Medicines suppressing the cental nervous system (CNS

Medicines suppressing the cental

nervous system (CNS depressant)

NATIONAL PHARMACEUTICAL UNIVERSITY

Department of Pharmacology

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Neuroleptics

(ANTIPSYCHOTIC MEDICINES)

Neuroleptics are psychotropic medicines that are

able to reveal the inhibitory action on the CNS (without

consciousness disturbing) eliminate hallucinations,

delirium and stop the psychomotor excitation (motor and

speech).

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Classification of neuroleptics

Derivatives of

phenotiazine butyrophenone Thioxanthene *,

dibenzodiazepine #,

benzamide &,benzisoxazole $

Chlorpromazine

Levomepromazine

Perphenazine

hydrochloride

Droperidol

Haloperidol

Clozapine #

Chlorprothixene *

Sulpyrid &

Risperidone $

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Pharmacological action

Antipsychotic effect (elimination of delusions, aggression)

is associated with blockade of dopaminergic D2 receptor reticular

formation (removed activating influence on the cortex of the

brain), nuclei, midbrain, limbic system, hypothalamus. With the

same linked primary and side effects - extrapyramidal disorder, a

syndrome similar to Parkinson's disease.

Potential action is caused by blockade a-AR and reticular

formation.

Antiemetic effect is related to the blockade of dopaminergic (D2)

and serotonin receptors "trigger zone“ of medula oblongata and

termination of the signals in the emetic center.

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The Hypothermic effect is the result of adreno- and

serotonin receptors blockade and, therefore, decrease of the activity

of the hypothalamic thermoregulation centres (decrease of the heat

production and increase of the heat emission).

The Antihistamine effect implemented by the blockade of H1-

histamine receptors.

The Hypotensive effect - the result of blockade of AR and a-

dofaminoretseptors in the hypothalamus and peripheral vessels.

The Neuroleptic (weakness, drowsiness, paralysis of will", motor

inhibition) action - blockade of central and a-AR reticular

formation, limbic system, hypothalamus.

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Effects and related indications

Pharmacodynamics (effects) → Indications

Antipsychotic Psychosis (schizophrenia etc.)

Potentiating

(for medicines that suppress CNS)

Neuroleptanalgesia, potentiation

of narcosis

Anti-emetic Uncontrolled vomiting of the

central genesis (in pregnant women

with anti-tumor therapy)

Hypothermic Controlled hypothermia during

narcosis

Antihistaminic Severe neurodermitis

Hypotensive Severe forms of arterial

hypertension with psychomotor

excitation (chlorpromazine only)

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Side effects → Contraindications

Neuroleptic syndrome, drug-

induced parkinsonism, dyspepsia

Depression, parkinsonism

Derivatives of phenotiazine, butyrophenone, thioxanthene

called "typical" neuroleptics, as they lead to the development of

medicinal parkinsonism ( D2 receptor in the black substance and

striped body region)-extrapyramidal disorders.

Risperidone, clozapine are atypical neuroleptics

Side effects of typical neuroleptics and related

contraindications

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These new medications were approved for use in the 1990s.

Clozapine, asenapine, olanzapine, quetiapine, paliperidone,

risperidone, sertindole, ziprasidone, zotepine, and aripiprazole are

atypical antipsychotic drugs. With the discovery of clozapine in

1959, it became evident that this drug was less likely to produce

extrapyramidal effects (physical symptoms such as tremors,

paranoia, anxiety, dystonia, etc. as a result of improper doses or

adverse reactions to this class of drug) in humans at clinically

effective doses than some other types of antipsychotics. Clozapine

was categorized as the first atypical antipsychotic drug. This

category of drugs has also been of great value in studying the

pathophysiology of schizophrenia and other psychoses.

