Activating CNS agentsActivating CNS agents

Lector prof. Posokhova K.A.Lector prof. Posokhova K.A.

PSYCHOTROPIC DRUGSPSYCHOTROPIC DRUGSDrugs withDrugs with depressivedepressive type of actointype of actoin

1.1. Neuroleptics Neuroleptics ((antipsychoticantipsychotic))2.2. Tranquilizers Tranquilizers ((anxiolyticsanxiolytics))3.3. Sedative drugsSedative drugs4.4. Normotymics Normotymics ((tymolepticstymoleptics, , tymoanalepticstymoanaleptics))

Drug withDrug with stimulativestimulative actionaction1.1. Antidepressants Antidepressants 2.2. Psychomotor stimulantsPsychomotor stimulants3.3. Nootropic drugsNootropic drugs4.4. Drugs which increase general tone Drugs which increase general tone

((adaptogensadaptogens))

PsychotomimeticsPsychotomimetics ((psychodyslepticspsychodysleptics))1.1. LSD LSD 2.2. Cannabis sativa L.Cannabis sativa L.

ANTIDEPRESSANTSANTIDEPRESSANTS

WHOWHO: 3-6 % : 3-6 % of Earth population suffer from of Earth population suffer from depressiondepression

Depression and somatic-vegetative symptoms Depression and somatic-vegetative symptoms which accompany depression are quite often which accompany depression are quite often psychical disorders which happen in general psychical disorders which happen in general medical practice.medical practice.

There areThere are::

1.1. EndogenEndogen ( (psychogenicpsychogenic)) depressiondepression – – schizophreniaschizophrenia, , maniac-depressive psychosismaniac-depressive psychosis

2.2. Secondary Secondary ((somatogenicsomatogenic)) depressiondepression – – organic diseasesorganic diseases ( (oncology patientsoncology patients, , hypertensionhypertension, , ulcer diseaseulcer disease, , climacteric disorders etc.climacteric disorders etc.))

More thanMore than 50 % 50 % of patients with depressive disorders don’t of patients with depressive disorders don’t realize that they have any psychological problems and realize that they have any psychological problems and

complain only on certain somatic dischargescomplain only on certain somatic discharges

Most frequent complaints of patients with depressionFeeling of hopelessness, indifference, fear, panic attacks,

tiredness, weakness, headache, dizziness, dream disorders, dyspepsia, unpleasant feelings and pain in different parts of

the body

Depressive conditions “mask” as vegetal-vascular, neuro-circulative dystonia (various vegetative disorders), gastro-

intestinal pathology, pathology of cardio-vascular, respiratory systems, manifest as diskinesia, functional motor disorders, insomnia, toothache, disorders of sexual activity, recidivate

eczema and many other disorders

Function of adrenergic synapse in Function of adrenergic synapse in physiological conditionsphysiological conditions

ANTIDEPRESSANTSANTIDEPRESSANTS

Drugs which inhibit neuronal uptake of monoamines

1. Nonselective action (block uptake of noradrenaline and serotonine): imisin, amitriptilin

2. Selective action: а) heterocyclic compounds (block neuronal uptake of noradrenaline): amoxapin, maprotilin (ludiomil); б) selective blockers of neuronal uptake of serotonin: fluoxetin (prozak, framex), sertralin (zoloft), paroxetin (rexetin)

Inhibitors of monoaminoxidase (IMAO)1. nonselective (block МАО-А and МАО-В): а) irreversible

action – nialamid; b) reversible action – transamin

2. Selective ІМАО (block МАО-А): moklobemid, pirasidol

Blockers of neuronalBlockers of neuronal uptake of uptake of serotonin serotonin

Modern point of view on mechanism of development of depression

Primary deficiency of serotonin in synaptic cleft

Compensatory growing of quantity and sensitivity of postsynaptic 5-НТ2 receptors

Compensatory decreasing of quantity and sensitivity of presynaptic 5-НТ1 receptors in hippocampus and

nuclei row (these structures play an important role іn development of depression)

Blockers of neuronalBlockers of neuronal uptake of serotoninuptake of serotonin

fluoxetinfluoxetin, , sertralinsertralin, , paroxetinparoxetin

Mechanism of actionMechanism of actionIncreasing of active concentration of serotonin in synaptic cleft on a level

of postsynaptic

5-НТ2 serotonin receptors of cerebral structures

Blockers of neuronalBlockers of neuronal uptake of serotoninuptake of serotonin

fluoxetinfluoxetin, , sertralinsertralin, , paroxetinparoxetin

Mechanism of action of IMAOMechanism of action of IMAO

Usage of antidepressantsUsage of antidepressants

SchizophreniaSchizophrenia, , MDSMDS

Atherosclerosis of brainAtherosclerosis of brain

Reactive depressionsReactive depressions

Parkinsonism Parkinsonism

Organic diseases of CNSOrganic diseases of CNS

Oncology patientsOncology patients

General somatic diseasesGeneral somatic diseases

Psychotropic action of Psychotropic action of antidepressantsantidepressants

1. Drugs with psychosedativepsychosedative action:

ААmitriptilinmitriptilin, , maprotilinmaprotilin,, asafen asafen, , fluvoxaminfluvoxamin

