difference between types are included

1. CASE STUDY
DHANADHARANI VENKATESH

2. Ms. RS, a 35 year old female patient
 PAST MEDICAL HISTORY:
 Schizophrenia for 8 years.
 Hypothyroidism for 12 years.
 PAST MEDICATION HISTORY:
SCENARIO

3.  PRESENT MEDICAL HISTORY:
 C/O Auditory and visual hallucinations, disturbed sleep, suspicious thoughts.
 She has been doing all her work at crawling speed.
 GENERAL EXAMINATION:
 She was found to have negative symptoms.
 Delusions of persecutions,
 Delusions of reference,
 Somatic delusions,
 Lack of activeness.

4.  DRUGS:
 She was started on Olanzepine 5mg HS, Risperidone 3mg BD.
 On later observation it was found that she developed resistance to typicals.
 Hence she was stopped on Haloperidol and Fluphenazine
 Started with Clozapine 50mg HS in addition.

5. QUESTIONS -1 Discuss the clinical symptoms of
schizophrenia and analyse the symptoms of Ms RS

6. CLINICAL SYMPTOMS OF SCHIZOPHRENIA
TYPES SYMPTOMS
POSITIVE “Positive” symptoms are referred to as positive because the symptoms
are additional behaviors not generally seen in healthy people. For some people,
these symptoms come and go. For others, the symptoms become stable over time.
Includes: Hallucination, Delusion, Thought & Movement Behavior
NEGATIVE “Negative” symptoms refer to social withdrawal, difficulty showing emotions, or
difficulty functioning normally. People with negative symptoms may need help
with everyday tasks.
COGNITIVE Cognitive symptoms are not easy to see, but they can make it hard for people to
have a job or take care of themselves. The level of cognitive function is one of the
best predictors of a person’s ability to improve how they function overall. Often,
these symptoms are detected only when specific tests are performed. Cognitive
symptoms include:
• Difficulty processing information to make decisions
• Problems using information immediately after learning it
• Trouble paying attention

7. SYMPTOMS OF RS
TYPES SYMPTOMS
POSITIVE  Auditory &visual hallucination,
 Suspicious thoughts,
 Delusions of persecutions,
 Delusions of reference,
 Somatic delusions
NEGATIVE  Disturbed sleep,
 Doing all her work at crawling speed,
 Lack of activeness

8. QUESTIONS -2 Comment on the patient’s past medications
and explain their side effects

9. DRUG CLASS MOA SIDE EFFECTS
Holoperidol 1ST generation
antipsychotics
(phenylbutylpiperadine
derivative with
antipsychotic,
neuroleptic, and
antiemetic activities)
Haloperidol competitively blocks
postsynaptic dopamine (D2) receptors in
the mesolimbic system of the brain,
therebyeliminating dopamine
neurotransmission and leading to
antidelusionary and antihallucinagenic
effects. Antagonistic activity mediated
through D2 dopamine receptors in the
chemoreceptive trigger zone (CTZ)
accounts for its antiemetic activity.
Extrapyramidal
symptoms
Akathisia,Dystonia
Muscle stiffness,
Parkinsonism
Tardive dyskinesia
Sedation,Weight gain
Insomnia,Restlessness
Fluphenazine 1ST generation
antipsychotics
(Phenothiazine)
Fluphenazine exerts its actions by
blockingpostsynaptic dopamine
D2 receptors in the limbic, cortical
system and basal ganglia. This prevents
the actions of dopamine, thereby
reducing the hallucinations and delusions
that are associated with schizophrenia.
Extrapyramidal
symptoms
Akathisia.Dystonia
Muscle stiffness
Parkinsonism
Tardive dyskinesia
Sedation,Weight gain
Insomnia,Restlessness

10. DRUG CLASS MOA SIDE EFFECTS
Trihexylphenidyl
HCL
Anticholinergic Trihexyphenidyl is a selective M1
muscarinic acetylcholine receptor
antagonist. Trihexyphenidyl partially
blocks cholinergic activity in the CNS,
which is responsible for the symptoms of
Parkinson's disease. It is also thought to
increase the availability of dopamine and it
also indicated in treatment of
extrapyramidal reactions caused by drugs
Bloating
Constipation,hallucinati
ons, delusions of
persecution (less than
0.1%) Nervousness ,
Restlessness,Euphoria,
Depression,anxiety ,
agitation, Insomnia
Eltroxin
(Levothyroxine)
Thyroid hormones Synthetic T4; thyroid hormone increases
basal metabolic rate, increases utilization
and mobilization of glycogen stores,
promotes gluconeogenesis; involved in
growth development and stimulates protein
synthesis
Angina
pectoris,Arthralgia,
Flushing, Palpitations,
Arrhythmias,
Nervousness,Anxiety.
Choking sensation,
Emotional
lability,Insomnia,
Alopecia, Dyspnea

11. QUESTIONS -3 Discuss the pharmacology of the atypical
antipsychotics given for the patient

12. Clozapine
Clozapine is a synthetic dibenzo-diazepine derivative, atypical antipsychotic
Clozapine blocks several neurotransmitter receptors in the brain
(dopamine type 4, serotonin type 2, norepinephrine, acetylcholine,
and histamine receptors). Unlike traditional antipsychotic agents, it weakly
blocks dopamine type 2 receptors. It relieves schizophrenic symptoms
(hallucinations, delusions, dementia).

