pharmacology- General steps involved in neurohumoral transmission

ADVANCED PHARMACOLOGY I
1
DEPARTMENT OF PHARMACOLOGY
Faculty of Pharmaceutical Sciences
PES University
HN Campus

TITLE: PHARMACOLOGY OF DRUGS USED IN
MANAGEMENT OF PSYCHOSIS
NANDISH GOWDA.R
PES3PG21PL008
23-09-2021 2

PHARMACOLOGY OF DRUGS USED IN MANAGEMENT OF PSYCHOSIS
23-09-2021 3
❑ CONTENTS
❑ Introduction to antipsychosis
❑ Defnition of antipsychosis
❑ Mechanism of antipsychotic drugs
❑ Classification of antipsychotic drugs
❑ Clinical significance
❑ Reference

INTRODUCTION
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• The antipsychotic drugs are used primarily to treat schizophrenia, but they are also
effective in other psychotic and manic states
• The use of antipsychotic medications involves a difficult trade-off between the
benefit of alleviating psychotic symptoms and the risk of a wide variety of adverse
effects.
Antipsychotic drugs are they often decrease the intensity of hallucinations and
delusions and permit the person with schizophrenia to function in a supportive
environment.

Certain drugs like:
• chlorpromazine
• thyropiridone
• haloperidol
• chlozapine etc.
• Schizophrenia
• Schizophrenia is a type of chronic psychosis characterized by delusions,
hallucinations (often in the form of voices),and disturbances in thought.
INTRODUCTION
5

• . The onset of illness is often during late adolescence early adulthood.
• Schizophrenia has a strong genetic component
• and probably reflects some fundamental developmental and biochemical
abnormality, possibly a dysfunction of the mesolimbic or mesocortical
dopaminergic neuronal pathways.
INTRODUCTION
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DEFINITION
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A medication that is believed to be effective in the treatment of psychosis

MECHANISM OF ACTION
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▪ 1. Dopamine antagonism
▪ All of the first-generation and most of the second-generation antipsychotic drugs
block D2 dopamine receptors in the brain and the periphery1. Dopamine
antagonism
▪ All of the first generation and most of the second- generation antipsychotic drugs
block dopamine receptors in the brain and the periphery (except clozapine-like
atypical). – The clinical efficacy of the typical antipsychotic drugs correlates closely
with their relative ability to block D2 receptors in the mesolimbic system of the
brain.

MECHANISM OF ACTION
9

MECHANISM
● ADVANCED PHARMACOLOGY I
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2.Serotonin receptor–blocking activity:
● Most of the second-generation agents exert part of their action through
inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors
● Clozapine has high affinity for D1 , D4 , 5-HT2 , muscarinic, and α-
adrenergic receptors, but it is also a weak dopamine D2 receptor
antagonist
● The secondgeneration antipsychotics aripiprazole [a-rih-PIP-ra-
zole],brexpiprazole [brex-PIP-ra-zole], and cariprazine [karIP-ra-zeen]
are partial agonists at D2 and 5-HT1A receptors, as well as antagonists of
5-HT2A receptors.

MECHANISM OF ACTION
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● Quetiapine is relatively weak at blockade of D2 and 5-HT2A receptors
● Pimavanserin [pim-a-VAN-ser-in] appears to act as an inverse agonist and
antagonist at the 5-HT2A receptor and the 5-HT2C receptor, with no appreciable
affinity for dopamine receptors..
● Pimavanserin is indicated for psychosis associated with Parkinson disease.

MECHANISM OF ACTION
Relative affinities of
clozapine, , and
halchlorpromazineoper
idol at D1 and D2
dopaminergic
receptors.

ACTIONS
● The clinical effects of antipsychotic drugs reflect a blockade at dopamine
and/or serotonin receptors
● Many any antipsychotic agents also block cholinergic, adrenergic, and
histaminergic receptors
Various effects include:
1. Antipsychotic effects
2. Extrapyramidal effects
3. Antiemetic effects
4. Anticholinergic effects
5. Other effects

ACTIONS
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1. Antipsychotic effects:
● All antipsychotic drugs can reduce hallucinations and delusions
associated with schizophrenia (known as “positive” symptoms) by
blocking D2 receptors in the mesolimbic system of the brain.
● The “negative” symptoms, such as blunted affect, apathy, and impaired
attention, as well as cognitive impairment, are not as responsive to
therapy, particularly with the first-generation antipsychotics.
● second-generation agents, such as clozapine, can ameliorate the
negative symptoms to some extent.

ACTIONS
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2. Extrapyramidal effects
● Dystonias (sustained contraction of muscles leading to twisting, distorted
postures), Parkinson-like symptoms, akathisia (motor restlessness), and
tardive dyskinesia (involuntary movements, usually of the tongue, lips,
neck, trunk, and limbs) can occur with both acute and chronic treatment
● Blockade of dopamine receptors in the nigrostriatal pathway is believed
to cause these unwanted movement symptoms.
● The second-generation antipsychotics exhibit a lower incidence of EPS.

