cns stimulants. psychotropic drugs drugs with depressive type of actoin 1.neuroleptics...
TRANSCRIPT
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CNS StimulantsCNS Stimulants
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PSYCHOTROPIC 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.
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ANTIDEPRESSANTSANTIDEPRESSANTS
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DEPRESSION
• Types
• Symptoms
• Diagnosis
• Causes
• Treatment
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TYPES OF DEPRESSION• Major depression
• Chronic depression (Dysthymia)
• Atypical depression
• Bipolar disorder/Manic depression
• Seasonal depression (SAD)
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CAUSES OF DEPRESSION
• Genetics
• Death/Abuse
• Medications
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SYMPTOMS• persistently sad, anxious, or empty moods• loss of pleasure in usual activities (anhedonia)• feelings of helplessness, guilt, or worthlessness• crying, hopelessness, or persistent pessimism• fatigue or decreased energy• loss of memory, concentration, or decision-making
capability• restlessness, irritability• sleep disturbances• change in appetite or weight• physical symptoms that defy diagnosis and do not respond to
treatment (especially pain and gastrointestinal complaints)• thoughts of suicide or death, or suicide attempts• poor self-image or self-esteem (as illustrated, for example,
by verbal self-reproach)
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More than 50 % of patients with depressive disorders don’t realize that they have any psychological problems and
complain only on certain somatic discharges
Most frequent complaints of patients with depressionFeeling of hopelessness, indifference, fear, panic
Tiredness, weakness, headache, dizziness, dream disorders, dyspepsia, unpleasant feelings and pain in different parts of
the body
Depressive conditions “mask” as vegetovascular, neurocirculative 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
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TREATMENT FOR DEPRESSION
• Psychotherapy
• Electroconvulsive therapy
• Natural alternatives
• Medication• SSRIs
• MAOIs
• TCAs
• SNRIs
• NDRIs
• TeCAs
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NEUROTRANSMITTERS AND THE CATECHOLAMINE
HYPOTHESIS• Neurotransmitters pass along signal
• Smaller amount of neurotransmitters causes depression
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Function of adrenergic synapse in Function of adrenergic synapse in physiological conditionsphysiological conditions
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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
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TCAS MECHANISM OF ACTION
• TCAs inhibit serotonin, norepinephrine, and dopamine transporters, slowing reuptake
• TCAs also allow for the down regulation of post-synaptic receptors
• All TCAs and SSRIs contain an essential amino group that appears to interact with Asp-98 in hSERT
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TCAS SIDE EFFECTS• Muscarinic M1 receptor antagonism - anticholinergic effects
including dry mouth, blurred vision, constipation, urinary retention and impotence
• Histamine H1 receptor antagonism - sedation and weight gain
• Adrenergic α receptor antagonism - postural hypotension
• Direct membrane effects - reduced seizure threshold, arrhythmia
• Serotonin 5-HT2 receptor antagonism - weight gain (and reduced anxiety)
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TCAS SIDE EFFECTS• Nonselectivity results in
greater side effects
• TCAs can also lead to cardiotoxicity– Increased LDH leakage– Slow cardiac conduction
• High potency can lead to mania– Contraindicated with persons
with bipolar disorder or manic depression
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MONOAMINE OXIDASE (MAO) AND DEPRESSION
• MAO catalyze deamination of intracellular monoamines– MAO-A oxidizes epinephrine, norepinephrine, serotonin– MAO-B oxidizes phenylethylamine– Both oxidize dopamine nonpreferentially
• MAO transporters reuptake extracellular monoamine
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MAOIS MECHANISM OF ACTION
• MAO contains a cysteinyl-linked flavin
• MAOIs covalently bind to N-5 of the flavin residue of the enzyme
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Mechanism of action of IMAOMechanism of action of IMAO
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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 gap
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)
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Blockers of neuronalBlockers of neuronal uptake of serotoninuptake of serotonin
fluoxetinfluoxetin, , sertralinsertralin, , paroxetinparoxetin
Mechanism of actionIncreasing of active concentration of
serotonin in synaptic gap on a level of postsynaptic
5-НТ2 serotonin receptors of cerebral structures
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Blockers of neuronalBlockers of neuronal uptake of serotoninuptake of serotonin
fluoxetinfluoxetin, , sertralinsertralin, , paroxetinparoxetin
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SSRIS SIDE EFFECTS
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SSRIS SIDE EFFECTS• Many disappear within 4 weeks (adaption
phase)
• Side effects more manageable compared to MAOIs and TCAs
• Sexual side effects are common
• SSRI cessation syndrome– Brain zaps– Sexual dysfunction
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SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS)
• Slightly greater efficacy than SSRIs
• Slightly fewer adverse effects than SSRIs
• Current drugs
– Venlafaxine (Effexor)
– Duloxetine (Cymbalta)
• Mechanism of Action
– Very similar to SSRIs
– Works on both neurotransmitters
• Side effects
– Similar to SSRIs
– Suicide
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Usage of antidepressantsUsage of antidepressants
Schizophrenia, Bipolar disease
Atherosclerosis of brain
Reactive depressions
Parkinsonism
Organic diseases of CNS
Oncology patients
General somatic diseases
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Psychotropic action of Psychotropic action of antidepressantsantidepressants
1. Drugs with psychosedative action:
Аmitriptilin, maprotilin, asafen, fluvoxamin
2. Drugs with psychostimulative action:
Imisin, nialamid, fluoxetin
3. Drugs with regulative influence
PirasidolPirasidol
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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
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Side effects of antidepressantsSide effects of antidepressants
• М-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 effect: sharp hypotension, orthostatic collapse (especially in combination of amitriptiline with clopheline), for correction of which adrenomimetics can’t be used (it is necessary to increase volume of circulating blood, put the legs up)
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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
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Rules of transferring from one kind of antidepressants to another
• From three-cyclic to IMAO – break time– 2-3 days
• From IMAO to three-cyclic – break time – not less than 2 weeks
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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
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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, kefir
Marinated herring
Smoked meat, fish
Red vine, beer, yeast
Beans
Any BAA are also dangerous
In case of treatment with IMAO new products should In case of treatment with IMAO new products should be introduced intobe introduced into ration very carefullyration very carefully
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• 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
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PSYCHOMOTOR PSYCHOMOTOR STIMULANTSSTIMULANTS
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PSYCHOMOTOR STIMULANTSPSYCHOMOTOR STIMULANTS
• Derivatives of purine – caffeinecaffeine
• Phenilalkilamines – phenaminephenamine ((amphetamineamphetamine))
• Phenilalkilsydnonimins - sydnocarbsydnocarb
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Properties of psychomotor Properties of psychomotor stimulantsstimulants
• Stimulate intellectual activity, speed up thinking processes, temporarily eliminate tiredness, somnolence
• Eliminate such manifestations of neurosis as: subdepression, fatigue, retardness
• Aren’t able to eliminate endogen depression, which accompanies psychical diseases
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CaffeineCaffeine
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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.
