Anti-Schizophrenics: The chemistry & route of these drugs and the
Neurotransmitters involved.
By: Jennifer Lisa Wisefield
It is suggested that people diagnosed with schizophrenia have an
increased activation of dopamine2 receptors. Most anti-schizophrenic
drugs therefore block dopamine2 receptors and cause many therapeutic
effects. The term anti-schizophrenic, in this case, when referring to
the particular medications discussed here are synonymous with anti-
psychotics. It is thought that delusions and hallucinations, two
symptoms of schizophrenia, are both caused by an increase in the
dopamine levels in the brain. The following medications described
block dopamine receptors and cause possibility to both external and
internal stimuli.
Traditional anti-psychotic drugs are classified as low, medium
and, high potency drugs. Potency refers to the dose given to produce
desired effects; all the drugs in this category are basically equal in
the desired effects they produce. If one were to say that
chlorpromazine is less potent than haloperidol that would mean that the
dose of haloperidol is given in a lower dosage than chlorpromazine to
produce the same desired effects. In this case, chlorpromazine
(Thorazine) will represent low-potency drugs, and haloperidol (Haldol)
will represent the high-potency drugs. When both drugs are given
within the therapeutic range, they will produce equal anti-psychotic
effects. Not only are the drugs classified by potency, but also by
chemical classification. There are two chemical categories in respect
to anti-psychotics, the phenothiazine and the butyrophenones.
Chlorpromazine is in the phenothiazine family where as haloperidol is
in the butyrophenones family. Both of these drugs are referred to under
the category of traditional anti-psychotics.
The phenothiazines can be further broken down into three
subclasses. These subclasses are the alophatics, piperidines, and the
piperazines. The aliphatics consist of chlorpromazine, promazine, and
trifluoperazine. Promazine and trifluoperazine are rarely prescribed.
The piperidines are thioridazine and mesoridazine. Thioridazine is
mostly used for disorders related to anxiety and depression.
Mesoridazine is mostly used for alcohol abuse. The piperazines consist
of fluphenazine, trifluorperazine, and perphenazine. These drugs are
used for a plethora of disorders.
Both within and outside the CNS the anti-psychotic group of drugs
have been found to block receptors for dopamine, acetylcholine,
histamine, and norepinephrine. The way in which anti-psychotic drugs
produce therapeutic effects is unknown. One theory states that these
drug produce their desired effects by blocking dopamine2 receptors,
working as antagonists, in the regions of the brain that may be
associated with the production of psychotic symptoms, such as those
seen in schizophrenia. Two theories seem to exist when it comes to
schizophrenic patients, they either have an increase in their amount of
dopaminergic neurons and therefore more dopamine is released or they
have a greater amount of dopamine receptors and therefore receive more
dopamine. Other theories include that there could be less dopamine
autoreceptors which prevent too much of the neurotransmitter from being
released. Another possibility is that the neurons that receive the
dopamine are excessively sensitive to it and will produce greater
responses to normal amounts of dopamine.
Chlorpromazine (Thorazine), a low-potency agent, can be given
orally, in an intramuscular (IM) injection, and via a rectal
suppository. Chlorpromazine's anti-psychotic effects are unclear. It
is thought to depress areas of activity, which controls aggression and
block the neurotransmission produced, by dopamine at the synaptic
cleft. Chlorpromazine is available in six different formulations.
Tablets, sustained-release capsules, syrup, liquid concentrate, rectal
suppositories, and injection form. IM injections are the most
effective at lower doses, however, most people on this medication do
take it orally and IM injections are reserved for acute psychosis. It
takes 60 minutes for this drug to have the same therapeutic effects as
it would in just 10 minutes of an IM injection. Orally this drug is
given at a general maintenance dose of about 400 mg per day.
In the case of Haloperidol, a high-potency agent, this medication
can be given only orally and in an IM injection. 2 mg of this drug is
equal to 100 mg of chlorpromazine and tends to have less anti-
cholinergic side effects than that of the low-potency drugs. It also
depresses the activity that controls aggression and blocks the
neurotransmission produced by dopamine at the synaptic cleft. Anti-
cholinergic side effects refer to those side effects associated with
the parasympathetic nervous system, such as a dry mouth. This drug is
available in liquid tablets and an oral liquid concentrate. The
injectable forms are, haloperidol lactate which is used in acute
situations, and haloperidol decanoate which is used in a long-term
treatment setting. In oral therapy, a typical dose for an adult is
about 100 mg per day.
Clozapine is an atypical anti-psychotic drug and was developed
under the premise that the drugs, which I discussed above, worked well
but 30% of patients who had mental illness showed little improvement.
While the traditional anti-psychotic agents tend to block the dopamine2
receptors, clozapine, which is a dibenzodiazepine, seems to block
dopamine2 & 4 receptors as well as serotonin2 receptors. Dopamine4
receptors have been found in increased amounts in the brains of
schizophrenics. Clozapine interferes with dopamine receptor binding
and also acts as an adrenergic, cholinergic, histaminergic,
serotonergic antagonist. In some patients, where traditional anti-
psychotics had no effect on their schizophrenic symptoms have responded
to clozapine. Therefore clozapine is frequently prescribed when other
anti-schizophrenic drugs fail to work. Atypical anti-psychotics are
also ordered more frequently because they cause fewer side effects and
less sedation. Clozapine is only given orally and the normal range is
400 mg per day.