Atypical Antipsychotics,

or Second Generation Antipsychotic Drugs

The pharmacological “face” of neuroleptics

Antipsychotic effect :

Haloperidol Droperidol Closapine Chlorprothixene =

Chlorpromazine =Perphenazine hydrochloride=Sulpyrid

Levomepromazine

Potentiating effect:

Haloperidol Droperidol Levomepromazine Chlorpromazine.

Anti-emetic effect :

Haloperidol Perphenazine hydrochloride Droperidol

Sulpyrid Chlorpromazine

Neuroleptic effect :

Derivatives of phenothiazine = butyrophenone thioxanthene

Closapine Sulpyrid.

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TRANQUILIZERS

(ANXIOLYTICS, ATARACTICS, ANTIPHOBIC

MEDICINES)

Tranquilizers (in Latin tranquillare – „to make calm”)

are medicines that remove selectively fair, anxiety, emotional

tension increased restlessness and are used mainly in neuroses

and the related states.

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Classification of tranquilizers

Derivatives of benzodiazepines Derivatives of

diphenylmetanum and other

chemical groups

Diazepan Alprazolam

Phenazepam Lorazepam

Chlordiazepoxide Gidazepam

Hydroxysine*

Meprobamat

Medazepam, Gidazepam, Trimetosine are “day time”

tranquilizers as they cause less inhibition of CNS than other

medicines, therefore,they can be used in day time.

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The mechanism of action

They decrease the excitability of subcortical regions of

the brain (the limbic system, thalamus, the reticular formation,

the hypothalamus), that are responsible for emotional reactions,

inhibit the interaction between these structures and the brain

cortex.

Benzodiazepines stimulate mainly benzodiazepine

receptors and that leads to activation of GABA-receptors and

intensification of the inhibitory functions of GABA .

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Benzodiazepines

GABA

The mechanism of Benzodiazepines action

Ion

channel

Extracellular

compartment

Cytoplasm

Membrane

of neuron



Аnxiolytic Neuroses

Stress-protective Stress-reaction

Hypnotic Insomnia (especially caused by

negative emotions)

Sedative Neurogenic diseases

Anticonvulsant Convulsions (epilepsy)

Potentiating Premedication

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Drowsiness, weakness,

disorders of attention and

locomotion, tolerance, addiction

Activities that require rapid

psychomotor reactions. Long-

term courses of treatment.

Increase of doses

Side effects and related contraindications

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The pharmacological «face» of tranquilizers

Medicines Tranquili-

zing effect

Addiction/

tolerance

Side

effects

Other effects

Phenazepam ++++ +/+ + Anticonvulsant, hypnotic, sedative,

spasmolytic (diazepam)Diazepam +++ +/+ ++

Chlordiaze-

poxide

++ +/+ +

Lorazepam ++ - + Accumulation, anticonvulsant, hypnotic

Alprazolam + - + Anticonvulsant, antidepressant

Gidazepam + - Anticonvulsant, potentiating, stimulating

Hydroxysi-

ne

- + Analgesic, myorelaxant, antiemic

Meproba-

mat

+ ++/+ ++ Anticonvulsant

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Sedative Medicines

Sedative medicines (in Latin sedatio is

calming) are medicines that cause a moderate

sedative effect as a result of decrease of CNS

excitability and its reactivity of different stimuli


They increase of the inhibitory processes in the

CNS and decrease of the excitability of the reticular

formation and the brain cortex.

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Classification of medicines

Plant

origin

Bromide compounds *

and Combined **

Persenum**

Valerian extract

Novo-passit**

Sodium bromide*

Corvalol** (Valocordin)

Valocormide**

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Sedative Neuroses, increased irritability,

neurogenic disease, insomnia

Stress-protective Stress-reaction

Potentiating Intensification of effects of CNS

depressants, the early stage of

hypertension


Decrease of the mental and

physical activity, feeling of

fatigue, drowsiness

Activities that require rapid

psychomotor reactions

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The features of sedative medicines is the lack of

significant side effects because they are widely used in

outpatient practice and in elderly patients.

