nerve cells
to each other and to muscle cells (transmission of information)
Acetylcholine caused the heart to slow down
ā
Epinephrine (adrenalin) caused the heart to speed up
ā
Information flows along the axon and stimulate the
nerve cell adjacent
ā
Dendrite is stimulated by neurotransmitters, message
goes down the axon, neurotransmitters are released to
the next cell (how information is passed along
ā
Serotonin, dopamine, norepinephrine, gamma
aminobutyric acid are other neurotransmitters that
were discovered
ā
Neurotransmitters are released into the synapse which
triggers the info to flow down
ā
Both chemical system and electrical system in the cell
End of the cell electricity causes neurotransmitters
to be released
Ā§
ā
"Lock and key effect"
ā
Some of neurotransmitter can be sucked back into the
synapse
Neurotransmitters are synthesized from diet and
are stored in vesicles
Ā§
There are drugs that can prevent or enhance the
release of the NT in the vesicle
Ā§
There are drugs that can prevent the reuptake
Ā§
ā
-
Drugs
Reserpine causes noepinephrine to leak out of the
vesicles
ā
Amphetamines squeeze noephinephrine and dopamine
out of vesicles
Causes rapid stimulation
Ā§
ā
Tricyclics prevent the reuptake of neurotransmitters
Can help with mood elevation
Ā§
ā
MAO inhibitors prevent the breakdown of certain
neurotransmitters by an enzyme
ā
Neuroleptics block receptors for dopamine
ā
-
Schizophrenia
Not dual or multiple personalities, but it is a loss of
contact with reality
ā
They have visual and auditory hallucinations and
delusions of persecution (ie. Neighbours are aliens, etc.)
ā
History of the treatment is very sad, it is a class of
mental illness where it is obvious there is something
wrong
Historically people were locked up in mental
asylums, chained
Ā§
Wasn't until the 1950s where viable treatments
began to emerge - started in France
Ā§
ā
Henri Laborit (1952)
Frightening number of deaths on the operating
table after the administration of anesthesia and
Laborit wanted to know what caused the sudden
death
Ā§
He wondered whether or not it was a sudden
release of histamine that caused the deaths on the
operating table
Ā§
Wanted to see if antihistamines prior to surgery
would be beneficial
Ā§
Promethazine (phenergan) was an antihistamine
being prescribed so he decided to use it, it wasn't
effective in stopping deaths, but it had a calming
effect on patients when they took it before
surgery (told his colleagues)
Ā§
Tried promethazine on schizophrenics, it calmed
them a little bit, but it triggered researched to see
if there were other drugs with similar molecular
structures that worked better
Ā§
ā
Antihistamine (chlorpromazine/thorazine) had a calming
effect on people before surgery and it had a huge
calming effect on schizophrenics, but eventually they
developed Parkinson like symptoms
Already established that Parkinson's disease was a
disease of dopamine defficiency
Ā§
Chlorpromazine was working because it was
blocking dopamine receptors
Ā§
This meant blocking dopamine receptors, it was
blocking the action of dopamine, the conclusion is
that schizophrenia is caused by an excess of
dopamine (need drugs to block dopamine and
would have to deal with effects)
Ā§
ā
Nathan Kline was experimenting with reserpine to treat
Schizophrenia
Was interested in this because of a plant called
snakeroot (contains hundreds of compounds,
there was a compound called reserpine that could
be isolated and could bring down blood pressure)
Ā§
Was looking into this to bring down blood
pressure and it had a tranquilizing effect - he tried
it on his schizophrenia patients and it worked
Ā§
It worked but again induced Parkinson like effects
Ā§
The two drugs that worked had very different
molecular structures
Chlorpromazine blocked dopamine
receptors (wrong key fit into key hole and
blocked right key from working)
ā”
Reserpine caused dopamine to leak out of
vesicles from which is was stored slowly,
when stimulation happened there was not
enough dopamine become release to have
an effect
ā”
Ā§
ā
It is clear that schizophrenia is due to too much
dopamine activity
ā
Perphenazine is more potent than chlorpromazine
ā
There is a legion of meds that have been developed to
intefere with the dopamine system (such as Haliperidol)
Doesn't have as bad Parkinson-like side effects
and a huge calming effects on anyone who is
overactive
Ā§
Clozapine, Risperidone, Olanzapine
Ā§
Possible one medication doesn't work in one
patient but works very well in another patient
Ā§
ā
Eventually 25% of schizophrenics achieve remission with
appropriate medications (can hold a job, go to school,
etc.)