One of the newest drugs currently being prescribed is
resperidone, a bezisoxazole and another atypical, which block dopamine2
receptors weakly but strongly blocks serotonin 2. By blocking the
serotonin2 it is thought that the brain will free dopamine in that area
and alleviate more schizophrenic symptoms while also blocking the
dopamine2 receptors. It therefore has antiserotonergic effects and is
a drug responsible for releaving many schizophrenic symptoms. Most
adults receive 6 mg of this drug per day. Many drugs are still being
evaluated for their therapeutic effects including sertindole
(multireceptor blocking drugs, atypical), remoxipride (selective
dopamine2 & 3 antagonists), roxindol (autoreceptor agonists),
ritanserin (serotenergic agents), ondansetron (serotonin3 antagonists),
and rimcazole (glutamate/sigma receptor agonists). These are just a
few of the many drugs being currently tested and evaluated.
Anti-psychotic drugs are lipophilic. This means that they
accumulate in fatty tissue. This means that even when a patient stops
taking the drug, it is still being released from fatty stores and the
patient will still feel the effects of this drug for some time.
Bibliography
Carlson, N. R. (1998). Physiology of Behavior. Boston: Allyn and Bacon
Frisch, N. C.,
Frisch, L. E. (1998). Psychiatric Mental Health Nursing: Understanding
the Client Well as the Condition. Albany: Delmar PublishersKeltner, N.
L., Folks, D. G. (1997). Psychotropic Drugs
(2nd ed.). St. Louis: MosbySkidmore-Roth, L., McKenry, L. (1999).
Mosby's Drug Guide (3rd ed.) St. Louis: Mosby
Schizophrenia:
Parts of the neuron affected, potential changes and ion channels
effected.
By: Sara Pieschl
Psychosis is a condition characterized by loss of contact with
reality. Often sufferers' capacity to perceive, process, and respond
to environmental stimuli becomes so impaired and disorted that they may
be unable to achieve even marginal adaptive functioning. Schizophrenia
is the most common type of psychosis where sufferers have distorted
perceptions, disturbed thought processes, deviant emotional states, and
motor abnormalities. Symptons of schizophrenia are grouped in to three
categories; positive symptoms, negative symptoms, and psychomotor
symptoms. Positive symptoms include delusions, disorganized thinking
and speech, heightened perceptions and hallucinations, and
inappropriate affect. Negative symptoms include poverty of speech,
blunted and flat affect, loss of volition, and social withdrawl. Loss
of spontaneity in movement and the development of odd grimaces,
gestures, and mannerisms are the psychomotor symptoms of schizophrenia.
Throughout the history of the disorder many different types of
treatments have been experimented with which has lead scientists to the
dopamine theory of schizophrenia and the development of antipsychotic
drugs.
Dopamine is a neurotransmitter found in the brain which is
responsible for movement, attention, learning and pleasure. Dopamine
produces both excitatory and inhibitory postsynaptic potentials
depending on the type of postsynaptic receptor it binds to. When an
impulse is received by a neuron's dendrites it travels down the axon of
the neuron to its terminal buttons where the neurotransmitters, such as
dopamine, are released in to the synapic gap and finally reaches a
receptor of a postsynaptic neuron, such as D2, triggering another
impulse. If the impulse is excititory, sodium ion channels open
allowing sodium to enter the cell creating enough depolarization to
generate another impulse. If the impulse is inhibitory, potassium ion
channels open allowing potassium to exit the cell causing
hypopolarization, decreasing the chance of another impulse occurring.
The dopamine theory of schizophrenia involves the excess of this
process resulting in dopamine firing too often and transmitting too
many messages in the behavioral centers of the brain including the
frontal lobes.
Drugs used to treat schizophrenia are called neuroleptics. These
drugs have an antipsychotic effect. The term neuroleptic means to
"grasp the neuron" from its action on the nervous system. These drugs
decrease the level of dopamine from the neurons also called dopamine
antagonists by binding to dopamine receptors, preventing dopamine from
binding there and thus preventing dopamine receiving neurons from
firing. The discovery of the dopamine theory was stumbled upon in the
1950's when phenothiazines where developed to combat allergies.
Phenothiazines were not effective as an antihistamine but reduced
schizophrenic sypmtoms because it had a calming effect on patients.
The most popular drug used in the class of phenothiazines is
chlorpromazine. This drug binds to the same neuron receptors,
D1,D2,D3,D4, as dopamine. It mainly binds to D2 receptors. When
dopamine binds to a receptor on a neuron it opens ion channels in the
membrane of the neuron which increases the likelihood that it would
produce an action potential which would in turn produce signals in
other neurons. Chlorpromazine would bind to the same receptors but
would not have any effect on the ion channels in the neural membrane.
They compete to occupy the same receptors. Chlorpromazine therefore,
has the effect of blocking the action of dopamine in the brain.
Chlorpromazine has little effect on the negative symptoms associated
with schizophrenia but it does reduce the positive symptoms of
schizophrenia such as the display of emotions and affect.
Another neurolptic drug similar in function to chlorpromazine is
haloperidol. Haloperidol is also attributed to the inhibition of
dopamine action by blocking the neural transmission. Haloperidol has
been found to be highly selective as an antagonistto dopamine receptors
D2 and D3 and has variable affinity to receptor D4. This drug is also
only effective reducing the positive symptoms of schizophrenia. Both
chlorpromazine and haloperidol have serious side effects which has
urged science to find other treatments.
