Anti psychotic drugs classification ppt l

Anti psychotic drugs

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CLASSIFICATION OF ANTIPSYCHOTIC DRUGS
More than 20 different antipsychotic drugs are
available for clinical use, but with certain
exceptions the differences between them are
minor.
An important distinction is drawn between the
main group, often referred to as classical or typical
antipsychotic drugs atypical antipsychotic drugs
“Atypical” commonly refers to the diminished
tendency of some newer compounds to cause
unwanted motor side-effects. Their
pharmacological profile somewhat different from
that of “classical” pre-1980 drugs (phenothiazines,
thioxanthines and butyrophenones).

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MECHANISM OF ACTION
There are many type of DA-receptors (see upper).
The antipsychotic drugs probably owe their therapeutic effects mainly to
blockade of D2 receptors. The main groups, phenothiazines, thioxanthines
and butyrophenones, show preference for D2 over D1 receptors; some newer
agents (e.g. remoxipride) are highly selective for D2 receptors, whereas
clozapine is relatively non-selective between D1 and D2, but has high affinity
for D4.
DA, the naturally occurring agonist, interacts with D1 and D2 receptors, and
both receptors are found in high density in the corpus striatum and nucleus
accumbens. Most striatal neurons have D1 responses and most
accumbens neurons have D2 responses.

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Although D-receptor blockade occurs rapidly after initial
antipsychotic drug treatment, a therapeutic response is
not usually observed for several weeks. The time it takes
for the clinical response to be manifested is thought to
correlate with the delayed induction of depolarization
blockade of mesolimbic DA neurons. Induction of
depolarization blockade also correlates with a reversal of
initial increase in the concentration of DA metabolites in
cerebrospinal fluid.

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EFFECTS OF ANTIPSYCHOPTIC DRUGS
1.Central Nervous System
Effects of antipsychotic drugs differ in normal and
psychotic individuals.
In normal individuals they produce indifference to
surrounding, paucity of thought, psychomotor
slowing, emotional quiet, reduction in initiative and
tendency to go off to sleep. Spontaneous
movements are minimized, but slurring of speech,
ataxia or motor uncoordination does not occur.
This has been referred to as the “neuroleptic
syndrome” and is quite different from the sedative
action of barbiturates and other similar drugs.
The effects are appreciated as “neutral” and
“unpleasant” by most normal individuals.

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Catalepsy arises primarily from acute blockade
of postsynaptic D2 receptors in basal ganglia.
Chlorpromazine lowers seizure threshold and
can precipitate fits in untreated epileptics. The
piperazine side chain compounds have a lower
property for this action. The temperature control
is knocked off at relatively higher doses
rendering the individual poikilothermic – body
temperature falls if surrounding are cold. The
medullary respiratory and other vital centers are
not affected, except at high doses. It is very
difficult to produce coma with these drugs.
Neuroleptics, except thioridazine, have potent
antiemetic action exerted through the central
trigger zone. However, they are ineffective in
motion sickness.

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3.Local anaesthetic
Chlorpromazine is as potent a local
anaesthetic as procaine. However, it is
not used for this purpose because of
its irritant action. Others have weaker
membrane stabilizing action.

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5.Skeletal muscle
Neuroleptics have no effects on muscle
fibers or neuromuscular transmission.
They reduce certain types of
spasticity: the site of action being in
the basal ganglia or medulla
oblongata. Spinal reflexes are not
affected.

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PHARMACOKINETICS
Most neuroleptic drugs are highly lipophilic, bind avidly to
proteins, and tend to accumulate in highly perfused tissues.
Oral absorption is often incomplete and erratic, whereas IM
injection is more reliable. With repeated administration,
variable accumulation occurs in body fat and possibly in
brain myelin. Half-lives are generally long, and so a single
daily dose is effective. An esterified derivate of
fluphenazine requires dosing only once every few weeks.
After long-term treatment and drug administration is
stopped, therapeutic effects may outlast significant blood
concentrations by days or weeks. This may result from tight
binding of parent drug of active metabolites in the brain.