13. Olanzepines
Olanzapine is an atypical (second-generation) antipsychotic that exerts its
action primarily on dopamine and serotonin receptors. It works on dopamine
D2 receptors in the mesolimbic pathway as an antagonist, blocking
dopamine from having a potential action at the post-synaptic receptor.
Olanzapine binds loosely to the receptor and dissociates easily, allowing for
normal dopamine neurotransmission. The effect on the D2 receptors leads to
a decrease in positive symptoms in patients, including hallucinations,
delusions, and disorganized speech, thought, and behavior. Olanzapine
works similarly on serotonin 5HT2A receptors in the frontal cortex as an
antagonist. Its effects on serotonin lead to a decrease in negative symptoms,
including anhedonia, flat affect, alogia, avolition, and poor attention.

14. Risperidone
Risperidone is a benzisoxazole derivative with antipsychotic property.
Risperidone selectively antagonizes serotonin (5-HT) effects via
cortical 5-HT2 receptor, and, to a lesser extent, competes
with dopamine at the limbic dopamine D2 receptor. The antagonism
leads to decreased psychotic effects, such as hallucinations and
delusions. In addition, risperidone has low to moderate affinity
for histamine H1, 5-HT1A, 5-HT1C, and 5-HT1D receptors, while it
has weak affinity for dopamine D1 and haloperidol-sensitive sigma site
receptors.

15. DRUGS PHARMACOLOGY
A D M E
Olanzepines Peak plasma
time: 6 hr (PO)
PB: 93%
Vd: 1000 L
Extensively
metabolized through
direct glucuronidation
and CYP450 oxidation
t1/2: 21-54 hr (ir); 30
days (er)
Excretion: Urine (57%),
feces (30%)
Risperidone Peak plasma
time: 4-6 hr
(SC)
BA: 70%
PB: Risperidone,
90%; metabolite,
77%
Vd:1-2 L/kg
Metabolized in liver by
CYP2D6
Metabolite: 9-
hydroxyrisperidone
t1/2: 8-9 days (9-
hydroxyrisperidone and
total active moiety)
Excretion: Urine (70%),
feces (14%
Clozapine BA:50-60%
Peak plasma
time: 1.5-2.5 hr
Protein bound: 97%
Vd: 4.67 L/kg
Metabolized by hepatic
P450 enzyme CYP1A2
Metabolites:
Norclozapine
t1/2: 12 hr
Excretion: Urine (50%),
feces (30%)

16. QUESTIONS -4 State the differences between the typical
and atypical antipsychotics

17. TYPICAL ATYPICAL
DRUGS 1. Phenothiazines: Chlorpromazine
Triflupromazine Thioridazine
Trifluoperazine Fluphenazine
2. Butyrophenones: Haloperidol
Trifluperidol Penfluridol
3. Thioxanthenes; Flupenthixol
4. Other heterocyclics: Pimozide,
Loxapine
1. Clozapine
2. Aripiprazole
3. Risperidone
4. Ziprasidone
5. Olanzapine
6. Amisulpiride
7. Quetiapine
8. Zotepine

18. Typical
1st generation discovered in
early 1950's
D2 receptor blockade
EPS & hyperprolactinemia due to
strong D2 blockade
Effective aganist positive
symptoms
Atypical
Newer generation discovered after
1990's
Lesser incidence of EPS &
hyperprolactinemia, has metabolic
side effect
Effective aganist positive &
negative symptoms

19. QUESTIONS -5 Discuss the role of depot preparations in the
management of schizophrenia

20. DEPOT INJECTION
A depot injection is an injection, usually subcutaneous, intradermal, or intramuscular, that
deposits a drug in a localized mass, called a depot, from which it is gradually absorbed by
surrounding tissue. Such injection allows the active compound to be released in a consistent way
over a long period. Depot injections are usually either solid or oil-based

21. ROLE IN SCHOZOPHRENIA:
Poor adherence to oral formulations was found to be a critical issue in management. This led to
the development in 1966 of the first LAI AP fluphenazine enanthate, and fluphenazine decanoate
some 18 months later, to reduce the incidence of side effects of the former. Haloperidol decanoate
became available in Europe in 1981 and in the USA in 1986. Clinical trial results showed a
dramatic reduction in the morbidity of schizophrenia. Once steady-state is achieved, plasma
levels remain relatively stable, avoiding the daily peaks and troughs that occur with oral agents.
In addition, the Local Aggregates Assessment depots facilitate the use of the lowest effective
dose principle, thereby reducing the probability of medication overdose and the frequency of
adverse events such as akathisia, dysphoria, and antipsychotic-induced deficit syndrome, and
thus enhancing the patient’s quality of life.

22. ADVANTAGES OF DEPOT PREPARATION:
 Early identification of nonadherence
 Eliminates bioavailability problems
 Providing a mechanism for monitoring adherence with injections
 No need to remember to take medication every day
 Regular interactions between patient and medical staff
 Reduced relapse frequency and rehospitalization rates
 Reduces risk of an overdose of medications in suicidal intention

23.  Clear attribution of the cause of relapse or nonresponse, discriminating between nonadherence
or lack of response
 Treating patients with more stable plasma concentrations than oral medications
 Structured management of the patient, his/her illness and his/ her treatment far beyond the
simple administration of a drug
 Avoidance of first-pass metabolism-better relationship between dose and blood level of drug
 Lower and less frequent peak plasma level-reduced side effects

24.  In many low- and middle-income countries, continuous availability of antipsychotic
medicines in nonspecialized health care is a challenge; therefore, depot preparations may
have the advantage of requiring a smaller quantity of medications per year
 Depot formulation can be beneficial for treatment adherence in settings where there is low
human resource availability to provide continued care through follow-up or where access to
care is difficult. In many countries, per day cost may be reduced with the use of depot
preparations.

25. THANK YOU