Psychopharmacology is the scientific study of how drugs act on the mind and behavior. Antipsychotic drugs are used to treat psychotic disorders like schizophrenia. Typical or first-generation antipsychotics block dopamine receptors and have higher risks of side effects like extrapyramidal symptoms. Atypical or second-generation antipsychotics also block serotonin receptors and have lower risks of extrapyramidal symptoms but can cause weight gain. Long-term treatment and monitoring of side effects is often needed for chronic psychotic disorders.

1. psychopharmacology
and
Antipsychotic Drugs
Inderjit kaur

2. psychopharmacology
 Is the scientific study of medicine and drugs acting upon
psychic aspects of human being and animals.
 Introduction
psychopharmacology is a branch of medicine
that study of the actions of drugs on the
psychological function of brain such as mood ,
thinking, sensation and behavior.

3. Antipsychotic Drugs: Classification
Typical anti psychotics is first
generation drugs
(Neuroleptics)
Atypical antipsychotics:
 Clozapine
 Amisulpiride
 Risperidone
 Olanzapine
 Quetiapine,
 Aripiprazole
 Ziprasidone

4. Classification of antipsychotics
Typical antipsychotics :
first generations discovered in 1950s. Use full in the
treatment of psychosis. But side effects are higher.
Haloperidol
Fluphenazine
Chlorpromazine
M.O.A: block dopamine receptor

8. Mechanism (action) of psychotropic
drugs
1. Psychotropic drugs help to treat the symptoms of mental
disorders where person feel better and Can function effectively
with the help of drugs
2. These drugs act on target neurotransmitters and there receptors
for proper functioning
3. Most antipsychotic drugs block some of the dopamine
receptore in the brain
4. Act against psychotic symptoms
5. But these medications cannot "cure" the illness

9. Antipsychotic Drugs:
Indications
Primary indication is
 Schizophrenia
 Schizoaffective disorders
 Bipolar
 Delusion disorder
 Psychotic depression


10. PARANOID SCHIZOPHRENIA
Parveen Babi accused many foreign dignitaries and
her former co-star, Amitabh Bachchan, of conspiring
to kill her

11. What is Psychosis?
Psyche (mind)
–osis (diseased or abnormal condition)

14. Psychopharmacology
Ideal Psychotropic Drug
 Cure
 Benefit
 No side effects or toxicity
 Rapid onset of action
 No dependence / Withdrawal
 No lethal in overdose
 Given in both settings (IPD & OPD)

15. CNS complexity
• Functionally, the CNS is the most complex
part of the body, and understanding drug
effects is difficult
• Complex interactions mediated by
different neurotransmitters
• The effect of psychotropic drugs to target
neuron is more like buckshot than an
intravenous drip

16. ANTIPSYCHOTICS
Introduction
Most antipsychotic drugs block some of the
dopamine receptore in the brain
 Act against psychotic symptoms
 Discovered in the 1950 s & research into how these
drugs works has provided an understanding of the
etiology of psychotic disorders
 But these medications cannot "cure" the illness

17. Case Vignette
Mr. X ,24 yr/M/Hindu/Punjab/+2/unemployed mainly taking T. Cloazapine
225mg/0D has been discharged with an advice to continue the drug
During discharge visit the nursing officer advices about the importance of
 taking blood samples
 report any symptoms of fever ,sore throat, malaise etc ….dyscrasia
 get abstinent from smoking & alcohol
Client ‘s parent asks
 Whether he want to take it for a long time????
 much concerned about the cost burden of the drug????
 What is the scientifically sound rationale behind the nurses advice?????
 What should be the effective response that addresses the clients family's
concerns?????