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Chemical PropertiesMolar Mass = 194.19 g mol−1 Density: 1.2 g/cm³
Phase: Solid
Melting Point: 237 °C
Boiling Point: 178 °C
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Uses of Caffeine
• Caffeine 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.
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Metabolizing Of Caffeine• Caffeine is completely absorbed by the stomach and
small intestine within 45 minutes of ingestion. After ingestion it is distributed throughout all tissues of the body and is eliminated by first-order kinetics. The half-life of caffeine varies widely among individuals according to such factors as age, liver function, pregnancy, some concurrent medications, and the level of enzymes in the liver needed for caffeine metabolism. In healthy adults, caffeine's half-life is approximately 3-4 hours. In women taking oral contraceptives this is increased to 5-10 hours, and in pregnant women the half-life is roughly 9-11 hours. Caffeine can accumulate in individuals with severe liver disease when its half-life can increase to 96 hours.
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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
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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
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Influence of caffeine on cardiac-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
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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
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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
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CNS STIMULANTS
• Medically approved use is for the treatment of Attention deficit/hyperactivity disorder (ADHD), narcolepsy, obesity & reversal of respiratory distress
• Drugs used to treat migraine headache
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Pathophysiology
• ADHD may be caused by disregulation of the neurotransmitters serotonin, norepinephrine & dopamine. This occurs in children less than 7 y/o but may persist through the teenage years. More common in boys. Characterized by inattentiveness, inability to concentrate, restlessness, hyperactivity, inability to complete tasks & impulsivity.
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A: My son is hyperactive.B: Kids are like that sometimes.A: No, I''m serious. He is constantly on the go from 5 a.m. to 10
p.m.
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Pathophysiology
• Narcolepsy is characterized by falling asleep during normal waking activities. Sleep paralysis usually accompanies it & affects voluntary muscles.
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AMPHETAMINE-LIKE DRUGS
• MOA: stimulate the release of NE & Dopa• For the treatment of ADHD & Narcolepsy• increases attention span, cognitive performance & to decrease
impulsiveness, hyperactivity & restlessness• SE: restlessness, insomnia, tachycardia, hypertension,
palpitation, dry mouth, anorexia, weight loss, diarrhea, impotence
• Antihypertensive & barbiturates decrease action & Caffeine increase its action
• Methylphenidate (Ritalin)Pemoline (Cylert)
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AnalepticsAnaleptics ( (BemegridumBemegridum,, Camphora Camphora, , CordiaminumCordiaminum))
CamphoraCamphora
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ANALEPTICS
• CNS stimulants mostly affecting the brainstem & spinal cord but also affects the cerebral cortex
• Primary use is to stimulate respiration like in newborns with respiratory distress
• SE: nervousness, restlessness, tremors, palpitations, insomnia, diuresis, GI irritation
• Methylxanthines – caffeine, theophylline
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RESPIRATORY CNS STIMULANT
• CNS & respiratory stimulant used to treat respiratory depression caused by drug overdose, pre- & postanesthetic respiratory depression & chronic obstructive pulmonary disease (COPD)
• Doxapram HCl (Dopram)
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NOOTROPIC DRUGSNOOTROPIC DRUGS
((NEUROMETABOLIC NEUROMETABOLIC CEREBROPROTECTORS)CEREBROPROTECTORS)
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Neurometabolic cerebroprotectors
• 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
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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
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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 if mental insufficiency
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Piracetam Piracetam ((nootropilnootropil))
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CerebrolysinCerebrolysin
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CinnarizinCinnarizin ( (stugeronstugeron))
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ADAPTOGENSADAPTOGENS
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AdaptogensAdaptogensDrugs of
Ginseng, Schizandrum, Rodiola, Eleutherococcus, Leusea,
Echinacea
Apilac, propolis, mumie, heparin, dybazol
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GINSENGGINSENG
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RODIOLARODIOLA
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Schizandrum
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Echinacea purpurea MaximaEchinacea purpurea Maxima
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ADAPTOGENSIncrease general resistance of the organism
towards unfavorable factors
Stimulating actionAntistress action Anabolic action
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Side effects of adaptogens
Increasing of AP
disturbance of sleep if administered in evening time, overwhelming excitation, psychic dependence