Recent research has found a new atypical drug to treat
schizophrenia. This drug is clozapine and has shown to be an
effective antipsychotic medication. Clozapine blocks another brain
chemical serotonin in addition to blocking dopamine. Unlike
chlorpromazine and haloperidol it has little effect on dopamine recetor
D2. Rather, clozapine is highly affinitive to the dopamine receptor D4
and the seretonin receptor 5HT2. Clozapine and other newer atypical
antispychotic drugs have reduced the effects of negative symptoms of
schizophrenia.
Comer. Ronald J.(1998). Abnormal Psychology. ( 3rd ed.). NewYork: W.H.
Freeman and Company.
Information From Your Family Doctor. Schizophrenia: New Medicines. In
http://familydoctor.org/handouts/266.html.
Limbird, Lee E. and Hardman, Joel G. (eds). (1996). Goodman and
Gillman's The Phamacological Basis of Theraputics. (9th e.d.). New
York: McGraw Hill Company.
Mann,Rupinder. The Role of Dopamine Receptors in Schizophrenia. In
wwwehem.csustan.edu/chem44x0/SJBR/Mann.htm.
Owens,Richard, M.D. Antipsychotic Agents. In
www.uams.edu/department_of_psychiatry/syllabus/antipsychotic/antipsycho
tics.htm.
Physiological Side Effects of Anti-Schizophrenic Drugs
by Shannon Stuart
Anti-schizophrenic drugs have been invaluable to the development
and evolution of psychiatric treatment. They act as a catalyst to a
normal way of living for those individuals suffering from psychotic
symptoms including delusions, paranoia, social and withdrawal.
However, though the positive effects of symptomatic relief are
unprecedented, the other effects of the drug must be taken into
consideration. Anti-Schizophrenic drugs have a considerable number of
physiological side effects. Some are merely uncomfortable or
inconvenient, but others may have serious implications on the client's
health. These side effects slightly vary in form and occurrence rate
for different drugs. This paper will concentrate on three of the most
well known anti-schizophrenic medications: Chlorpromazine, Haloperidol,
and Clozapine. Chlorpromazine, also known as Thorazine, is one of
the oldest traditional anti-psychotics. It is also the one know for
the most undesirable side effects. It was originally used as a
tranquilizer supplementing analgesics in surgery. This tranquilizing
effect is very strong and can cause extreme lethargy and blurred vision
in patients. The other common effects are dry mouth, blurred vision,
constipation, weight gain, difficulty urinating or stiffness. Some of
these can be treated simply and symptomatically, for example, only
taking the medication before bed works to counteract lethargy, and
maintaining a healthy diet and exercise to combat weight gain. There
are other effects are also usually not life-threatening and occur a bit
more rarely, but are definitely more serious and a physician should be
consulted. These are racing heartbeat or palpitations, dizziness,
sexual problems (usually in the form of impotence and decreased sex
drive), skin rash or restlessness.
The more serious side effects are also ones somewhat unique to
the medicinal category of anti-schizophrenics. They are the topic of
much current research into how serious their implications are,
especially when it comes to long term use. The most commonly discussed
are it's effects on the central nervous system (CNS), and the disorders
Tardive Dyskinesia (TD) and Neuroleptic Malignant Syndrome (which will
be discussed in further detail later in reference to Haloperidol).
Chlorpromazine is a dopamine receptor blocker. Dopamine is known
to be related to the disorder Parkinson's disease and the effect
Chlorpromazine can have on the central nervous system (CNS) can bring
on a reaction called Pseudoparkinsonism. The symptoms are similar to
that of Parkinson's, such as motor retardation, rigidity, mask like
faces, tremors and drooling. It hinders the patients' ability to do
basic motor movements: walking, turning, eating, and keeping balance.
During long term use many of these symptoms have been known to become
permanent.
Also as a result of its effects on the CNS, Chlorpromazine has
been know to create dystonic (muscle disorder) reactions in
individuals. This includes oculogyric crises (rolling of the
eyeballs), tics, trismus (face spasms), difficulty swallowing,
torticollis (twisting of the neck to once side, cause abnormal carriage
of the head), jaring or protrusion of the tongue, and opisthotonos of
the back muscles (causing the to bend backwards and the trunk of the
body to arch forward).
Along these same lines is the disorder tardive dyskinesia. It as
well involves muscle control. It is characterized by rhythmic
involuntary movements: protrusion of the tongue, puffing of the
cheeks, puckering of the mouth, shaking, and involuntary movements of
the extremities. TD is the effect of long term use of Chlorpromazine
as well as most other anti-schizophrenic drugs. It may even appear
long after drug therapy has stopped, and in some patients is
irreversible. There is no known effective treatment for TD. If these
symptoms begin to appear, the client should be taking off all anti-
schizophrenics if possible. If it is a necessary treatment, they
should be switched to a different anti-schizophrenic treatment,
preferably not a neuroleptic.
Across the entire spectrum of anti-schizophrenic drugs, the types
of side effects that are exhibited tend to be generalized. What
differs is the degree or emphasis of concern on the exhibition of a
particular symptom. Depending on the drug, certain side effect may be
more likely to present itself, while the likelihood of different one
developing may be less in comparison to another medication. Some of
this depends on the potency of the drug. According to research, high
potency drugs tend to be less sedating, and yield less anticholinergic
side effects (i.e. dry mouth, constipation, blurred vision). They also
tend to be generally safer than low-potency medications. Haloperidol
(Haldol) is one of these high potency anti-schizophrenic, roughly fifty
times more potent than Chlorpromazine. As would be expected, most of
the common side effects experienced with patients taking Haloperidol
are the same or similar to those with Chlorpromazine: lethargy,
dizziness, weight gain, difficulty urinating, rash, tremors, and
involuntary facial/tongue movements. As with Chlorpromazine sexual
dysfunctions are quite common, but have more variety in symptoms. The
most predictable one is impotence, but in contrast Haloperidol also
creates an increase in libido. The use of this medicine has also been
associated with painful ejaculation, menstrual irregularity, breast
enlargement, mastalgia (pain in the breast), and galactorrhea
(spontaneous flow of milk from the nipple). Haloperidol, along with
other anti-schizophrenic agents, increase serum prolactin
concentrations in the body. There is concern because there is a
possible connection between increased serum prolactin and breast
cancer. However, the evidence linking the two at this time is limited.
