Transcript Antipsychotic drugs

 Drugs in this group are used for violations of
human mental activity. They are used in the
treatment of psychosis, as well as the neurotic
and neurotic disorders accompanied with
standing stress, fear, worry, anxiety and other
symptoms.
The mechanisms of action of psychotropic
substances investigated only to a small extent,
although the extent of such research are great.
The most interesting information on the effect
of these substances on the interneuron
transmission to the exchange of biogenic
amines in the cholinergic system of head of the
brain to interact with peptides with amino
acids that provide stimulating and inhibitory
effect on neurons, etc.
 For some neuroleptics (e.g., phenothiazine






derivatives) in the development of psychotropic
effects can be set to their blocking effect on the
serotonin receptors and m-cholinergic receptors in
the brain.
Antipsychotics in chemical structure related to the
following group memory.
1.Derivatives of phenothiazine
Chlorpromazine
Triftazin
Etaperazin
Ftorfenazin
2.Derivatives of thioxanthene
Chlorprothixene
3. Derivatives of butirofenone
Haloperidol
4. Derivative dibenzodiazepina
Clozapine
 The most typical representative of
phenothiazine is chlorpromazine
(chlorpromazine hydrochloride, largaktil,
plegoma-zine, hlorazin, fenaktil,
propafenin).
Chlorpromazine has a wide range of actions.
The drug has expressed ¬ zhennoe effect on
the central nervous system, as well as
peripheral nerve, executive bodies and
metabolism. Effect on central nervous
system is manifested in a number of effects.
So, for chlorpromazine as one of the main
representatives of antipsychotic neuroleptic
characteristic and sedation, as well as the
ability to cause extrapyramidal disorder
(long-term use).
 In large doses, chlorpromazine is a hypnotic
effect: light sleep comes easily interrupted by
external stimulation.
Typical of chlorpromazine is a decrease in
motor activity (muscle relaxant effect). This is
due to inhibition of supraspinal regulation of
muscle tone. In particular, chlorpromazine
reduces or completely eliminates the floor
descending facilitating effect of the reticular
formation on spinal reflexes. Directly on the
spinal cord chlorpromazine does not work. In
addition, chlorpromazine inhibits the center of
thermoregulation. Final effect depends on the
ambient temperature. Most often, there is a
slight hypothermia (due to the increase of heat
transfer).
 At the same time, when combined with
chlorpromazine natural cooling occurs marked
reduction in body temperature.
Chlorpromazine has a distinct anti-emetic effect,
which work by blocking the chemoreceptor trigger
zone (trigger zone), located at the bottom of the IV
ventricle. With this chlorpromazine preanticipates
vomiting caused by apomorphine, morphine,
protivoblastomnymi means of mustard group.
One of the manifestations of the effect of
chlorpromazine on the central nervous system is its
ability to potentiate the effect of a number
neyrotrop the fixed assets - facilities for anesthesia,
sleeping pills, narcotic analgesics. However, the
strengthening of their effects, in part due to the
inhibition of aminazine processes of
biotransformation of these drugs.
 Chlorpromazine has an effect on the peripheral nerve.
The most ¬ more pronounced in his α-adrenoceptor
blocking action. So, for example, against the backdrop
of chlorpromazine pressor response to adrenaline is
sharply reduced or comes "perversion" effect of
adrenaline and blood pressure pa ¬ give. In addition,
some peculiar aminazinu m-anticholinergic (atropine)
properties. This is evident not great ¬ decreased
secretion of salivary, bronchial and digestive glands.
Transfer of excitation in the autonomic ganglia, he does
not break.
Chlorpromazine affects not only the efferent, but also on
the afferent innervation. When the local action it causes
marked irritation, which is replaced by anesthesia. In
chlorpromazine there is significant antihistaminic
activity (blocking H1-receptors). He is a ¬ is also
myotropic antispasmodic action.
 It is characteristic of chlorpromazine its effect
on the cardiovascular system. The symptom is
more or less pronounced decrease in arterial
pressuretion. The mechanism of hypotension is
quite complex. It is linked to the oppression
centers of the hypothalamus, with α-adrenergic
blocking and antispasmodic properties of
chlorpromazine, with the suppression of
compensatory vasoconstrictor reflexes, as well
as with a reduction in force of heart
contractions.