Other 75% are not at the stage where their life can
become completely normal
Ā§
Newer drugs were not significantly effective than
the old ones, pharmacy pushed new ones because
they were more expensive
Ā§
There is talk to introduce new drugs that have a
second criteria
Should have to show that new drug works
better than old drugs that are already in use
ā”
Show that the drug works better than a
placebo
ā”
Ā§
ā
-
Depression
A situation where you feel hopeless, pessimistic and
useless with the reason that there is no reason for you
to feel like that
Every day becomes a challenge to the extent that
you don't want to get out of bed
Ā§
ā
Antidepressants
Highly controversial area
Ā§
First effective drugs are tricyclics
Resulted from a search for an improved
version of chlorpromazine to treat
schizophrenia
ā”
One chemical was looked at was imipramine
because it had a similar chemical structure
to chlorpromazine
ā”
Turned out that imipramine was ineffective
to treat schizophrenia but it had an elevated
mood effect
ā”
This interacted with neurotransmitters that
blocked the reuptake of serotonin and
norephinephrine (happy chemicals)
When they are found in a high enough
concentration in the synapse, they
result in mood elevation
Ā®
These neurotransmitters are
recycled - swim across synapse to be
retaken by original nerve cell
Ā®
If you block reuptake you will increase
concentration of neurotransmitters in
the synapse
Ā®
ā”
Ā§
Anafranil was given by the company that supplies
it
10-15 years where a company can sell the
drug under its trade name, when the patent
is done any one can manufacture it as long
as you show you are making a chemically
similar drug
ā”
Ā§
Side effects
Anticholinergic (dry mouth, blurred vision) ā”
Antiadrenergic (irregular heart beats)
In addition to blocked the reuptake
they also block acetylcholine and
epinephrine receptors
Ā®
ā”
Ā§
ā
-
How do you increase serotonin and norephinephrine in
synapse without the side effects of tricyclics?
Develop a molecular structure that didnāt fit into the
unwanted receptors and this was the birth of Prozac
Became on of the most popular antidepressants
Ā§
Selective serotonin re-uptake inhibitors (SSRIs) -
blocks serotonin
You want specific activity, not broad
spectrum of activity
ā”
Ā§
Prozac blocks reuptake of serotonin into the
uptake
Ā§
Increased the concentration of serotonin in the
gap and this achieved the mood increase effect
Others: sertraline, fluovoxamine,
maprotiline, paroxetine, trazodone,
citalopram but have different side effect
profiles and depends on individuals
ā”
Ā§
ā
Side effects
Nausea, anxiety, sleep disturbances and sexual
dysfunction
Ā§
Side effects have to be weighed against the
benefits of the medication
Ā§
Even if side effect has only been documented in
one person, it has to be listed therefore it doesn't
mean that it will happen to you
Ā§
ā
Prozac works for many people and brings them out of
depression, but in 1989 there was a huge shooting
incident in Louisville
Joseph Wesbecker shot a store and he had a
history of mental illness and had been on Prozac
Ā§
Prozac was blamed for this
Ā§
The relatives of the victims launched a lawsuit
against the manufacturer for Prozac
Ā§
ā
Allegations that SSRIs cause an increase in suicide
But you don't know if suicides are caused by the
drugs or the condition
Ā§
ā
Since early 2000s there was concern among young
people that Prozac was causing suicide
We have had studies that show in controlled trials
there was no difference in the frequency of
suicidal thoughts in subjects taking Prozac, a
tricyclic or a placebo
It is the disease that causes suicidal
thoughts
ā”
People's conditions are very good in
controlling the illness
ā”
Ā§
ā
Drugs are overprescribed, more widely used than it
should be and should only be used for serious situations
ā
Prozac can also be used for OCD
ā
-
OCD is obsessive compulsive disorder
Affects 2% of the population
ā
Chemistry graduate student who had cats at home and
was constantly worried whenever he was using his
washing machine or fridge that somehow one of the
cats would climb into it and he wouldn't notice it and
the animal would be locked into the machine or fridge
Knew this could not have happened if he
repeatedly opened and closed the washing
machine
Ā§
ā
OCD interferes to a large extent of your life
People cannot leave their house till they have
made sure their door is closed a certain number of
times and this can be up to 350 times
Ā§
People think they need to do a certain number of
sit ups a day or else something horrible would
happen
Ā§
Lady was in a supermarket and saw a cockroach
run across the store, disturbed her so much that
every item of food had to be washed because it
could be cockroach contaminated
Ā§
There are people who are counters who need to
count things (# of light poles, etc) in an obsessive
way, if they think they missed a count they have
to stop, go back and start again
Ā§
ā
Very often highly intelligent people who know full well
their door is locked but they can't get away from the
thought
ā
About 20% of first degree relatives of people with OCD
have the disease (genetic issue)
ā
About 20% of OCD patients have tics and 50% of
patients have Tourettes
ā
-
Tourette Syndrome (Georges Gilles de la Tourette)
Person suffers from involuntary tics and vocalizations
ā
Many people who have Tourette syndrome also have
OCD
ā
-
Obsession: unwanted, unreasonable, intrusive thought that
you can't get away from
They are about contamination concerns, harm to self or
others, symmetry concerns, saving concerns, perfection
concerns
ā
-
Compulsions: rituals performed to gain release from obsessive
thoughts
-
OCD is not due to some deeply rooted emotional imbalance
Injury to the head or seizures, stroke can trigger OCD
which suggests that it is something physical that
happens to the brain and triggers it
ā
Man had a stroke and developed gourmand syndrome
which is an obsession with food
ā
People with OCD have been examined with scans and
there are more parts of the brain that are active with
people with OCD
ā
Evidence that the strep infection in children can trigger
OCD and this has been referred to as PANDA
ā
-
Diagnoses
Really interferes with life
ā
Do you have repetitive thoughts that make you anxious
and that you cannot get rid of no matter how you try?