2. Drugs with psychostimulativepsychostimulative action:

ImisinImisin, , nialamidnialamid, , fluoxetinfluoxetin

3. Drugs with regulativeregulative influence

PirasidolPirasidol

Principles of antidepressants usagePrinciples of antidepressants usage

• Endogen depression – the deeper it is, the larger doses, rate of their increasing and duration of treatment should be administered

• Step-by-step dose increasing till obtaining of effect, administration of effective dose during 4-6 weeks – 3-6 months, gradual decreasing of dose (during 5-6 weeks)

• Effect can appear only after 7-14 days after beginning of therapy (this fact should be taken into consideration in patients with suicidal dispositions)

• In case of rapid abolishing withdrawal syndrome may develop

Side effects of antidepressantsSide effects of antidepressants

• ММ-cholinoblocking action-cholinoblocking action: dry mouth, increasing of intraocular pressure, disturbance of accommodation, constipation, ischuria (important in a case of adenoma of prostatic gland!), tremor, hallucinations, disorders of consciousness, excitation

• Alpha-adrenoblocking, papaverine-like effectAlpha-adrenoblocking, papaverine-like effect: sharp hypotension, orthostatic collapse (especially in combination of amitriptiline with clopheline), for correction of which adrenomimetics cannot be used (it is necessary to increase volume of circulating blood, put the legs up)

Side effects of antidepressantsSide effects of antidepressants

• Acute attacks of epilepsy epilepsy

• CardiotoxicCardiotoxic action (sudden death), three- cyclic antidepressants increase arrhythmogenic activity of drugs for general anesthesia, antihistamines etc.

• Combination of three-cyclic antidepressants Combination of three-cyclic antidepressants with IMAO is absolutely contraindicatedwith IMAO is absolutely contraindicated:: danger of development of hypertensive crisis, seizures, rapid excitation, tachycardia, cardiac arrhythmias, increasing of temperature

Rules of transferring from one kind of Rules of transferring from one kind of antidepressants to anotherantidepressants to another

• From three-cyclic to IMAO – break time– 2-3 days

• From IMAO to three-cyclic – break time – not less than 2 weeks

It is absolutely contraindicated to It is absolutely contraindicated to administer adreno(sympato)mimetics in administer adreno(sympato)mimetics in case of treatment with antidepressantscase of treatment with antidepressants

Even small doses of adrenomimetic (sympatomimetic) substances in such patient

can cause hypertensive crisis:hypertensive crisis: • Nose drops for rhinitis• If few drops were added to solutions of local

anesthetics• In case of administration of drugs which

contain pseudoephedrine (they are widely used for cold at nowadays)

Diet in case of administration Diet in case of administration of IMAOof IMAO

It is necessary to exclude such products which contain DOPA and thiramine (which is formed from casein during the process of

transforming under the influence of bacteria)

aged cheese, kefirMarinated herringSmoked meat, fish

Red vine, beer, yeastBeans

oranges, tangerines, lemons, grape, bananas, chocolate, caviar (red and black)…

…Any BAA are also dangerous

In case of treatment with IMAO new products should be In case of treatment with IMAO new products should be introduced intointroduced into ration very carefullyration very carefully

• In case of administration of inhibitors of uptake of serotonin the previously indicated side effects are observed much more rarely

• Administration of antidepressants with any other drugs should be performed only after precise studying of possible negative consequences of their interaction

PSYCHOMOTOR PSYCHOMOTOR STIMULANTSSTIMULANTS

PSYCHOMOTOR STIMULANTSPSYCHOMOTOR STIMULANTS

• Derivatives of purine – caffeinecaffeine

• Phenilalkilamines – phenaminephenamine ((amphetamineamphetamine))

• Phenilalkilsydnonimins - sydnocarbsydnocarb

Properties of psychomotor Properties of psychomotor stimulantsstimulants

• Stimulate intellectual activity, speed up thinking processes, temporarily eliminate tiredness, somnolence

• Eliminate such manifestations of neurosis neurosis as:as: subdepression, fatigue, retardness subdepression, fatigue, retardness

• Aren’t able to eliminate endogen depression, which accompanies psychical diseases