 Hypotension is usually accompanied by a reflex
tachycardia. Furthermore, chlorpromazine
marked antiarrhythmic properties.
 With prolonged use of chlorpromazine to it
develops addictive. However, this applies
only to the sedative, hypotensive, and a
number of other effects, antipsychotic
action is not changed.
The group of phenothiazine derivatives is
also a large number of other drugs. In
general, they are similar to aminazinu and
differ from it only by the severity of the
individual properties.
Of great interest are compounds in which a
side chain kidney related phenothiazine
nitrogen atom, a piperazine ring. This group
includes meterazin, etaperazin, triftazin,
ftorfenazin etc.
 Meterazin (prochlorperazine maleate,
Compazine) has potent antipsychotical
activity. According to the sedative effect of
losing aminazine). It has a 3-5 times greater
antiemetic activity. Muscle relaxation is less
than chlorpromazine. Hypotensive effect,
adrenoblocking, anticholinergic and
spazmolitical properties, antihistaminic
activity are less pronounced (approximately
2-fold) than chlorpromazine. This
characterizes meterazin with a favorable
side, as rehese effects are undesirable.
 Has similar properties etaperazin
(perphenazine, Trilafon). It is an assetion
antipsychotic and sedative. It also relates to
the most effective anti-emetic agents
(chlorpromazine greater than 5-10 times).
Atropine, crampinglytic and antihistaminic
properties are expressed in his less than
chlorpromazine.
 Much in common with the last two neuroleptics in
Triftazin (trifluoperazina hydrochloride, stelazin,
fluperin). Compared with the aminazine it is
characterized by a more selective antipsychotic
effection and less sedating effect. According to the
antiemetic effect exceeds chlorpromazine. It differs
from the weaker hypotensive, adrenoblocking and
relaxing effect.
Ftorfenazin (fluphenazine hydrochloride, DITT,
Mirren) in efficiency as an antipsychotic similar
triftazin. As an antiemetic slightly exceeds triftazin.
This released a neuroleptic drug in the form of
prolonged action - ftorfenazina decanoate (DITT
depot, on flufenazindecanoate), whose action
continues 7-14 days and more.
 Phenothiazine drugs row cause a variety of side
effects. This may be a general lethargy, apathy,
drowsiness, dry mouth, discomfort in the heart, in
the epigastric region; impact hypotension,
orthostatic collapse (all this is more often observed
when using chlorpromazine). Sometimes develop
congestive jaundice (usually in the appointment of
chlorpromazine). For a number of phenothiazine
neuroleptics (especially for products containing
piperazine ring) are characteristic of
extrapyramidal disorders (Parkinson's disease).
With prolonged use of neuroleptics may develop
depression.
Often there are diarrheal disorders - loss of
appetite, nausea. Phenothiazines cause irritation of
skin and mucous shells check.
 Irritability may occur on routes of administration
preparations (into a vein, muscle, enteral). Severe
complications include leukopenia, and
agranulocytosis.
At the medical staff and the persons associated
with the manufacture and packaging of
phenothiazine derivatives are relatively common ¬
Xia allergic skin lesions.
The derivatives thioxanthene is chlorprothixene
(truksal). It is chemically similar to
chlorpromazine. Characterized in that, as
compared with phenothiazine in tioksantenic
heterocycle in place of nitrogen is a carbon atom
having a double bond. According to anti-psychotic
action chlorprothixene inferior fenotiazinic pro
water. The drug is interesting because it also has
some antidepressive activity.
 Of great interest as antipsychotic drugs are
derivatives of butirofenone.
From this series of compounds for the treatment of
mental illness is mainly used haloperidol
(halophytes). Its action occurs relatively quickly
and lasts a long time. When administered into the
maximum concentration in the blood plasma
observed after 2-6 hours and kept at a high level for
about 3 days. After 5 days kidneys displayed about
40% of the injected substance.