The more severe side effects that are concerns are also the same
as those discussed in reference to Chlorpromazine, though they tend to
be to a less of a degree. The dangerous side effects that tend to be of
most concern when taking Haloperidol are ventricular arrhythmias
(alteration of the heartbeat either in time or force), cardiac arrest,
and Neuroleptic Malignant Syndrome (NMS).
NMS is a life threatening side effect of any anti-schizophrenic
drug, but is more common in high-potency anti-schizophrenics. The
symptoms may come on abruptly. Usually the first sign is the patient
will suddenly develop an extremely high fever, sometimes up to 108
degrees, and muscles will become extremely ridged. The heart and
breathing rate increase, blood pressure drops, and they may begin
profuse sweating and drooling. The patient usually becomes extremely
confused and may become mute. White blood cell count and the amount of
creatine kinase (an enzyme that is released when muscle tissue breaks
down) will soar. Occasionally the patient may undergo seizures. If
the problem is not immediately treated the patient may have heart,
respiratory, or renal failure.
There are injections that can counteract NMS but need to be
administered immediately to prevent it from escalating to a potentially
fatal level. Once a patient experiences NMS they are very likely to
develop it again, and should not be put back on neuroleptics. If every
other alternative is quashed, then they should be only administered a
low-potency neuroleptic, and monitored frequently. Clopazine is one
of the atypical anti-schizophrenic drugs developed in response to the
amount of side effects of the traditional drugs. It seems to be
effective with patients who have not responded to other anti-
schizophrenics and it causes much fewer, and less sever muscle side
affects. Clozapine is also far less likely to induce tardive dyskinesia
in patients, and in fact there is some suggestion that it may make the
existing tardive dyskinesia symptoms in patients improve. Also
because, in contrast to other conventional anti-schizophrenics,
Clozapine produces no prolactin response. So the sexual dysfunctions
related with other medications such as impotence, decrease/increase of
libido, galactorrhea and amenorrhea are seldom reported with Clozapine
therapy.
However, other common anti-schizophrenic side effects tend to be
much severe with the use of Clopazine. There is an extremely potent
sedative effect, patients often report feeling "drugged". It also
causes more profound anticholeric side effects and weight gain than
other anti-schizophrenic medications. Clopazine has also been known to
lower the seizure threshold; seizures occur in about 5% of consumers.
The occurrence of seizure increases with higher doses. Other, non-
dangerous side effects are fever, headache, nausea, rapid pulse, and
increased salivation.
The most dangerous and potentially fatal reaction experienced on
Clozapine is angranulocytosis. Angranulocytosis is when a person stops
making white blood cells. This makes the patient susceptible to
infection, and creates inability to fight it off. The visible symptoms
are swelling of the neck, sore throat sometimes accompanied by local
ulceration and sores. If caught early enough Angranulocytosis is
reversible through hospitalization and a drug that increases white
blood cell production. The best defense is a weekly blood cell count,
and more frequent monitoring in individuals whose cell count drops down
to 3,000 to 3,500. Currently in the United States, patients cannot get
their following weeks medication without first taking a blood test.
All patients' taking anti-schizophrenic drugs should be under the
close supervision of a physician, and be frequently monitored for
changes in the cardio and respiratory system, renal functioning and
blood cell count. If any severe alteration in these systems should be
found, alternative therapy should be considered. As well, though many
side effects are common and expected during treatment, if any symptom
becomes extreme or exceptionally aggravating, a doctor should be
consulted.
References:
Sedvall, G., Uvnasn, B., & Zotterman Y. (1974). Antipsychotic Drugs:
Pharmacodynamics and Pharmacokinetics. (Vol. 25) Proceeding of the
International Symposium Held in Wenner_Gren Center, Stockholm. Oxford:
Pergamon Press.
Diamond, R.J. (1998) Instant Psychopharmacology. New York: W.W Norton
and Company. pgs. 27-53.
Phillip W. Long, M.D.(1995-1999). Internet Mental Health.
Adverse effects of Chlopromazine:
http://www.mentalhealth.com/drug/p30-c01.html#Head_5
Adverse effects of Haloperidol: http://www.mentalhealth.com/fr30.html
Adverse effects of Clozapine:
http://www.mentalhealth.com/fr30.html
PSYweb (1998) Psychoactive Drugs. Chlopromazine
link:http://www.psyweb.com/Drughtm/chlor.html
Ken Klinker (1999) Drug FAQs: Chlopromazine, Pharmaceutical Information
Network.
http://pharminfo.com/drugfaq/thor_faq.html
Medscape (1994-1999) Psychiatry and Mental
Healthhttp://www.medscape.com/Home/Topics/psychiatry/psychiatry.html
Medscape (1994-1999) Generic Drug Queries. (Psychiatry and Mental
Health)
http://www.medscape.com/FirstDataBank/cfdocs/fdb_genframe.cfm?qt=gen&gn
n=Clozapine%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20
%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2
0%20%20%20%20%20%20%20&hicl_seqno=4834
PSYweb (1998) Psychoactive Drugs. Haloperidol link:
http://www.psyweb.com/Drughtm/halope.html
Infomed-Verlags AG (1996) Informed Drug Guide: Haloperidol.
http://www.infomed.org/100drugs/halofram.html
Phillip W. Long, M.D.(1995-1999). Internet Mental Health.