18. Antipsychotic Drugs: Indications
• Organic & Non- organic Psychiatric disorders
• Child hood Psychiatric disorders
• Medical disorders (rarely used)
Anti –emetics ( chlorpromazine)
Huntington’s Chorea (Haloperidol)
Intractable hiccupps ( chlorpromazine)
Tourette’ s syndrome –tics- ( haloperidol, pimozide)

19. Antipsychotic Drugs: Contra-Indications
• In known hyper sensitivity cases
• Evident CNS depression
• Existing blood dyscrasias
•Parkinsons disease
•Liver ,renal ,cardiac insufficiency

20. Mechanism of Action
-Antipsychotic blocks D₂ receptors in the brain's
Dopaminergic pathway
-Some also block or partially block serotonin receptors
(particularly 5HT2A, C and 5HT1A receptors)
-But antipsychotic drugs can also block wide range of
receptor targets.

21. Dopaminergic pathway in Brain
 Mesolimbic, Mesocortical: Control behavior, cognitive
funtion regulated by D₂ Receptor
 Nigrostriatal: Control Voluntary Movement regulated by D₁
and D₂ receptor
 Tuberoinfundibular: Control prolactin secretion regulated by
D₂ receptor

22. Antipsychotics blocks the Mesolimbic- Mesocortical
and Nigrostriatal pathway

23. How do we know they work?
• Mostly “accidentally” for early drugs - designing drugs to
reduce anxiety in surgical patients
• Clinical experience
• Clinical trials - especially more recent drugs
• PET scanning showing blockade of central D2 receptors
• Understanding the different properties like agonist,
antagonist& inverse antagonist of the drugs

24. Typical / conventional antipsychotics
• Chlorpromazine (Largactil®)
• Flupenthixol (Fluanxol®)
• Haloperidol (Serenace®, Haldol®)
• Pericyazine (Neulactil®)
• Pimozide (Orap®, Orap Forte®)
• Sulpiride (Dogmatil®)
• Thioridazine (Melleril®)
• Trifluoperazine (Stelazine®)
• Thiothixene (Navane®)

25. • Refers to agents introduced in US before 1990
• Also known as
– “Dopamine receptor antagonists”
• Pharmacologic activity at blocking central dopamine
receptors (esp. D2 receptors)
– “Neuroleptics”
• Due to tendency to cause neurologic Adverse effects
– “Major tranquilizers”
• Inappropriate as these agents (esp. high potency) can
improve psychosis without sedating or making patients
tranquil
Typical / conventional antipsychotics

26. • Properties
– Effective in reducing positive symptoms during
acute episodes and in preventing their
reoccurrence
– Less effective in treating negative symptoms
• Some concern that they may exacerbate negative
symptoms by causing akinesia
– Higher incidence of EPS / sedation /
anticholinergic Adverse effects
Typical / conventional antipsychotics

27. • Low potency
– Chlorpromazine, thioridazine
• Medium potency
– Perphenazine
• High potency
– Trifluoperazine, thiothixene, fluphenazine,
haloperidol (haif life- 24 hr), pimozide
Typical / conventional antipsychotics

28. Atypical antipsychotics
• Refers to newer agents
• Also known as
– “Serotonin-dopamine antagonists”
• Postsynaptic effects at 5-HT2A and D2 receptors

29. Atypical antipsychotics
• Amisulpiride (Solian®)
• Quetiapine (Seroquel®)
• Ziprasidone (Zeldox®)
• Risperidone (Risperdal®)
• Olanzapine (Zyprexa®)
• Clozapine (Clozaril®)
• Aripiprazole (Abilify®)

30. Atypical antipsychotics
• Mechanism of action
– Similar blocking effect on D2 receptors
– Seem to be a little more selective, targeting the
intended pathway to a larger degree than the others
– Also block or partially block serotonin receptors
(particularly 5HT2A, C and 5HT1A receptors)
– Aripiprazole: dopamine partial agonist (novel
mechanism)

31. Typical Versus Novel agents
• Distinction between ‘typical’ and ‘atypical’
groups is not clearly defined, but rests on:
– Incidence of extra pyramidal side-effects (less in
‘atypical’ group)
– Efficacy in treatment-resistant group of patients
– Efficacy against negative symptoms

