Psychiatric Drugs. Central Nervous System Stimulants

AnalepticUsed to stimulate respiration when natural

reflex is lostH-cholinomimetic (reflex analeptic)Central analeptic (Aminophyllin,

theophylline,Caffeine, Doxapram)

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

CamphoraCamphora

CNS Stimulants: Adverse effectsCVS: Palpitation, tachycardia, hypertension,

angina, dyshythmiaCNS: Nervousness, restlessness, anxietyEndocrine: Hypoglycemia, hyperglycemiaGIT: Nausea, vomiting,diarrhea

Usage of Usage of psychostimulating psychostimulating influence of caffeineinfluence of caffeine

For stimulation of psychological processes, workability, to eliminate somnolence

Enuresis, narcolepsyIn case of poisoning with alcoholTo 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 vesselsContraction of brain vesselsDilation of kidney vessels, increasing of diuresisDilation of kidney vessels, increasing of diuresisDilation of coronary vesselsDilation of coronary vessels

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

shows stimulating propertiesshows stimulating properties, , increases increases blood pressure, stimulates breathingblood pressure, stimulates breathing – –

analeptic actionanaleptic action

Did You Know?Caffeine is a xanthine alkaloid compound that

acts as a stimulant in humans. Caffeine is sometimes called guaranine when found in guarana, mateine when found in mate, and theine when found in tea. It is found in the leaves and beans of the coffee plant, in tea, yerba mate, and guarana berries, and in small quantities in cocoa, the kola nut and the Yaupon Holly. Overall, caffeine is found in the beans, leaves, and fruit of over 60 plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding upon them.

Chemical Properties

Molar Mass = 194.19 g mol−1 Density: 1.2 g/cm³

Phase: Solid

Melting Point: 237 °C

Boiling Point: 178 °C

CaffeineCaffeine

Uses of CaffeineCaffeine is a central nervous system (CNS)

stimulant, having the effect of temporarily warding off drowsiness and restoring alertness. Beverages containing caffeine, such as coffee, tea, soft drinks and energy drinks enjoy great popularity: caffeine is the world's most widely consumed psychoactive substance. In North America, 90% of adults consume caffeine daily.

CaffeineAPHate rateRespiratory stimulationAdjunctive effect

SIDE EFFECTS OF CAFFEINESIDE EFFECTS OF CAFFEINE If administered regularlyIf administered regularly – –

psychological addictionpsychological addiction – – theismtheism,, which is accompanied by which is accompanied by development of abstinent syndromedevelopment of abstinent syndrome ((retardness, fatigue, somnolence, retardness, fatigue, somnolence, depressiondepression))

ToleranceToleranceTeratogenic action (innate Teratogenic action (innate

abnormalities)abnormalities) Increasing of frequency of IHD, Increasing of frequency of IHD,

essential hypertensionessential hypertensionAcute attacks of ulcer diseaseAcute attacks of ulcer disease

(it increases gastric secretion(it increases gastric secretion))Acute poisoning in case of overdosingAcute poisoning in case of overdosing

Amphetamines Produce mood elevation or euphoria,

increase mental alertness and capacity for work, decrease fatigue and drowsiness, prolong wakefulness.

Amphetamines

USAGE:

ADHD (attention-deficit/hyperactivity disorderNarcolepsy

TOXICITY

TolerancePsychological dependenceHigh abuse potential (under Control Substance

Act

ADHD – ADHD – attention deficit hyperactivity disorder – attention deficit hyperactivity disorder – more frequently in childrenmore frequently in children

Cured by potent stimulators (ritalin, adderal Cured by potent stimulators (ritalin, adderal and others)and others)

They all can provoke addiction !!!They all can provoke addiction !!!

MethylxanthinesCOPD (chronic obstructive pulmonary

diseaseRespiratory depression in postoperative

recovery period

AnorexantsCentral acting (Benzphetamine,

diethylpropion, Sibutramine)Metabolism acting (orlistat)

Function of adrenergic synapse in physiological Function of adrenergic synapse in physiological conditionsconditions

ANTIDEPRESSANTSANTIDEPRESSANTS

Drugs which inhibit neuronal uptakeDrugs which inhibit neuronal uptake of of monoaminesmonoamines

1.1. Nonselective actionNonselective action – tricyclic compounds – tricyclic compounds ((blockblock uptakeuptake of noradrenaline and serotonineof noradrenaline and serotonine): ): imisinimisin, , amitriptilinamitriptilin