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ANWANTED EFFECTS
Neuroleptic drugs are replete with side effects. Many
side effects occur early during treatment and result
from neuroleptic blockade of receptors in the central
and peripheral nervous systems; others appear later in
the course of treatment (fig.12).
1.”Extrapyramidal” reactions include
•Parkinsonism, which can mimic idiopathic
Parkinson’s disease but is usually of mild degree. It
responds to anticholinergic drugs or amantadine;
•Akatisia is a subjective sense of restlessness usually
accompanied by wild to moderate motor hyperactivity.
It is among the most common of side effects and
usually responds to α-adrener gic receptor
antagonists, anticholinergics, antihistamines or
amantadine. Akathisia is sometimes misinterpreted as
increased agitation, leading to increased neuroleptic
dosing, resulting in greater akathisia.

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2.Endocrine effects
DA, released in the median eminence by
neurons of the tuberohypophyseal pathway
acts physiologically via D2 receptors as an
inhibitor of prolactin secretion. The result of
blocking D2 receptors by antipsychotic drugs
is therefore to increase the plasma prolactin
concentration, resulting breast swelling,
pain and lactation, which can occur in men
as well as women. Other less pronounced
endocrine changes including a decrease of
growth hormone secretion, but these, unlike
the prolactin response, are unimportant
clinically.

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4. Sedation, which tends to decrease
with continued use, occurs with many
antypsychotic drugs. Antihistamine (H1)
activity is a property of phenothiazines
and contributes to their sedative and
antiemetic properties, but not to their
antipsychotic action.

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6.Various idiosyncratic and
hypersensitivity reaction can occur, the
most important being.
Jaundice, which occurs with older
phenothizines, such as chlorpromazine.
The jaundice is usually mild, and of
obstructive origin; it disappears quickly
when the drug is stopped of substituded
by an antipsychotic of different class.

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CLINICAL USE AND EFFICACY
Although the underlying cause of psychosis is unknown, treatment
with neuroleptic drugs usually results in a specific improvement in
psychotic sings and symptoms and does not simply cause sedation
or reduce agitation. Modern antipsychotic drugs allow many
schizophrenics to lead productive lives outside hospitals or less
restrictive lives within hospitals. Unfortunately, for about half of
patients with schizophrenia, classical neuroleptics are not
completely effective in controlling positive symptoms. The
progression of negative symptoms can lead to progressive
deterioration. In schizophrenia, negative signs and symptoms are
generally more resistant to antipsychotic drug therapy and are
commonly the cause of chronic disability. It is likely that negative
sings and symptoms have a pathophysiological description different
from that of positive sings and symptoms and are associated more
with decreased frontal lobe metabolic rate. In some patients,
negative sings and symptoms way worsen with neutoleptoic
treatment. The increased efficacy of clozapine compared to
traditional neuroleptics derives primary from its greater efficacy in
improving negative sings and symptoms.

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1.The major use of antipsychotic drugs is in the
treatment of schizophrenia and other psychotic
disorders . The neuroleptics are the only efficacious
treatment for schizophrenia. Not all patients respond,
and complete normalisation of behavior is seldom
achieved. The traditional neuroleptics are most
effective in treating positive symptoms of
schizophrenia (delusions, hallucination and thought
disorders). The newer agents with 5-HT blocking
activity (e.g.sulpirid ) are effective in many patients
resistant to the traditional agent, especially in treating
negative symptoms of schizophrenia and depression.

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REFERENCES
1.Pharmacology, Fourth Edition, H.P.Rang, M.M.Dale,
J.M.Ritter, CHURCHILL LIVINGSTONE, 2001.
2.Human Pharmacology, Molecular to Clinical, Third
Edition, T.Brody, J.Larner, K.Minneman, Mosby,
1998 by Mosby-Year Book,Inc.
3.Basic & Clinical Pharmacology. A LANGE medical
book. 8 EDITION, B.G.Katzung, 2001, McGraw-Hill
Comp.
4.Lippincott’s Illustrated Reviews: Pharmacology, 2nd
Edition, M.J.Mycek, R.A.Harvey & P.C.Champe,
LIPPINCOTT WILLIAMS & WILKINS, 2000.