Caffeine Caffeine

Mechanism of action

• Binds to adenosine adenosine (“(“purinepurine”) ”) receptorsreceptors in brain (endogen ligand of these receptors – adenosine decreases processes of excitation in CNS)

• Inhibiting of phosphodiesteraseInhibiting of phosphodiesterase, which leads to accumulation of cAMP and stimulation of many physiological processes and metabolism

CaffeineCaffeine

Usage of psychostimulating Usage of psychostimulating influence of caffeineinfluence of caffeine

• For stimulation of psychological processes, workability, to eliminate somnolence

• Enuresis, narcolepsy• In case of poisoning with alcohol• To speed up awakening after narcosis

Influence of caffeine on Influence of caffeine on cardiac-vascular systemcardiac-vascular system

Vessels Vessels 1. Stimulation of vasomotor center –

contraction of vessels, increasing of AP2. Peripheral myotropic spasmolytic action

– dilation of vessels, decreasing of AP

HeartHeart1. Central action (increasing of n. vagus

tone) – bradycardia2. Peripheral action (direct influence on

heart) – tachycardia, possible extrasystolia

Influence of caffeine on cardio-Influence of caffeine on cardio-vascular systemvascular system

• Contraction of brain vessels• Dilation of kidney vessels, increasing of diuresis• Dilation of coronary vessels

In case of depression of centers of brain stem (medulla oblongata) caffeine

shows stimulating properties, increases blood pressure, stimulates breathing –

analeptic actionanaleptic action

SIDE EFFECTS OF CAFFEINESIDE EFFECTS OF CAFFEINE• If administered regularly – psychological

addiction – theism, which is accompanied by development of abstinent syndrome (retardness, fatigue, somnolence, depression)

• Tolerance• Teratogenic action (innate abnormalities)• Increasing of frequency of IHD, essential hypertension• Acute attacks of ulcer disease (it increases gastric

secretion)• Acute poisoning in case of overdosing

NOOTROPIC DRUGSNOOTROPIC DRUGS

((NEUROMETABOLIC NEUROMETABOLIC CEREBROPROTECTORS)CEREBROPROTECTORS)

Neurometabolic Neurometabolic cerebroprotectorscerebroprotectors

• Derivatives of pyrrolidone – pyracetam (nootropil)• Derivatives of GABA – aminalon, sodium

oxybutyrate• Neuropeptides – melatonin, sinacten-depot• Cerebrovascular drugs – sermion (nicergolin),

cavinton (vinpocetin), stugeron (cinnarisin), pentoxyphylline (trental, agapurine), xantynole nicotinate

• Derivatives of piridoxine – piritinol (encephabol)• Antioxidants – mexidol, tocopherole acetate• Other – cerebrolysine, actovegin, solkoseryl, plant

preparations

Properties of nootropic drugsProperties of nootropic drugs

• Improvement of brain blood circulation, promotion of collaterals development

• Psychostimulating effect, antiasthenic action

• Sedative, antidepressive action

• Antiepileptic, antiparkinsonic action

• Nootropic action

• Mnemotropic action

• Vasovegetative action

• Antihypoxic action

Administration of nootropic drugsAdministration of nootropic drugs

• Atherosclerosis of brain, vascular parkinsonism, Alzheimer's disease

• Disorders of brain blood circulation in case of traumas and intoxications, vascular diseases of brain

• Diseases of CNS, accompanied by decreasing of intellect, memory

• Disorders of psychology (in elderly with schizophrenia, depressions)

• To decrease manifestations of abstinence (alcoholism, drug addiction)

• In neurology (neurasthenia, migraine, neuralgias, radiculitis)

• In pediatrics in case of mental insufficiency

Piracetam Piracetam ((nootropilnootropil))

CerebrolysinCerebrolysin

CinnarizinCinnarizin ( (stugeronstugeron))

ADAPTOGENSADAPTOGENS

AdaptogensAdaptogensDrugs of

Ginseng, Schizandrum, Rodiola, Eleutherococcus, Leusea,

Echinacea

Apilac, propolis, mumie, heparin, dybazol

GINSENGGINSENG

RODIOLARODIOLA

EleutherococcEleutherococc

Schizandrum

Echinacea purpurea MaximaEchinacea purpurea Maxima

ADAPTOGENSIncrease general resistance of the organism

towards unfavorable factors

Stimulating actionAntistress action Anabolic action

Side effects of adaptogens

Increasing of AP

disturbance of sleep if administered in evening time, overwhelming

excitation, psychical dependence

AnalepticsAnaleptics ( (BemegridumBemegridum,, Camphora Camphora, , CordiaminumCordiaminum))

CamphoraCamphora