ANTIPSYCHOTIC

DRUGS
PSYCHIATRIC ILLNESSES

Diseases characterized by impairment

of behavior and abnormal
thought process

Major illnesses Minor illnesses

 PSYCHIATRIC SYMPTOMS

 Hallucinations
 Delusions
 Illusions
 Paranoia
 Ruminations
 PSYCHIATRIC ILLNESSES
MINOR ILLNESSES OR NEUROSES

• ANXIETY NEUROSIS (Unpleasant emotions,

fear, apprehension, sympathetic stimulation)
• CONVERSION DISORDER (Symptoms produced
by autosuggestion/ Hysteria)
• OBSESSIONAL NEUROSIS (Irrational ideas)
• PHOBIC NEUROSIS (Irrational fears)
• DEPRESSIVE NEUROSIS
• HYPOCHONDRIASIS (preoccupation with health)
MAJOR ILLNESSES OR PHYCHOSES
Marked impairment of behavior,
abnormal thought process, loss of
insight into reality
• ORGANIC PSYCHOSES
 DELIRIUM (Excitement, restlessness,
hallucinations, disorientation
 DEMENTIA (impaired intellect and
cognitive function)
• FUNCTIONAL PSYCHOSES
 SCHIZOPHRENIA
 MANIC – DEPRESSIVE ILLNESS
(BIPOLAR AFFECTIVE DISOREDER)
 BIOCHEMICAL BASIS OF
PSYCHIATRIC ILLNESSES

NEUROSIS
Over-activity of nor adrenergic
pathways

MANIA/HYPOMANIA
Excessive activity of catecholamines
Increased sensitivity of receptors
DEPRESSION
Decreased activity of serotinergic and
nor-adrenergic pathways
Upregulation of postsynaptic receptors

DEMENTIA
Loss of cholinergic neurons in forebrain

SCHIZOPHRENIA
Excessive dopamine activity in
mesolimbic pathway
 JOHN NASH, a U.S. mathematician and joint winner of the 1994
Nobel Prize for Economics, suffered from schizophrenia. His life has
been the subject of the 2001 Academy Award winning film
A BEAUTIFUL MIND
SCHIZOPHRENIA
• Affects 1% of population
• Hereditary factor
• Slow virus infection
• Autoimmune reaction ?
• High density of D receptors
• Responds to D receptor blockers
 ATARACTICS/NEUROLEPTICS

Drugs that suppress the spontaneous

motor activity and complex behavior
thus producing psychomotor slowing
with minimal drowsiness while spinal
and unconditioned reflexes
remain intact
 ANTIPSYCHOTIC DRUGS
CLASSIFICATION

TRICYCLIC ANTI PSYCHOTICS

 PHENOTHIAZINES
Aliphatic Derivatives
Chlorpromazine
Piperadine Derivatives
Thioridazine
Piperazine Derivaties
Fluphenazine HCl
Fluphenazine decanoate
Trifluoperazine
 The Era of Antipsychotics

 The discovery of the first antipsychotic

drug - the first drug specific to mental
illness - marked a radical shift in the care
of mental illness and earned Pierre
Deniker (1917-1998), Henri Labourit
(1914-1995), and Heinz Lehmann (1911-
1999) the 1957 Lasker Award "for the
development of chlorpromazine as a
therapeutic agent in schizophrenia.
 S

Phenothiazine Nucleus
 THIOXANTHINES
Thiothixene
Chlorprothixene
HETEROCYCLIC ANTI PSYCHOTICS
 BUTYROPHENONES
Haloperidol
Droperidol
ATYPICAL ANTIPSYCHOTICS

 Clozapine
 Olanzapine
 Quetiapine
 Risperidone
 Ziprasidone
 Aripiprazole
 Molindone
 Pimozide
 RECEPTOR BLOCKADE BY
ANTIPSYCHOTIC DRUGS

Chlorpromazine: 1 = 5-HT2A > D2 > D1

Haloperidol: D2 .> 1 > D4 > 5-HT2A > D1 > H1
Clozapine: D4 = 1> 5-HT2A >D2 = D1

Olanzapine: 5-HT2A > H1 > D4 > D2 > 1 > D1

Aripiprazole: D2 = 5-HT2A > D4 > 1 = H1 >> D1
Quetiapine: H1 > 1 > M1,3 >D2 > 5-HT2A
PHARMACOLOGICAL ACTIONS

• Behavioral
• Motor Activity
• Reflex Activity
• Antiemetic Activity
• Sleep
 ADVERSE EFFECTS OF
ANTIPSYCHOTIC DRUGS
CNS
• Drug – induced Parkinsonism
• Akathisia
• Acute dystonias.
• Tardive Dyskinesia
• Seizures
• Neuroleptic malignant syndrome
• Perioral tremor
ANS
• Antimuscarinic effects
• Hypotension
ENDOCRINE
• Hyperprolactinemia
CARDIOTOXICITY
• Q-T Prolongation
• Cardiac arrythmias
• Heart Block
HYPERSENSITIVITY REACTIONS
• Agranulocytosis
• Cholestatic jaundice
• Skin rashes
 USES OF ANTIPSYCHOTIC DRUGS

Schizophrenia
Manic phase of bipolar affective disorder
Excitement states (non manic)
Tourette’s Syndrome
Nausea/Vomiting/Hiccup
Neuroleptanalgesia
 DIFFERENCES AMONG
ANTIPSYCHOTIC DRUGS

• Chemical differences
• Differences in receptor selectivity
• Differences in potency
• Differences in adverse effects
Extrapyramidal effects
Autonomic effects
CVS toxicity
Ocular Toxicity