High antipsychotic activity of haloperidol
combined with a mild sedative effect. The
mechanism of action of psychotropic haloperidole
associated with the blockade of dopamine
receptors in the central α-adrenergic blocking
properties, as well as in violation of the inversetion
process of neuronal uptake of norepinephrine and
deposition.
 Haloperidol in small doses blocks the
chemoreceptors trigger zone of the vomiting
center. Potentiates the action for narcosis,
governmental hypnotic and narcotic analgesics.
In contrast to haloperidol, phenothiazines not
shorten REM sleep. At therapeutic doses of
haloperidol and atropine no ganglioblocking
properties, it significantly inhibits the
peripheral α-adrenergic receptors. Blood
pressure usually does not reduce orthostatic
collapse does not cause.
Of the side effects of haloperidol is most likely
to breachtion of the extrapyramidal system
(Parkinson's). Skin reactions may be. Rarely
leykopoeza oppression. In case of overdose
appear anxiety, fear, sleeplessness.
 Butirofenona derivative is also the drug
droperidol. It differs from a short-acting
haloperidol. Droperidol is used mainly in
neuroleptanalgesia (in conjunction with a
painkiller - fentanyl).
The derivatives dibenzodiazepina is
clozapine (leponeks, azaleptin). It has high
antipsychotic activity. At the beginning of
the application can cause marked sedation,
which soon passes. Much less frequently
and to a lesser extent than other
neuroleptics cause extrapyramidal effects,
which is a significant advantage of the drug.
 Features of the pharmacodynamics of the drug,
possibly due to the fact that, according to existing
ideas, classical neuroleptics and clozapine
(phenothiazine derivatives, butyrophenones)
interact with different types of dopamine receptors.
It should also be noted that clozapine very
pronounced blocking activity against Mcholinergic receptors in the brain.
Clozapine is well tolerated. However, the treatment
they need to be under the control of peripheral
blood, as one group of patients (albeit limited)
were cases of agranulocytosis.
By neuroleptic applies alkaloid plant Rauwolfia
serpentina in enth. - P ithout e r n and n. Currently,
however, in honors antipsychotic drug, it is used
very rarely - only in case of intolerance of all other
neuroleptics.
 Prescribe antipsychotics for psychosis
(especially with a pronounced impact
excitation of, affective reactions, aggression,
presence of delusions, hallucinations).
Furthermore, they may be useful in the
treatment medicament relationship with
respect to narcotic analgesics, and ethyl
alcohol. The phenothiazines and
butyrophenones are also used as antiemetics and persistent hiccups. The
practical significance is its ability to
potentiate the effect of neuroleptics funds
for drug goat, sleeping pills, narcotic
analgesics.
 With long-term use of antipsychotic drugs
for the majority of them develop addictive.
Drug dependence arises.
Antipsychotics are contraindicated or
should be used with caution in the
pathology of the liver, kidney,
cardiovascular disease with symptoms of
decompensation in organic diseases General
of the nervous system, in violation of
hematopoiesis.
 Tranquilizers (anxiolytics)
The main groups of substances is an
anxiolytic (tranquillizers) and sedative
effects. Anxiolytic effect is manifested in the
elimination of fear, worry, anxiety, reduced
internal stress ¬ him. Tranquilizers are used
mainly in neurotic and neurotic (reactive)
states. Tranquillizers neuroleptics
congestion differ from that for most of them
psychosis little or ineffective, the autonomic
innervation by main products (except
amizila) has no effect, tranquilizers not
cause extrapyramidal disorders, seizure
threshold increase.
 Sibazon, hlozepida, phenazepam and nozepam
have strong anxiolytic and sedative properties.
Reducing emotional stress, they also contribute to
the onset of sleep. Psychoactive effects of these
drugs is mainly attributed to their effect on the
limbic system. For example, it is shown that
sibazon and analogs largely reduced spontaneous
activity of hippocampal neurons than
hypothalamus and brainstem reticular formation of
the brain. Benzodiazepines also suppress impulsive
aftereffect in Limbical system, as well as in the
hypothalamus. Apparently, some value has a
depressing effect on the reticular activating
formation of the brain stem, as benzodiazepines
inhibit the reaction EEG activation that occurs on
stimulation of the reticular formation.