32. Typical Versus Novel agents

33. Pharmacokinetics
Absorption( Movement of drug from ingestion to elimination )
 Antacids can prevent absorption & inhibit/ decrease the effects of
other drugs. Can it be avoided ???
(Excess acid can inactivate the drug preventing reaching the brain)
Distribution ( How drug moves through blood stream to various body
target site)
 Plasma proteins “ grab up” drug molecule. Ex: In 10 mg tab---- I-2
mg will remain in brain
 In a protein deficient body does not have enough albumin bind
drugs; whether it causes a well therapeutic effect ????
(More side effects)

34. Pharmacokinetics contd….
Metabolism (Biotransformation- how the body increase charge on drug &
targets them for excretion by the enzymatic breakdown)
 Inducer: a drug that increases amount of enzyme product.
 Clozapine Vs Cigerette smoking ( both are inducers )
 When two or more drugs use the same system the presence of one drug
can increase or inhibit the others rate of metabolism
Elimination ( How drugs are moved from the body)
 Elimination of drug by kidney is p H dependent;
 What goes into stomach as acid comes out in urine as alkaline & vice versa
 Ex : If drug p H is acid ,G-I p H acid …Then Urine p H is base & Drug
elimination increases.

35. Antipsychotic Drugs
Pharmacokinetics
• Highly lipophilic (haloperidol)
• Rapidly but incompletely absorbed from GIT
• Given orally; also given intramuscularly/
intravenously
• Undergo significant “first pass” hepatic metabolism
• Metabolized by cytochrome P450
• Highly protein bound
• Plasma half-life 15-30 hours
• Renal excretion

36. Receptor type Consequence of blockade
D2 dopaminergic Extrapyramidal symptoms; prolactin
release
H1 histaminergic Sedation
Muscarinic cholinergic Dry mouth, blurred vision, urinary
retention, constipation, tachycardia
Alpha1-adrenergic Orthostatic hypotension; reflex
tachycardia
5-HT2 serotonergic Weight gain
Receptor blockade and Adverse effects

37. Antipsychotics - Adverse effects &
Nursing Management
– Extrapyramidal symptoms (EPS)
• Early reactions – can be managed with drugs
– Acute dystonia
– Parkinsonism
– Akathisia
• Late reaction – drug treatment unsatisfactory
– Tardive dyskinesia (TD)
• Early reactions occur less frequently with low
potency drugs
• Risk of TD is equal with all agents

38. SIDE EFFECTS OF ANTIPSYCHOTIC DRUGS – (EPS)
ACUTE DYSTONIA
 This includes any of the following:
 Acute muscular rigidity and cramping
 A stiff or thick tongue with difficulty of swallowing
 In severe cases, laryngospasm and respiratory difficulties.

39. SIDE EFFECTS OF ANTIPSYCHOTIC
DRUGS – (EPS) – ACUTE DYSTONIA
 Spasms or stiffness in
muscle groups can produce
torticollis (twisted head and
neck)

40. SIDE EFFECTS OF ANTIPSYCHOTIC
DRUGS – (EPS) – ACUTE DYSTONIA
 Spasms or stiffness in
muscle groups can produce
opisthotonus (tightness in
the entire body with the head
back and an arched neck)

41. SIDE EFFECTS OF ANTIPSYCHOTIC
DRUGS – (EPS) – ACUTE DYSTONIA
 Spasms or stiffness in
muscle groups can produce
an oculogyric crisis (eyes
rolled back in a locked
position)

42. Extra pyramidal symptoms (EPS)- A glimpse

43. Drug Advantages Disadvantages
Clozapine For treatment-resistant cases,
little EPS
Risk of fatal agranulocytosis,
orthostatic hypotension
Risperidone Broad efficacy, little or no EPS at
low doses
EPS and hypotension at high doses
Olanzapine Effective with positive and
negative symptoms, little or no
EPS
Weight gain
Quetiapine Similar to risperidone, maybe
less weight gain
Dose adjustment with associated
hypotension, bd dosing
Ziprasidone Perhaps less weight gain than
clozapine, Inj A/V
QT prolongation
Aripiprazole Less weight gain, novel
mechanism potential
Uncertain
Comparison of representative atypical
antipsychotics