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❖Actions
3. Antiemetic effects :
● antipsychotic drugs hTheave antiemetic effects that are mediated by blocking
D2 receptors of the chemoreceptor trigger zone of the medulla
● It summarizes the antiemetic uses of antipsychotic agents, as well as other
drugs that combat nausea.

Actions
4. Anticholinergic effects:
● Some of the antipsychotics, particularly thioridazine, chlorpromazine,
clozapine, and olanzapine, produce anticholinergic effects.
● The effects include blurred vision, dry mouth (the exception is clozapine,
which increases salivation), confusion, and inhibition of gastrointestinal and
urinary tract smooth muscle, leading to constipation and urinary retention.
● The anticholinergic effects may actually assist in reducing the risk of EPS with
these agents.

Actions:
5. Other effects:
● Blockade of α-adrenergic receptors causes orthostatic hypotension
and light-headedness
● Antipsychotics also alter temperature-regulating mechanisms and
can produce poikilothermia (condition in which body temperature
varies with the environment)
● In the pituitary, antipsychotics that block D2 receptors may cause an
increase in prolactin release.

Actions
23-09-2021
19
● Sexual dysfunction may also occur with the antipsychotics due to various receptor-
binding characteristics.
● Sedation occurs with those drugs that are potent antagonists of the H1 -histamine
receptor, including chlorpromazine, olanzapine, quetiapine, and clozapine.
● Weight gain is also a common adverse effect of antipsychotics and is more significant
with the second-generation agents.
.

CLASSIFICATION
The Anti psychotic drugs are usually divided into:
1. First generation agents
They are further classified as:
● low potency
● High potency
2. Second generation agents

CLASSIFICATION
21

CLASSIFICATION
22
First-generation antipsychotics:
● The first-generation antipsychotic drugs (also called conventional) are competitive
inhibitors at a variety of receptors, but their antipsychotic effects reflect competitive
blockade of dopamine D2 receptors.
● First-generation antipsychotics are more likely to be associated with movement
disorders known as extrapyramidal symptoms (EPS), particularly drugs that bind
tightly to dopaminergic neuroreceptors, such as haloperidol

CLASSIFICATION
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. Second-generation antipsychotic drugs
○ The second-generation antipsychotic drugs (also called “atypical”
antipsychotics) have a lower incidence of EPS than the first-generation
agents but are associated with a higher risk of metabolic adverse
effects, such as diabetes,hypercholesterolemia, and weight gain
○ The second-generation drugs as unique activity to blockade of both
serotonin and dopamine receptors.

CLASSIFICATION
24
Second generation antipsychotic drugs
1.
Drug selection:Second-generation agents are generally used as first-line
therapy for schizophrenia to minimize the risk of debilitating EPS
associated with the first-generation drugs that act primarily at the
dopamine D2 receptor
They exhibit an efficacy that is equivalent to, and occasionally
exceeds, that of the first generation antipsychotic agents

NATURAL ANTIOXIDANTS
ADVANCED PHARMACOLOGY II
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2. Refractory patients:
● Approximately 10% to 20% of patients with schizophrenia have
an insufficient response to first- and :secondgeneration
antipsychotics. For these patients, clozapine has shown to be an
effective antipsychotic with a minimal risk of EPS
● Clozapine can produce bone marrow suppression, seizures, and
cardiovascular side effects, such as orthostasis.

PHARMACOLOGY
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PHARMACOLOGY OF CHLORPROMAZINE (low potency)

PHARMACOLOGY
27
PHARMACOLOGY OF HALOPERIDOL (High potency)

PHARMACOLOGY
28
PHARMACOLOGY OF RISPERIDONE

THERAPEUTIC USES OF ANTIPSYCHOTICS DRUGS
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1. Treatment of schizophrenia:
● The antipsychotics are the only efficacious pharmacological treatment for
schizophrenia.
. The first-generation antipsychotics are generally most effective in treating
the positive symptoms schizophrenia

USES
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2. Prevention of nausea and vomiting:
● The older antipsychotics (most commonly, prochlorperazine [PROE-klor-PER-a-zeen])
are useful in the treatment of drug-induced nausea.
3. Other uses
● The antipsychotic drugs can be used as tranquilizers to manage agitated and
disruptive behavior secondary to other disorders
● Chlorpromazine is used to treat intractable hiccups

ADVERSE EFFECTS
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Adverse effects of the antipsychotic drugs can occur in practically all
patients and are significant in about 80%
They are:
● Urinary retention
● Weight gain
● Seizure
● Sedation
● Sexual dysfunction
● Dry mouth

REFERENCE
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Reference
● lippincott text book of pharmacology
● goodmann gillmans text book
● slideshares

THANK YOU
Nandish gowda.R
Department of pharmacology
23-09-2021 33

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