2.2. Selective actionSelective action: а) : а) heterocyclic compoundsheterocyclic compounds ( (block block neuronalneuronal uptakeuptake of noradrenalineof noradrenaline): ): amoxapinamoxapin, , maprotilinmaprotilin ((ludiomilludiomil));; б) б) selective blockers of neuronal uptake of selective blockers of neuronal uptake of serotoninserotonin: : fluoxetinfluoxetin ( (prozak, framexprozak, framex), ), sertralinsertralin ( (zoloftzoloft), ), paroxetinparoxetin ( (rexetinrexetin))

Inhibitors of monoaminoxidaseInhibitors of monoaminoxidase ( (IMAOIMAO))1.1. nonselectivenonselective ( (blockblock МАО-А МАО-А andand МАО-В): а) МАО-В): а) irreversibleirreversible

actionaction – – nialamidnialamid; ; bb) ) reversible actionreversible action – – transamintransamin

2.2. SelectiveSelective ІМАО ( ІМАО (blockblock МАО-А): МАО-А): moklobemidmoklobemid, , pirasidolpirasidol

Blockers of neuronalBlockers of neuronal reuptake of reuptake 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- 2НТ receptors

Compensatory decreasing of quantity and sensitivity of presynaptic 5- 1НТ receptors in

hippocampus and nuclei row (these structures play an important role іn

development of depression)

Blockers of neuronalBlockers of neuronal reuptake of serotoninreuptake 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 reuptake of serotoninreuptake 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: acute 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 Combination of three-cyclic antidepressants with IMAO is absolutely antidepressants with IMAO is absolutely contraindicatedcontraindicated:: danger of development of hypertensive crisis, seizures, rapid excitation, tachycardia, cardiac arrhythmias, increasing of temperature

Rules of transferring from one Rules of transferring from one kind of antidepressants to kind of antidepressants to anotheranother

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

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

Diet in case of administration of Diet in case of administration of IMAOIMAO

It is necessary It is necessary to excludeto exclude such products which containsuch products which contain

DOPADOPA andand thiraminethiramine ((which is formed from casein during the process which is formed from casein during the process of transforming under the influence of bacteriaof transforming under the influence of bacteria) )

aged cheese, kefiraged cheese, kefirMarinated herringMarinated herringSmoked meat, fishSmoked meat, fish

Red vine, beer, yeastRed vine, beer, yeastBeansBeans

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

……Any BAA are also dangerousAny 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

Neurometabolic Neurometabolic cerebroprotectorscerebroprotectors

Derivatives of pyrrolidoneDerivatives of pyrrolidone – – pyracetampyracetam ( (nootropilnootropil))Derivatives of GABA Derivatives of GABA – – aminalon, sodium aminalon, sodium

oxybutyrateoxybutyrateNeuropeptides Neuropeptides – – melatoninmelatonin, , sinacten-depotsinacten-depotCerebrovascular drugsCerebrovascular drugs – – sermionsermion ( (nicergolinnicergolin), ),

cavintoncavinton ( (vinpocetinvinpocetin), ), stugeronstugeron ( (cinnarisincinnarisin), ), pentoxyphyllinepentoxyphylline ( (trental, agapurinetrental, agapurine), ), xantynole xantynole nicotinatenicotinate

Derivatives of piridoxine Derivatives of piridoxine – – piritinolpiritinol ( (encephabolencephabol))Antioxidants Antioxidants – – mexidol, tocopherole acetatemexidol, tocopherole acetateOther Other – – cerebrolysinecerebrolysine, , actovegin, solkoseryl, plant actovegin, solkoseryl, plant

preparationspreparations

Properties of nootropic Properties of nootropic drugsdrugs

Improvement of brain blood circulation, promotion of collaterals development

Psychostimulating effect, antiasthenic actionSedative, antidepressive actionAntiepileptic, antiparkinsonic actionNootropic actionMnemotropic actionVasovegetative actionAntihypoxic action

Administration of nootropic Administration of nootropic drugsdrugs

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))

AdaptogensAdaptogensDrugs of

Ginseng, SchizandrumGinseng, Schizandrum, , RodiolaRodiola, , EleutherococcusEleutherococcus, , LeuseaLeusea, , EchinaceaEchinacea

Apilac, propolis, mumieApilac, propolis, mumie, ,

heparin, dibazolheparin, dibazol

GINSENGGINSENG

RODIOLARODIOLA

EleutherococcEleutherococcusus

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