44. Drugs Sedation EPS Anticholinergic Orthostasis Seizure Prolactin
elevation
Weight
gain
Clozapine ++++ + ++++ ++++ ++++ 0 ++++
Risperidone +++ + ++ +++ ++ 0 to
++++
++
Olanzapine +++ + +++ ++ ++ + +++++
Quetiapine +++ + ++ ++ ++ 0 ++
Ziprasidone ++ + ++ ++ ++ 0 +
Aripiprazole ++ + ++ ++ ++ 0 +
Relative incidence of Adverse effects

45. Antipsychotic oral-dispersible and solution
preparations
• Oral-dispersible preps available for
– 2 atypicals
• Risperidone (Risperdal Quicklet®)
• Olanzapine (Zyprexa Zydis®)
– Carefully peel off packing, allow tablet to dissolve on tongue and swallow
– Some may be dispersed in fluids (consult manufacturer literature)
• Solutions available for
– 1 typical
• Haloperidol (Haldol® drops)
– 1 atypical
• Risperidone (Risperdal® solution)
– Very concentrated, avoid from contact with skin (dermatitis)

46. Antipsychotic injections
• Available for
– 2 typicals
• Chlorpromazine (Largactil®)
• Haloperidol (Haldol®)
• Fluphenazine decanoate
– 2 atypicals
• Olanzapine (Zyprexa®)
• Ziprasidone (Zeldox®)
– Useful for acutely agitated patients

47. Non-antipsychotic agents
• Benzodiazepines
– Useful in some studies for anxiety, agitation, global
impairment and psychosis
– Schizophrenic patients are prone to BZD abuse
– Limit use to short trials (2-4 weeks) for management
of severe agitation and anxiety
• Lithium
– Limited role in schizophrenia mono-therapy
– Improve psychosis, depression, excitement, and
irritability when used with antipsychotic in some
studies

48. Non-antipsychotic agents
• Carbamazepine
– Weak support when used alone and with antipsychotic
– Alters metabolism of antipsychotic
– NOT to be used with clozapine (risk of agranulocytosis)
• Valproate
– Concurrent administration with risperidone and olanzapine
resulted in early psychotic improvement in recent investigation
• Propranolol
– Research showed improvement in chronic aggression
– Treat aggression or enhance antipsychotic response
– Reasonable trial  240mg/day

49. Research input

51. Case Vignette
Mr. X ,24 yr/M/Hindu/Punjab/+2/unemployed mainly taking T. Cloazapine
225mg/0D has been discharged with an advice to continue the drug
During discharge visit the nurse advices about the importance of
 taking blood samples
 report any symptoms of fever ,sore throat, malaise etc &
 get abstinent from smoking & alcohol
Client ‘s parent asks
 Whether he want to take it for a long time????
 Am much concerned about the cost burden of the drug????
 What is the scientifically sound rationale behind the nurses advice?????
 What should be the effective response that addresses the clients family's
concerns?????

52. Conclusion
Schizophrenia Pharmacologic
pathophysiology profile of APDs
Past excess dopaminergic dopamine D2-receptor
activity antagonists
Present renewed interest in the combined 5-HT2/D2
role of serotonin (5-HT) antagonists
Future
 imbalance in cortical more selective
communication and antagonists
Cortical-midbrain mixed agonist/
integration, involving antagonists
multiple neurotransmitters neuropeptide analogs

53. The middle part of 20th century saw the advent & wide spread use of anti-
psychotics but not extended up to “ cure” Mental illness….
Lets hope it be fulfilled in 21st century….
“The woods are lovely, dark and deep. But I have promises to keep,
And miles to go before I sleep And miles to go before I sleep”
Robert Frost
THANK YOU
Take Home Message
Wishing a Blessed and
Some Fulfilled Blissful
Dreams