At long use drugs generates bromine "bromizm": general

retardation, drowsiness, weakening of memory, apathy,

decreased potency, tearing, cough, running nose, skin rash.

Treatment: immediately stop taking the drug, the

introduction of large numbers of sodium chloride (20 g per

day) and need to drink a lot.

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Pharmacological «face» of sedative drugs

Preparations EffectsComposition/other effects

Sedative Spasmolytic

Sodium

bromide

+++ Anticonvulsant

Urticae

Canine

Tincture

++

Valerian

extract

+ + Spasmolytic

Persen + + Mint, Melissa

Corvalol ++ + Phenobarbital, mint oil

Valocordin + + Sodium bromide, Convallaria,

Belladonna, Menthol

Novo-passit ++ + Guaphenesine, extracts of Crataegus,

Humulus, Hypericum, Milissa,

Passiflora, Sambucus

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Hypnotic medicinesDisorders of sleep (insomnia, hyposomnia) are one of the

states that are common and occur independently (primary

insomnia), and at the different somatic and psychiatric

pathologies (the secondary insomnia).

If the sleep disorder is repeated more than 4 times a week,

which requires pharmacological correction as insomnia

(violation of physiological rhythms in the CNS) leads to

overexcited, fatigue, exhaustion of the brain and, consequently,

to different forms of pathology of neurogenic origin.

Hypnotics are products that tend to restore the process of

falling asleep, sleep duration and depth of their violation.

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of sedative medicinesInhibit some brain structures (mainly cerebral cortex).

Weaken the activating reticular formation of the discharges in the

cerebral cortex.

In the mechanism of action of benzodiazepine and barbituric acid

an important part plays their relationship with benzodiazepine

receptors and barbiturate-benzodiazepine-GABA receptor

complex, leading to strengthening of the natural inhibitory

neurotransmitter GABA (gamma amino butyric acid)

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Hypnotics


Hypnotic Disorder of sleep

Potentiating Intensification of the effects of CNS

depressants

Sedative(low doses) Mild neuroses, neurotic syndrome


Apathy, drowsiness, weakness Activities that require the rapid

psychomotor reactions

Most sleeping drugs causes the violation of the structure sleep

syndrome "aftereffect", "return", “withdrawal", physical and psychological

dependence, addiction, cummulation (especially barbiturates).

Closest to the ideal of sleeping drugs - zopiklon and zolpidem.

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Derivatives of

benzodiazepine,

barbituric acid

Derivatives of

cyclopyrrolone,

imidazopyridine,*

methylbutamide**

Combined medicines

Nitrozepam

Phenobarbital

Cyclobarbital*

Zopiclone

Zolpidem*

Bromisoval**

Reladorm

(cyclobarbital +

diazepam)

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The pharmacological «face» of hypnotic medicinesPhenobarbital reladorm bromisoval zolpidem = zopiclon nitrazepam

Medicines Sleep

duration

Accu-

mulati

-on

Addiction Effective in disorder of Withdra-

wal

Disorder

of the

sleep

phases

After

action

Falling

asleep

Sleep

duration

Phenobarbital 8-10 +++ +++ + + +++ + +++

Cyclobarbital 5-6 ++ +++ + +++ + ++

Nitrazepam 6-8 + ++ + + ++ + ++

Zopiderm 6-8 - + + + -

Zopiclone 6 - + + -

Bromisoval 6 ++ - + - ++

Reladorm 6 ++ +++ + + +++ ++

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Anticonvulsants

Anticonvulsant medicines decrease or stop

convulsions in pathological states of the organism

Mechanism of action

Inhibition the pathological activity of neurons in epileptic

foci of motor cortex areas and subcortical structures by

reducing the utilization of O2, energetic and exciting action

of amino acids (glutaminum and aspartamum), blocking Ca-

and Na-channels in the epileptic foci, stimulation of GABA-

ergic inhibitory mechanisms

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Classification

Benzodiazepines Valproates Barbiturates

Diazepam

Clonazepam

Valproic acid Benzobarbital

Phenobarbital

Succinimides Iminostilbens Others

Ethosuccimide Carbamazepine Tolperizone

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Anticonvulsant effect Convulsions of different origin