ā
Do you keep things extremely clean or was your hands
frequently?
ā
-
Anaphranil is given for depression but improved OCD
symptoms
Increases serotonin levels
ā
Side effects:
Dizziness, sedation, etc.
Ā§
ā
40-60% will respond to SSRIs with an improvement in
symptoms of some 30%
ā
At least 10-12 weeks are required
ā
Treatment
Behaviour therapy - forcing the person to do the
thing that they fear; 10-20 sessions can improve
symptoms by 85%
Ā§
Psychoptherapy doesn't work
Ā§
Confrontation therapy - if someone is afraid to sit
on the toilet, force them to sit on the toilet
Ā§
Transcranial magnetic stimulation
Ā§
ā
MAO inhibiters
Tuberculosis is a bacterial infection of the lungs
Ā§
Until the 1950s when antibiotics were developed,
patients were locked up in sanitariums
Ā§
Only treatment for tuberculosis is to be exposed
to the sunshine
Drug iproniazid was developed - first
antitubucular drug
It improved their medical condition
and caused patients to be cheery
Ā®
Nathan Kline tried the drug on his
depressed patients but some of the
patients developed high blood
pressure or strokes
Ā®
There was a dietary component,
patients had taken the drugs had
salami, aged cheese, etc.
Ā®
The drug inhibited an enzyme MAO
(enzyme that breaks down serotonin,
etc.)
Ā®
ā”
MAO degrades important neurotransmitters ā”
MAOIs increase important
neurotransmitters
Foods contain tyramine that can
elevate blood pressure
Ā®
When MAO is inhibited, the break
down of tyramine is inhibited as well
and causes hypertension (high blood
pressure)
Ā®
ā”
Ā§
Patients on MAO have to stay away from foods
that are high in things that will raise their blood
pressure (beer, wine, chocolate, chicken liver,
herring, aged cheeses and certain drugs like
demerol and decongestants)
Ā§
ā
-
Manic
Periods of being manic, and periods of being depressed
Manic shoppers, engage in more sex
Ā§
Followed by a period of depression
Ā§
ā
Due to a chemical imbalance in the brain
ā
John Cade was imprisoned by the Japanese during the
war
Noted that there were periods of suffering and
periods of them being highly elated
Ā§
Maybe is due to a toxin that builds up in the brain
and is excreted in the urine
Ā§
Took urine from mentally ill patients and injected
into guinea pigs
Found the urine in the manic phase killed
guinea pigs more frequently
ā”
Wondered if it was the concentration of uric
acid in the urine that was the bi product of
something that was happening in the brain
ā”
Wanted to see if injecting uric acid would
have an effect on animals - not very soluble
in water, but salts of uric acids were
ā”
The base he used to neutralize was lithium
oxide
ā”
Made lithium urate and this had a calming
effect on animals, but it was hard to make
so he tried lithium carbonate
ā”
This evened the manic patients and lithium
carbonate became the drug of use to treat
manic patients
Interferes with the synthesis of
inositol (triggers electrical conduction)
Ā®
ā”
Ā§
Side effects: trembling, nausea
Ā§
ā
None of these drugs will cure the disease
ā
-
Some anti-cancer drugs that can cure diseases
-
Antianxiety agents
Feeling of apprehension, uncertainty or fear that is out
of proportion to a stimulus
ā
Sometimes it can result in panic attacks (pounding heart,
hyperventilation, sweating and feeling jittery)
ā
Drugs used in treatment were barbiturates - problem is
they are too sedative and addictive
Became mainstream in the 1950s-60s
Ā§
ā
-
Frank Berger
Tested drugs for antibiotic activity in England
ā
He tested a chemical called mephenesin which was a
muscle relaxant
When he treated animals with this they became
extremely calm
Ā§
This had an anti-anxiety effect
Ā§
Had too many side effects to be used commonly
but lead to meprobamate (miltown)
Extensive search to find substances that had
an antianxiety effect
ā”
Librium was introduced as antianxiety drug,
followed by valium
Increase activity of GABA which is an
inhibitory neurotransmitter
Ā®
Xanax, lorazepam, etc. are given to
people who are anxious or people
who have trouble sleeping
Some people gives rise to bad
dreams so they can't take it
ā
If they are taken with
alcohol/barbiturates it can
cause central nervous system
depression
ā
Ā®
ā”
Ā§
ā
-
What is the role of cannabis?
Use it as medical marijuana
ā
Claims about it helping with depression but also that it
can cause depression
It can help depression but only while it is in your
blood stream
Ā§
It depends on which kind of marijuana you use
because the strains have difference balances of
TCH and CBD
CBD has the antidepressant effect ā”
Ā§
ā
-
Mental Illness Notes
Tuesday, November 14, 2017 5:24 PM
10
CHEM 183 Full Course Notes
Verified Note
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