2. Psychotic Disorders
Definition: Psychotic disorders are defined as mental
disorders in which the personality is severely altered and a
person’s contact with reality is impaired.
Characteristics: delusions, hallucinations, odd behavior, and
incoherent or disorganized speech
Causes: Traumatic Experience, Stressful Event, and Drug Use
4. Treatment Before Drugs Came into PlayTreatment Before Drugs Came into Play
Patients were kept isolated from everybody else.Patients were kept isolated from everybody else.
Shock Treatment: consisted of twirling patients on a stool untilShock Treatment: consisted of twirling patients on a stool until
they lost consciousness or dropping them through a trap doorthey lost consciousness or dropping them through a trap door
into an icy lakeinto an icy lake
Insulin-Shock Therapy: consisted injecting insulin into theInsulin-Shock Therapy: consisted injecting insulin into the
patient until he or she became hypoglycemic enough to losepatient until he or she became hypoglycemic enough to lose
consciousness and lapse into a comaconsciousness and lapse into a coma
InstitutionalizedInstitutionalized
5. Anti-psychotic DrugsAnti-psychotic Drugs
Antipsychotic drugs (also known as major tranquilizersAntipsychotic drugs (also known as major tranquilizers
because they tranquilize and sedate) mitigate orbecause they tranquilize and sedate) mitigate or
eliminate the symptoms of psychotic disorders but theyeliminate the symptoms of psychotic disorders but they
do not cure them.do not cure them.
Antipsychotic drugs were initially called neurolepticsAntipsychotic drugs were initially called neuroleptics
because they were found to cause neurolepsy, which isbecause they were found to cause neurolepsy, which is
an extreme slowness or absence movement.an extreme slowness or absence movement.
6. New Era in Psychiatric MedicineNew Era in Psychiatric Medicine
• Chlorpromazine was theChlorpromazine was the
first anti-psychotic drugfirst anti-psychotic drug
developeddeveloped
• Initially this drug was administered toInitially this drug was administered to
patients before a surgery because itpatients before a surgery because it
produced anti- anxiety effects. It wasproduced anti- anxiety effects. It was
then tried on patients with mentalthen tried on patients with mental
illnesses and it was discovered thatillnesses and it was discovered that
it relieved psychotic episode symptoms.it relieved psychotic episode symptoms.
7. PhenothiazinesPhenothiazines
Chlorpromazine belongs to this class of drugs.Chlorpromazine belongs to this class of drugs.
Other examples include:Other examples include:
Fluphenazine
Perphenazine
Trifluoperazine
8. Mechanism of Action of PhenothiazinesMechanism of Action of Phenothiazines
The drugs found in this class are antagonists.The drugs found in this class are antagonists.
They work by blocking the D2 receptors in the dopamineThey work by blocking the D2 receptors in the dopamine
pathways of the brain; thus, decreasing the normal effect ofpathways of the brain; thus, decreasing the normal effect of
dopamine release.dopamine release.
Blocking the D2 receptors in the mesolimbic pathway resultsBlocking the D2 receptors in the mesolimbic pathway results
in the antipsychotic effect.in the antipsychotic effect.
9. Side Effects Associated withSide Effects Associated with
PhenothiazinesPhenothiazines
• Pharmacological SidePharmacological Side
EffectsEffects
• ConstipationConstipation
• Retention of urineRetention of urine
• Increased heart rateIncreased heart rate
• Dry mouthDry mouth
• Dilated pupilsDilated pupils
Serious Side EffectsSerious Side Effects
• ParkinsonianlikeParkinsonianlike
syndromesyndrome
• DystoniaDystonia
• DiskinesiaDiskinesia
• Neuroleptic MalignantNeuroleptic Malignant
Syndrome (NMS)Syndrome (NMS)
10. ButyrophenonesButyrophenones
Butyrophenones are high-potency antipsychoticsButyrophenones are high-potency antipsychotics
(potency refers not to effectiveness but rather to the(potency refers not to effectiveness but rather to the
ability to bind to dopamine receptors)ability to bind to dopamine receptors)
Haloperidol (Haldol) is the most common of theHaloperidol (Haldol) is the most common of the
butyrophenones:butyrophenones:
12. Mechanism of ActionMechanism of Action
All the butyrophenones work in the same mannerAll the butyrophenones work in the same manner
as the phenothiazines.as the phenothiazines.
They block the D2 receptors in the dopamineThey block the D2 receptors in the dopamine
pathways, thus, thwarting any possible overpathways, thus, thwarting any possible over
excitation of the dopamine receptors.excitation of the dopamine receptors.
13. Side Effects of Butyrophenones
Pharmacological effects includePharmacological effects include::
– Dry mouthDry mouth
– Urinary retentionUrinary retention
– Dimmed sightDimmed sight
More Serious Side effects includeMore Serious Side effects include::
-Dystonia-Dystonia
-Tardive Dyskinesia-Tardive Dyskinesia
- Akathisia- Akathisia
14. Comparisons Between the Two Classes ofComparisons Between the Two Classes of
DrugsDrugs
PhenothiazinesPhenothiazines
– Low potencyLow potency
– Are sedativeAre sedative
– Block D2 receptorsBlock D2 receptors
– metabolism and removal ofmetabolism and removal of
phenothiazines is complexphenothiazines is complex
and among the slowest ofand among the slowest of
any group of drugsany group of drugs
– cause extra pyramidalcause extra pyramidal
symptomssymptoms
ButyrophenonesButyrophenones
– High potencyHigh potency
– Non-sedativeNon-sedative
– Block D2 receptorsBlock D2 receptors
– Metabolism and removal isMetabolism and removal is
quickerquicker
– Cause extra pyramidalCause extra pyramidal
symptomssymptoms
15. Typical AntipsychoticsTypical Antipsychotics
Phenothiazines and Butyrophenones are typical antipsychoticsPhenothiazines and Butyrophenones are typical antipsychotics
These drugs are no longer regarded as the best practice for treatingThese drugs are no longer regarded as the best practice for treating
psychotic disorders, even though they are still commonly utilized inpsychotic disorders, even though they are still commonly utilized in
emergency treatmentsemergency treatments..