What is Neuroleptic Malignant Syndrome
?http://www.mentalhealth.com/mag1/p5h-nms1.html
PSYweb (1998) Psychoactive Drugs. Clozapine link:
http://www.psychweb.com/Drughtm/Cloza.htm
PHYSIOLOGICAL EFFECTS OF CHLORPROMAZINE
by Stacy Cooper
Chlorpromazine, more commonly known as Thorazine, is one of the
most widely known phenothiazine neuroleptics that is most commonly used
to treat schizophrenia, an advanced psychological disorder.
Phenothiazines are used to treat disorders from mild depression to full
blown manic depressive illness, manic phase and severe behavioral
problems in children. Phenothiazines are thought to elicit their
antipsychotic and antiemetic effects via interference with the central
dopaminergic pathways in the mesolimbic and medullary chemoreceptor
trigger zone areas of the human brain. This means simply that they
have a calming, tranquilizing effect on the patient. The blocking
action of chlorpromazine creates a feeling of sleepiness combined with
a marked slowed and altered reality within the patient's mind.
Extrapyramidal side effects are usually a result of interaction with
dopaminergic pathways in the basal ganglia. Although they are often
termed dopamine blockers, the exact mechanism of dopaminergic
interference responsible for the drugs antipsychotic activity has not
yet been determined. When administered to a patient chlorpromazine
is readily absorbed from the gastrointestinal tract, however, its
bioavailability is variable due to considerable first pass metabolism
by the liver. Chlorpromazine is highly bound to plasma proteins,
principally albumin. It is not dialysable. It is distributed widely
throughout the body, crossing the blood barrier, the placenta and its
distributed into milk. The onset of the action after chlorpromazine
has been administered usually takes fifteen to thirty minutes, after
which the patient will begin to feel the first side effects of the
drug. These side effects include: dry mouth, nausea, vomiting, blurred
vision, constipation, ileus, nasal congestion, and photophobia
(sensitivity to any form of light). The aforementioned are just a few
of the unpleasant side effects a patient feels. There is much more
going on beneath the skin, within the inner workings of the patient's
body. Chlorpromazine has peripheral alpha-adrenergic blocking
activity. It's effects are felt a great deal by the patient's heart.
Chlorpromazine has direct negative inotropic action. Meaning, it
prolongs PR and QT intervals, blunts the T wave and depresses the S-T
segment. These changes appear to be reversible and related to
disturbance in repolarization. All Phenothiazines tend to have this
effect on the heart and should be given lightly and cautiously to
patients with a history of heart disease. This means simply that the
patient's heart may react to the drug with a "flutter" and seem to stop
beating for a mili-second only to resume beating again as if nothing
had happened. The patient knows the difference. Chlorpromazine has
also been known to cause severe dizziness and hypertension, or high
blood pressure. Patients with a history of heart disease should
always lay supine when the drug is administered. Tachycardia, fainting
and dizziness have occurred. Hypotension can also develop after an
oral administration. Chlorpromazine effects on the central
nervous system can be even more unpleasant. Common reactions are:
pseudoparkinsonism (motor retardation, rigidity, mask like features,
drooling, limping, or using a shuffling gait ect...), dystonic
reactions (including spasms, ticks, tremours, protrusion of the tongue,
difficulty swallowing, carpopedal spasm, slowing of the EEG rhythm,
disturbed body temperature, and lowering of the convulsive threshold
have commonly occurred. Common use of chlorpromazine may result in
additive CNS depressant effects. Patients should always be monitored
to avoid excessive sedation or respiratory depression. Chlorpromazine
should also be used with caution when treating patients with an
impaired liver function or alcoholic liver disease, due to its
weakening effects on the liver. Another large danger in the use of
chlorpromazine is the drug's ability to mask signs of overdose of toxic
drugs and may obscure conditions such as intestinal obstruction and a
brain tumor. Tardive dyskinesia may appear in some patients on long
term antipsychotic therapy or may even appear after the therapy has
been discontinued. The risk appears to be greater in elderly patients
on high-dose therapy, especially females. The symptoms are persistent
and in some patients appear to be irreversible. Rhythmical movements
of the tongue, face, mouth or jaw characterizes the syndrome.
Sometimes involuntary movements of the extremities may accompany these
as well. The outer layer of the human body (dermatological) is
mildly effected and irritated by the presence of chlorpromazine. This
is shown through minor skin irritations to rashes and itching and
irritated skin. This combined with photosensitivity, a heightened
sensitivity to any and all forms of light are common complaints. The
more serious side effects on the skin include; angioneurotic edema,
erythema, allergic purpura, exfoliative dermatitis (incredibly itching
skin), and contact dermatitis have occurred in personnel handling of
solutions or injections of chlorpromazine. Endocrine effects
of Chlorpromazine include an altered libido, prolactin secretion,
menstrual irregularities, weight gain and weight loss, mastagia, and
alterations in glucose tolerance and bowel movements, as well as false
pregnancy tests have occurred. The cause of these effects in patients
is unknown, doomed to remain a mystery to doctors while they still
prescribe the drugs and the patients still suffer.