 The body benzodiazepines react with the so-
called benzodiazepine receptors, which are
closely related to the GABA receptors. Upon
stimulation of benzodiazepine receptor
activation is observed GABA receptors. The
interaction between the benzodiazepine
receptors with the same name appears as a
GABA-mimetic effect.
One of the most effective tranquilizers is
phenazepam. By anxiolytic and hypnotic effects
it surpasses sibazon about 5 times.
Allocate benzodiazepine anxiolytic action with
and no or minimal sedative-hypnotic effect.
These drugs are sometimes referred to as "day
tranquilizers." These can be classified
Medazepam (rudotel).
 Benzodiazepines cause muscle relaxation,
which is caused by inhibition of this
polysynaptic spinal reflexes and the
violation of their supraspinal regulation
(such substances are considered among the
central governmental muscle relaxants).
Benzodiazepines have anticonvulsant ac ¬
ciency. Potentiate the depressant effect on
the central nervous system of substances
with narcotic type of action. The autonomic
Innervation they do not affect (manticholinergic, adrenergic blocking
properties ganglioblokiruyuschie and they
are not available). Blood pressure in the
usual therapeutic doses does not change.
 When administered hlozepida and sibazon absorbed
quickly nozepam - relatively slow. For the duration of
action of a substance can be arranged in the following
order: fenazepam> hlozepida> sibazon> nozepam.
For fenazepama shown to reduce its blood plasma by
50% occurs in 24-72 hours
In the body, benzodiazepines are biotransformation.
Meta, conjugates, and small amounts of drugs are
derived unchanged in the kidneys, in part - the
gastro-intestinal tract. Benzodiazepines are well
tolerated. However, in their application may
experience side effects: drowsiness, headache,
nausea, menstrual disorders, decreased sex on , skin
lesion. Chronic administration of benzodiazepines
develops addiction, drug dependence may occurence
(mental and physical).
Similar to the properties of benzodiazepines has
derived propanediol - meprotan (meprobamate,
andaksin).
 Meprotan well absorbed from the gastrointestinal
tract. 1-2 h after administration of plasma observed
maximum concentration of a substance that after 10
hours is starting to decline. Meprotan causes the
induction of microsomal liver enzymes. Reaction
products and the unchanged meprotan allocated
advantage considerably in the urine and partly with
excrement.
By meprotanu develop addiction and drug
dependence (physical and mental). When using
meprotan may experience drowsiness, lethargy,
muscle weakness, allergic reactions, rarely leukopenia.
Significantly different from the groups considered
derivative of diphenylmethane - amizil
(benaktizin).
 It belongs to the group of central cholinergic
antagonists. Its sedative action, obviously, to a
certain extent due to the inhibition of Mcholinergic reticular formation of the brain. This is
evidenced by the ability to remove the reaction
amizila EEG activation induced by
holinomimetikami. The EEG has amizil
synchronizing effect: there are high-voltage slow
oscillations.
Amizil increases the effects of substances such as
drugs and narcotic analgesics. Has anticonvulsant
activity. Suppresses the cough reflex.
For amizila also characteristic peripheral manticholinergic action (less pronounced than the
effect on the central m-cholinergic receptors).
 As a result, it reduces the spasms of smooth
muscles, dilates pupils of the eyes, inhibits
the secretion of the glands. Furthermore,
there amizila anesthetics, antihistaminic
and antiserotonin property.
Absorbed from the intestine amizil well.
Active within a few hours. Excreted in the
urine.
Side effects are mainly associated with its
action atropine (dry mouth, tachycardia,
pupillary dilation, etc.). The drug is
contraindicated in glaucoma.
By tranquilizers are also trioxazine, oksilidin
(benzoklidina hydrochloride) and a number
of other drugs.
 Tranquilizers are used mainly in the
neuroses and the neuroselike states. They
are appointed for sedation before Provence
surgery. They are widely used for insomnia.
Benzodiazepines and meprotan effective in
epilepsy, tetanus and other neurological
disorders involving skeletal muscle hyper.
Persons whose profession requires special
attention and fast reaction (eg, transport
drivers), appointed outpatient chat
tranquilizers should not be.