The reason for this is that they are not very selective. They do not onlyThe reason for this is that they are not very selective. They do not only
block the D2 receptors of the mesolimbic pathway but also block the D2block the D2 receptors of the mesolimbic pathway but also block the D2
receptors in the nigrostriatal pathway, mesocortical zone, andreceptors in the nigrostriatal pathway, mesocortical zone, and
tuberoinfundibular pathway.tuberoinfundibular pathway.
The fact that they are not very selective causes the extra pyramidalThe fact that they are not very selective causes the extra pyramidal
symptoms such as tardive diskinesiasymptoms such as tardive diskinesia
16. Atypical Anti-psychoticsAtypical Anti-psychotics
Were developed in an attempt to minimize the sideWere developed in an attempt to minimize the side
effects of typical anti-psychoticseffects of typical anti-psychotics
They have proven to cause fewer extraThey have proven to cause fewer extra
pyramidal symptoms (EPS) when comparedpyramidal symptoms (EPS) when compared
to typical anti-psychotics.to typical anti-psychotics.
They produce fewer EPS because they areThey produce fewer EPS because they are
more selective.more selective.
19. Mode of ActionMode of Action
AntagonistsAntagonists
Atypical antipsychotic drugs have a similar blocking effect onAtypical antipsychotic drugs have a similar blocking effect on
D2 receptors but appear to be more selective in targeting theD2 receptors but appear to be more selective in targeting the
intended pathway to a larger degree than typicalintended pathway to a larger degree than typical
antipsychotics.antipsychotics.
They also interact with other neurotransmission systems,They also interact with other neurotransmission systems,
particularly with the serotonergic and noradrenergicparticularly with the serotonergic and noradrenergic
pathways.pathways.
20. Side Effects Associated with AtypicalSide Effects Associated with Atypical
AntipsychoticsAntipsychotics
Glucose Metabolism Disorders such as hyperglycemia, onset ofGlucose Metabolism Disorders such as hyperglycemia, onset of
diabetes type 2, and worsening of pre-existing diabetes ( This wasdiabetes type 2, and worsening of pre-existing diabetes ( This was
particularly seen with patients treated with olanzapine and clozapine)particularly seen with patients treated with olanzapine and clozapine)
Weight Gain has been seen with patients taking Olanzapine; theWeight Gain has been seen with patients taking Olanzapine; the
increase of weight gain can result in other heart diseases such asincrease of weight gain can result in other heart diseases such as
hypertension and coronary heart disease.hypertension and coronary heart disease.
QTc prolongation which occurs when there is an abnormally long delayQTc prolongation which occurs when there is an abnormally long delay
between the electrical excitation and relaxation of the ventricles of thebetween the electrical excitation and relaxation of the ventricles of the
heart which can cause deathheart which can cause death
21. Most Common Problems Associated withMost Common Problems Associated with
Antipsychotic TreatmentAntipsychotic Treatment
• The slow onset of antipsychotic efficacyThe slow onset of antipsychotic efficacy
• The development of antipsychotic-induced sideThe development of antipsychotic-induced side
effectseffects
• Patients’ vulnerability to relapse followingPatients’ vulnerability to relapse following
antipsychotic drug discontinuation.antipsychotic drug discontinuation.
22. Current and Future Work in AntipsychoticCurrent and Future Work in Antipsychotic
TreatmentTreatment
• Synthesis of compounds acting on N-Methyl-D-AspartateSynthesis of compounds acting on N-Methyl-D-Aspartate
(NMDA) sub-group of glutamate receptors, which are believed(NMDA) sub-group of glutamate receptors, which are believed
to be involved in the pathogenesis of psychoticto be involved in the pathogenesis of psychotic
symptomatology.symptomatology.
• Aripiprazole is a new atypical antipsychotic drugAripiprazole is a new atypical antipsychotic drug thatthat showsshows
both partial agonist activity at the D2 and 5HT1A receptorsboth partial agonist activity at the D2 and 5HT1A receptors
and potent antagonism activity at the 5HT2A receptors.and potent antagonism activity at the 5HT2A receptors.
• Individualized treatment based on genetic profile in attemptsIndividualized treatment based on genetic profile in attempts
to eliminate side effectsto eliminate side effects
23. ReferencesReferences
• http://en.wikipedia.orghttp://en.wikipedia.org
• Currier Glenn W. and Adam Trenton “Pharmacological Treatment ofCurrier Glenn W. and Adam Trenton “Pharmacological Treatment of
Psychotic Agitation”Psychotic Agitation” CNS DrugsCNS Drugs 2002.2002.
Serretti Alessandro et al. “New Antipsychotics and Schizophrenia: ASerretti Alessandro et al. “New Antipsychotics and Schizophrenia: A
Review on Efficacy and Side Effects” Current Medicinal Chemistry,Review on Efficacy and Side Effects” Current Medicinal Chemistry,
2004.2004.