Gastrointestinal effects of chlorpromazine include nausea,
vomiting, dry mouth, fatigue, increase or decrease in appetite, gastric
irritation, constipation, dry mouth and occasionally diarrhea. The
anticholinergic blocking action of chlorpromazine may be a factor in
some cases of intestinal pseudo-obstruction. In this one instance
the blocking action of chlorpromazine is not serving a purpose of
greater good. The blocking action is distinctly harmful to the
individual taking the drug.
Chlorpromazine has also been known to cause cholestic jaundice
infrequently and is usually a part of hypersensitivity reaction.
Jaundice usually occurs within two to four weeks of initiation of
therapy and chlorpromazine should be discontinued immediately. Rarely
progression to chronic jaundice has occurred. Pre-existing liver
dysfunction has not yet been proven to be a risk factor for this
reaction. Signs and symptoms of cholestatic jaundice include; upper
abdominal pain, nausea, vomiting, flu-like symptoms, yellow skin and
conjunctiva, high fever, elevated liver enzymes, and biliuria. A
peculiar skin-eye syndrome has been recognized as an adverse effect
following long-term Treatment with Phenothiazines. Progressive
pigmentation of areas of the skin or conjunctiva and / or discoloration
of the exposed sclera and cornea mark this reaction. Opacities of the
anterior lens and cornea described as irregular or stellate in shape
have also been reported. Patients receiving higher doses of
Phenothiazines for prolonged periods should have periodic eye
examinations, at least once every two months. As with other
neuroleptic drugs, a symptom complex sometimes referred to as
neuroleptic malignant syndrome (NMS) has been reported. Cardinal
features of NMS are hyperpyrexia, muscle rigidity, altered mental
status, (including catatonic signs), and evidence of autonomic
instability (irregular pulse or unstable blood pressure). Additional
signs may include elevated CPK, myoglobinuria, and acute renal
failure. NMS is rare but potentially fatal and therefore requires
intensive symptomatic and supportive treatment. NMS has been
successfully managed with various agents.
BIBLIOGRAPHY
Immunology Today
Micro/film MF2526
Index Medicus
Periodicals R5 C863
Molecular Expressions
The Pharmaceutical
Collectionhttp.MCROmagnet.fsu.edu.pharmaceuticals/pages/chlorpromazine/
htm
Olanzapine has simular efficay to
Chlorpromazinewww.futur.com/webtrac/cJanssen - zGliag Organon 1999-
Belgium
Internet Mental Health www.MentalHealth.comcopyright 1995 1999 Phillip
Wong M.D.
Behavior Changes
by Caroline Harper
A definition of schizophrenia is "a break from reality caused by
disorganization of the various functions of the mind so that thoughts
and feelings no longer work together normally"(Carlson, 1998). From
the time of onset the disease runs a chronic fluctuating course of
exacerbation and remission. As the disease runs its course, there's
deterioration in the person's ability to handle work or school, social
relations and self-care. Schizophrenics are exquisitely sensitive to
environmental stress (Koda-Kimble & Young, 1992).
There are four types of schizophrenia, and a person can have some
or all of the behaviors described for each category. The disorganized
schizophrenics show incoherence with an unresponsive or inappropriate
affective presentation, poorly thought out delusions and
hallucinations, grimaces and other repetitive unconscious behaviors,
hypochondriac complaints and extreme social withdrawal. Catatonic
schizophrenia is characterized by psychomotor disturbances, which can
present as stupor, rigidity, strange body language or excitement,
sometimes alteration between excitement and stupor and not talking is
common. Paranoid schizophrenics have grandiose delusions or
hallucinations with persecutory content, anxiety, anger,
argumentativeness, violent behavior, doubts, fears concerning gender
identity, and preoccupation with homosexual ideation. Undifferentiated
schizophrenia is when the behavior cannot be classified because it may
have a combination of more than one of the descriptions in the other
categories (Koda-Kimble & Young, 1992).
Schizophrenic behavior is divided into two categories. Positive
symptoms, caused by a biochemical disorder make themselves known. They
are: irrational thinking, such as coming to absurd conclusions and
jumping from one topic to another, hallucinations, mostly consisting of
hearing voices in their heads, and delusions such as the false belief
that others are conspiring against them or trying to control them.
Negative symptoms, caused by brain damage to the frontal lobes are the
absence of normal behavior. They are flat emotional responses, lack of
speech, lack of pleasure and social withdrawal (Carlson, 1998).
Chlorpromazine, Haloperidol, and Clozapine are three tranquilizing
drugs that attempt to alleviate the symptoms of the mental disorder.
They are all dopamine receptor blockers, and have sedative and anti-
anxiety effects, so unfortunately they only diminish the positive and
not the negative symptoms of schizophrenia (Carlson, 1998). They also
produce some unfortunate side effects.
The dopamine hypothesis suggests that in schizophrenic's brains
there's an overactivity of dopaminergenic neurons, probably those of
the mesolimbic pathway. Research has found that there are increased
dopamine receptors in their brains (Carlson, 1998). Of the five types
of dopamine receptors, D4 receptors are an important locus of activity
for clozapine, one of the newest antipsychotic drugs. There are less
movement disorder side effects with this drug, which is an improvement
from the older drugs (Koda-Kimble & Young, 1992).
