ANTIPSYCHOTIC

DRUGS

REPORTED BY REX MENDOZA

 Psychosis
• Losing contact with reality

• Characterized by more than one symptom,

but these may include difficulty in
processing information and coming to a
conclusion, delusions , hallucinations,
incoherence, catatonia and aggressive or
violent behavior.
 Antipsychotics
• Also known as neuroleptics or
psychotropics

• Any drug that modifies psychotic behavior

and exerts an antipsychotic effect
 Modes of Action
• All anti-psychotic drugs have inhibitory
effects on the D2 receptor
• Some have actions against the D4 receptor
• All have other effects - to varying degrees
– Serotonin blockade (may improve negative
symptoms)
– Histamine H1 blockade (drowsiness)
– Alpha adrenoceptor blockade (postural
hypotension)
 Clinical Effects
• Control the ‘positive’ features of the disease, but
little effect on the ‘negative’ features (clozapine
may be superior in this regard)
• The main side-effects are on the extrapyramidal
motor system - leading to rigidity, tremor, and
loss of mobility and dyskinesia
• Tardive dyskinesia is a late onset disorder
characterised by repetitive abnormal movements
of face and upper limbs. This may be due to
proliferation of D2 receptors in the striatum
 … Clinical Effects
• Newer ‘atypical’ anti-psychotic drugs are
less inclined to produce these effects -
possible due to their greater affinity for the
mesolimbic over the striatal areas of the
brain
 Other Effects
• some are effective anti-emetics
• anti-muscarinic effects lead to dry mouth, blurred vision,
difficulty with micturition
• antagonist effects lead to hypotension
• antihistamine effects (H1 receptor) lead to drowsiness
• prolactin stimulation may lead to breast development
• agranulocytosis is fairly common with an ‘atypical’ drug
- clozapine
• ‘Neuroleptic malignant syndrome’ is a rare but serious
effect leading to autonomic instability and hyperthermia
 Classification of anti-psychotic
drugs
• “classical/ typical” • “atypical”
chlopromazine (gen) clozapine (sec100)
haloperidol (gen)
fluphenazine (gen) risperidone (auth)
thioridazine (auth) olanzapine (auth)
note: classification is based quetiapine (auth)
on fewer EPS side-
effects,fewer long-term
ADRs, efficacy in
treatment-resistant
groups, negative
symptoms
 Phenothiazines
• Chlorpromazine
Pharmacologic effects and mechanism:
(1)CNS: a. neuroleptic effect--- D1, D5---D1-like
receprtors
D2-4------D2-like receptors

b. antiemetic effect--- inhibit chemoreceptor

trigger zone or directly depress the medullary vomiting
center.
c. temperature-regulating effect--- produce
hypothermia
 Phenothiazines
• Pharmacologic effects:
• (2) autonomic nervous system: block α-
adrenergic and M-Cholinergic receptors and
result in hypotension, dry mouth, constipation
and blurred vision.
• (3) Endocrine system: increase the release of
prolactin and decrease corticotropin release and
secretion of pituitary growth hormone.
 Therapeutic uses
• (1) treatment of psychotic disorders:
schizophrenia, mania, paranoid states,
alcoholic hallucinosis.
• (2) treatment of nausea and vomiting of
certain causes.
• (3) anesthesia in hypothermia and artificial
hibernation (used with pethidine and
promethazine).
 Adverse Effects
• Extrapyramidal motor disturbances: (1)
Parkinson-like symptoms; (2) akathisia; (3)
acute dystonias.

Treatment: anticholinergic
 Adverse Effects
• Tardive dyskinesia comprises mainly
involuntary movements of face and tongue,
but also of trunk and limbs, appearing after
months or years of antipsychotic treatment.
It may be associated with proliferation of
dopamine receptors (possibly presynaptic)
in corpus striatum. Treatment is generally
unsuccessful.
 Adverse Effects
• Pseudodepression and Schizophrenia-like
syndrome.
• Seizures.
• Cardiac toxicity and endocrine effects.
 Adverse Effects
• Other side-effects (dry mouth,
constipation, blurred vision, hypotension,
etc.) are due to block of other receptors,
particularly α–adrenoceptors and
muscarinic ACh receptors.
• Contact dermatitis, blood dyscrasias,
obstructive jaundice sometimes occurs
with phenothiazines.
 Thioxanthenes
• Chlorprothixene: mild antipsychotic
action, and antianxiety and antidepressant
action.
 Butyrophenones
• Haloperidol: control psychomotor
excitement.
• Adverse effects: severe extrapyramidal
symptoms.
 Others
• Clozapine:
• (1) be effective in treating some patients with
psychosis unresponsive to standard neuroleptic
drug.
• (2) blocks D4 receptor and have low affinity
for D1 and D2 dopamine receptors.
• (3) lacks extrapyramidal side effects.
• (4) must monitor the granulocyte counts
weekly.
 Others
• Risperidone: be used first episode in and
chronic schizophrenia.