Antipsychotics

1. Antipsychotics or Neuroleptics
These are agents which having primary effect on “ mental processes” and
used to treat psychiatric disorders
Classification
1. Phenothiazines
a) Aliphatic side chain – Chlorpromazine, Triflupromazine
b) Piperidine side chain – Thioridazine
c) Piperazine side chain – Trifluoperazine, Fluphenazine
2. Butyrophenones – Haloperidol, Trifluperidol, Penfluperidol
3. Thioxanthenes – Flupethixol
4. Other heterocyclics – Pimozide, Loxapine
5. Atypical neuroleptics – Clozapine, Risperidone, Olanzapine, Quetiapine, Aripiprazole
Sreenu Thalla
Associate Professor
Department of Pharmacology

2. Mechanism of action
The actual mechanism is not clear, but they proposed multiple theories which
provide partial explanations.
They are
 Genetic theory
 Dopamine theory
 Neuro-developmental theory
 Psycho-social theory
• Dopamine hyperactivity in the brain is responsible for psychotic symptoms
• Due to dopamine hyperactivity the meso-limbic pathway, other areas of brain such as
prefrontal, frontal and temporal cortices have decreased dopamine activity during acute
psychosis

3. • Glutamate deficiency has been found to cause similar effects to that of dopamine hyperactivity
Symptoms
Positive symptoms
Delusions
Hallucinations
Insomnia
Negative symptoms
Affetive flattering
Alogia (poverty of speech )
Anhedonia(inability to gain pleasure)
Apathy (imperfect)
Amotivation
Asocial behaviour
Disorganised symptoms
Disorganised speech
Thought disorder
Disorganised behaviour
Poor attention

4. Pharmacological actions
CNS
In normal patients – Paucity of thought, neutral/unpleasant, emotional quietening
In pschotic patients – relives anxiety and disturbed thoughts, Suppression of hallucinations.
ANS – differ depending on the agent used
CPZ= Fluphenazine > Thioridazine> Clozapine > Fluphenazine> Haloperidol>
Trifluoperazine > Pimozide
LOCAL ANAESTHETIC
CVS – Hypotension, Reflex tachycardia, Arrhythmia
SKELETAL MUSCLE – no effect but reduces spasticity
ENDOCRINE – increase Prolactin release

5. Tolerance and dependance
 Sedative and hypotensive actions develops within days or weeks
 It do not display tolerance due to DA antagonism
 Absence of physical dependance
Pharmacokinetics
 Oral absorption is unpredictable and bioavailability is low
 I.V administration, highly bound to plasma proteins
 Volume of distribution is large i.e 20l/kg
 Metabolized in liver mainly by CYP2D6 into number of metabolites
 Elimination half life is in range of 18-30hours

6. Adverse effects
• Photosensitivity
• Extrapyramidal side-effects (EPS)
1.Akathisia: (Gk. Not being able to sit). Feeling restless or jittery, needing to fidget, pace
around, be about
2. Dystonia: sudden muscle spasm characterized by torticollis (twisting of neck), opisthotonos
(spasm of the neck and back forcing the head backwards), oculogyric crisis (a fixed gaze that
cannot return to lateral)
3. Parkinsonism: tremor, stiffness, rigidity, stooped posture, shuffling gait, akinesia (feeling
slowed down), pill-rolling movement of fingers, oscillations of distal parts of extremities
4. Neuroleptic malignant syndrome: muscle rigidity, hyperpyrexia, hypertension, confusion,
delirium
5.Tardive dyskinesia: involuntary movements of face and body (lip smacking, tongue
protrusion, rocking, foot tapping), impaired gait and posture

7. •Risperidone (Risperdal): Psychosis, Dementia, Mood Instability
•Olanzapine (Zyprexa): Psychosis, Mood Instability
•Quetiapine (Seroquel): Psychosis, Dementia
•Tricyclic antidepressants: Depression, Panic Disorder
•SSRIs: Depression, Panic Disorder
•Fluoxetine (Prozac, Sarafem): Depression, Obsession/Compulsions, PPMD (Premenstrual
Dysphoria Disorder), Panic Disorder
•Sertraline (Zoloft): Depression, Obsessions/Compulsions
•Paroxetine (Paxil): Depression, Panic Disorder, Social Phobia
•Fluvoxamine (Luvox): Depression, Obsessions/Compulsions, Panic Disorder
•Bupropion (Wellbutrin, Zyban): Depression, Cigarette Smoking
•Divalproex (Depakote): Dementia, Mood Instability, Convulsions, Migraine
•Carbamazepine (Tegretol): Mood Instability, Convulsions
Uses of medications

8. Treatment
 Minimize symptoms
 Improve quality of life and social/ occupational functioning
 Prevent relapse and hospitalization
 Minimize adverse effects of medications
 Prevent suicide attempts or self- harm