The limbic system, a part of the brain stem, is associated with
emotions, thought control and behavior. In schizophrenics, there is a
failure to inhibit arousal and incoming stimuli because of an
abnormally functioning limbic system filter. The result is
psychobiological vulnerabilities at the cortical and subcortical
levels. The consequence of the impaired limbic filter functions is a
loss of control of behavior. The use of Chlorpromazine, Haloperidol
and Clozapine attempt to improve limbic functions, targeting the
positive symptoms, which allow the individual to handle increased
levels of stress, the goal being to live in society and be able to take
care of oneself, rather than having to be institutionalized (Koda-
Kimble & Young, 1992).
There are four stages of response to neuroleptic (tranquilizing)
therapy and the behaviors that go with them. 1) Medicated cooperation:
the patient responds to the calming properties of the tranquilizers.
2) Improved socialization: the patient begins to obey ward or society
rules and begins to act in a socially appropriate way (Many severely
ill never reach this stage). 3) Elimination of thought disorder:
thinking and behaving more normally, a decrease in delusions,
disturbances, paranoid ideas and sensory overload. The handicap is
handled but eradication of thoughts not necessarily complete. 4)
Maintenance therapy stage: when the patient can most benefit from non
drug therapies such as behavior modification, vocational training and
resocialization training (Koda-Kimble & Young, 1992).
There is still much research to be done because although many
people are helped by antipsychotic drugs and can live relatively normal
lives, the symptoms of up to a third of schizophrenic patients aren't
helped by these drugs (Carlson, 1998). Also, new drugs need to be
developed that don't produce as many side effects.
References
Carlson, N.R., (1998). Physiology of Behavior. Needham Heights, MA:
Allyn and Bacon.
Koda-Kimble, M.A., Young, L.Y. (1992). Applied therapeutics the
clinical use of drugs. Vancouver, WA: Applied Therapeutics.
Effects Reported by Users and/or Survivors of the Use of Drugs for the
Treatment of Symptoms Associated with Schizophrenia
by Niels Bartels.
Because the drugs used to treat schizophrenia profoundly effect
how people experience themselves and their reality, subjective accounts
of the experience of a drug's effects are a valuable part of
understanding that drug's benefits. The following is a review of first
hand accounts of the effects of various drugs used to treat
schizophrenia.
Vonnegut (1975) gives this account of his experiences with
Thorazine, "I hated Thorazine... . Thorazine has lots of unpleasant
side effects. It makes you groggy, lowers your blood pressure... If
you go out in the sun your skin gets red and hurts like hell. It makes
your muscles rigid and twitchy." He continues, "The side effects were
bad enough, but I liked what the drug was supposed to do even less.
It's supposed to keep you calm, dull, uninterested, and
uninteresting... Thorazine made heroism impossible... . What I think
it does is just fog up your mind so badly you don't notice
hallucinations or much else." He continues, "On Thorazine everything
is a bore. Not a bore, exactly. Boredom implies impatience. You can
read comic books and Reader's Digest forever. You can tolerate talking
to jerks forever. The weather is dull, the flowers are dull, nothing's
very impressive. Muzak, Bach, Beatles, Lolly and the Yum Yums, Rolling
Stones. It doesn't make any difference."(Pp. 195 to 197).
Van Putten (1983) quotes more subjective experience related to
Thorazine. He quotes from testimony given in court; "From a young
woman: 'My tongue was fuzzy, so thick, I could barely speak... It was
so hard to think, the effort was so great; more often than not I would
fall into a stupor of not caring... I could not focus my blurred eyes
to read... People's voices came through filtered, strange. They could
not penetrate my Thorazine fog; and I could not escape my drug
prison.'"(Pg. 331).
In other testimony quoted by Van Putten Prolixin is discussed. He
writes, "From a young man: '...the effects of Prolixin began building
up in my system... Different muscles began twitching. My mouth was
like very dry cotton no matter how much water I drank. My tongue
became all swollen up. My entire body felt like it was being twisted
up in contortions inside by some unseen wringer... But most disturbing
of all was that I feared that all these excruciating experiences were
in my mind, or caused by my mind...'"(Pg. 332).
Peter Wyden has written a book about his struggle to make sure
that his son with schizophrenia receives adequate and effective
treatment. Wyden writes that his son, "...habitually wants all
medications reduced or eliminated in memory of old pills that caused
him grief long ago"(Pg. 279). His son, Jeff, did not enjoy Thorazine.
Wyden writes, "He requested that his medication be cut down... The
medication, Thorazine, which Jeff called 'Horrorzine', was indeed
reduced, leaving Jeff worse"(Pg. 68). Wyden also writes about others
who have experienced Thorazine. About a man named Michael Lauder, he
writes, "Thorazine... made him listless and drowsy and caused him to
gain weight, so eventually he secretly refused to swallow the
medication..."(Pg. 99). A description of Jeff's reaction to another
drug, Clozapine, illustrates how negative side effects can quickly lead
toward a tendency for noncompliance. Wyden writes, "As soon as Jeff's
dosage was pushed beyond 550 milligrams, he vomited... understandably
my son went into his rebellion mode"(Pg. 163). Wyden cites many
success stories involving Clozapine. He writes about a man named Kevin
Buchberger before Clozapine, "He couldn't sit still. He couldn't stop
smoking. His hands shook. He couldn't concentrate enough to read.
His vision was blurred from the Stellazine, the Navane, the Prolixin
that didn't help." Then he writes about Kevin after Clozapine, "Kevin
was sharing a house with friends these days and seeing a girlfriend.