(epilepsy, craniocerebral traumas,

tumours of the CNS, meningitis)


CNS inhibition, mental confusion,

drowsiness, depression, tolerance

Activities that require attention,

depression

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The principles of correct usage of anticonvulsants:

- Individually assemble the necessary combination of drugs;

- Increase the dose gradually;

- Evaluate the effectiveness of drugs in a few weeks of treatment

(number of convulsions should decrease by 50%);

- If necessary to make the gradual replacement of one drug,

reducing its dose, the second (in increasing doses);

- Conduct continuous therapy (discontinuation of the drug allowed

after 4-5 years in the absence of pathological changes in

electroencephalogram).

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Antiparkinsonian medicines


Antiparksionian effect Parkinsons desease, Parkinson syndrome


Antiholynergic tachycardia

glaucoma, constipation

Dophaminenergic psychosis

Antiglutamatergic Epilepsy, hypotension

All medications must be taken with brief intervals

(1-2 days / week) for the prevention of tolerance (habituation).

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The pharmacological «face» of anticonvulsantsMedicines Convulsive attacks:

g\s

Epyleptic status SE Other effects

Benzobarbital +

-

- + Sedative, hypnotic

Phenobarbital +

-

+ ++

Diazepam

-

+ +++ Sedative, hypnotic,

tranquilizing

Clonazepam +

+

+ ++

Carbamazepine +

-

- +++ Antidepressant,

normothymic, analgesic

Valproic acid +

+

- + Anxiolytic

Ethosuccimide -

+

- + Tranquilizing, analgesic

Tolperizone -

+

- + Sedative, hypnotic

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Drugs used to treat Parkinson disease and syndrome of

parkinsonism, including medicinal parkinsonism.

Mechanism of action

At these diseases in the CNS is disturbed balance of neurotransmitters:

the quantity of dopamine and acetylcholine content is increased. These

means restoring the balance between dopaminergic and cholinergic brain

systems.

The mechanism of action of drugs are divided into:

I. Anticholinergic - blocking the central (reducing the influence of

acetylcholine in the CNS) and peripheral M-cholinoreceptors.

II. Dopaminergic - restore the dopamine deficiency in the CNS.

III. Antyglutamatergic - reduce the exciting action of glutamate neurons

in the CNS, which develop on the background of dopaminergic system

failure.

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Drugs for parkinsonism treatment


Anticholinergic

(cholinolytic)

Dophaminer-

gic ones

Antiglutamatergic

ones

Trihexiphenydil Levodopa

Levodopa +

carbidopa (Nacom)

Bromocriptine

Selegiline

Amantadine

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Dopaminergic ending

LevodopaLevodopa

DOPA decarboxylase

Amantadine

Bromocriptine

CNS

Amantadine

Postsinaptic D2-receptors

Selegiline

Dopamine

reuptake

Dopamine

release

Dopamine

Mechanism of action

The pharmacological «face» of antiparkinsonian medicines

Medicines Antiparkinsonian

effectSide

effects

Other effects

Levodopa +++

(gold standard

therapy)

+ The maximum effect in a month.Little impact on theautonomic and mental disorders, a characteristicphenomenon of "inclusion and exclusion"

Nacom +

(briefly)

+,

tolerance

Combination: levodopa, carbidopa. The effect is rapid,

less toxic

Selegiline ++ + Antidepressant.The need to combine with levodopa or

nakomom

Trihexilphe-

nydil

+ ++ Cholinolytic

Amantadine + +,

tolerance

Cholinolytic, antiviral

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Thank you!

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Medicines suppressing the cental nervous system (CNS