He saw his psychiatrist only once every two months and his Clozapine
dosage had been reduced at least slightly...". Wyden quotes Kevin as
saying, "The first thing I noticed was that I stopped pacing... One
day I was pacing; the next day I wasn't." And, "I feel so good, I can't
believe it..."(Pg. 164). Wyden quotes another man, Brandon Fitch,
describing the thoughts he had upon his early realization that
Clozapine was helping, "'...I think something has changed,' he
remembered telling himself. ...I'm enjoying myself! People aren't
staring at me and saying, 'He looks like a creep!''"(Pg. 165).
Martha Lautenbach Wolff has written about her experiences with
Clozapine. She writes, "Before trying Clozapine, I had struggled with
depression for many years, and I finally entered a hospital. I spent
two and one half harrowing years there trying every drug for what was
by that time diagnosed a schizo affective disorder. Nothing worked...
I was able to be the first person to try Clozapine at the New York
Hospital/Cornell Medical Center. Within about three months I was able
to leave the hospital and function on my own."
Lori Schiller reports the benefits of Clozapine in her life, "If
it weren't for the new medication, clozapine...I would never have
survived this continuously exhausting mental illness. I felt a though
I was weakening; the Voices were going to conquer. With the assistance
of that new medication and the comfort and support from my psychiatrist
and others, I have been able to make distances down my path to
recovery."
Another example of a negative reaction to Clozapine comes from a
woman named Pamela Spiro Wagner. She describes her experience,
"Profoundly sedated, I was awake maybe eight hours out of every twenty
four. Then the drooling started, and an inability to swallow my saliva
that came on an hour or so after I took my nightly pills. Worst of
all, though, was an agonizing sensation I called 'the electrocution
feeling.' This last, later thought to be a result of pre seizure
activity in my brain, was largely ignored, since it didn't seem to my
doctor to fit in with Clozapine's 'side effects profile.'"
Wyden, in his book, cites many success stories involving the drug
Olanzapine. He quotes a man named John, "...It turned me around,' he
said. 'I feel great. I used to have terrible headaches. I haven't had
a headache in nearly two years.'" He quotes John's doctor, "'He's
solid as a rock...'"(Pg. 229). He writes about a man named Ron, "Ron,
thirty two, had been hearing voices almost nonstop for years. After
seven months on Olanzapine, he was busy filling out job applications.
'My mind came back,' he told the doctor"(Pg.231).
Pamela Spiro Wagner also has many good things to say about her
experience with olanzapine, "...ways of being, patterns of behavior and
habits I'd always assumed were 'just me,' that is, character
deficits... seemed to disappear one by one as the weeks went by. ...I
took a bath, not because someone suggested I needed it, but because it
suddenly seemed to me that I'd feel better if my body were clean." She
says, "For years listening to even the most harmless program left me
paranoid, convinced messages were being sent me, even when just music
or advertisements were played. And suddenly, there I was, listening to
the radio, and enjoying it!" She says, "Then, and this was really most
astounding of all, one night I decided I didn't want to sleep in my
clothes (and shoes) anymore and put on regular pajamas for the first
time in years." She also demonstrates how somebody might come to a
decision to discontinue even a highly beneficial medication. She says,
"I have gained substantial weight... and I'd be lying if I said this
doesn't greatly disturb me. It is, in fact, the one adverse effect
that, if it continues, could lead me to revealute (sic) the olanzapine
æcost/benefit ratio.'"
Haldol is another drug discussed in Wyden's book. He describes
the experiences of women named Marion; "Marion... began hearing voices
at age seventeen... She was given Haldol. 'It was awful,' Marion said.
'I had tremors, drooling. I had a feeling I was not being there and I
was still hearing voices.'"(Pg. 231).
Kenneth Kendler describes the negative effects of Haldol. He was
a Medical Student who was injected with Haldol as part of a research
study. He describes his experience; "...the drowsiness had dissipated
and was replaced by a diffuse, slowly increasing anxiety. My
uneasiness soon began to focus on the idea that I could not possibly
sit still for the rest of the experiment... As soon as I could move, I
found myself pacing up and down the lab, shaking and wringing my hands.
Whenever I stopped moving, the anxiety increased... the intensity of
the dysphoria was striking. With the possible exception of going on
stage on a opening night, I cannot remember any feeling of anxiety so
intense... the sense of a foreign influence forcing me to move was
dramatic"(Pp. 454 to 455).
Kendler, K.S. (1976). A Medical Student's Experience with Akathesia.
American Journal of Psychiatry,133 no4, 454 455.
Schiller, L. Waking from a SchizophrenicÆs Nightmare.
In http://www.schizophrenia.com [on line]. Available:
http://www.schizophrenia.com/newsletter/news125.html#Lori , from
http://www.schizophrenia.com go to success stories, Lori Schiller's
Story.
Van Putten, T. (1983). Adverse Psychological (or Behavioral) Responses
to Antipsychotic Drug Treatment of Schizophrenia. In A. Rifkin. (Ed.),
Schizophrenia and Affective Disorders (Pp. 323 338). Sittleton,
Mass.and Bristol, UK: John Wright.
Vonnegut, M. (1975). The Eden Express. New York: Praeger Publishers.
Wagner, P.S. One "Noncompliers Case for Olanzapine. In
http://www.schizophrenia.com [on line]. Available:
http://www.schizophrenia.com/newsletter/197/197pwagner.html , from
http://www.schizophrenia.com go to success stories, Pam Wagner's story.
Wolff, M.L. A Consumer Speaks Out Clozapine and Pregnancy: One Women's
Decision. In www.nami.org/ [on line]. Available:
http://www.nami.org/update/consumeroct.html .
Wyden, P. (1998). Conquering Schizophrenia. New York: Alfred A. Knopf.
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